Manual of Pediatric Cardiac Intensive Care (1)

“This page intentionally left blank"

Manual of

Pediatric Cardiac Intensive Care

Manual of

Pediatric Cardiac Intensive Care Pre- and Postoperative Guidelines

Manoj Luthra MS, DNB, MCh (Cardiothoracic Surgery), FIACS Professor of Cardiothoracic Surgery and Dean Armed Forces Medical College Pune, Maharashtra, India

ERRNVPHGLFRVRUJ

ELSEVIER A division of Reed Elsevier India Private Limited

Manual of Pediatric Cardiac Intensive Care Luthra ELSEVIER A division of Reed Elsevier India Private Limited Mosby, Saunders, Churchill Livingstone, Butterworth-Heinemann and Hanley & Belfus are the Health Science imprints of Elsevier. © 2012 Elsevier All rights are reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior written permission of the publisher. ISBN: 978-81-312-3050-3 Medical knowledge is constantly changing. As new information becomes available, changes in treatment, procedures, equipment and the use of drugs become necessary. The authors, editors, contributors and the publisher have, as far as it is possible, taken care to ensure that the information given in this text is accurate and up-to-date. However, readers are strongly advised to confirm that the information, especially with regard to drug dose/usage, complies with current legislation and standards of practice. Please consult full prescribing information before issuing prescriptions for any product mentioned in this publication.

Published by Elsevier, a division of Reed Elsevier India Private Limited. Registered Office: 305, Rohit House, 3, Tolstoy Marg, New Delhi – 110 001. Corporate Office: 14th Floor, Building No. 10B, DLF Cyber City, Phase-II, Gurgaon, Haryana – 122 002. Senior Commissioning Editor: Shukti Mukherjee Bhattacharya Managing Editor (Development): Shabina Nasim Development Editor: Shravan Kumar Manager – Publishing Operations: Sunil Kumar Manager – Production: NC Pant Typeset by Olympus Premedia Pvt. Ltd. ( formerly Olympus Infotech Pvt. Ltd.), Chennai, India. www.olympus.co.in Printed and bound at Shree Maitrey Printech Pvt. Ltd., Noida

“While it is human to err, it is inhuman not to try, if possible, to protect those who entrust their lives into our hands from avoidable failures and danger” —Max Thorek (1880–1960)


Foreword

The ability to escort the cardiac patient through the pre- and postinterventional or operative period in the intensive cardiac care unit successfully is the most important part of a clinician’s commitment. A pediatric cardiac patient requires to be handled by an integrated group of specialists that may include not only the surgeon, cardiologist and intensivist but a host of other related specialities. Given this complexity, there is a need for guidelines and protocols to be laid down and a common approach to be followed at any institution. There is an exhaustive amount written on cardiac intensive care as the subject is vast and varied, but not always readily accessible. This book is a practical reference guide with a balanced perspective that can be consulted when faced with a challenging pediatric cardiac case or read otherwise. It is never easy to remember pediatric doses of even common drugs and this manual would serve as a useful aid. Newer techniques and consensus statements have been incorporated. A number of related aspects and complications have been covered which of course is highly relevant as we are dealing with situations where in a large number of drugs are being used on a sick child often in a background of altered ‘milieu interior’. Writing a foreword for this book has brought to the forefront, my own involvement of over three decades, in the surgical treatment of children with heart disease. There have been exciting new developments occurring in the field of intensive care all the time, however, the fundamental issues in management have not changed greatly. Often variations in management amongst the treating specialists are more variations in style rather than substance, and accepted institutional norms of treatment will be of immense benefit to our junior colleagues. Despite the explosive growth of digital technologies, residents and fellows still need that “manual” which is a concise and readable summary of established clinical methods and protocols. I believe this book can stand as one of those cornerstones of intensive care therapy of a child. Graham Nunn FRACS Consultant Pediatric Cardiothoracic Surgeon Formerly, Director of Pediatric Cardiac Surgery, Mater Children’s Hospital, Brisbane, Australia


Preface

The ability to manage a pediatric cardiac surgical patient in the pre- and postoperative period is as important as the surgery itself. Undoubtedly, the continued improvement in monitors, ventilators, and analyzers has made the task easier, and the results today are better than ever before. Despite the advancement, the precision of a medical device can only compliment a clinician’s knowledge and his practical abilities, and is not going to prevent complications and errors in medical or surgical management. So much has been written about the prevention and management of complications and errors, yet there is no substitute for simple protocols, check lists, and guidelines. This book is an effort in that direction. It summarizes and reiterates the accepted pre- and postoperative guidelines in the intensive care of pediatric cardiac surgery patients. It has been my endeavor to prepare a practical sort of a book that can be easily read at leisure and referred to at the bedside and provide relevant information with drug doses and protocols. I have aimed to keep the chapters short and highly relevant thereby providing simple solutions and explanations to clinical problems rather than offering detailed physiological explanations. Drugs relevant to the system under consideration have been given in tables so that these can be easily referred to at the point of care. Drug doses have been quoted primarily from two sources, the online pharmaceutical reference drugs.com web site (http://www.drugs.com/) and “Martindale: The Complete Drug Reference” (Pharmaceautical Press, Great Britain). Wherever applicable, the current international guidelines on the topic under consideration have been quoted. In several of the chapters, I have taken the liberty of mentioning a relevant quotation at the beginning to provide the reader something to think about! Even though this book is specifically written for the perioperative management of the child undergoing cardiac surgery, it will be equally useful to physicians and nursing staff who are actively involved in the bedside management of any acutely ill child. This book targets cardiac surgery, pediatric and critical care residents working in cardiac intensive care units and junior cardiac surgery consultants. It will address the need of a reference

x

Preface

manual for general surgery and medicine residents too, while on rotation in the cardiac care unit. In the end, I do sincerely hope that I have been able to write something worthwhile for the new cardiac surgeon in the making, which will in some small way contribute to his ascent to the pinnacle of his profession. I am sanguine that this book will also prove adequate for others involved in the intensive care of children.

Acknowledgments In the preparation of this manual I owe a deep debt of gratitude to many of my colleagues from various departments at the college who spared their valuable time to review the chapters in their areas of specialization— Drs. JK Kairi and Sharmila Sinha from the Department of Pharmacology, Drs. Mukti Sharma and Daljit Singh from Pediatrics and Neonatogy, Drs. Ravi Chaturvedi and Vipul Sharma from Anesthesiology, Dr. Velu Nair from Medicine, Dr. Jyoti Kotwal from Hematology, Dr. Subroto Dutta from Cardiology, and Dr. Gaurav Kumar from my Department of Cardiothoracic Surgery. I am grateful to Dr. Prabel Deb for verifying the bibliography and sources. I had the opportunity to interact with some very fine people of the editorial staff of Elsevier, the publishers of this book, and in particular wish to express my gratitude to Mr. Shravan Kumar, Ms. Shabina Nasim, and Ms. Shukti Mukherjee for their professional attitude and support for this project. I would like to thank Mr. Benjamin Jacob who was involved with the initial conception of the book and provided the time and encouragement. The excellent line diagrams and ECGs were made by Mr. Nishant Shinde from the Medical Arts Department. I guess the maximum contribution to any medical text is none other than the patient himself. He provides us not only the purpose of the text but the practical experience to go with it. Even though I mention them last, I owe my wife and daughters so much more than patience, cheer, and sound judgment. Manoj Luthra

Contents

Foreword Preface Acknowledgments

vii ix x

1

Hemodynamic Monitoring

2

Low Cardiac Output

15

3

Inotropes and Other Vasoactive Drugs

24

4

Congestive Heart Failure

32

5

Cardiac Tachyarrhythmias

37

6

Bradyarrhythmias and Pacemakers

63

7

Hypertensive Emergencies

78

8

Pulmonary Hypertension

83

9

Cyanotic Spells

87

10

Pediatric Resuscitation

89

11

Fluid and Electrolytes

100

12

Arterial Blood Gas Analysis

112

13

Parenteral Nutrition

124

14

Enteral Feeding

130

15

Gastrointestinal Drugs

136

16

Postoperative Respiratory Complications

140

17

Acute Respiratory Distress Syndrome

146

1

xii

Contents

18

Postoperative Bronchospasm

150

19

Ventilation

156

20

Ventilator Associated Pneumonia

176

21

Antibiotics

182

22

Sepsis and Multiorgan Dysfunction

202

23

Systemic Antifungal Agents

211

24

Sedatives, Analgesics, and Muscle Relaxants

217

25

Seizures

227

26

Management of the Comatose Child

233

27

Acute Kidney Injury

241

28

Coagulation Disorders in the Postoperative Period

256

29

Antithrombotic Agents

267

30

Management of Anaphylaxis

273

Appendices A B C D E F G H I J K L M N O

International System of Units (SI Units) and Conversion Factors Vital Signs Anthropometric Measurements and Major Motor Milestones Hematological Parameters Normal Laboratory Values for Children Composition of Frequently Used Parenteral Fluids Size and Length of Pediatric Endotracheal Tubes and Suction Catheters Postoperative Checklist on Arrival in ICU Postoperative Instructions Fluid Prescription after Open Heart Surgery Calculations of Drug Infusions Preparation of Various Concentrations of Solutions Cries Pain Scale Drug Prescription in Renal Failure Pediatric Blood Levels of Commonly Used Drugs

Index

277 280 281 283 285 287 289 290 291 295 297 299 301 302 306 307

Hemodynamic Monitoring “Everything that can be counted does not necessarily count; everything that counts cannot necessarily be counted” — Albert Einstein (1879 –1955)

Isovolumic relaxation Isovolumic contraction

Pressure (mmHg)

Ejection Aortic valve opens 120 100 80 60 A-V valve closes 40 a 20 0 R P

Diastasis Rapid Atrial systole inflow Aortic valve closes

A-V valve opens c

Aortic pressure Atrial pressure

v Ventricular pressure ECG

T

Q S Fig. 1: Cardiac cycle.

Mean Arterial Pressure The mean arterial pressure (MAP) determines the volume of blood flow to various organs of the body. It is dependent upon the cardiac output (CO), systemic vascular resistance (SVR), and central venous pressure (CVP) based on the following relationship: MAP = (CO × SVR) + CVP At normal resting heart rates, MAP can be approximately calculated by adding one-third of the pulse pressure to the diastolic pressure: MAP = DBP + 1⁄ 3 (SBP − DBP) (SBP: systolic blood pressure, DBP: diastolic blood pressure)

ERRNVPHGLFRVRUJ

2

Manual of Pediatric Cardiac Intensive Care

However, at higher heart rates, because of the altered shape of the arterial pressure waveform, the MAP is approximated more closely by the arithmetic mean of systolic and diastolic pressures. The 5th percentile systolic and 5th and 50th percentile mean arterial pressure in normal children can be estimated by the following clinical formulae: SBP (5th percentile at 50th height percentile) = (2 × age in years) + 65 MAP (5th percentile at 50th height percentile) = (1.5 × age in years) + 40 MAP (50th percentile at 50th height percentile) = (1.5 × age in years) + 55. The 5th percentile SBP values have been used to define hypotension in various age groups.

Pulse Pressure Systolic pressure

Pulse pressure (mmHg)

120 Dicrotic notch

Diastolic pressure

80 Fig. 2: Normal arterial pressure waveform.

The pulse pressure is the difference between the systolic and diastolic pressures. An increase in stroke volume or vasodilatation causes widening of the pulse pressure; examples of causes include, anemia, fever, aortic regurgitation, and AV malformation. A decrease in stroke volume or vasoconstriction results in narrowing of the pulse pressure as in hypovolemia, congestive cardiac failure, aortic stenosis, and cardiac tamponade.

Analysis of the Arterial Pressure Waveform The arterial pressure waveform consists of an upstroke to the level of the peak systolic pressure, and then a decline to the level of the end diastolic pressure. The down slope is interrupted by the dicrotic notch, which is a

ERRNVPHGLFRVRUJ


3

mmHg

150

100 Normal 50

mmHg

150

100 Overshoot 50

mmHg

150

100 Damped trace 50 Fig. 3: Systolic overshoot and damped arterial waveforms.

reflection of the closure of the aortic valve. The characteristics of the pressure recordings depend upon various factors: Systolic overshoot is a false higher blood pressure reading than the actual pressure because of the dynamic response characteristics of the monitoring system. This may happen when there is a sudden rise in the pressure upstroke of the wave form, as in the pressure recordings in hypertension or rapid heart rates. Damping of the blood pressure tracing abnormally narrows the pulse pressure and should be suspected when the dicrotic notch is not visible on the recording. Damping can be caused by air bubbles or blood in the monitoring lines or kinking of the arterial cannula. The level of the transducer has an effect on the blood pressure recording. Transducer level above the actual level of the left atrium results in under-estimation of the blood pressure and vice versa. (1 cm difference in transducer level causes a 0.74 mmHg variation in the measured pressure, i.e., a level 10 cm below will result in an overestimation of 7.4 mmHg). Correct transducer level is more important for recording CVP and PA pressures, since these pressures are much lower with a smaller range of variation.

ERRNVPHGLFRVRUJ

4


Ascending aorta

Abdominal aorta

Radial artery Fig. 4: Change in the arterial waveform as the arterial pulse travels peripherally.

Site of recording: The arterial pressure waveform also changes as it travels from the central aorta to the periphery, the systolic pressure rises and the diastolic pressure falls (i.e., the pulse pressure widens) and in addition the dicrotic notch appears later. The MAP in the aorta is slightly higher than in the radial artery. Cardiac lesions: Various pathological conditions of the heart also result in alteration of the morphology of the arterial pressure waveform: ■

Pulsus tardus et parvus occurs in aortic stenosis, the upstroke of the pulse rises slowly and peaks late (tardus), the pulse amplitude is small (parvus) with an anacrotic notch on the upstroke and an absent dicrotic notch.

■

In a collapsing pulse, a large stroke volume causes the arterial pulse to rise rapidly and an increased runoff results in a lower diastolic pressure with a wide pulse pressure, e.g., aortic regurgitation and patent ductus arteriosus.

■

In a bisferiens pulse, the arterial pressure pulse has two systolic peaks because of the large stroke volume and a wave of reflection. The bisferiens pulse may be present in aortic regurgitation, in patients with mixed aortic regurgitation and stenosis, and in hypertrophic cardiomyopathy.

■

Pulsus alternans is recognized by the presence of alternating large and small systolic peaks. It is a sign of severe left ventricular systolic dysfunction and may become evident during general anesthesia. Ventricular bigeminy also creates alternating pressure peaks in the arterial pressure waveform, but the ECG rhythm reveals bigeminy. In pulsus alternans, the ECG is regular with a normal QRS configuration.

ERRNVPHGLFRVRUJ


5

Normal pulse

Pulses tardus et parvus

Collapsing pulse

Bisferiens pulse

Pulsus alternans Fig. 5: Different arterial waveforms in diseased conditions of the heart.

Pulsus paradoxus is an exaggeration of the inspiratory fall in systolic arterial pressure (more than 10 mmHg) noted during spontaneous respiration. Some inspiratory reduction of blood pressure is normal, and pulsus paradoxus is an exaggeration of this normal phenomenon. It is found in cardiac tamponade, constrictive pericarditis, and in patients with airway obstruction or bronchospasm. Baseline pressure 110 mmHg

■

70 0 Inspiration

Expiration

Inspiration

Fig. 6: Pressure variation during intermittent positive pressure ventilation.

ERRNVPHGLFRVRUJ

6


Blood pressure variation during positive pressure ventilation: A phenomenon that is reverse of pulsus paradoxus is seen during positive pressure ventilation due to changes in systemic venous return. During inspiration, there is an augmentation of systolic pressure and a later decrease in pressure during expiration (in an adult patient, up to a 5 mm increase followed by a 5 mm fall below the baseline measured at end expiration). Hypovolemia results in an increase in this variation, especially downwards even if the systolic pressure is normal.

Analysis of the Central Venous Pressure R P

T Q S

a

ECG v

c x

y

Normal JVP

a c

v x

y

Cannon ‘a’ wave

v a

Giant ‘v’ wave Fig. 7: CVP waveforms and its correlation with the ECG.

The central venous pressure (CVP) is a measure of the mean right atrial pressure, and the waveform reflects the events of cardiac contraction. There are three positive waves (a, c, and v) and two negative descents (x and y), and these correlate with different phases of the cardiac cycle and ECG. ■

‘a’ wave: This wave is a reflection of right atrial contraction and immediately follows P wave on ECG.

■

‘c’ wave: During early ventricular contraction, there is a slight elevation of the tricuspid valve into the right atrium resulting in the c wave. It therefore correlates with the end of the QRS segment on ECG.

ERRNVPHGLFRVRUJ


7

■

‘x’ descent: The x descent is caused by the downward movement of the ventricle during systole.

■

‘v’ wave: Right atrial filling results in the v wave.

■

‘y’ descent: The y descent is produced by blood flow into the right ventricle in diastole. It therefore precedes P wave on ECG.

Central venous pressure falls slightly with spontaneous inspiration, and increases marginally with positive pressure inspiration and forced exhalation. Addition of positive end expiratory pressure (PEEP) further increases the CVP, though this may not be significant. (A PEEP of 10 cm H2O is likely to increase the CVP by less than 3 mmHg). The CVP falls because of hypovolemia, shock, and vasodilatation. It is elevated in case of hypervolemia, increased pulmonary vascular resistance, or right ventricular failure.

Abnormal CVP Waveforms Trace

Lesion

Cannon ‘a’ waves

Complete heart block, tricuspid stenosis, pulmonary hypertension, pulmonary stenosis

Absent ‘a’ waves

Atrial fibrillation

Giant ‘v’ waves

Tricuspid regurgitation

Canon ‘a’ waves are produced in AV dissociation because of contraction of the atrium against a closed tricuspid valve. These may also be seen in tricuspid stenosis, pulmonary hypertension, and pulmonary stenosis due to resistance to RV filling. In tricuspid regurgitation, the c wave and x descent are replaced by giant ‘v’ waves because of the regurgitation of blood into the right atrium during ventricular contraction. This can cause a false elevation in the mean CVP. In cardiac tamponade, the CVP is elevated and the y descent is absent.

Normal Pressures and Saturations in Pediatric Heart Chamber

Pressure (mmHg)

O2 saturation (%)

Right atrium (mean)

2–6

60–80

Right ventricle

30/3

60–80

Pulmonary artery (systolic)

15–25

Pulmonary artery (diastolic)

6–12

ERRNVPHGLFRVRUJ

8


Chamber

Pressure (mmHg)

Pulmonary artery (mean) Left atrium (mean)

O2 saturation (%)

15 6–12

97–100

Left ventricle

100/6

97–100

Aorta

100/60

97–100

Left ventricular end diastolic pressure (LVEDP) is a reflection of LV function, and in the absence of mitral valve disease the LVEDP is equal to the left atrial pressure (LAP). Further, if there is no obstruction in the pulmonary venous or capillary blood circulation, the LAP will equal the pulmonary capillary wedge pressure (PCWP). Therefore, the LAP or PCWP is used to monitor left heart function in addition to the volume status of the patient. The LAP can be measured by a direct LA line placed at surgery, and the PCWP can be measured by a pediatric Swan Ganz catheter (4-5 F). Right ventricle

Pulmonary artery

25 mmHg

20 15

Wedge

10 Right atrium 5 0 Fig. 8: Pressure trace in various locations on the right side of the heart.

Central venous pressure is equal to the right atrial pressure and right ventricular end diastolic pressure (RVEDP) provided there is no obstruction to central venous return (e.g., SVC syndrome, IPPV with high airway pressures) or tricuspid valve disease and is a reflection of the RV function and the volume status of the patient. Pulmonary artery pressure provides objective evaluation of pulmonary hypertension and can be measured by a thermistor PA catheter or a Swan Ganz placed via a large vein or by a direct PA catheter placed at surgery. A continuous postoperative recording is useful in the management of children with pulmonary artery hypertension.

Systemic Arterial Oxygen Saturations In normal individuals, systemic arterial oxygen saturation (SpO2) is 97–100% and systemic venous oxygen saturation (SvO2) is 60–80%. The

ERRNVPHGLFRVRUJ


100

100

98 97

90

91 90

9

80

SpO2 (%)

70 60 50 40 30 20 10 27

0 0

10

20

30

40 50 60 PaO2 (mmHg)

70

80

90

100

Fig. 9: Normal oxygen dissociation curve (Centre graph) with shift to the left and right.

SpO2 varies with the partial pressure of oxygen, but the relationship is not linear and is described by the oxygen dissociation curve. The implication of the sigmoid shape of the oxygen dissociation curve is that at the lower and upper end of the curve, i.e., at PaO2 of less than 20 mmHg and more than 60 mmHg, a significantly large change in PaO2 results in little change in SpO2. At PaO2 range of 20–60 mmHg, a small change in PaO2 results in a marked change in SpO2. Provided the patient’s pH is normal, one can approximately estimate the PaO2 from the recorded SpO2 by the rule of 4-5-6, 7-8-9. 1. SpO2 of 90% : 60 mmHg PaO2 2. SpO2 of 80% : 50 mmHg PaO2 3. SpO2 of 70% : 40 mmHg PaO2 However, with a shift of the oxygen dissociation curve to the left (↑ pH, ↓ temperature, ↓ PaCO2) there is an increased affinity of hemoglobin for oxygen and the same O2 saturation implies a lower PaO2. With a shift of the curve to the right (↓ pH, ↑ temperature, ↑ PaCO2), there is a decreased affinity for oxygen and with the same O2 saturation, the PaO2 is higher.

ERRNVPHGLFRVRUJ

10


Systemic Venous Oxygen Saturation

Decreased SvO2

Causes

Remark

Decreased oxygen supply

Hypoventilation, pulmonary edema, atelectasis, anemia, residual intracardiac R–L shunt.

Increased oxygen demand

Fever, pain, shivering, arrhythmia, cardiac failure.

Decreased cardiac output Increased SvO2

Increased oxygen supply Decreased oxygen demand

Mechanical ventilation, PEEP, sedation, anesthesia. Inotropic support, tachycardia.

Increased cardiac output

Systemic venous oxygen saturation (SvO2, normal range: 60–80%) can be monitored continuously with a specialized PA catheter or in vitro, with blood samples obtained from the right atrium or superior vena cava. SvO2 monitoring provides assessment of tissue oxygenation. It shows whether the oxygen supply is adequate to meet the tissue demands and is thus a non-specific indicator of the cardiac output.

Hemodynamic Calculations Calculation

Child normal values

Adult normal values

Cardiac output (CO)

CO = Stroke volume × heart rate

At birth: 300–400 mL/kg/min

5–6 L/min

Cardiac index (CI)

CI =

3.0–4.5 L/min/m2

2.7–4.3 L/min/m2

Systemic vascular resistance (SVR: dynes-sec-cm−5)

SVR =

MAP − CVP × 80 CO

1200–2800 dynes-sec-cm−5


Pulmonary vascular resistance (PVR: dynes-sec-cm−5)

PVR =

MPA − PCWP × 80 CO



Cardiac output BSA

MAP: mean arterial pressure, CVP: central venous pressure, MPA: mean pulmonary artery pressure, PCWP: pulmonary capillary wedge pressure, BSA: body surface area.

ERRNVPHGLFRVRUJ


11

Cardiac Output Cardiac output (liters/minute) is defined as the amount of blood ejected from the left ventricle in 1 minute. Stroke volume (SV) is the amount of blood ejected from the left ventricle with each beat. CO = Stroke volume (SV) × Heart rate (HR) Stroke volume = End diastolic volume (EDV) – End systolic volume (ESV) Ejection fraction (EF) = (SV/EDV) × 100% The average cardiac output for an adult is about 5–6 liters per minute at rest and the stroke volume 50–80 mL per beat. Cardiac output can be measured by a number of clinical methods ranging from intracardiac catheterization to non-invasive assessment of the arterial pulse. The standard method of measuring CO used in the laboratory is by the Fick’s oxygen consumption method, which requires measurement of: 1. ‘O2 consumption per minute’ using a spirometer, 2. ‘The arterial O2 content’ of peripheral arterial blood, 3. The ‘mixed venous O2 content’ from a sample of blood taken from the pulmonary artery. Then, CO =

O2 consumption (Arterial O2 content − Venous O2 content)

“Arterial O2 content − Venous O2 content” is also known as the arterio-venous oxygen difference. The arterial and venous oxygen content of the blood can be calculated from the fact that the oxygen in the blood is bound to hemoglobin and that one gram of hemoglobin can carry 1.34 mL of O2 and a small amount of oxygen is in a dissolved state. O2 content of blood = [Hb (g/dL) × 1.34 × % saturation of blood] + [0.0032 × Partial pressure of O2 (mmHg)] At the bedside, the cardiac output can be calculated by the thermodilution technique, using a cardiac output computer after placing a thermistor PA catheter or a pediatric Swan Ganz catheter (4-5 F).

Systemic Vascular Resistance An abnormally high SVR indicates peripheral vasoconstriction (e.g., in response to hypovolemia or inotropes). An abnormally low SVR reflects

ERRNVPHGLFRVRUJ

12


peripheral vasodilation (e.g., in septic shock or as a result of administration of vasodilator drugs).

Pulmonary Vascular Resistance Normal PVR is approximately one-sixth of the SVR. PVR may be abnormally high in cardiac disease associated with pulmonary hypertension, in lung disease, pulmonary embolism, acidosis or hypoxia.

Calculation of Shunts BODY

BODY

AO

SVC/IVC

LV LA

RA RV

PV

PA

AO

LV LA

SVC/IVC

L–R

PV

RA RV

PA

LUNGS

LUNGS

Fig. 10: Line diagram of normal circulation (L); Circulation in L–R shunt (R). AO: aorta, SVC: superior vena cava, IVC: inferior vena cava, RA: right atrium, RV: right ventricle, PA: pulmonary artery, PV: pulmonary veins, LA: left atrium, LV: left ventricle.

Qp (SpO2 − MVO2 ) = Qs (PVO2 − PAO2 ) Qp: pulmonary blood flow, Qs: systemic blood flow, SpO2: systemic arterial O2 saturation, MVO2: mixed venous O2 saturation (MVO2 is the average of SVC, IVC, and RA saturation and the average of SVC and IVC saturations, in case of VSD), PVO2: pulmonary venous O2 saturation (assumed 98% if not measured), PAO2: pulmonary artery O2 saturation.

The ratio of pulmonary to systemic blood flow (Qp/Qs) is used to quantify the shunt. Oxygen saturation of blood samples obtained from various cardiac chambers are used to calculate pulmonary and systemic blood flow as noted in the formula above. The shunt can also be calculated

ERRNVPHGLFRVRUJ


13

more accurately by obtaining systemic and pulmonary blood flows by the Fick’s method. Qp/Qs > 1.5:1.0 is a significant shunt. In the normal circulation, the systemic and the pulmonary circulation are in series. The blood which is ejected into the aorta, returns to the right heart via the SVC/IVC and then is pumped into the pulmonary circulation. Thus, the pulmonary blood flow is equal to the systemic blood flow. In L–R shunt, part of the systemic blood flow bypasses the systemic circulation and flows directly into the pulmonary part of the circulation with every cycle, so that the systemic circulation is depleted of this blood and the pulmonary circulation has this additional amount of blood flow. Therefore, the effective pulmonary blood flow in: ■

Left-to-right shunt = Systemic blood flow + Shunt flow

■

Right-to-left shunt = Systemic blood flow − Shunt flow.

Bibliography 1. Beerbaum P, Körperich H, Barth P, et al. Noninvasive quantification of left-to-right shunt in pediatric patients. Phase-contrast cine magnetic resonance imaging compared with invasive oximetry. Circulation 2001;103:2476–82. 2. Bell DR. Cardiac muscle mechanics and the cardiac pump. In: Rhodes RA, Bell DR eds. Medical Physiology. Principles for Clinical Medicine 3rd ed. Philadelphia: Lippincott Williams and Wilkins; 2009:243–62. 3. Grap MJ. Pulse oximetry. Crit Care Nurse 2002;22:69–74. 4. Gupta R, Yoxall CW, Subedhar N, Shaw NJ. Individualised pulse oximetry limits in neonatal intensive care. Arch Dis Child Fetal Neonatal Ed 1999;81:F194–6. 5. Haque IU, Zaritsky AL. Analysis of the evidence for the lower limit of systolic and mean arterial pressure in children. Pediatr Crit Care Med 2007;8(2):138–44. 6. Heitmiller ES, Nyhan D. Perioperative monitoring. In: Nichols DG, Cameron DE, Greeley WJ, Lappe DG, Ungerleider RM, Wetzel RC eds. Critical Heart Disease in Infants and Children St Louis: Mosby; 1995:467–96. 7. Joao PRD, Faria F Jr. Immediate post operative care following surgery. J Pediatr (Rio J) 2003;79(Suppl 2):S213–22. 8. Klabunde RE. Central venous pressure waveforms. University of Virginia, School of Medicine. [Updated: 2005 Apr 21; cited: 2011 Oct 15] Available at: http://www.healthsystem.virginia. edu/internet/anesthesiology-elective/cardiac/cvpwave.cfm. 9. López-Herce J, Bustinza A, Sancho L, et al. Cardiac output and blood volume parameters using femoral arterial thermodilution. Pediatr Int 2009;51:59–65. 10. Mark JB, Slaughter TF, Reeves JG. Cardiovascular monitoring. Practice Guidelines for Perioperative Transesophageal Echocardiography and Practice Guidelines for Pulmonary Artery Catheterization. Churchill Livingstoine. © 1979 [Updated: 2000; cited: 2011 Feb 22] Available at: http://web.squ.edu.om/med-Lib/MED_CD/E_CDs/anesthesia/site/content/v03/ 030267r00.HTM 11. McGhee BH, Bridges EJ. Monitoring arterial blood pressure: what you may not know. Crit Care Nurse 2002;22:60–4, 66–70, 73 passim. 12. O’Rourke RA, Silverman ME, Shaver JA. The history, physical examination & cardiac auscultation. In: Fuster V, Alexander RW, O’Rourke RA eds. Hurst’s The Heart Vol 1. The McGraw-Hill Companies Inc; 2004:217–94.

ERRNVPHGLFRVRUJ

14


13. Powell FL Jr. Oxygen and carbon dioxide transport in the blood. In: Johnson LR ed. Essential Medical Physiology 3rd ed. California, USA: Academic Press. An Imprint of Elsevier; 2003:289–98. 14. Salyer JW. Neonatal and pediatric pulse oximetry. Respir Care 2003;48(4):386–96. 15. Schlame M, Blanck TJJ. Cardiovascular system. In: Gabrielli A, Layen AJ, Yu M eds. Civetta, Taylor & Kirby’s Critical Care 4th ed. Philadelphia: Lippincott Williams and Wilkins; 2009:682–99. 16. Tamer DM, Watson DD, Kenny PP, et al. Noninvasive detection and quantification of left-toright shunts in children using oxygen-15 labeled carbon dioxide. Circulation 1977;56:626–31.

ERRNVPHGLFRVRUJ

Low Cardiac Output “The heart is the chief mansion of the soul, the organ of vital capacity, the beginning of life, the foundation of the vital spirits… the first to live, the last to die” —Ambroise Paré (1510–1590)*

Clinical Evaluation of Low Cardiac Output Parameter

Normal perfusion

Low cardiac output

Skin

Warm, brisk capillary fill

Sluggish capillary refill (>3–4 sec), mottled appearance, peripheral cyanosis

Color of mucous membranes

Pink

Pallor

Temperature

Normal

Cool periphery, core temperature >39°C

Heart rate

As per age

Tachycardia

Blood pressure

As per age

↓ BP, narrow pulse pressure ↑ respiratory variation of BP in hypovolemia

Urine output

Normal

Oliguria, anuria

Neurological status

Age appropriate activity

Irritable, lethargic

Feeding

Eats well/strong sucking reflex

Weak sucking reflex, tires during feeding

GIT

Normal

↑ gastric tube aspirate, abdominal distension, later jaundice, ↑ liver enzymes

Hydration

Normal

Sunken fontanelle, poor skin turgor, dry mucous membranes in prolonged hypovolemia

CVP/LAP

2–6 mmHg/6–12 mmHg

↓ in hypovolemia, CVP ↑ in RV failure

Mixed venous saturation

60–80%

<60%

Serum electrolytes

Normal

Metabolic acidosis

BP: blood pressure, CVP: central venous pressure, LAP: left atrial pressure, RV: right ventricle.

*Ambroise Paré was the official surgeon to four French kings. He is known as the “father of modern surgery” for his numerous innovations in operative methods.

ERRNVPHGLFRVRUJ

16


Skin, Temperature, and Peripheral Pulses Early signs of low cardiac output include tachycardia, peripheral cooling, and prolonged capillary refill times (>3–4 sec). Absent pulses, mottling of the skin, and peripheral cyanosis are late signs.

Blood Pressure In the initial phases of low cardiac output, the blood pressure may be well maintained by vasoconstriction. In hypovolemia, even though the blood pressure is normal, a narrow arterial pulse pressure (<15 mmHg in small children)—which is associated with an increased variation of the systolic blood pressure with respiration—is an early sign. Hypotension becomes evident when the loss in the circulating volume can no longer be compensated by tachycardia and vasoconstriction (decompensated shock).

Urine Output Urine output gradually diminishes, and oliguria (urine output <0.5–1 mL/kg/h) progresses to anuria.

CNS Manifestations Neurological deterioration becomes apparent with low cardiac output; the child initially becomes irritable, then lethargic, and subsequently unresponsive.

GIT Impaired gastrointestinal perfusion causes feeding intolerance, abdominal distension, and increased feeding tube aspirate because of paralytic ileus. Over a period of time, there may be mild jaundice with elevation of hepatic enzymes.

Dehydration Signs of dehydration eventually become apparent in children in whom the cause of low cardiac output is hypovolemia.

ERRNVPHGLFRVRUJ

Low Cardiac Output

17

Filling Pressures CVP and LAP levels depend on the cause of the low cardiac output. Both are low in a volume depleted patient (hemorrhage, vasodilatation).

Mixed Venous Saturation Mixed venous saturation is low due to excessive oxygen extraction (i.e., <60%).

Biochemistry Biochemical parameters reveal metabolic acidosis and elevation of serum lactate levels (normal 1–2 mmol/L).

Septic Shock The clinical manifestations are different in patients with vasodilatory shock (sepsis or anaphylaxis). These patients initially have a normal or high cardiac output and low systemic vascular resistance. They present with brisk capillary refill, bounding pulses, and a warm periphery. The classical signs of low cardiac output appear subsequently.

Factors Controlling Cardiac Output Parameter

Factors increasing CO

Factors decreasing CO

Heart rate

↑ HR results in ↑ CO within a range

↓/↑ HR beyond a point

Preload

High (to a limit)

Low

Atrial kick

Present

Absent (e.g., atrial fibrillation)

Afterload

Low

High

Myocardial contractility

Inotropes

Ischemic/non-compliant myocardium

CO: cardiac output, HR: heart rate.

Heart Rate In general, the heart rate (HR) and cardiac output (CO) have a direct relationship up to a maximum heart rate. As the HR increases, so does CO up to a

ERRNVPHGLFRVRUJ

18


Cardiac output

point, depending upon the age of the patient and the state of the myocardium. Beyond this point, a rise in HR results in a fall in CO because of increased myocardial oxygen consumption and a shorter ventricular filling time. With a diseased myocardium, the ability to increase CO with an increasing HR is restricted compared to the normal myocardium. On the other hand, in such a ventricle, the cardiac output also falls more rapidly with a decrease in HR. The non-compliant ventricle is unable to compensate for changes in preload associated with changes in heart rate.

0

50

100 200 Heart rate

250

Fig. 1: Relationship of heart rate and cardiac output.

Stroke Volume Stroke volume is dependent on the preload, afterload, and myocardial contractility.

Cardiac output

Frank–Starling Law

End diastolic volume Fig. 2: Frank–Starling law. Relationship of cardiac output and end diastolic volume.

ERRNVPHGLFRVRUJ

Low Cardiac Output

19

The Frank–Starling law of the heart states that the more the myocardial muscle fiber is stretched in diastole, the more forceful will be the next systolic contraction. In other words, an increase in the end diastolic volume or preload results in an increase in the stroke volume. This is sustained only until a physiological limit has been reached thereafter any further increase in fiber length will cause the force of contraction to decline.

Preload

Contractility

Normal heart

Diseased heart

12 Left ventricular end diastolic pressure (mmHg) Fig. 3: Relationship of contractility and left ventricular end diastolic pressure.

The stroke volume generated by the heart varies with the end diastolic volume or preload of the heart (Frank–Starling law). At the bedside, it is not feasible to measure the ventricular end diastolic volume hence the end diastolic pressure is used as a measure of the preload. The actual relationship between end diastolic volume and end diastolic pressure is however not linear and is dependent upon the compliance of the cardiac muscle. With normal compliance, relatively large increase in volume causes only a small elevation in pressure. Whereas in a non-compliant ventricle, a small increase in volume causes a greater rise in pressure. Thus, when one compares the ‘left ventricular end diastolic pressure/ contractility curves’ of the diseased heart with that of the healthy heart, it is noted that the diseased heart requires higher pressures to achieve the same preload and contractility. Also note that the atrial kick contributes up to 35% of the preload, especially in children. Atrial fibrillation can reduce cardiac output by the loss of this atrial contribution.

ERRNVPHGLFRVRUJ

20


Afterload

Stroke volume (mL)

60

Normal

40

Increased afterload

20

0 0

5 10 15 20 25 Left ventricular end diastolic pressure

Fig. 4: Relationship of stroke volume and left ventricular end diastolic pressure.

Afterload refers to the pressure that the ventricle must overcome to eject its blood volume. Afterload is determined by a number of factors, including the wall thickness of the ventricle, the diastolic blood pressure, and the systemic vascular resistance or the pulmonary vascular resistance in the case of the right ventricle. Afterload has an inverse relationship with the stroke volume. As resistance increases, the force of contraction and stroke volume decreases and this is more evident when there is myocardial dysfunction.

Causes of Low Cardiac Output in the Postoperative Period 1. Rhythm disorders ■

Severe bradycardia/tachycardia

■

Arrhythmias, e.g., AF, heart block, ventricular arrhythmias

2. Decreased LV preload ■

Hypovolemia/vasodilatation

■

Cardiac tamponade

■

RV dysfunction/pulmonary hypertension/high PEEP/tension pneumothorax

3. Increased afterload—acidosis/hypothermia/α-adrenergic agents 4. Poor myocardial contractility ■

Cardiac failure

■

Myocardial stunning

ERRNVPHGLFRVRUJ

Low Cardiac Output ■

Electrolyte/acid–base disorder, e.g., acidosis, hypokalemia, hypocalcemia, hypoxia

■

Sepsis

21

Diagnosis CVP LAP

SVR

CI

↓

↓

↑

↓

Cardiac failure ↑

↑

↑

↓

Septic shock

↑

↑

↓↑

Initially increases CO initially maintained by increased then falls heart rate

Tamponade

↑

↑

↑

↓

Hypovolemia

LAP is low in isolated right heart failure

Equalization of diastolic pressure in all chambers

CVP: central venous pressure, LAP: left atrial pressure, SVR: systemic venous resistance, CI: cardiac index, LAP: left atrial pressure, CO: cardiac output.

An elevated CVP suggests RV dysfunction, increased pulmonary vascular resistance, or cardiac tamponade; in the absence of any of these disorders, the CVP is a reflection of the volume status of the patient. An increased LAP shows left ventricular dysfunction and is normal in isolated right heart failure. Like the CVP is used to assess the volume status of the patient, the LAP is the appropriate monitor of the LV preload provided the LV function is normal (or adequate allowance needs to be given for a raised LAP because of LV dysfunction). In hypovolemia both the CVP and LAP are low and are associated with other features of low cardiac output. Pulmonary hypertension may cause low cardiac output by affecting leftsided preload. When severe pulmonary hypertension or right ventricular failure is the cause of low cardiac output, the CVP will be raised, while the LAP is low/normal. In cardiac tamponade, there is equalization of the CVP, LAP, and diastolic pressures of the LV and RV. Oliguria, peripheral cooling, and other signs of low cardiac output become evident. If the tamponade is caused by a collection of blood in the pericardium, there is also a fall in the hematocrit. ECG, x-ray chest, and 2-D echocardiography will confirm the diagnosis.

Management Transient postoperative cardiac dysfunction and low CO after cardiopulmonary bypass (CPB) is not unexpected. Typically, cardiac output is adequate immediately after surgery and then gradually declines to reach its nadir

ERRNVPHGLFRVRUJ

22


8–12 hours after surgery. With appropriate management, the CO recovers in the next 24 hours or so. Cardiac output is monitored by an assessment of the clinical signs, urinary output, acid–base status, and mixed venous saturations. Blood pressure may not be a true reflection of CO if it is being maintained by an increased SVR. Invasive monitoring (Swan Ganz/pulmonary artery catheters) of CO may not be feasible in small children. 1. Optimize Preload LAP is a reflection of LV contractility and preload. The early phase after CPB is associated with a decrease in compliance of the ventricles, which may require a higher LA pressure for adequate preload to be maintained. The optimum LA pressure that augments the CO may therefore be higher than normal. Raising the LA pressure beyond this point may however, decrease the CO (Frank–Starling law) and also cause pulmonary edema. In the absence of an LA line, CVP is used as a guide to fluid therapy. Preload is optimized by repeated fluid boluses of 5–10 mL/kg based on the LAP/CVP and the clinical parameters. Fluid administered may consist of FFP, 5% albumin, or crystalloids. There is no evidence-based support for one type of fluid over another. 2. Inotrope and Vasodilator Agents Blood pressure

SVR

Indicated drugs

Low

Low

Adrenaline/dopamine (in a dose >5 mcg/kg/min)/noradrenaline

Low

Normal/high

Dopamine (in a dose <5 mcg/kg/min) Dopamine + milrinone Adrenaline + milrinone

Normal

Low/normal/high

Dobutamine/milrinone

High

High

NTG (labetalol/esmolol in severe hypertension)

SVR: systemic vascular resistance, NTG: nitroglycerin.

After the LA pressure has been optimized, the need for inotrope/ vasodilator therapy is dictated by the blood pressure and SVR. Poor capillary refill, acidosis, and a cool periphery are signs of peripheral vasoconstriction. A core temperature over 39°C is also a reflection of high SVR, because of the inability of the vasoconstricted periphery to dissipate heat. In the presence of a low blood pressure and a high SVR, in addition to a β-1 agonist (dopamine, adrenaline), a vasodilator is indicated (milrinone, dobutamine, NTG). A low blood pressure associated with a low SVR requires therapy with a drug with β-1, α-1 action (adrenaline, noradrenaline, dopamine).

ERRNVPHGLFRVRUJ

Low Cardiac Output

23

Various institutions have different inotrope preferences. In the immediate postoperative period, some degree of cardiac dysfunction is anticipated and the SVR is also likely to be increased secondary to a number of factors including hypothermia, pain, and drugs. Therefore, the heart is supported with a predominantly β-1 agent (low dose dopamine or adrenaline.) and the after load is reduced by a vasodilator (milrinone/NTG). Alternatively, dobutamine (which has β-1 and β-2 activity) may be used alone to support the heart.

Bibliography 1. Auler Jr. JOC, Baretto AC, Giminez SC, Abellan DM. Pediatric cardiac postoperative care. Rev Hosp Clin Fac Med S Paulo 2002;57(3):115–23. 2. Cuadrado AR. Management of postoperative low cardiac output syndrome. Crit Care Nurs Q 2002;25(3):63–71. 3. Doyle AR, Dhir AK, Moors AH, et al. Treatment of perioperative low cardiac output syndrome. Ann Thorac Surg 1995;59:S3–11. 4. Haque IU, Zaritsky AL. Analysis of the evidence for the lower limit of systolic and mean arterial pressure in children. Pediatr Crit Care Med 2007;8(2):138–44. 5. Hoffman TM, Wernovsky G, Atz AM, et al. Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation 2003;107(7):996–1002. 6. João PRD, Faria F Jr. Immediate post-operative care following cardiac surgery. J Pediatr (Rio J) 2003;79(Suppl 2):S213–S22. 7. Kumar G, Iyer PU. Management of perioperative low cardiac output state without extracorporeal life support: What is feasible? Ann Pediatr Cardiol 2010;3(2):147–58. 8. Massé L, Antonacci M. Low cardiac output syndrome: identification and management. Crit Care Nurs Clin North Am 2005;17(4):375–83. 9. Rao V, Ivanov J, Weisel RD, et al. Predictors of low cardiac output syndrome after coronary artery bypass. J Thorac Cardiovasc Surg 1996;112:38–51. 10. Ravishankar C, Tabbutt S, Wernovsky G. Critical care in cardiovascular medicine. Curr Opin Pediatr 2003;15(5):443–53. 11. Salenger R i, Gammie J Si, Vander Salm T Ji. Postoperative care of cardiac surgical patients. In: Cohn LH, Edmunds LH Jr, eds. Cardiac Surgery in the Adult New York: McGraw-Hill; 2003: 439–69. 12. Shirai LK. Congestive heart failure. In: Yamamoto LG, Inaba AS, Okamoto JK, Patrinos ME, Yamashiroya VK, eds. Case Based Pediatrics for Medical Students and Residents. Department of Pediatrics, University of Hawaii, John A. Burns School of Medicine; 2004:269–72. 13. Wessel DL. Managing low cardiac output syndrome after congenital heart surgery. Crit Care Med 2001;29:S220–30.

ERRNVPHGLFRVRUJ

Inotropes and Other Vasoactive Drugs “Life is short and art is long; the crises is fleeting, experience risky, decision difficult” —Hippocrates (460–377 BC)

Adrenergic Receptors Receptor

Tissue

Action of agonist

Agonists/antagonists

β1

Heart

↑ Heart rate, contractility and A-V conduction ↑ Cardiac output

Agonists: noradrenaline, adrenaline, isoprenaline, dobutamine Antagonists: metoprolol, atenolol

β2

Blood vessels of skeletal muscles and liver. Smaller coronary vessels

Vasodilatation Bronchodilation

Agonists: salbutamol, isoprenaline, levalbuterol, terbutaline Antagonists: propranolol

Smooth muscle of bronchi, bladder, uterus, intestine

Relaxation of intestine, uterus, bladder

Blood vessels of skin, GIT, kidney

Vasoconstriction

α1

Smooth muscle of ureter, uterus, bronchioles, ciliary body α2

Sphincters of the gastrointestinal tract, bladder

Contraction (Contraction of ciliary body causes mydriasis) Contraction of the sphincters of the GIT and bladder

Agonists: noradrenaline, adrenaline, phenylephrine Antagonists: phenoxybenzamine, phentolamine Agonists: clonidine, dexmedetomidine Antagonist: phentolamine

The actions of adrenergic drugs are based on the type of receptors the drugs act upon. The clinically relevant types of receptors are α1, α2, β1, β2, and dopaminergic (δ) receptors. Myocardial adrenergic receptors are of β1 type, and stimulation of these leads to increased heart rate, AV conduction, myocardial contractility, and cardiac output.

ERRNVPHGLFRVRUJ


25

Blood vessels supplying the skin, GIT, and kidneys have α1 receptors, while skeletal, hepatic, and smaller coronary vessels predominantly possess β2 receptors. Stimulation of α1 receptors causes vasoconstriction and increase in venous return, while β2 stimulation results in vasodilatation and a decrease in venous return. During adrenergic stimulation, both α and β receptors are activated leading to decreased blood supply to skin, GIT, and kidneys and increased blood to the skeletal and cardiac musculature. β2 stimulation also causes bronchodilatation. This constitutes the fight and flight reaction, which diverts blood to the organs important in such a response.

Vasoactive Agents: Dose and Hemodynamic Actions Agent

Dose

Site of action

Effect

Dopamine

0.5–2.5 mcg/kg/min IV infusion 2.5–7.5 mcg/kg/min IV infusion 7.5–20 mcg/kg/min IV infusion

δ δ, β1 α1, β1

↑ RBF ↑ CO, ↑ HR ↑ CO, ↑ HR, ↑ SVR, ↑ MAP, ↓ RBF

Dobutamine

1–20 mcg/kg/min IV infusion

β1, β2

↑ CO, ↑ HR, ↓ SVR, ↑↓ MAP, ↑ RBF

Isoproterenol

0.05–2 mcg/kg/min IV infusion

β1, β2

↑ CO, ↑ HR, ↓ SVR, ↓ MAP

Adrenaline

<0.025 mcg/kg/min IV infusion 0.025–1 mcg/kg/min IV infusion

β1, β2 α1, β1

↑ CO, ↑ HR, ↓ SVR ↑ CO, ↑ HR, ↑ SVR, ↑ MAP, ↓ RBF

Noradrenaline


α1, α2, β1

↑ CO, ↑ HR, ↑↑ SVR, ↑↑ MAP, ↓ RBF

Phenylephrine

Children: 5–20 mcg/kg/dose slow IV bolus, can be repeated every 10–15 min Alternatively, 100 mcg/kg/dose IM/SC can be repeated every 1–2 h up to a max of 5 mg Adults: 100–500 mcg slow IV bolus

α1, α2

↓ HR, ↑ SVR, ↑ PVR, ↑ MAP

Sodium nitroprusside


Nitric oxide ↓ SVR, ↑ CO, ↓ MAP mediated vasodilator (arterial > venous)

Nitroglycerin (NTG)

1–20 mcg/kg/min IV infusion

Nitric oxide ↓ SVR, ↑ CO, ↓ MAP mediated vasodilator (venous > arterial)

ERRNVPHGLFRVRUJ

26


Agent

Dose

Site of action

Effect

Milrinone

25–50 mcg/kg bolus over 10 min, infusion 0.25–0.75 mcg/ kg/min

Phosphodiesterase-3 inhibitor

↑ CO, ↑ HR, ↓ SVR

Vasopressin

0.0003–0.006 units/kg/min

Vasoconstrictor and antidiuretic effect

↑ SVR, ↑ MAP

Alprostadil (PgE1)


Prostanoid receptors

↓ SVR, maintains patency of ductus arteriosus

Epoprostenol (PgI2, prostacyclin)

0.5–16 ng/kg/min

Causes vasodilatation ↓ SVR and PVR, and inhibits platelet ↑ CO aggregation

RBF: renal blood flow, CO: cardiac output, HR: heart rate, SVR: systemic vascular resistance, MAP: mean arterial pressure, PVR: pulmonary vascular resistance.

Dopamine, in a dose of less than 2.5 mcg/kg/min, has a selective dopaminergic effect on the renal blood flow, which increases urine output. In doses of 2.5–7.5 mcg/kg/min, dopamine also acts on β1 receptors to increase the cardiac output. It may, however, cause unpredictable tachycardia. In higher doses, in addition to β1 effects, it has an effect on α1 receptors, which causes an increase in SVR and afterload. Dobutamine is a selective β agent (β1 action > β2), it therefore increases the cardiac contractility, heart rate, and cardiac output with some decrease in SVR. The degree of tachycardia is variable. The reduction in SVR may rarely cause hypotension, and thus dobutamine is not indicated by itself in a hypotensive patient. In patients with poor LV function but without significant hypotension, dobutamine (β1, β2 action) is superior to dopamine (α1, β1 action) as dobutamine decreases the afterload and preload, and results in an improvement in myocardial function. However, in patients with poor LV, severe hypotension and high SVR, dopamine or adrenaline used in combination with a vasodilator (NTG/nitroprusside/milrinone/dobutamine) may be more appropriate. Isoproterenol acts on β1 and β2 receptors. It causes significant increase in heart rate in addition to increasing the force of contraction and bronchodilation. It is therefore used in complete heart block to increase the ventricular rate, overdose of beta-blocker, or severe bradycardia unresponsive to atropine. It is administered in a dose of 0.05–2 mcg/kg/min by IV infusion or as 5–20 mcg IV bolus (Adult dose: 2–20 mcg/min IV infusion; 20–60 mcg IV bolus). Adrenaline in low doses (<0.025 mcg/kg/min) stimulates the β1 and β2 receptors. The β1 action increases the heart rate, force of contraction, and cardiac output. β2 stimulation results in a fall in SVR, but the mean arterial pressure is maintained or increased due to the increase in cardiac output. As the dose is increased, α1 receptors are stimulated causing vasoconstriction of the vascular beds increasing the SVR and the blood pressure significantly.

ERRNVPHGLFRVRUJ


27

The β2 properties of adrenaline produce bronchodilatation and an elevation in the blood sugar level because of glycogenolysis. Noradrenaline is a potent α1 stimulant, which causes increased SVR with the smallest dose. The moderate β1 action increases the heart rate, force of contraction, and cardiac output. However, it is less likely to cause tachycardia than adrenaline. It is indicated in systemic hypotension because of vasodilatory shock (sepsis, trauma, cardiopulmonary bypass, or spinal block), which does not respond to volume expansion and adrenaline or dopamine. Since it acts by increasing the afterload, it may not be appropriate for use in patients with poor LV function. Blood supply to kidneys and periphery may be reduced. Phenylephrine is a selective α-receptor (α1 and α2) agonist and results in increased SVR and increased BP without any direct action on the myocardium. The heart rate may decrease because of reflex action. Sodium nitroprusside is a direct acting vasodilator of both arteries and veins (arteries > veins). The arterial vasodilator effects are prompt and manifest at low doses. It causes fall in blood pressure, but the cardiac output is increased due to afterload reduction. The pulmonary artery pressure falls but may show a rebound increase when treatment is withdrawn. High doses or prolonged use can result in cyanide or thiocyanate toxicity. Cyanide toxicity and thiocyanate toxicity are breakdown products of sodium nitroprusside (SNP) metabolism in the body. Cyanide in excess interferes with cellular oxygen utilization, and clinical features of toxicity are known to occur with cumulative doses of SNP of >0.5 mg/kg/h. Cyanide toxicity is more likely if hepatic dysfunction is present; thiocyanate is cleared by the kidney and toxicity is more likely if there is renal dysfunction or with prolonged infusion. An early sign of cyanide toxicity is increasing resistance to doses of nitroprusside (tachyphylaxis). Subsequent clinical features include metabolic acidosis, tachycardia, hypertension, cardiac arrhythmias, CNS dysfunction, metabolic acidosis, and increased mixed oxygen saturation (as a result of the inability to utilize oxygen). Treatment consists of mechanical ventilation with 100% oxygen and administration of sodium thiosulfate (150 mg/kg over 15 min) or 3% sodium nitrite (5 mg/kg over 5 min). Manifestations of thiocyanate toxicity include abdominal pain, vomiting, weakness, tinnitus, tremor, agitation, progressing to lethargy, seizures and coma. Treatment requires clearance of excess thiocyanate by dialysis. NTG causes venodilatation more than arteriolar dilatation. This results in a decrease in LV filling pressure (preload) relatively more than systemic vascular resistance (afterload). As low-dose infusions are titrated upward, the earliest response is a decrease in cardiac filling pressures (i.e., CVP and LAP) with little or no change in cardiac output. As the dose rate is increased further, the cardiac output begins to rise as a result of progressive arterial vasodilatation. Further increases in the dose rate will eventually produce a drop in blood pressure.

ERRNVPHGLFRVRUJ

28


Milrinone is an inodilator and has an inotropic effect on the heart, and a dilator effect on the circulation, which significantly decreases the SVR and PVR. It increases the CO with little effect on HR and myocardial oxygen demand. Milrinone has a longer half-life than dobutamine and is very useful in pulmonary HTN. It is administered with a loading dose followed by a continuous infusion. Reductions in infusion rate may be necessary in patients with renal impairment and should not be used in patients with a creatinine >2.5. It has a long half-life and if not excreted by the kidneys can cause severe hypotension and right sided heart failure. Milrinone in combination with adrenaline or dopamine is advocated in the management of low cardiac output in the postoperative cardiac patient with pulmonary hypertension. Vasopressin is a potent vasopressor that may be used in several forms of shock, notably septic shock. The vasoconstrictive action of vasopressin is mediated through V1 receptors in the vessels of the skin, skeletal muscle, and small intestines. In recommended doses, blood flow to the coronaries, cerebral, pulmonary, and renal vascular beds, is preserved. It leads to increase in blood pressure, decrease in heart rate, and reduction in the dose requirements of other catecholamines. It has an antidiuretic effect, which is mediated through V2 receptors in the capillaries at the renal distal tubules and collecting ducts, which causes increased reabsorption of water to augment systemic blood volume. High doses of vasopressin cause intense vasoconstriction, which can result in gangrene of the tips of fingers and toes, and ischemia of other organs, including the gastrointestinal tract and kidneys. Extravasation may result in tissue necrosis. Other complications include arrhythmias, hyponatremia, thrombocytopenia and bronchial constriction. The halflife of vasopressin is 10–35 minutes, and its vasoconstrictive effect can be counteracted by vasodilators, such as nitroglycerin or nitroprusside. Alprostadil (PgE1) is indicated in infants with congenital heart defects and a duct dependant pulmonary or systemic circulation to keep the ductus temporarily open. Infants with decreased pulmonary blood flow will respond with an increase in PaO2, and infants with diminished systemic blood flow will show an improvement in the blood pressure and a decrease in the acidosis. Alprostadil injection should be infused for the shortest time and at the lowest dose that produces the desired result. Apnea has been reported in about 12% of the neonates on alprostadil infusion. Other adverse reactions include fever, irritability, seizures, hypotension, thrombocytopenia, cerebral bleeding, and gastric outlet obstruction when the duration of infusion has exceeded 120 hours. Infusion is started at 0.05–0.1 mcg/kg/min. It may be necessary to increase the dose to obtain a therapeutic response. After an adequate response, the infusion rate is reduced to provide the lowest possible dosage (0.01–0.025 mcg/kg/min) to maintain the response. (500 mcg of alprostadil is added to 50 mL saline/dextrose for infusion).

ERRNVPHGLFRVRUJ


29

Epoprostenol (PgI2, prostacyclin) is a prostaglandin that causes vasodilatation of the vascular beds, including the pulmonary and cerebral circulation, and is a potent inhibitor of platelet aggregation. There is a fall in the mean systemic and pulmonary artery pressures and a decrease in the SVR and PVR. Indications for its use include long-term intravenous treatment of primary pulmonary hypertension and for the management of pulmonary hypertension secondary to congenital heart diseases and congenital diaphragmatic hernia. It is initiated at the rate of 0.5–2 ng/kg/min and increased by 0.5–1 ng/kg/min every 30–60 min until dose limiting clinical effects are noted or to a maximum of 16 ng/kg/min. Symptoms of overdose include flushing, headache, hypotension, tachycardia, nausea, vomiting, and diarrhea, which require the dose to be reduced. Epoprostenol enhances the hypotensive effects of other vasodilators and increases risk of bleeding with anticoagulants and other antiplatelet agents.

Method of Preparation of Infusion and Dose Calculation Two alternative methods of drug formulation that allow for ease of calculations are described below. Various formulas for dose calculation are given in Appendix K. Method 1 Drug

Formulation

Method of dose calculation

Dopamine/dobutamine

3 mg/kg in 50 mL 15 mg/kg in 50 mL

1 mL/h = 1 mcg/kg/min 1 mL/h = 5 mcg/kg/min

Adrenaline/noradrenaline/ isoprenaline

0.3 mg/kg in 50 mL

1 mL/h = 0.1 mcg/kg/min

NTG/sodium nitroprusside

3 mg/kg in 50 mL

1 mL/h = 1 mcg/kg/min

Milrinone

0.75 mg/kg in 50 mL

1 mL/h = 0.25 mcg/kg/min

Method 2 Drug

Formulation

Method of dose calculation

Dopamine/dobutamine

50 mg in 50 mL (1000 mcg/mL)

0.3 × body wt (mL/h) = 5 mcg/kg/min

Sodium nitroprusside/NTG/ milrinone

5 mg in 50 mL (100 mcg/mL)

0.3 × body wt (mL/h) = 0.5 mcg/kg/min

Adrenaline/isoprenaline/ noradrenaline

0.5 mg in 50 mL (10 mcg/mL)

0.3 × body wt (mL/h) = 0.05 mcg/kg/min

Vasopressin

5 units in 50 mL (0.1 unit/mL)

0.3 × body wt (mL/h) = 0.0005 unit/kg/min

ERRNVPHGLFRVRUJ

30


In children, to decrease the fluid intake, usually 2 × the above strength of solutions are prepared (dopamine/dobutamine: 100 mg in 50 mL; milrinone/NTG/ sodium nitroprusside: 10 mg in 50 mL; adrenaline/noradrenaline/isoprenaline: 1 mg in 50 mL and vasopressin 10 units in 50 mL), so that “0.3 × body wt ÷ 2” in mL/h would then provide the doses noted in the Method 2 table above. In a 12 kg child, dopamine prepared in a concentration of 100 mg in 50 mL of 5% dextrose administered at a rate of 1.8 mL will give a dose of 5 mcg/kg/min (0.3 × 12 ÷ 2 in mL/h = 5 mcg/kg/min). Similarly, in adults 4 × strength may be prepared, then “0.3 × body wt ÷ 4” in mL/h would give the above doses, e.g., for dopamine, 200 mg in 50 mL in a 50 kg adult, 3.75 mL/h would give 5 mcg/kg/min (0.3 × 50 ÷ 4 in mL/h = 5 mcg/kg/min). Diluents: Diluents may be 5% dextrose in water, 5% dextrose in halfnormal saline, normal saline, or Ringer’s lactate. SNP and NTG are prepared in dextrose only.

Bibliography 1. Alprostadil injection. Available at: dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=14726 2. Aung K, Htay T. Vasopressin for cardiac arrest: a systematic review and meta-analysis. Arch Intern Med 2005;165(1):17–24. 3. Bellomo R, Giantomasso DD. Noradrenaline and the kidney: friends or foes? Crit Care 2001;5:294–8. 4. Biaggioni I, Robertson D. Adrenoceptor agonists & sympathomimetic drugs. In: Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology 11th ed. USA: McGraw Hill Inc.; 2009:127–48. 5. Buck ML. Low-dose vasopressin infusions for vasodilatory shock: adverse effects. Pediatr Pharm 2003;9(9) [Updated: 2003 Sep 10; cited: 2011 Sep 28]. Available at: http://www.medscape.com/viewarticle/462394. 6. Choudhury M, Saxena N. Inotropic agents in pediatric cardiac surgery patients: current practice, concerns, and controversies. Indian J Anaesth 2003;47:246. 7. Esoprostenol. Available at: http://nursing.ucsfmedicalcenter.org/NursingDept/AdultProcedures/ PDFsafter12-29-2003/FlolanInfusionforPulmonaryHypertensionAdult.pdf 8. Epoprostenol. Package insert: information for healthcare professionals flolan 1.5. Available at: www.medicines.ie/pdfviewer.aspx?isattachment=true...9841. 9. Gilmore K. Pharmacology of vasopressors and inotropes. Pharmacology 1999;10:4. [Cited: 2011 Dec 17] Available at: http://www.nda.ox.ac.uk/wfsa/html/u10/u1004_01.htm. 10. Gomersall C. Nitroprusside. The Chinese University of Hong Kong. [Updated: 1999 Dec; cited: 2011 Sep 28]. Available at: http://www.aic.cuhk.edu.hk/web8/sodium_nitroprusside.htm. 11. Helfaer MA, Wilson MD, Nichols DG. Pharmacology of cardiovascular drugs. In: Nichols DG, Cameron DE, Greeley WJ, Lappe DG, Ungerleider RM, Wetzel RC, eds. Critical Heart Disease in Infants and Children. St Louis: Mosby; 1995:185–213. 12. Hill NS, Antman EM, Green LH, Alpert JS. Intravenous nitroglycerin. A review of pharmacology, indications, therapeutic effects and complications. Chest 1981;79(1):69–76.

ERRNVPHGLFRVRUJ


31

13. Ilbawi MN, Idriss FS, DeLeon SY, Berry TE, Duffy CE, Paul MH. Hemodynamic effects of intravenous nitroglycerin in pediatric patients after heart surgery. Circulation 1985;72(3 Pt 2): II101–7. 14. Infusions. In: Alder Hey Book of Children’s Doses 6th ed. Liverpool: Royal Liverpool Children’s Hospital (Alder Hey); 1994:254–5. 15. McAuley DF. What are the current recommendations regarding the use of vasopressin in the treatment of shock? [Cited: 2011 Apr 14]. Available at: http://www.globalrph.com/vasopressin_shock.htm. 16. Milrinone. South Thames retrieval service. 2008 Jan [Cited: 2011 Sep 28]. Available at: http:// www.strs.nhs.uk/resources/pdf/guidelines/milrinone.pdf. 17. Nitroprusside toxicity treatment. Available at: www.openanesthesia.org/index.php?title= Nitroprusside_toxicity. 18. Patel BM, Chittock DR, Russell JA, Walley KR. Beneficial effects of short-term vasopressin infusion during severe septic shock. Anesthesiology 2002;96:576–82. 19. Sodium nitroprusside. In: Sweetman SC, ed. In Martindale The Complete Drug Reference 36th ed. IL, USA: Pharmaceutical Press 2009:1397–8. 20. Vasopressin. In: USP Drug Dispensing Information Vol I. Massachusetts: Drug Information of the Health Care Professional. Thompson Micromedex; 2004:2816–7. 21. Westfall TC, Westfall DP. Neurotransmission: the autonomic and somatic motor nervous systems. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman’s The Pharmacological Basic of Therapeutics 12th ed. USA: McGraw Hill Inc.; 2011:171–218.

ERRNVPHGLFRVRUJ

Congestive Heart Failure “For suddenly a grievous sickness took him, that makes him gasp and stare and catch the air” —King Henry VI; Part II - William Shakespeare (1564–1616)

Clinical Manifestations Low cardiac output ● ● ● ● ●

Failure to thrive Sweating during feeding Tachycardia Cool periphery Oliguria

Left heart failure ●

● ●

Respiratory distress (tachypnea, chest retractions) Rales/crepitations Pulmonary edema

Right heart failure ● ● ● ● ●

Raised jugular venous pulse Hepatomegaly Edema Pleural effusion Ascites

In general, heart failure results either from an excessive volume overload (left-to-right shunts, regurgitant lesions), pressure overload (aortic stenosis, coarctation), or from a primary myocardial abnormality (myocarditis, cardiomyopathy). Other lesions that can result in congestive heart failure (CHF) are arrhythmias, pericardial diseases, and a combination of various factors. Clinical manifestations of CHF are a combination of features of low cardiac output, left heart failure, and right heart failure. The decrease in cardiac output because of CHF triggers a compensatory sympathetic response resulting in tachycardia, vasoconstriction, and renin–angiotensin mediated fluid retention. Fluid retention initially increases the cardiac output by increasing the end diastolic volume (preload) but eventually results in renal and other organ dysfunction. Left-sided heart failure is associated with signs of pulmonary venous congestion (tachypnea, chest retractions, rales, pulmonary edema), whereas right-sided heart failure is associated with signs of systemic venous congestion (raised jugular venous hepatomegaly, edema, ascites, pleural effusion). In pediatric patients, failure of one ventricle invariably affects the other ventricle and children usually present with signs of biventricular failure. CHF with normal cardiac output is called compensated CHF, and CHF with inadequate cardiac output is called decompensated failure.

ERRNVPHGLFRVRUJ


33

Signs of CHF vary with the age of the child. Infants have sweating during feeding, inability to complete feeding (taking <90–100 mL/feed or >40 min/feed), and failure to thrive. Pulsus alternans (alternate strong and weak pulse) or pulsus paradoxus (an inspiratory fall in systolic pressure of >10 mmHg) are observed in infants with severe CHF. A gallop rhythm may be present. Signs of pulmonary venous congestion include tachypnea (sleeping respiratory rate of >50/min) and chest retractions. Right-sided venous congestion is characterized by hepatosplenomegaly and, less frequently, edema, ascites, and a distended jugular venous pulse. In severe cases, persistent low cardiac output may result in signs of renal and hepatic failure. Chest X-ray shows cardiac enlargement, i.e., a cardiothoracic ratio of >60% in the newborn and >55% in older infants. However, it is well to note that an expiratory film can often be misinterpreted as showing cardiac enlargement. Older children may have fatigue or sometimes syncopy. Clinical findings include hypotension, cool extremities with poor peripheral perfusion, a low volume pulse, and decreased urine output. Left-sided venous congestion causes tachypnea and wheezing. Right-sided congestion results in hepatosplenomegaly, raised jugular venous pulse, edema, ascites, and pleural effusion. Renal and liver function tests may be deranged.

Drugs Used in the Treatment of Heart Failure Drug

Dosage

Remarks and side effects

Digoxin

Children Digitalizing dose Preterm: PO 20 mcg/kg/day, IV 15 mcg/kg/day Term: PO 30 mcg/kg/day, IV 20 mcg/kg/day < 2 yr: PO 40–50 mcg/kg/day, IV 30–40 mcg/kg/day 2–10 yr: PO 30–40 mcg/kg/day, IV 20–30 mcg/kg/day >10 yr: PO 10–15 mcg/kg/day, IV 8–12 mcg/kg/day 50% dose is given initially, 25% at 8 h, and 25% at 16 h. Maintenance dose is started 24 h after loading. Maintenance dose Preterm: PO 2.5 mcg/kg q12h Neonate–10 yr: PO 5 mcg/kg q12h >10 yr: PO 2.5 mcg/kg q12h IV: 75% of oral dose is given.

Approx time to steady state is 5–10 days and the therapeutic range is 0.8–1.2 ng/mL (sample is taken 6 h after oral/IV dose). The bioavailability of the tablet is 70%, and syrup 80% of the IV dose.

ERRNVPHGLFRVRUJ

Digoxin is potentiated by amiodarone, diltiazem, verapamil, and quinidine; the maintenance dose should be halved if any of these are also given.

34


Adults Digitalizing dose IV 0.5–1 mg PO 0.75–1.5 mg 50% of total dose is given initially, then 25% dose in each of 2 subsequent doses at 8–12 h intervals. Maintenance dose IV 0.1–0.4 mg q24h PO 0.125–0.5 mg q24h Renal failure Crcl 10–15 mL/min—reduce dose by 50%; Crcl <10 mL/min—reduce dose by 75% Digoxin is not cleared by dialysis.

Digoxin toxicity is enhanced by hypokalemia (administration of diuretics or amphotericin) and hypercalcemia. Toxic effects Cardiac arrhythmias (esp bradycardia and bigeminy); Gastrointestinal (nausea and vomiting is the most common); Ocular (aberrant color perception).

Digoxin is administered IV over 10 min diluted with NS, 5% D or IGS. Digitalization dose is given over 30 min.

Diuretics Furosemide

Children PO: 1–2 mg/kg q6–12h (max 4 mg/kg/day) IV: 0.5–1 mg/kg q6–12h IV infusion: 0.05–2 mg/kg/h

Hyponatremia, hypokalemia, chloride depletion, metabolic alkalosis, hyperuricemia, hyperglycemia, ↑ LDH, ↑ triglycerides, ototoxicity may occur. Nephrocalcinosis is possible due to increased calcium excretion.

Adults PO: 20–80 mg q6–24h IV: 10–80 mg q6–24h IV infusion: 0.1 mg/kg stat, followed by 0.1–0.4 mg/kg/h Hydrochlorothiazide

Children 2–4 mg/kg/day in divided doses q12h PO Adults 25–100 mg/day in divided doses q12–24h PO

Electrolyte imbalance may occur.

Metolazone

Children 0.2–0.4 mg/kg/day in divided doses q12–24h PO Used with loop diuretics Adults 2.5–5 mg/day in divided doses q12–24h PO

Electrolyte imbalance may occur.

ERRNVPHGLFRVRUJ


35

Spironolactone

Neonates 1–3 mg/kg/day in divided doses q12–24h PO Children 1.5–3.5 mg/kg/day in divided doses q6–24h PO Adults 25–50 mg/day in divided doses q12–24h PO

Hyperkalemia, anorexia, gastritis, gastric bleeding, diarrhea, gynecomastia, hirsutism, and menstrual irregularities may occur as adverse effects.

Captopril (ACE inhibitor)

Neonates 0.4–1.6 mg/kg/day in divided doses q8h PO Children 0.3–3.0 mg/kg/day in divided doses q8h PO Adults 6.25–50 mg q8–12h PO

Start with lowest dose and increase every 4th–5th dose. Monitor BP, and renal parameters to titrate the dose. Hypotension with the first dose may occur, especially if a diuretic has been administered at the same time. Hyperkalemia (avoid ACEI with spironolactone). Dry cough due to increased levels of bradykinin, altered taste, and rashes.

Enalapril (ACE inhibitor)

Children 0.1–0.5 mg/kg/day in divided doses q12–24h PO. Avoid in neonates. Adults 2.5–5 mg/day in divided doses q12–24h PO. Can be increased to a max of 20 mg/day.

Start with lowest dose and increase dose daily. Monitor BP, and renal parameters to titrate the dose. Hypotension, hyperkalemia (avoid ACEI with spironolactone). Dry cough due to increased levels of bradykinin.

Losartan (Angiotensin receptor blocker)

Children 0.5–0.75 mg/kg q24h PO Adults 50–100 mg q24h PO

Monitor BP, and renal parameters to titrate the dose. Hypotension may occur.

Metoprolol

Children 0.1–0.5 mg/kg q12h PO

Vasodilators

Beta-blockers Efficacy and safety not established in children. Indicated in mild/ moderate heart failure associated with ventricular dysfunction. Start with lowest dose and gradually increase the dose over weeks to achieve the desired dose. Modest β1 selectivity. Bronchospasm, bradycardia, heart block may take place.

ERRNVPHGLFRVRUJ

36


Adults 12.5–25 mg q24h PO may be increased to a max of 200 mg/day in divided doses q12–24h Carvedilol

Children Start with 0.05 mg/kg q12h and increase to a max of 0.5 mg/kg q12h. Adults Start with 3.125 mg q12h PO and increase to a dose of 12.5–25 mg q12h PO

Non-selective β-blocker and some α-blocking activity. Watch for bronchospasm, bradycardia, heart block, hyperglycemia in patients who are at risk.

Bibliography 1. Bernstein D, Fajardo G, Zhao M. The role of B-adrenergic receptors in heart failure: differential regulation of cardiotoxicity and cardioprotection. Prog Pediatr Cardiol 2011;31(1):35–8. 2. Bruns LA, Chrisant MK, Lamour JM, et al. Carvedilol as therapy in pediatric heart failure: an initial multicenter experience. J Pediatr 2001;138:505–11. 3. Heart Failure Society of America. Executive summary: HFSA 2006 Comprehensive Heart Failure Practice Guideline. J Card Fail 2006;12:10–38. 4. Hsu DT, Pearson GD. Heart failure in children: Part I: history, etiology, and pathophysiology. Circ Heart Fail 2009;2:63–70. 5. Hsu DT, Pearson GD. Heart failure in children: part II: diagnosis, treatment, and future directions. Circ Heart Fail 2009;2(5):490–8. 6. Jong P, Demers C, McKelvie RS, Liu PP. Angiotensin receptor blockers in heart failure: metaanalysis of randomized controlled trials. J Am Coll Cardiol 2002;39:463–70. 7. Khan MG. Management of heart failure. In: Khan MG, ed. Cardiac Drug Therapy 5th ed. London: W.B. Saunders Company Ltd; 1999:209–46. 8. Malcolm J, Arnold O. Heart failure. The Merck Manuals: online medical library. [Updated: 2009 Dec; cited: 2011 Sep 21] Available at: http://www.merckmanuals.com/professional/ cardiovascular_disorders/heart_failure/heart_failure_hf.html?qt=&sc=&alt= 9. Margossian R. Contemporary management of pediatric heart failure. Expert Rev Cardiovasc Ther 2008;6:187–97. 10. Park MK. Use of digoxin in infants and children with specific emphasis on dosage. J Pediatr 1986;108:871–8. 11. Prescription Drug Information, Interactions & Side Effects. [Cited: July 2012] Available at: http://www.drugs.com/ 12. Satou GM, Halnon NJ. Pediatric congestive heart failure. [Updated: 2009 Mar 19; cited: 2011 Feb 21] Available at: http://emedicine.medscape.com/article/901307-overview. 13. Saxena A, Juneja R, Ramakrishnan S. Drug therapy of cardiac diseases in children. Working Group on Management of Congenital Heart Diseases in India. Indian Pediatr 2009;46(4):310–38. 14. Shaddy RE, Penny D. Chronic cardiac failure: physiology and treatment. In: Enderson RH, Baker EJ, Penny DJ, et al. eds. Paediatric Cardiology 3rd ed. USA: Churchill Livingstone, an imprint of Elsevier Ltd; 2010:257–68. 15. Tweddell JS, Hoffman GM. Postoperative management in patients with complex congenital heart disease. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2002;5:187–205.

ERRNVPHGLFRVRUJ

Cardiac Tachyarrhythmias “The heart has its reasons of which reason knows nothing: we know this in countless ways” —Blaise Pascal (1623–1662)*

Normal ECG QRS R

ST T P

PR

Q S QT

Fig. 1: Components of a normal ECG complex.

The P wave represents atrial depolarization. Normal P duration is age dependant (<0.08 sec in infants, <0.10 sec in children, and <0.12 sec in adults) with an amplitude of not >0.25 mV (2 and ½ small squares). The axis of the P wave is +0° to +90°, and thus the P wave is positive in lead I, II, and aVF and negative in lead aVR. Retrogradely conducted impulses originating in the AV node produce inverted P waves in lead II and upright in aVR. However, if atrial and ventricular depolarization occurs simultaneously, the P waves may be obscured in the QRS complexes. The PR interval (from the beginning of the P wave to the beginning of the QRS complex) is the time from the onset of atrial activation to the *Blaise Pascal was a French mathematician, physicist, author, and philosopher. He is the inventor of the mechanical calculator.

38


start of ventricular activation (upper limit of normal in infants <0.14 sec; 8–12 yr <0.18 sec; adults <0.21 sec). The QRS complex represents ventricular depolarization, and the T wave represents ventricular repolarization. The normal QRS duration is shorter in childhood (birth – 2 yr: 0.03–0.08 sec; 3–15 yr: 0.04–0.09 sec; adult: 0.06–0.10 sec) and with fast ventricular rates. The QT interval (from the beginning of the QRS complex to the end of the T wave) represents the duration of ventricular depolarization and repolarization. Normal values for the QT interval are longer in females and are also prolonged with a slower heart rate. The QT interval is corrected for influence of heart rate by Bazett’s formula. Corrected QT (QTC ) =

QT interval , (RR interval)

where RR interval = 60/HR. Normal QTC in children is <0.44 sec, in adults <0.425 sec.

ECG Recording The normal speed of an ECG recording is 25 mm/sec. The width of each small square (1 mm × 1 mm) at this speed represents 0.04 sec and the height 0.1 mv (each large square is 5 × 5 mm and is equivalent of 0.20 sec × 0.5 mv). At this speed, 300 large squares (or 1500 small squares) are covered in a minute. The heart rate can therefore be calculated by dividing 300 by the number of large squares between two RR complexes (or 1500 by the number of small squares).

Atrial Electrocardiograms (AEG) An AEG is useful to determine the position of the P wave relative to the QRS complex in the diagnosis of various types of arrhythmias and heart blocks, when P waves are not visible on the surface ECG. The AEG can be recorded on a rhythm strip of a bedside monitor or as a standard 12-lead ECG. Simultaneous recording of the AEG and a surface ECG lead allows comparison of the two recordings. The AEG recording is done by attaching one atrial pacing wire to the right upper limb electrode and the second atrial wire to the left upper limb electrode. The leg electrode is attached as for a normal ECG. Lead I then records a bipolar AEG, and leads II and III record a unipolar AEG. If only one atrial lead is present, unipolar AEG can be recorded by attaching the wire to the left upper limb electrode and normal electrodes to the right upper limb and lower limb and recording either lead I or II.

ERRNVPHGLFRVRUJ


39

In the absence of postoperative atrial pacing wires, a transvenous electrode placed in the right atrium or an esophageal electrode can be used to record a unipolar AEG. In the unipolar AEG, P waves are recorded as large complexes and the QRS as a small deflection; while in a bipolar AEG, generally, only P waves are recorded and QRS complexes are not visible. The relationship between atrial and ventricular complexes will help differentiate sinus tachycardia, and supraventricular arrhythmias. In sinus tachycardia, the P waves are in the normal position (PR interval < RP interval); while in reentrant tachyarrhythmias, the P waves may either precede or fall within the QRS complex or follow it (PR interval > RP interval). In junctional ectopic tachycardia, either the P waves fall within the QRS complex or there is AV dissociation with the P waves occurring at a slower rate than the R waves. The AEG can also be utilized in the diagnosis of wide complex tachycardias to differentiate ventricular tachycardia from SVT with aberrant conduction (bundle branch block), by identification of a P wave with each QRS complex in SVT and AV dissociation in VT.

Normal Sinus Rhythm

Fig. 2: Normal sinus rhythm at the rate of 120/min, in a 6-month-old child.

A normal sinus rhythm implies a heart rate appropriate for age, with a regular rhythm, P waves of normal morphology, with an axis from +0° to +90°, which are followed by a normal PR interval and QRS complex.

Rhythm Disorders Site of origin of arrhythmia

Arrhythmia

Sinoatrial node

Sinus tachycardia Sinus bradycardia Sinus arrhythmia Sinus arrest

ERRNVPHGLFRVRUJ

40


Atrium

Atrial ectopics Wandering pacemaker Atrial ectopic tachycardia Multifocal atrial tachycardia Atrial flutter Atrial fibrillation

A-V junction

Atrioventricular reentrant tachycardia Atrioventricular nodal reentrant tachycardia Junctional ectopics Junctional rhythm Junctional ectopic tachycardia

Ventricles

Ventricular ectopics Ventricular tachycardia Ventricular fibrillation Pulseless electrical activity

Sinus Node Arrhythmias Sinus Tachycardia

Fig. 3: Sinus tachycardia at the rate of 160/min with a simultaneous recording of a unipolar AEG. The larger atrial and the smaller ventricular recordings on the AEG coincide respectively with the P waves and the R waves on the normal ECG.

Heart rate is faster than the normal for age. The impulse originates in the sinoatrial (SA) node with a normal P wave morphology, PR interval, and QRS complex.

Sinus Bradycardia The heart rate is slower than the normal for age. The impulse originates in the SA node with normal P wave morphology, PR interval, and QRS complex.

ERRNVPHGLFRVRUJ


41

Fig. 4: Sinus bradycardia at the rate of 60/min.

Sinus Arrhythmia

Fig. 5: Sinus arrhythmia.

ECG of sinus arrhythmia shows a varying RR interval, which has no relationship to respiration. The P wave and QRS complex are normal. An increase in RR interval with inspiration and a decrease with expiration may be a normal finding (respiratory sinus arrhythmia).

Sinus Arrest

Fig. 6: Sinus arrest with junctional escape beats (marked by arrows).

When SA pacemaker activity is absent and a subsidiary pacemaker takes over either in the atrium, A-V junction, or ventricle. Atrial escape beats are similar in configuration to atrial ectopics, morphologically abnormal P waves precede normal QRS complexes. With junctional escape beats, normal QRS complexes are preceded or followed by retrogradely conducted

ERRNVPHGLFRVRUJ

42


P waves (negative in lead II and positive in aVR) or the P waves may not be discernible. A ventricular escape beat is evident by its wide QRS complex. Sinus arrest may occur with increased vagal tone, hypoxia, hypothermia, digitalis toxicity, or sick sinus syndrome.

Atrial Arrhythmias Atrial Ectopics

a

b

c

d

e

Fig. 7: Atrial ectopics (marked by arrows).

The P wave impulse does not generate in the SA node but elsewhere in the atrium and thus has a different morphology. It is followed by a normal QRS complex (except in aberrant conduction). The ectopic comes early in the cardiac cycle and is followed by an incomplete compensatory pause (in Fig. 7, interval ab + bc > cd + de). Atrial ectopics may occur with digoxin toxicity, anxiety, drugs, heart failure, atrial hypertrophy, electrolyte disorders, post cardiac surgery, and may sometimes be a normal benign finding.

Wandering Pacemaker

Fig. 8: Wandering pacemaker.

When there are three or more pacemakers beating at a rate faster than the sinus node but <100/min. In such a situation, the rhythm will be irregular,

ERRNVPHGLFRVRUJ


43

P wave morphology and the PR interval will keep varying from beat to beat, but the QRS will be normal. It may be a precursor to multifocal atrial tachycardia (when rate >100/min). Occurs with hypoxia, digoxin toxicity, sick sinus syndrome, and sometimes in otherwise healthy children.

Atrial Ectopic Tachycardia (AET)

Fig. 9: Atrial ectopic tachycardia.

AET is caused by a single ectopic focus within the atria, resulting in a P wave of abnormal (positive or negative axis) but uniform morphology, which falls before a narrow, regular QRS complex (in the absence of aberrancy). The rate ranges from 120 to 300 beats per minute (typically >200) and commonly with an associated first or second degree AV block. The tachycardia may exhibit a “warming up” (i.e., a progressively shortening PP interval for the first few beats) and a “cooling down” period at its termination.

Multifocal Atrial Tachycardia (MAT)

Fig. 10: Multifocal atrial tachycardia.

MAT is a tachycardia resulting from at least three ectopic foci within the atria, distinguished by P waves of at least three different morphologies;

ERRNVPHGLFRVRUJ

44


the rhythm is irregular and the PR interval varies from beat to beat, but the QRS complex is normal. It is in fact akin to a wandering pacemaker with a heart rate >100 beats/min. Can be confused with AF, however, MAT has discernible P waves and similar QRS complexes. Occurs in patients with a structural heart disorder, pericarditis, and digoxin toxicity.

Atrial Flutter

Fig. 11: Atrial flutter with 4:1 AV block with a simultaneous recording of a unipolar AEG.

The P waves have a saw tooth configuration and a rate >300/min with 2–4:1 AV block. The QRS complexes are normal (except in aberrant conduction). Atrial flutter may occur after atrial surgery, in atrial enlargement, digoxin toxicity, or myocarditis.

Atrial Fibrillation (AF)

Fig. 12: Atrial fibrillation.

There are no discernible P waves (atrial rate >350/min). The rhythm is irregular, and the RR interval and the size of the QRS complex vary from beat to beat. AF is seen after atrial surgery, in atrial enlargement, digoxin toxicity, myocarditis, etc.

ERRNVPHGLFRVRUJ


45

Rhythm Disorders Arising from the AV Node Atrioventricular Reentrant (or Reciprocating) Tachycardia (AVRT)

Fig. 13: Atrioventricular reentrant tachycardia.

There is an extra-nodal accessory conduction pathway (AP) between the atria and ventricle, in addition to the normal AV conduction system. In orthodromic AVRT, the impulse originates in the AV node and travels down the normal pathway to first activate the ventricles and up the AP to activate the atria. The impulse then returns back to the AV node by the normal pathway forming a reentry circuit. The rhythm is regular, rate 150–250/min, and the QRS complex is narrow with a retrograde P wave (negative in lead II and positive in aVR), which may not be discernible within the QRS complex (Fig. 13) or may follow the QRS. In antidromic AVRT (in <5%), the reentry circuit occurs in the opposite direction, the impulse from the AV node first activates the atrium retrogradely via the normal pathway and then the ventricle via the AP. The rhythm is regular, but the QRS complex is wide because of its abnormal activation and looks exactly like ventricular tachycardia. Retrograde P waves precede the wide QRS complex. AVRT is more common in infants and children than is AVNRT.

Wolfe–Parkinson–White (WPW) Syndrome

Fig. 14: Wolfe–Parkinson–White syndrome (delta waves are marked by arrows).

ERRNVPHGLFRVRUJ

46


The ECG pattern of this condition is produced by the presence of an extranodal AP. In normal sinus rhythm, initial antegrade activation of the ventricle via this AP results in a delta wave (Fig. 14) on ECG. This is then followed by normal antegrade pathway activation of the ventricles resulting in a normal QRS complex. Patients with WPW syndrome are susceptible to both orthodromic and antidromic AVRT.

AV Nodal Reentrant Tachycardia (AVNRT) AVNRT has also been called junctional reciprocating tachycardia. In addition to the normal pathway, there is an accessory pathway within the node itself. In 90% cases, the impulse stimulates the ventricle through the normal pathway and then retrogradely the atria via AP (similar to orthodromic AVRT). The ECG recording of the arrhythmia is similar to AVRT. AVNRT is the most common recurrent SVT in adults.

Junctional Ectopics

Fig. 15: Junctional ectopics (marked by arrows).

A premature beat arising from the AV node will have a QRS complex with normal configuration. There may be no P wave or a retrograde P wave (negative in lead II and positive in aVR) because of reverse activation of the atria, which may follow or precede the QRS complex. The compensatory pause is complete.

Junctional Rhythm Enhanced automaticity of the AV node, faster than the SA node, will result in a junctional rhythm (Fig. 16).

Junctional Ectopic Tachycardia JET is caused by increased automaticity of the AV node with a ventricular rate of 180–200/min and regular, narrow QRS complexes. JET may be

ERRNVPHGLFRVRUJ


47

Fig. 16: Junctional rhythm.

Fig. 17: Junctional ectopic tachycardia at the rate of 200/min. In the bipolar AEG recorded at the same time, atrial complexes also occur at the rate of 200/min, indicating 1:1 AV conduction. The retrogradely conducted P waves on the AEG are noted to occur almost at the same time as the QRS complexes on the normal ECG because of simultaneous activation of the atria and ventricles.

associated with atrioventricular dissociation and slower atrial than ventricular rate. When JET manifests as 1:1 atrioventricular conduction, almost simultaneous activation of the atria and ventricles takes place. The atrial impulse is conducted retrogradely, and the P wave (axis – 120°) falls anywhere in relation to the QRS complex. JET is poorly tolerated hemodynamically because of loss of atrial contribution, which usually adds 20–30% to the cardiac output. It is an incessant tachycardia, which shows no response to β-blockers or calcium channel blockers. A child who has undergone surgical manipulation in the close vicinity of the AV node is more likely to have this supraventricular arrhythmia in the immediate postoperative period.

Ventricular Arrhythmias Ventricular Ectopics The premature ventricular contraction (PVC) originates in the ventricle and is not preceded by a P wave. The QRS complex is wide (>0.09 sec in children) with a T wave pointing in the opposite direction to the QRS.

ERRNVPHGLFRVRUJ

48


a

b

c

d

e

Fig. 18: Unifocal ventricular ectopics (marked by arrows).

Fig. 19: Multifocal ventricular ectopics.

Fig. 20: Bigeminy.

A complete compensatory pause is present, i.e., the interval between the preceding and subsequent QRS waves is the same as between two normal adjacent RR intervals (Fig. 18, interval ab + bc = cd + de). PVCs can be distinguished from atrial ectopics, because the compensatory pause is shorter (i.e., incomplete) with atrial ectopics. Multiple ventricular ectopics of the same morphology are referred to as unifocal, whereas those with different morphologies are called multifocal. This may be due to ectopics arising from different foci or progressing through the ventricular myocardium in different ways. PVCs occurring after every normal beat are called ventricular bigeminy. PVCs that occur at intervals of two normal beats are termed trigeminy. Runs of three or more beats constitute ventricular tachycardia. Causes of PVCs include hypokalemia, hypomagnesemia, digoxin toxicity, and catecholamine administration.

ERRNVPHGLFRVRUJ


49

Ventricular Tachycardia (VT)

Fig. 21: Monomorphic ventricular tachycardia at the rate of 160/min. Simultaneous recording of a bipolar AEG shows AV dissociation with a slower atrial rate of 120/min.

Monomorphic VT is a regular rhythm originating from a single focus with identical wide, bizarre QRS complexes at a rate more than 100 per minute (usually 150–200). There is usually atrioventricular dissociation but ventriculoatrial conduction may be present. Ventricular tachycardia usually causes severe hemodynamic compromise and may progress rapidly to ventricular fibrillation but may also occur without hemodynamic deterioration.

Fig. 22: Polymorphic ventricular tachycardia.

Polymorphic VT is an irregular rhythm of wide bizarre QRS complexes of varying configuration at a rate of more than 100 per minute (usually 150–200).

Fig. 23: Torsades de pointes.

Torsades de pointes is a variant of polymorphic VT where the QRS axis keeps shifting as if the heart is rotating and the ECG shows a spindle effect.

ERRNVPHGLFRVRUJ

50


Nonsustained VT is defined as a run of tachycardia of <30 seconds duration. Sustained VT is of a longer duration than 30 seconds.

Fig. 24: Idioventricular rhythm.

Idioventricular rhythm: QRS complexes are wide and bizarre (>0.10 sec) occurring at a rate of <60/min, in regular rhythm. P waves are absent or, if visible, have no consistent relationship to the QRS complex. It invariably causes hemodynamic instability.

Fig. 25: Accelerated idioventricular rhythm.

Accelerated idioventricular rhythm is similar to idioventricular rhythm but with a rate of 60–100/min and is usually not associated with hemodynamic compromise. Pulseless VT: When there is no effective cardiac output and there is no pulse because of a rapid ventricular rate of contraction. It is treated like a VF.

Ventricular Fibrillation

Fig. 26: Ventricular fibrillation.

ERRNVPHGLFRVRUJ


51

VF presents as a rapid, irregular rhythm with low amplitude QRS complexes and no cardiac output. It may result from degeneration of SVT or VT.

Pulseless Electrical Activity (PEA) PEA (formerly known as electromechanical dissociation) is recognized by slow, wide QRS complexes without palpable pulses; at other times, the ECG may be relatively normal but the pulses are absent. True PEA is defined as the total absence of myocardial contraction, while pseudo PEA is characterized by weak myocardial contractions that do not produce a measurable aortic pressure. PEA encompasses various rhythms (V-fibrillation or V-tachycardia) that do not produce a pulse including junctional and idioventricular or escape ventricular rhythms. Three sets of conditions will result in PEA: (i) poor intrinsic myocardial contractility caused by a severe cardiovascular insult (e.g., prolonged hypoxia, acidosis, hyperkalemia or hypokalemia, hypoglycemia and hypothermia); (ii) hypovolemia; and (iii) obstruction to the circulation (e.g., massive pulmonary embolus, tension pneumothorax, and cardiac tamponade). Patients with prolonged VF are sometimes defibrillated to a state of PEA with slow broad QRS complexes.

Clinical Classification of Tachyarrhythmias Supraventricular tachycardias (SVT): Three types of tachycardias are generally included in this term—(i) atrial ectopic tachycardia, (ii) AV reentrant tachycardias (AVRT and AVNRT), and (iii) junctional ectopic tachycardia. By convention, atrial fibrillation and atrial flutter are often categorized separately even though they are supraventricular in origin. A tachyarrhythmia with a narrow QRS complex (≤0.09 sec in children and ≤0.12 sec in adults) indicates a supraventricular origin, while a wide QRS complex (>0.09 sec in children and >0.12 sec in adults) indicates a ventricular arrhythmia. However, a supraventricular arrhythmia with an aberrant conduction also presents as a wide complex arrhythmia. In children, almost all wide complex arrhythmias are VT. Tachyarrhythmias may be divided into four groups: 1. Narrow QRS complex, irregular tachycardias are atrial fibrillation, atrial flutter with varying AV block or multifocal atrial tachycardia. 2. Narrow QRS complex, regular tachycardias include sinus tachycardia, atrial flutter, AET, reentrant tachycardias (AVNRT, AVRT) and JET. 3. Wide QRS complex, irregular tachycardias include polymorphic VT and the irregular atrial tachyarrhythmias with aberrant conduction.

ERRNVPHGLFRVRUJ

52


4. Wide QRS complex, regular tachycardias include monomorphic VT and the regular atrial tachyarrhythmias with aberrant conduction.

Differential Diagnosis of Narrow QRS Complex Arrhythmias Sinus tachycardia

AVRT/AVNRT

AET

‘P’ waves present and normal

‘P’ waves absent or retrograde (P −ve in lead II) may precede, follow or distort the QRS. (Pseudo RBBB in V1).

P waves present (positive or negative in lead II).

Gradual onset and termination, compatible with known cause (e.g., fever, pain, volume loss etc.)

Sudden onset and termination. Rate does not vary.

Gradually increases (warm up), and may gradually end. Rate may vary.

Infant HR <220 bpm

Infant HR >220 bpm

Infant HR >220 bpm

Child HR <180 bpm

Child HR >180 bpm

Child HR >180 bpm

PR interval normal, PR < RP

P absent or PR >RP

Normal (PR < RP) or 1°/2° block

Antiarrhythmic Drugs Drug

IV dose

Oral dose

Adenosine

Children 100 mcg/kg rapid IV bolus (max 6 mg) followed by a 5 mL saline flush. If required, repeat 200 mcg/kg IV (max 12 mg). This dose can be repeated twice.

Effective in reentrant SVT (AVRT, AVNRT) and rarely in some forms of VT. May transiently decrease the rate but does not convert other types of SVT.

Adults Initial dose: 6 mg rapid IV bolus (administered in 1–2 seconds), followed by a 5 mL saline flush.

May cause bronchospasm and a feeling of chest constriction as an adverse effect.

If required a12 mg IV dose can be repeated twice.

ERRNVPHGLFRVRUJ

Indication


Drug

IV dose

Oral dose

Indication

Amiodarone

Children Loading 5 mg/kg IV infusion over 30–60 minutes. Maintenance 5–10 mcg/kg/ min IV infusion (max total dose 15 mg/day).

Children Calculate doses for children <1 year on body surface area. Loading dose: 10–15 mg/kg/day (or 600–800 mg/1.73 m2/ day) in divided doses q12–24h for 4–14 days or until adequate control of arrhythmia. Then 5 mg/kg/day (or 200–400 mg/1.73 m2/ day) q24h for several weeks. Reduce to a maintenance dose of 2.5 mg/kg/day; maintenance doses may be given for 5 of 7 days/week.

Effective in all supraventricular and ventricular tachyarrhythmias.

Adults 150 mg IV over 10 minutes, followed by 360 mg (1 mg/min) for 6 hour, then 540 mg (0.5 mg/min) for 18 hour. Alternatively 300 mg IV is given over 30–60 minutes followed by 900 mg over 23 hour. In case of recurrence of arrhythmia, a supplemental dose of 150 mg over 10 minutes is given. Infusion at 0.5 mg/min is continued until oral therapy is initiated.

Adults Ventricular arrhythmias: 800–1600 mg/day in 1–2 doses for 1–3 weeks, then decrease to 600–800 mg/day in 1–2 doses for 4 weeks; maintenance: 200–400 mg/day in 1–2 doses. Lower doses are recommended for supraventricular arrhythmias. Conversion to initial oral therapy—If duration of IV infusion was <1 week, oral dose should be 800–1600 mg/day; IV infusion of 1–3 wk, oral dose 600–800 mg/day; IV infusion of >3 wk, oral dose 400 mg/day.

ERRNVPHGLFRVRUJ

53

Amiodarone IV may cause bradycardia and severe hypotension. It has an extensive adverse effect profile on prolonged use. No dose alteration is required in peritoneal or hemodialysis. After 4 weeks of therapy, optimum serum level each of amiodarone and desethyl amiodarone should be 1–2.5 mcg/mL.

54


Drug

IV dose

Oral dose

Indication

Diltiazem

Children 0.25–0.35 mg/kg IV bolus over 2 minutes. It can be repeated after 10 and 30 minutes.

Children 1.5–2 mg/kg/day in divided doses q6–8h.

May terminate reentrant SVT. Useful for rate control of atrial fibrillation, atrial flutter, and atrial tachycardias. Adverse effects are AV block and asystole, which requires reversal with 10% Inj. calcium gluconate 0.2–0.3 mL/kg IV.

Adults Initial dose 0.25 mg/kg (usually 20 mg) IV bolus over 2 minutes. If necessary, a second bolus of 0.35 mg/kg (usually 25 mg) IV may be given. An infusion of diltiazem 5 mg/h may be started, and advanced in 5 mg/h increments to 15 mg/h for up to 24 hour.

Adults 30–60 mg q6–8h; increase to a maintenance dose of 180–360 mg/day in divided doses q6–8h. SR dose: 60–120 mg q12h; increase to a maintenance dose of 180–360 mg/day in divided doses q12h.

Esmolol

Children and adults 500 mcg/kg IV bolus over 1–2 minutes. This may be followed by 50–300 mcg/kg/min IV infusion.

May terminate reentrant SVT and catecholamine sensitive VT. Useful for rate control of atrial fibrillation, atrial flutter, and atrial tachycardias.

Lignocaine

Children 1 mg/kg IV bolus, may be repeated in 5 minutes. Maintenance 20–50 mcg/ kg/min IV infusion. Adults 50–100 mg IV bolus. May be repeated if required. Maintenance 1–4 mg/min IV infusion.

Indicated in acute management of VT (including torsades), and multiple ventricular ectopics.

Magnesium sulfate

Children 25–50 mg/kg IV/IO over 10–20 minutes. Faster in torsades (max 2 g). Adults 1–2 g IV over 10–20 minutes. May be repeated in 15 minutes and 1–2 g continued as an IV infusion for 24–48 hour.

Antiarrhythmic indicated in ventricular ectopics and VT, especially torsades.

ERRNVPHGLFRVRUJ


55

Drug

IV dose

Oral dose

Indication

Metoprolol

Children 0.1 mg/kg slow IV (over 5 minutes). May be repeated every 5 minutes for a max of 3 doses. Can be followed by infusion 1–2 mcg/kg/min.

Children 1–17 years: 1–2 mg/kg/ day in divided doses q12h; increase to a max 6 mg/kg/day.

Efficacy and safety of IV metoprolol in children has not been established.

Adults 5 mg IV repeated for a max of 3 doses at 2 minutes intervals. Procainamide

Verapamil

Adults 100 mg/day in divided doses q12–24h; increase to max 450 mg/day.

Infants 7–10 mg/kg IV Children 10–15 mg/kg IV Administer loading dose over 30–45 minutes. Maintenance 40–50 mcg/kg/min IV infusion. Adults Loading dose 500 mg is administered over 20 minutes. Maintenance 2 mg/kg/h IV infusion.

Children 40–100 mg/kg/day in divided doses q4–6h

Children (>1 year age) 0.1–0.3 mg/kg/dose (max 5 mg) IV over 10 minutes. Repeat dose after 30 minutes if required (max 10 mg). Adults 2.5–5 mg IV. Repeat 5–10 mg every 15–30 minutes if required to a max 20 mg.

3–6 mg/kg/day in divided doses q8h.

Adults 500 mg q6h

Adults 240–320 mg/day in divided doses q6–8h (digitalized patient); 240–480 mg/day (nondigitalized patient).

Indicated in stable, regular VT. Contraindicated in torsades. 2nd line therapy in atrial fibrillation, atrial flutter, and reentrant SVTs.

Adverse effects include AV block and asystole, which requires reversal with 10% Inj. calcium gluconate 0.2–0.3 mL/kg IV (alternatively administer calcium gluconate IV prophylactically prior to verapamil).

IV: intravenous, IO: intra osseous, ET: via endotracheal tube. Drug requires to be flushed with 5 mL normal saline, followed by 5 ventilations.

ERRNVPHGLFRVRUJ

56

Manual of Pediatric Cardiac Intensive Care Flowchart for the Management of Tachyarrhythmias Evaluate patient Monitor blood pressure Monitor rhythm

Stable

Unstable

12 lead ECG

Narrow complex

Wide complex

• Synchronized DC shock (1–4 J/kg) • IV analgesia

Regular

Irregular

Monomorphic recurrent VT Sustained monomorphic VT • Amiodarone • Lignocaine • Procainamide • Cardioversion (sustained VT)

SVT with aberrant conduction • Adenosine • Diltiazem • β-blocker • Amiodarone

Polymorphic recurrent VT Sustained polymorphic VT • Cardioversion (sustained VT) • Follow-up with amiodarone or β-blocker • Magnesium sulfate for torsades

Regular Irregular

• Vagal maneuvers • Adenosine

Rhythm converted

Rhythm not converted

Re-entry SVT • Prevent recurrence with diltiazem or β-blocker

AET Atrial flutter JET Re-entry SVT • Diltiazem/β-blocker/ amiodarone

ERRNVPHGLFRVRUJ

Atrial fibrillation Atrial flutter with variable block MAT • Diltiazem/β-blocker/ amiodarone


57

Management of Narrow QRS Complex Tachycardias DC Cardioversion Cardioversion is used as the first line of therapy in the hemodynamically unstable patient with an atrial arrhythmia or VT. The dose of the initial shock for cardioversion in children is 0.5–1 J/kg, which is increased to 2 J/kg if there is no response to this shock. (In the adult, the shock sequence is an initial shock of 120 J followed by 200 J when a biphasic defibrillator is used. With a monophasic waveform, an initial shock of 200 J is followed by 360 J.) For cardioversion (atrial or ventricular), the DC shock must be synchronized to the QRS complex because a shock that falls on the T wave can induce VF. The initial dose for defibrillation in children in VF or pulseless VT is 2 J/kg, which is increased to 4 J/kg in subsequent shocks. (The default initial energy dose with a biphasic defibrillator recommended for defibrillation in adults is 120 or 200 J. If a monophasic defibrillator is used, the recommended initial dose is 360 J.) Defibrillation does not require synchronization. IV analgesia and sedation is necessary prior to cardioversion in all awake patients, e.g., fentanyl 1 mcg/kg + midazolam 0.05–0.1 mg/kg IV can be given. Midazolam may be repeated 0.05 mg/kg at 2–3 minutes intervals up to a total of 0.2 mg/kg. Alternatively, ketamine 1–2 mg/kg IV provides 5–10 minutes of surgical anesthesia.

Vagal Maneuvers In a hemodynamically stable patient with a regular rhythm, first vagotonic maneuvers can be tried. These vagotonic maneuvers include the Valsalva maneuver, unilateral carotid sinus massage, or application of an ice pack to the face. One method of Valsalva maneuver is to have the child blow through an obstructed straw. This may terminate the arrhythmia (AVRT, AVNRT) or transiently slow the ventricular rate so that the relationship of the P waves with the QRS complexes becomes evident and it becomes possible to diagnose the rhythm disorder. Normal P waves are present in sinus tachycardia and retrograde P waves (negative in lead II, positive in aVR.) may be apparent in reentrant tachycardias. P waves outnumber the QRS complexes in atrial flutter or AET with a block. Vagal maneuvers and adenosine are ineffective in atrial fibrillation.

Adenosine The action of adenosine is similar to vagotonic maneuvers and acts by slowing AV nodal conduction. It may terminate reentrant tachycardias or

ERRNVPHGLFRVRUJ

58


cause transient slowing of the ventricular rate. It acts in 10–20 seconds and causes a brief (2–3 seconds) period of cardiac standstill, which is followed by return of normal sinus rhythm or a recurrence of the arrhythmia. Its advantages are the short half-life (<2 seconds), no negative inotropic effects, and it has no adverse effects in wide QRS complex tachycardias. It can be repeated in up to 3 incremental doses. Thereafter, a number of alternative treatment options are available, which will control the fast ventricular rate or convert the arrhythmia to sinus rhythm viz. calcium channel blockers (e.g., diltiazem), β-blockers (e.g., esmolol), or Inj. amiodarone. Calcium channel blockers and β-blockers must not be combined because of the severe negative inotropic effect.

Calcium Channel Blockers IV diltiazem or verapamil can be given. Calcium channel blockers are contraindicated in infants (high risk of electromechanical dissociation) and in patients with wide QRS-complex tachycardias or with significant hemodynamic compromise. Side effects include hypotension, congestive heart failure, AV block, and asystole. These effects can however be managed with adrenergic agents and IV calcium gluconate.

Beta-Blockers Esmolol may effectively control the heart rate in narrow complex tachycardias. IV metoprolol needs to be used with caution in children as its efficacy and safety is yet to be established.

Amiodarone Amiodarone may cause cardioversion of both supraventricular and ventricular arrhythmias and has minimal negative inotropic effects. It however, often causes severe bradycardia and must be used with caution following β-blockers or calcium channel blockers. Its other cardiovascular adverse effects include hypotension, congestive heart failure, VT, AV blocks, and cardiac arrest.

Digoxin Digoxin may be given to patients of all forms of tachyarrhythmias with poor LV function as an adjunct to amiodarone, calcium channel blockers, or β-blockers, except in preexcitation syndrome (WPW).

ERRNVPHGLFRVRUJ


59

Therapeutic Overdrive Pacing Temporary atrial overdrive pacing (transthoracic or transvenous) may be attempted in narrow complex tachycardias. Pacemaker rates 10–20 beats faster than the tachycardia, with adequate pacing output may result in pacing the myocardium. Progressively faster rates are tried till pacing takes place and the pacemaker is then suddenly stopped, in an effort to terminate the arrhythmia. In AET, overdrive atrial pacing may result in a 2:1 AV block, thus decreasing the ventricular rate. Similarly, by increasing the degree of block, atrial pacing at rates faster than the atrial rate (not ventricular rate) may be effective in atrial flutter. In junctional ectopic tachycardia, it may sometimes be possible to establish AV synchrony by pacing the atrium at rates faster than the junctional rate.

Treat Possible Causes Possible causes of arrhythmias include hypoxia, acidosis, hypothermia, hypovolemia, hyperkalemia, hypokalemia, cardiac tamponade, tension pneumothorax, and various drugs.

Management of Atrial Fibrillation 1. Inj. amiodarone promotes cardioversion and controls the ventricular rate and may be preferable in the hemodynamically stable patient. 2. IV calcium channel blockers (diltiazem or verapamil) or β-blockers (esmolol) are alternatives to amiodarone and are indicated when a faster action is needed, e.g., when arrhythmia is the cause of hemodynamic instability. β-blockers and Ca channel blockers must not be combined and must be used with caution with amiodarone. 3. Digoxin can be used as adjunctive therapy to β-blockers, calcium channel blockers, or amiodarone in patients with heart failure or poor LV function. 4. Synchronized cardioversion 0.5–2 J/kg is indicated in the hemodynamically unstable patient either as first line of therapy, or in patients who do not respond to IV calcium channel blockers (or β-blockers).

Management of JET The problem with JET is that it is unresponsive to DC cardioversion, calcium channel blockers, and β-blockers. The patients are hemodynamically

ERRNVPHGLFRVRUJ

60


compromised, and its management may need to be prolonged for days before the arrhythmia settles down. 1. Chronotropic agents are withdrawn; electrolyte disturbances and all fluid deficits are corrected. 2. Induced hypothermia is usually very effective in slowing the arrhythmia rate. The patient is placed on a cooling blanket and ice packs utilized to bring down the core temperature by 1–2°C. 3. The patient needs to be ventilated, with full neuromuscular paralysis and sedation to decrease the basal metabolic rate. 4. Intravenous amiodarone: Loading 5 mg/kg (over 30 minutes) is followed by a maintenance 3–5 mcg/kg/min infusion. 5. The use of fixed-rate atrial pacing at a rate higher than the tachycardia rate may restore AV synchrony and improve hemodynamics in some patients.

Differential Diagnosis of Broad QRS Complex Tachycardias Ventricular tachycardia

Supraventricular tachycardia with bundle branch block or accessory pathway

Atrioventricular dissociation. Ventriculoatrial conduction may be present. Presence of capture beats and fusion beats are supportive evidence.

1:1 AV conduction

QRS >160 msec. (VT from the conduction system has QRS <140 msec)

QRS <160 msec. (SVT with accessory pathway – QRS >160 msec)

Left axis deviation > −30°. (Not valid in presence of left bundle branch block)

Right axis (posterolateral accessory pathway will have left axis deviation).

Occasionally concordant pattern in precordial leads. (Entirely +ve or –ve QRS complexes in all precordial leads)

Concordant pattern is absent in precordial leads. (Left posterolateral AP has concordant pattern)

Wide complex tachycardia has several potential causes, which include (i) VT; (ii) SVT with aberrant interventricular conduction (bundle branch

ERRNVPHGLFRVRUJ


61

blocks) or atrioventricular conduction over an accessory pathway (WolffParkinson-White); and (iii) QRS widening due to drugs, electrolyte abnormalities, or ventricular pacing.

Management of Broad QRS Complex Tachycardia (>0.09 Second) 1. Drugs In patients with VT, even though DC cardioversion is the most effective treatment, it requires systemic analgesia and sedation, thus monomorphic VT with adequate vital end-organ perfusion and no signs of hemodynamic compromise can initially be treated with intravenous amiodarone, lignocaine, or procainamide. As hypomagnesemia is a cause of VT, especially torsades, a stat dose magnesium sulfate (50 mg/kg over 20 minutes) can also be given. Any electrolyte abnormalities are corrected. 2. Cardioversion If medical therapy fails to correct the rhythm or the patient is unstable, synchronized cardioversion is given in increments (children 0.5–2 J/kg, adults 120 J initially, then 200 J if unsuccessful). Amiodarone is also indicated after electric cardioversion to prevent further episodes of VT. 3. Adenosine When it is not possible to differentiate VT from a supraventricular arrhythmia with aberrant conduction,the options available are: (i) Inj. adenosine (0.1 mg/kg IV) may be considered in a hemodynamically stable patient in regular rhythm with a monomorphic QRS. It may convert the supraventricular arrhythmia to sinus rhythm. (ii) IV amiodarone. (iii) Alternatively, synchronized cardioversion (0.5–2 J/kg in children, 120–200 J in adults) may be attempted in the first place.

Cardiac Arrest Cardiac arrest is classified into (i) shockable rhythm and (ii) non-shockable rhythm, based upon whether the particular arrhythmia responds to defibrillation or not. The two shockable rhythms are ventricular fibrillation and pulseless ventricular tachycardia, while the two non-shockable rhythms are

ERRNVPHGLFRVRUJ

62


asystole and pulseless electrical activity. These patients require emergency management as per the PALS protocols (see chapter on Pediatric Resuscitation).

Bibliography 1. Cardiac arrhythmias. South Thames Retrieval Service. 2009 Jan [Cited: 2011 Sep 21]. Available at: http://www.strs.nhs.uk/resources/pdf/guidelines/arrythmias.pdf 2. DeSouza IS, Ward CD. Ventricular tachycardia. [Updated: 2011 Jan 19; cited: 2011 Sep 21]. Available at: http://emedicine.medscape.com/article/760963. 3. Gillette PC, Case CL, Kastor JA. Junctional ectopic tachycardia. In: Kastor JA, ed. Arrhythmias Philadelphia: WB Saunders Company; 1994:218–23. 4. Iyer RV. Drug therapy considerations in arrhythmias in children. Indian Pacing Electrophysiol J 2008;8:202–10. 5. Kantoch MJ. Supraventricular tachycardia in children. Indian J Pediatr 2005;72:609–19. 6. Lawrence III JH, Kanter RJ, Wetzel RC. Pediatric arrhythmias. In: Nichols DG, Cameron DE, Greeley WJ, Lappe DG, Ungerleider RM, Wetzel RC. Critical Heart Disease in Infants and Children St Louis: Mosby; 1995:17–253. 7. Mennuni M, Bianconi L. Management of tachyarrhythmias in the emergency room. © 1998. [Cited: 2011 Sep 21]. Available at: http://www.xagena.it/einthoven/eint0137.htm 8. Myeburg RJ, Kessler KM. Ventricular fibrillation. In: Kastor JA, ed. Arrhythmias Philadelphia: WB Saunders Company; 1994:395–450. 9. Overview of Arrhythmias. The Merck Manuals: online medical library. [Updated: 2010 Jan; cited: 2011 Sep 21] Available at: http://www.merckmanuals.com/professional/cardiovascular_disorders/arrhythmias_and_conduction_disorders/overview_of_arrhythmias.html 10. Penny-Peterson ED, Naccarelli GV. Supraventricular tachycardia. In: Yusuf S, Cairns JA, Camm AJ, Fallen EL, Gersh BJ, ed. Evidence Based Cardiology 3rd ed. Blackwell Publishing; 2010:606–18. 11. Prescription Drug Information, Interactions & Side Effects. [Cited: July 2012] Available at: http://www.drugs.com/ 12. Reentrant Supraventricular Tachycardias (SVT, PSVT). The Merck Manuals: online medical library. [Updated: 2010 Jan; cited: 2011 Sep 21] Available at: http://www.merckmanuals.com/ professional/cardiovascular_disorders/arrhythmias_and_conduction_disorders/reentrant_ supraventricular_tachycardias_svt_psvt.html 13. Robida A. Early arrhythmias in children after cardiac surgery. Heart Views 1999;1:223–8. Available at: http://www.hmc.org.qa/heartviews/VOL1NO6/07CONGENITAL_HEART_DISEASE. htm 14. Rosenthal L, McManus DD. Atrial Fibrillation. [Updated: 2010 Jun 1; cited: 2011 Sep 21]. Available at: http://emedicine.medscape.com/article/151066-overview. 15. Sanatani S, Hamilton RM. Supraventricular Tachycardia, Atrial Ectopic Tachycardia. [Updated: 2011 Sep 12; cited: 2011 Sep 21]. Available at: http://emedicine.medscape.com/ article/898784. 16. Saxena A, Juneja R, Ramakrishnan S. Working Group on Management of Congenital Heart Diseases in India. Drug therapy of cardiac diseases in children. Indian Pediatr 2009;46:310–38. 17. Schlechte EA, Boramanand N, Funk M. Supraventricular tachycardia in the primary care setting: age-related presentation, diagnosis, and management. J Pediatr Health Care 2008; 22:289–99. 18. Valsangiacomo E, Schmid ER, Schüpbach RW, et al. Early postoperative arrhythmias after cardiac operation in children. Ann Thorac Surg 2002;74:792–6.

ERRNVPHGLFRVRUJ

Bradyarrhythmias and Pacemakers “I seriously doubt if anything I ever do will ever give me the elation I felt that day when my own two cubic inch piece of electronic design controlled a living heart” —Wilson Greatbatch (1919–2011)*

Heart Blocks

Fig. 1: First-degree heart block.

Fig. 2: Mobitz type 1 second-degree heart block.

Fig. 3: Mobitz type 2 second-degree heart block. *Wilson Greatbatch was the inventor of implantable cardiac pacemaker. He is credited with 320 inventions and more than 150 patents.

ERRNVPHGLFRVRUJ

64


Fig. 4: Complete heart block.

Types of Heart Block Type

ECG findings

Comments

First-degree AV block

PR interval is prolonged above the upper limit of normal for age. All QRS complexes are preceded by a P wave.

PR prolongation may be caused by drugs such as digoxin, β-blockers, or calcium channel blockers and also occurs in a variety of cardiac diseases.

Second-degree AV block Mobitz type 1 (also called Wenckebach block) Mobitz type 2

In Mobitz type 1, second-degree AV block, the PR interval is progressively prolonged with each beat, until a P wave is not followed by a QRS complex. The cycle is constantly repeated. In Mobitz type 2, second-degree AV block, after a number of normal beats a QRS complex is blocked (2:1 block, 3:1 block). The PR interval does not lengthen before a dropped beat. More than one dropped beat may occur in succession.

Drugs or disease processes that affect the AV node produce this type of block, e.g., digoxin or an inferior infarction. Mobitz type 2 block is usually caused by an organic lesion in the conduction pathway and is not the effect of drugs. It may progress to complete heart block and is an indication for a pacemaker implantation.

Third-degree AV block (complete heart block)

No conduction between the atria and Complete heart block can ventricles takes place and both function be congenital and also independently at different rates. caused by injury to the Normal P waves may be present or there conduction pathway during may be an atrial arrhythmia. Alternatively, surgery or as a side effect of drug toxicity. there may be no atrial activity. With associated junctional escape rhythm, the QRS complexes have a normal configuration; while with ventricular escape rhythm, the QRS has a wide abnormal configuration.

ERRNVPHGLFRVRUJ

65


NASPE/BPEG Generic Code for Pacemakers 1. Chamber(s) paced

2. Chamber(s) sensed

3. Response to sensing

4. Rate modulation

5. Multisite pacing

O None

O None

O None

O None

O None

A Atrium

T Triggered

R Rate modulation

A Atrium

V Ventricle

V Ventricle

I Inhibited

V Ventricle

D Dual (A + V)

D Dual (A + V)

D Dual (T + I)

D Dual (A + V)

The North American Society of Pacing and Electrophysiology (NASPE) and the British Pacing and Electrophysiology Group (BPEG) have devised a generic letter code to describe the types and functions of pacemakers. The first three letters are used to describe pacing functions in bradycardia and heart blocks. 1. The letter in the first position identifies the chamber paced (O, none; A, atrium; V, ventricle; D, dual chamber [A + V]). 2. The second is the chamber sensed (O, none; A, atrium; V, ventricle; D, dual). 3. The third letter corresponds to the response of the pacemaker to an intrinsic cardiac event (O, none; I, inhibited; T, triggered; D, dual [I + T]). 4. The fourth letter indicates both programmability and rate modulation. 5. The fifth position of the code is used to indicate whether multisite pacing is present.

Pacing Modes Parameters to be set in various modes Parameters

AAI

VVI

DVI

VDD

DDD

Rate

+

+

+

+

+

+

+

+

+

Upper rate A sense

+

A output

+

+

+

V sense

+

+

+

+

V output

+

+

+

+

+

+

+

+

PVARP AV interval

+

ERRNVPHGLFRVRUJ

66


External (or temporary) pacemakers may be single chamber or dual chamber pacemakers. Single chamber pacemakers are capable of pacing only the atria or ventricle at one time and can be programmed in the VVI, VOO, AAI, or AOO mode. Dual chamber pacemakers are capable of synchronously pacing the atria and the ventricle. Demand pacemakers are pacemakers with single and double chamber pacing modes with a sensing function, which causes triggering or inhibition of a paced event (AAI, VVI, DVI, VDD, DDD). 1. In AOO mode, the atria is paced at a fixed rate with no atrial or ventricular sensing. AOO pacing may be used for overdrive pacing in atrial arrhythmias. 2. In VOO pacing, the ventricles are paced at a fixed rate with no atrial or ventricular sensing. This type of pacing can be used in an emergency and also during surgery when electrocautery causes interference with demand pacing. 3. In AAI mode, the atria are paced and sensed. Intrinsic atrial activity inhibits the paced atrial impulse, otherwise the atria is paced at a set rate. This type of pacing is commonly used in sinus node dysfunction with intact AV conduction. 4. In VVI pacing, the ventricle is paced and sensed. If an intrinsic ventricular beat is sensed the paced impulse is inhibited, otherwise, the ventricle is paced at the set rate. In VVI pacing, there is no AV synchrony. This type of pacing may be used for episodic AV block or bradycardia in small infants. 5. In DVI pacing, both the atrium and ventricle are paced but only the ventricle is sensed. It allows AV sequential pacing, if after an atrial stimulus, AV conduction takes place, ventricular pacing is inhibited; otherwise, ventricular pacing occurs. Competing atrial rhythm may precipitate atrial flutter or fibrillation, since atria is not sensed. 6. In VDD mode, the ventricle is paced but both atrium and ventricle are sensed. Provided the intrinsic atrial rate is higher than the set atrial rate, sequential pacing will occur. In other circumstances when there is no atrial activity or the intrinsic atrial rate is slow, VDD mode functions like VVI. 7. A DDD device is a dual-chamber pacemaker, which is capable of sensing both atria and ventricles, and then triggering or inhibiting the paced output in either chamber. A sensed atrial impulse will inhibit the atrial pacing impulse and after the programmed AV delay, it will initiate a ventricular paced event. In case it senses an intrinsic ventricular impulse, ventricular pacing is inhibited.

ERRNVPHGLFRVRUJ


67

Access Sites for Pacing Site

Indication

Epicardial

Postoperatively

Transcutaneous

In an emergency till another method of pacing can be initiated

Transvenous

Used in the absence of epicardial pacing wires

Esophageal

Management of atrial arrhythmias by overdrive pacing

Epicardial pacing is used postoperatively after cardiac surgery. In the bipolar system of wire placement, two wires each are sutured to the right atrium and right ventricle, while in the unipolar system one negative electrode is attached to the RA and one to the RV and the two positive electrodes are attached to the subcutaneous tissue. The advantage of the bipolar system for temporary postoperative pacing is that lower pacing outputs and sensing thresholds are needed for pacing. Single or double chamber pacing is instituted by the appropriate set of wires. By convention, atrial wires are made to exit on the right of the sternum and the ventricular wires to the left of the sternum. Transcutaneous asynchronous ventricular pacing can be initiated in an emergency by an external pacing device or pacing capable defibrillator unit through skin electrodes. This method of pacing requires high energy for capture and is used only as a bridge for a couple of hours till pacing can be established by another method. Transvenous pacing is instituted via a lead inserted under fluoroscopic guidance to pace the RV (VVI/VOO). Transesophageal pacing can only be used to pace the atria so it is not useful in AV dissociation. Its main use is in the treatment of atrial arrhythmias for overdrive pacing using a specialized generator. High pacing output over a long period can cause esophageal perforation.

Pacemaker Parameters Pacemaker Output The lowest output (defined in mV or mA) that will result in contraction of atrium or ventricle is called the capture threshold. The duration of the pacing impulse (defined in milliseconds) is known as the pulse width. In temporary pacemakers, the pacing output can be set but the pulse width is a fixed parameter. To establish the pacemaker output required for capture of the atria, the following method is used. The pacing rate is set to 10 beats/min above the

ERRNVPHGLFRVRUJ

68


patient’s intrinsic heart rate and if the AV conduction is intact, the AV interval is kept less than the intrinsic AV interval. Starting with an atrial output of 5 mV, the output is decreased till capture is lost or increased till capture occurs. Capture is indicated by the presence of an atrial pacing spike followed by a P wave. For safety reasons, the pacing output is kept at twice the value which was required for capture. The output required for pacing the ventricle is similarly determined (start with 5 mV). Capture is indicated by the presence of a ventricular pacing spike followed by a wide pacing complex. The pacing output is again kept at twice the value determined for capture. If the AV conduction is intact, increasing the AV interval to more than the patients AV interval will allow conducted ventricular beats.

Sensing The sensing threshold is the highest voltage set on the pacemaker at which the pacemaker can still detect the intrinsic atrial or ventricular electrical impulse. Setting the threshold too high will cause failure of sensing (undersensing) leading to fixed-rate pacing (AOO/VOO), and setting it too low will result in sensing of other activity (oversensing) and loss of pacing. The optimal atrial sensing threshold is established by keeping the pacing rate to 10 beats/min below the patient’s intrinsic atrial rate and the pacing output set to a minimum. Starting with the maximum atrial sensing threshold, which results in fixed rate pacing, the sensing threshold is slowly reduced till the pacemaker starts to sense. The sensing threshold is set to half this value, but if muscle activity is sensed, this setting is increased. This is repeated for ventricular threshold.

Pacing Rate Single chamber pacing modes require a single rate setting. In AAI and VVI modes, the pacemaker will pace at the set rate unless exceeded by the intrinsic rate. Dual chamber pacing modes require a lower rate setting and an upper tracking rate setting. The upper rate is the maximum rate at which the pacemaker will pace the ventricle even if the sensed intrinsic atrial rate becomes higher than this set rate. At intrinsic atrial rates above the upper tracking rate, the ventricular response results in a second-degree AV block (Wenckebach response). This is a safety measure, which prevents pacemaker mediated tachycardia resulting from tracking of high atrial rates.

ERRNVPHGLFRVRUJ


69

Refractory Periods P

P

AVI

PVARP Fig. 5: Refractory periods. AVI: atrioventricular interval, PVARP: post ventricular atrial refractory period.

Total atrial refractory period (TARP) is the combination of the atrioventricular interval (AVI) (which is analogous to the PR interval) and the post ventricular atrial refractory period (PVARP) (which is the period beyond the ventricular sensed or paced impulse during which also the atria are refractory). The purpose of the refractory period is to prevent the atrial channel of the pacemaker from sensing the output impulse of the ventricular lead (cross talk), retrograde P waves, or the QRS complex (far field R waves) as atrial signals. Ventricular refractory period (VRP) follows the ventricular paced or sensed impulse and prevents the ventricular channel of the pacemaker from sensing of the pacing stimulus and the R waves. VRP is not programmable on temporary pacemakers (typical values for VRP are 200–350 msec). DDD pacemakers have settings for upper tracking rates, AVI, and PVARP. Higher tracking rates in children require shorter PVARP or/and AVI. Too short an AV interval may not allow adequate ventricular filling (generally set between 100–140 msec for children and 150–200 msec in adults when paced at 80–110/min) and too short a PVARP may result in oversensing or pacemaker-mediated tachycardia.

Initial Pacemaker Settings Atrial and ventricular output

Typical atrial: 5 mA/mV Typical ventricular: 8–10 mA/mV

AV interval (same as PR interval) In children 100–140 msec. Sets automatically with the set rate Atrial and ventricular sensing threshold

Typical atrial: 0.4 mV (<1 mV) Typical ventricular: 2.0 mV (2–5 mV)

Atrial/ventricular rate

Set at physiologic rate for individual patient

Upper rate

Automatically adjusts to 30 bpm higher than the set rate

Refractory period

PVARP (post ventricular atrial refractory period) sets automatically depending on the set rate

mA: milliamperes, mV: millivolts, PVARP: post ventricular atrial refractory period.

ERRNVPHGLFRVRUJ

70


Setting the Pacemaker in a Postoperative Patient A–V Sequential Pacing

Fig. 6: A–V sequential pacing: atrial and ventricular pacing spikes are followed by atrial and ventricular complexes. However, note that the P waves are often barely discernable between the pacing spikes, and ventricular pacing produces wide QRS complexes.

Sinus bradycardia with AV block requires sequential pacing of the atria and ventricles. The pacing rate is set at the normal rate for the patients age (to pace, the set rate must be higher than the intrinsic atrial rate), and the atrial and ventricular pacing outputs are set at 2 × the minimum required for capture. The atrial and ventricular sensing is appropriately set at half the noted sensing threshold. In temporary pacemakers, the AV interval, upper rate, and PVARP change automatically with set rate, however, can also be manually altered to ensure the best hemodynamics.

Synchronized Ventricular Pacing

Fig. 7: Synchronized ventricular pacing. Ventricle pacing follows P waves at the atrial rate of 140 beats/min.

Normal sinus rhythm with AV dissociation requires tracking of P waves with synchronized ventricular pacing. This needs the atrial pacing rate to be kept less than the intrinsic atrial rate. If it is more than the intrinsic atrial rate, the atria will also be paced in addition to the ventricle. This will also happen if the atrial P wave is not sensed for any reason.

ERRNVPHGLFRVRUJ


71

Single Chamber Atrial Demand Pacing

Fig. 8: Atrial pacing. Atrial pacing spikes are followed by P waves and normal QRS complexes.

In sinus bradycardia without AV block, single chamber pacing of the atria alone is required. With appropriate atrial sensing, pacing of the atria will take place as long as the set rate is higher than the intrinsic rate.

Troubleshooting Pacemakers Problem

Causes

Failure to capture (pacing spikes not followed by P waves/QRS complexes)

(1) Pacing output inadequate (1) Increase the pacing output (2) Dislodged or fractured lead, low (2) Try with reversing the wires battery connected to the pacemaker (3) Electrolyte abnormalities (acidosis, cable (reverse polarity) or convert hypokalemia) a bipolar system to a unipolar system or change battery, cables, pacemaker (3) Correct electrolytes

Solutions

Failure to sense (atrial/ ventricular pacing spikes not related to P/QRS)

(1) Sensitivity threshold set too high (1) ↓ Sensitivity threshold (↓ mV) (2) Dislodged or fractured lead, low (2) Try with reverse polarity or battery convert bipolar system to unipolar (3) Electrolyte abnormalities (acidosis, system or change battery, cables, hypokalemia) pacemaker (3) Correct electrolytes

Failure to pace (pacing spikes absent)

(1) Sensitivity threshold set too (1) Increase sensitivity threshold low or PVARP too short causing (↑ mV) or increase duration of oversensing PVARP (2) Dislodged or fractured lead, low (2) Try with reverse polarity or battery convert bipolar system to unipolar (3) Electrolyte abnormalities (acidosis, system or change cables, battery, hypokalemia) pacemaker (3) Correct electrolytes

ERRNVPHGLFRVRUJ

72


Problem

Causes

Solutions

Competition

Set pacemaker and patient’s intrinsic rates are similar and there is failure to sense or asynchronous pacing

(1) Increase rate of pacing (2) Troubleshoot as for failure to sense (decrease sensitivity threshold by ↓ mV)

Wenckebach response

(1) May occur with sinus tachycardia, atrial fibrillation and flutter (2) Upper rate limit may be set inappropriately low

(1) Treat cause of tachycardia: fever, pain, hypovolemia, antiarrhythmic drugs (2) Adjust pacemaker upper rate limit as appropriate

Pacemaker mediated tachycardia

In DDD, a reentrant tachycardia caused by retrograde conduction of P wave

Increase PVARP setting or convert to atrial nonsensing mode (DVI)

Failure to Capture

Fig. 9: Atrial non-capture. Note that atrial pacing spikes are not followed by P waves.

Fig. 10: Ventricular non-capture. Note that some ventricular pacing spikes are not followed by QRS complexes.

Failure of atrial capture is evident by presence of atrial pacing spikes that are not followed by P waves, and similarly failure of ventricular capture is shown by ventricular pacing spikes not followed by QRS complexes. In a

ERRNVPHGLFRVRUJ


73

critical setting, inappropriate pacing may result in bradycardia, low cardiac output, or cardiac arrest. In case of failure of capture, the first step is to confirm that the pacing output is adequate. Reversing lead polarity or conversion of a bipolar system to a unipolar system may resolve the problem. The integrity of the pacemaker leads and the battery is checked.

Failure to Sense

Fig. 11: Atrial undersensing. Atrial pacing spikes occur regardless of P waves, and the ventricular pacing is not synchronized to the normal P waves.

a

a

b

a

b

a

Fig. 12: Ventricular undersensing; ventricular pacing spikes occur at a fixed rate since intrinsic activity is not sensed. Pacing rate 110/min, intrinsic rate 150/min. a: Ventricular paced beats are noted whenever pacing take place during the non-refractory phases of the ventricle (Crest of preceding T wave to onset of next QRS), b: Fusion beats result with simultaneous occurrence of intrinsic and paced beats.

In atrial undersensing, atrial pacing spikes occur irrespective of inherent P waves; similarly in ventricular undersensing, ventricular pacing spikes occur regardless of QRS complexes. The pacemaker will continue to pace with no regard to the patient’s inherent rhythm. With undersensing, there is potential danger of a paced ventricular beat falling on the T wave and causing ventricular fibrillation. The sensitivity threshold is checked to confirm if it has not been set too high. Reversing lead polarity or conversion of a bipolar system to a unipolar

ERRNVPHGLFRVRUJ

74


system may correct the problem. The pacemaker leads and the battery may require replacement.

Failure to Pace a

b

Fig. 13: The pacemaker is inhibited by a T wave (arrow a). Similarly artifacts may inhibit the pacemaker (arrow b).

During the period when the pacemaker fails to pace, there is no pacing spike and no paced P or QRS complex is seen. Causes of failure of pacing include oversensing, dislodged or fractured leads, low battery, and electrolyte abnormalities (acidosis, hypokalemia). Oversensing occurs when the pacemaker sensing threshold has been set too low and the pacemaker senses other signals, e.g., skeletal muscle contraction, electromagnetic interference, etc. This is corrected by increasing the sensitivity threshold (i.e., decreasing the sensitivity). Increasing the threshold too high will convert demand pacing to asynchronous VOO pacing. The pacemaker is checked to confirm the function of the pacemaker, leads, and battery. Pacing is tried with the polarity of the leads reversed and if required, the bipolar system is converted to a unipolar system.

Competition

Fig. 14: Competitive pacing. The pacing rate is 136/min and the intrinsic rate 124/min. The intrinsic rhythm is not sensed resulting in unrelated ventricular pacing spikes to the QRS complexes, paced beats, and fusion beats (arrow).

In demand pacemakers, competition between the intrinsic cardiac rhythm and the pacemaker rhythm occurs when two things happen—(i) the intrinsic

ERRNVPHGLFRVRUJ


75

heart rate is similar to the paced rate and (ii) fixed rate pacing occurs because of failure of sensing of the intrinsic rhythm or alternatively if fixed rate pacing is being used. The ECG shows unrelated pacer spikes to P waves and QRS complexes, multiple paced beats and fusion beats. There is danger that the pacemaker spike can fall on the intrinsic T wave and cause ventricular fibrillation. To prevent competition, the pacing rate is increased and the sensitivity threshold of the pacemaker is reduced (↓ mV) to ensure sensing of the atrial impulses.

Wenckebach Response In case of a fast atrial rate, which rises above the upper tracking rate, a fast ventricular response is prevented by the occurrence of a second-degree AV block (Wenckebach block response). This is a safety measure, which prevents pacemaker mediated tachycardia resulting from tracking of high atrial rates. Treatment involves the control of tachycardia and increasing the pacemaker upper tracking rate limit in case it had been set inappropriately low.

Pacemaker Mediated Tachycardia During synchronous AV pacing (DDD, VDD), a ventricular extrasystole may result in retrograde VA conduction and a retrograde P wave. If this retrograde P wave is sensed by the atrial electrode, it will initiate a paced ventricular complex. This can again result in a retrograde P wave and a reentrant tachyarrhythmia will be established. This is prevented by setting a PVARP long enough to prevent the sensing of retrograde P waves or conversion to a P wave nonsensing mode (DVI).

Therapeutic Overdrive Pacing Temporary overdrive pacing may be effective as a means of terminating paroxysmal supraventricular tachycardias, atrial flutter, and JET. Pacing at rates 10–20 beats faster than the tachycardia may capture the myocardium, which is indicated by a change in the morphology of the P wave, or a change in the conducted RR interval. Adequate pacing output is required and progressively faster rates are tried till capture is confirmed, the pacing is then stopped abruptly to terminate the arrhythmia. In SVTs and atrial flutter, pacing is done at rates faster than the atrial rate and not the ventricular rate. In junctional ectopic tachycardia, it may be possible to establish AV synchrony by temporary dual chamber pacing at a faster rate than the junctional rate.

ERRNVPHGLFRVRUJ

76


Removal of Pacing Wires Once it is confirmed that the coagulation profile is normal, temporary epicardial pacing leads can be removed by gentle traction. The ECG is monitored for arrhythmias during the removal, and the patient is clinically observed for a few hours for any signs of cardiac tamponade. Occasionally, it may not be possible to remove the wires without use of force, in which case the wires are pulled only as far as possible and then cut close to the skin. This permits the wires to retract under the skin.

MRI in Patients with Pacing Wires MRI is avoided in patients with temporary epicardial pacing wires because of the risk of causing an arrhythmia or injury from excessive heat at the electrode tip. An MRI may however be performed in patients with retained epicardial wires, which are not exposed at the skin as these do not concentrate energy.

Bibliography 1. Batra AS, Balaji S. Post operative temporary epicardial pacing: When, how and why? Ann Pediatr Cardiol 2008;1:120–5. 2. Bojar RM. Adult cardiac surgery: Cardiovascular management. In: Bojar RM, ed. Manual of Perioperative Care in Cardiac and Thoracic Surgery 2nd ed. Boston: Blackwell Scientific Publications; 1994:180–90. 3. Ceresnak SR, Pass RH, Starc TJ, et al. Predictors for hemodynamic improvement with temporary pacing after pediatric cardiac surgery. J Thorac Cardiovasc Surg 2011;141:183–7. 4. Doniger SJ, Sharieff GQ. Pediatric dysrhythmias. Pediatr Clin North Am 2006;53(1):85–105. 5. Gregoratos G. Indications and recommendations for pacemaker therapy. Am Fam Physician 2005;71(8):1563–70. 6. Handel M. Intensive care service: nursing care and procedures – Temporary pacing. [Updated: 2005 November; cited: 2011 Jun 13]. Available at: http://intensivecare.hsnet.nsw.gov.au/five/ doc/pacing_temporary_S_c_rpa.pdf 7. Hayes DL. Pacemaker timing cycles and pacemaker electrophysiology. In: Hayes DL, Llyod MA, Friedman PA, ed. Cardiac Pacing and Defibrillation: A Clinical Approach 4th ed. New York: Blackwell Publishing; 2000:201–46. 8. Krongrad E. Postoperative arrhythmias in patients with congenital heart disease. Chest 1984;85:107–13. 9. Lawrence III JH, Kanter RJ, Wetzel RC. Pediatric arrhythmias. In: Nichols DG, Cameron DE, Greeley WJ, Lappe DG, Ungerleider RM, Wetzel RC, ed. Critical Heart Disease in Infants and Children. St Louis: Mosby; 1995:217–53. 10. Pacemakers: the basics. [Cited: 2011 June 13]. Available at: http://medresidents.stanford.edu/ TeachingMaterials/Pacemakers/Pacemakers%20Handout.doc. 11. Pacemakers in children. In: Park MK, Troxler RG, ed. Pediatric Cardiology for Practitioners 4th ed. NOIDA, U.P., India: Harcourt (India) Pvt Ltd; 2002:352–6.

ERRNVPHGLFRVRUJ


77

12. Pacing in cardiac surgery. [Cited: 2011 June 13]. Available at: http://www.cardiothoracicsurgeryservices.com/34.html 13. Skippen P, Sanatani S, Froese N, Gow RM. Pacemaker therapy of postoperative arrhythmias after pediatric cardiac surgery. Pediatr Crit Care Med 2009;10:000–000. DOI: 10.1097/ PCC.0b013e3181ae5b8a. 14. Reade MC. Temporary epicardial pacing after cardiac surgery: a practical review: part 1: general considerations in the management of epicardial pacing. Anaesthesia 2007;62:264–71. 15. Sliz NB Jr, Johns JA. Cardiac pacing in infants and children. Cardiol Rev 2000;8(4):223–39. 16. Sukhum P. Pacemakers of the 1980s. An overview. Postgrad Med 1986;79(4):173–4, 177–83, 186–8. 17. Temporary cardiac pacing, Cornell cardiology curriculum. [Cited: 2011 Jun 13]. Available at: http://www.amyanderan.com/eran/Temp%20Cardiac%20Pacing.pdf 18. Withcrall CL. Cardiac rhythm control devices. Crit Care Nurs Clin North Am 1994;6:95–102.

ERRNVPHGLFRVRUJ

Hypertensive Emergencies “All the causes of things cannot be seen, because they appear to depend on circumstances which are unknown, or appear to be accidental” —John Hunter (1728–1793)*

Parenteral Antihypertensive Agents Drug

Remarks

Diazoxide Children/Adults: 1–3 mg/kg (max 150 mg) is given every 5–15 minutes till optimal control of blood pressure. Dose may be repeated q4–24h. Alternatively, 3–5 mg/kg infused over 30 minutes may result in less hyperglycemia and a controlled fall in BP.

An arteriolar vasodilator with onset of action in 3–5 minutes and duration of action of 2–12 hours. Hyperglycemia, persistent hypotension, and salt and water retention are adverse effects.

Enalapril Children: 5–10 mcg/kg q6–8h IV over 5 minutes. Adults: 1.25–2.5 mg q6h IV.

IV enalapril is of variable effectiveness, with an onset of action of 30–60 minutes. These factors limit its use in hypertensive emergencies.

Esmolol Children and adults: Bolus 500 mcg/ kg IV over 1–2 minutes, followed by an IV infusion of 50–300 mcg/kg/min. Dilute to a concentration of 10 mg/mL in 5% dextrose or normal saline for infusion.

Selective β1–blocker; has a rapid onset of action and a short half-life of a couple of minutes.

Hydralazine Children: 100–500 mcg/kg IM/IV infusion over 20 min; repeat every 4–6 hours if required. Alternatively, IV infusion 12.5–50 mcg/kg/h may be given. Adults: 5–10 mg IV, repeat q4–6h if required. Alternatively, IV infusion 3–9 mg/h.

Directly acting arteriolar vasodilator. Onset of action is within 5–20 minutes and duration of action is about 2–6 hours. Prolonged hypotension and reflex tachycardia are important adverse effects.

*John Hunter is regarded as one of the most distinguished anatomists and surgeons of his day. The Hunterian oration of the Royal College of Surgeons of England is delivered in his honor.

ERRNVPHGLFRVRUJ


79

Drug

Remarks

Labetalol Children: Initially 250 mcg/kg is administered over 2 minutes. 250–500 mcg/kg may be repeated every 10 minutes until the desired BP is reached. Max dose 1 mg/kg. If required, this is followed by an infusion of 0.25–1.5 mg/kg/h titrated to blood pressure. Adults: Initially 20 mg IV is administered over 2 minutes. 20–80 mg may be repeated every 10 minutes up to a max dose of 300 mg. If required, this is followed by an infusion of 1–3 mg/min titrated to blood pressure.

Predominant β-blocker with some α-blocking action. Onset of action is 5–10 minutes and action lasts 3–6 hours after discontinuation of the drug. Its use is limited in cardiac failure and is to be used with caution in patients with asthma. No change in dosing is required in renal failure. It is the drug of choice in hypertensive encephalopathy.

Nicardipine Children: 0.5–3 mcg/kg/min IV infusion.

IV calcium channel blocker with onset of action in 10–15 minutes and a half life of 40 minutes. Advantages over nitroprusside include the ability to use it for more than a few days, as it does not produce toxic metabolites. It is used in a gradually increasing dose up to 3 mcg/kg/min. Unwarranted hypotension is treated with 10% calcium gluconate 0.2 mL/kg IV over 5 minutes.

Adults: 5 mg/h initially, increase dose by 2.5 mg/h every 10–15 minutes up to a max of 15 mg/h; then reduce to 1–3 mg/h. Sodium nitroprusside 0.5–10 mcg/kg/min IV infusion.

Arteriolar and venous vasodilator with immediate onset of action and a short half-life of a few minutes. Dose is titrated to achieve effect.

Oral Antihypertensive Agents Drug

Remarks

Amlodipine Children (>6 years): 2.5–5 mg q24h or in divided doses q12h.

A 12 hours dose may provide better efficacy in children. It has a gradual onset of action and may take 5–7 days for full effect thus dose adjustments should be made only after this period.

Adults: 5–10 mg q24h. Atenolol Children: 1–1.2 mg/kg q24h; increase to a max 2 mg/kg q24 h. Adults: 25–100 mg/kg q24h; increase to a max 200 mg q24h.

Cardio-selective β-blocker. Contraindicated in pulmonary edema and cardiogenic shock. May cause bradycardia, hypotension, second or third degree AV block. Exercise caution in diabetes and asthma.

ERRNVPHGLFRVRUJ

80


Drug

Remarks

Captopril Children: 0.3–6 mg/kg/day in divided doses q8h. Adults: 6.25–12.5 mg q8–12h; increase to a max 50 mg q8h.

Onset of action in 15–30 minutes and duration of action 8–12 hours. Starting with a lower dose, the dose is increased over 1–2 weeks.

Diltiazem Children: 1.5–2 mg/kg/day in divided doses q6–8h; increase to a max 3.5 mg/kg/day. Adults: 30–60 mg q6–8h; increased to a maintenance of 180–360 mg/day in divided doses q6–8h. (Diltiazem SR 60–120 mg q12h; increased to a maintenance of 180–360 mg/day in divided doses q12h)

Maximum antihypertensive effect is seen within 2 weeks.

Enalapril Children: 0.1–0.5 mg/kg/day divided q12–24h. Adults: PO 2.5–5 mg/day divided q12–24h; increase to a max 20 mg/day.

Starting with a lower dose, the dose is gradually increased over a period of 2 weeks. Cough is a common reported side effect.

Hydralazine Children: 0.75–1 mg/kg/day in divided doses q6h; increase to a max 8 mg/kg/day. Adults: 10–50 mg q6h.

Directly acting arteriolar vasodilator. May induce reflex tachycardia and increased cardiac output, which can blunt its hypotensive effect. After an oral dose, it has an effect in 20–30 minutes that lasts 2–4 h (less than IV).

Labetalol Children: 1–3 mg/kg/day in divided doses q12h PO; increase to a max 10 mg/kg/day. Adults: 100–400 mg q12h.

Predominant β-blocker with some α-blocking action. Peak plasma levels occur 1–2 hours after oral administration with a half life of 6–8h. Steady state is achieved on the third day of dosing.

Metoprolol Children (1–17 yr): 1–2 mg/kg/day in divided doses q12h; increase to a max 6 mg/kg/day. Adults: 100 mg/day in divided doses q12–24h; increase to a max 450 mg/day.

Modest β1 selectivity. Bronchospasm, bradycardia, heart block may take place.

Nifedipine Children: Hypertensive urgency: 0.25–0.5 mg/kg q4–6h PRN (max 10 mg/dose or 3 mg/kg/day). Hypertension: SR tablets 0.25–0.5 mg/kg/day in divided doses q12–24h; increase to a max 3 mg/kg/day.

Calcium channel blocker that reduces blood pressure within 5–20 minutes, with maximum effects in 60–90 minutes. Available for oral/sublingual use and is recommended only for children with hypertensive urgency.

ERRNVPHGLFRVRUJ


Drug

81

Remarks

Adults: Hypertension: 10 mg q8h; increase to max 180 mg/day in divided doses q6–8h. SR tablet 30–60 mg q24h; increase to max 120 mg q24h. Propranolol Children: 0.5–1 mg/kg/day in divided doses q6–12h; increase to a max 8 mg/kg/day. Adults: 40 mg/dose q12h; increase to a max 640 mg/day.

Non-selective β-blocker. Contraindicated in bronchial asthma, heart failure, and heart block. Starting with a lower dose, the dose is increased every 3–5 days till the desired effect.

A hypertensive crisis is an extreme elevation of blood pressure that may be life-threatening or likely to result in significant morbidity if untreated. It occurs infrequently in children but may be associated with renovascular hypertension, head injury, in the postoperative period following cardiopulmonary bypass, repair of coarctation of the aorta and supra-aortic stenosis. Hypertensive crisis is classified as either a hypertensive emergency or a hypertensive urgency. Hypertensive emergency is said to be present when the blood pressure is extremely high (1.3–1.5 times 95th percentile) and end-organ damage (cardiac, CNS, renal, lung, or eye) is evident. Hypertensive encephalopathy is an example of a hypertensive emergency and is suggested by the presence of vomiting, fever, ataxia, stupor, and seizures. Hypertensive urgency is present when the blood pressure is significantly high, but end-organ damage is not present. In response to a hypertensive crisis, it is important to select an agent with a rapid and controlled action and to carefully monitor the reduction of blood pressure. In hypertensive emergencies, the aim is to lower the mean arterial pressure by a maximum of 25% in a period of minutes by the use of IV antihypertensives and then gradually to normal over the next 48 hours. In hypertensive urgencies, the blood pressure is gradually reduced to normal in 48 hours with either IV or oral medication. There is a risk of cerebral and renal hypoperfusion if reduction of blood pressure is done at a rate faster than this. Vasodilators (sodium nitroprusside or nicardipine) may first be given to control the hypertension. In case optimum control of hypertension is not achieved by IV vasodilators, a β-blocker (esmolol or labetalol) can be added to the vasodilator or used in its place. Intravenous labetalol is the drug of choice in a hypertensive encephalopathy, where vasodilators may increase the cerebral blood flow and increase brain damage. Labetalol blocks both α- and β-adrenergic receptors and a controlled reduction of blood pressure can be achieved.

ERRNVPHGLFRVRUJ

82


IV/IM diazoxide, hydralazine, or oral nifedipine are other alternative drugs, especially in hypertensive urgencies. Sublingual administration of nifedipine is no longer recommended. Hypertensive crises may be associated with sodium and volume depletion, and volume expansion with isotonic sodium chloride must also be considered. Urine output requires diligent monitoring. A number of drugs, used alone or in combination, are available for the subsequent management of persistent hypertension. These include (i) calcium channel blockers—nifedipine, diltiazem, amlodipine; (ii) ACE inhibitors— captopril, enalapril; (iii) diuretics—furosemide, thiazides, K+ sparing diuretics; and (iv) β-blockers—propranolol, nadolol, metoprolol, atenolol.

Bibliography 1. Aggarwal M, Khan IA. Hypertensive crisis: hypertensive emergencies and urgencies. Cardiology Clin 2006;24:135–46. 2. Flanigan JS, Vitberg D. Hypertensive emergency and severe hypertension: what to treat, who to treat, how to treat. Med Clin North Am 2006;90:439–51. 3. Hari P, Sinha A. Hypertensive emergencies in children. Indian J Pediatr 2011;78(5):569–75. 4. Houtman P. Management of hypertensive emergencies in children. Paediatr Perinat Drug Ther 2003;5(3):107–10. 5. Hypertension in Children and Adolescents. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. U.S. Department Of Health And Human Services. National Institutes of Health National Heart, Lung, and Blood Institute. National High Blood Pressure Education Program NIH Publication No. 04-5230. August 2004. 6. Perez MI, Musini VM, Wright JM. Pharmacological interventions for hypertensive emergencies. Cochrane Database of Systematic Reviews 2008;1: CD003653. DOI: 10.1002/14651858. CD003653.pub3. 7. Prescription Drug Information, Interactions & Side Effects. [Cited: July 2012] Available at: http://www.drugs.com/ 8. Robertson J, Shilkofski N. Drug doses. The Harriet Lane Handbook 17 ed. Philadelphia: Mosby; 2005:1053–68. 9. Temple ME, Nahata MC. Treatment of pediatric hypertension. Pharmacotherapy 2000;20(2): 140–50. 10. Varon J, Marik PE. The diagnosis and management of hypertensive crises. Chest 2000;118: 214–27.

ERRNVPHGLFRVRUJ

Pulmonary Hypertension “All we know is still infinitely less than all that remains unknown” —William Harvey (1578–1657)*

Factors Controlling Pulmonary Circulation Parameter

Pulmonary vasoconstrictors

Pulmonary vasodilators

pH

Acidosis

Alkalosis

Oxygenation

Hypoxia

Oxygen

Temperature

Hypothermia

Normothermia

Stimulation

Pain, agitation

Sedation, analgesia

Ventilation

Hypoventilation, alveolar hyperinflation

Mild hyperventilation

The parameters for pulmonary arterial hypertension in children are the same as for adult patients. It is defined as a mean pulmonary artery (PA) pressure of more than 25 mmHg at rest (or more than 30 mmHg during exercise), with a pulmonary vascular resistance of more than 3 Woods units/m2 in the presence of a normal left atrial pressure (i.e., <15 mmHg). In the fetus, pulmonary vascular resistance (PVR) is high because the lungs are filled with fluid. PVR begins to fall immediately after birth and reaches adult levels within the first few weeks of life. In children with congenital heart disease with pulmonary hypertension or even with normal PA pressure, the pulmonary arteries may undergo intense vasoconstriction in response to various stimuli, such as hypoxia or acidosis. PA constriction then results in further increase in PA pressure, which may cause acute RV dysfunction. Such episodes of elevation of PA pressure may occur in infants in the immediate postoperative period, after repair of congenital heart diseases like large VSDs, TAPVCs, and AV canal defects. An acute rise in PA pressure that causes desaturation, tachycardia, hypotension, or hemodynamic deterioration is called a pulmonary hypertensive crisis.

*William Harvey was an English physician who was the first to accurately describe circulation of blood in his treatise Exercitatio Anatomica de Motu Cordis et Sanguinis in Animalibus [An Anatomical Exercise on the Motion of the Heart and Blood in Living Beings] (1628).

ERRNVPHGLFRVRUJ

84


Postoperative Measures to Optimize Hemodynamics in Pulmonary Hypertension Parameter

Treatment

Sedation and analgesia

Administer adequate sedation + analgesia (fentanyl or morphine IV infusion).

Paralysis

Paralyse if necessary (vecuronium or pancuronium) ET tube suctioning is done with extreme caution.

Mechanical ventilation

Hyperventilate to PaCO2 ∼ 30, pH ∼ 7.50 Optimize PEEP to a minimum (0–5 mmHg) and maintain low peak airway pressures (< 25–30 mmHg).

Fluid electrolyte balance

Correct electrolyte disturbances. Maintain alkalosis (administer inj. sodium bicarbonate 8.4% IV if required). Correct anemia.

Inotropic support

Minimize the use of pulmonary vasoconstrictors, e.g., dopamine. Administer pulmonary vasodilators milrinone, dobutamine, nitroprusside or isoprenaline.

Pulmonary vasodilator drugs

●

● ● ●

Phenoxybenzamine 0.25–0.5 mg/kg PO q12h (maximum dose <10 mg/day). Dose may be titrated upwards gradually. Epoprostenol (PgI2) 0.5–16 ng/kg/min IV infusion. Nitric oxide (5–80 ppm) is administered through the ventilator. Sildenafil: Children ≥1 month: 0.25–2 mg/kg/dose PO q4–6h; titrate dose upwards gradually.

An FiO2 of 1.0 is established on return from the operation theater, which is gradually reduced according to the blood gases such that the arterial PaO2 is maintained above 100 mmHg. Physiotherapy and tracheal suction should be gentle and preceded by a bolus of sedative plus analgesic and preoxygenation by hand bagging. Phenoxybenzamine (alpha block) 1 mg/kg can be given before CPB and again during rewarming. It is continued postoperatively in a dose of 0.25–0.5 mg/kg/dose every 12 hours.

Management of a Pulmonary Hypertensive Crisis In a pulmonary hypertensive crisis, sedation is increased and the child is paralysed (fentanyl 2–10 mcg/kg/h, vecuronium 0.1 mg/kg/h). Hand bagging with 100% oxygen improves the oxygen levels and at the same time increases respiratory alkalosis by elimination of carbon dioxide. Additional sodium bicarbonate is given to maintain metabolic alkalosis. The aim is to reduce the PaCO2 to less than 30 mmHg and pH to more than 7.5. Alkalosis, not hypocarbia, reduces PVR.

ERRNVPHGLFRVRUJ

Pulmonary Hypertension

85

If possible, the doses of catecholamines should be reduced and of pulmonary vasodilators increased to the maximum tolerated levels. Nitric oxide inhalation is commenced or increased. Extracorporeal membrane oxygenation may be considered in the child who remains unresponsive to the above therapeutic measures.

Weaning If the child is stable for a period of 24 hours, weaning of support should be attempted very slowly over at least 24–48 hours. Inotropes are gradually reduced. PaCO2 is allowed to rise to 30–35 mmHg, while a PaO2 of over 95 mmHg is maintained. Paralysis is discontinued and sedation reduced. The child is extubated and only then are pulmonary vasodilators gradually withdrawn. Recurrence of crisis would require reinstitution of measures for the control of PA pressure.

Management of Excessive Pulmonary Blood Flow In a child on ventilator support, when pulmonary blood flow is excessive (e.g., in single ventricles, transposition of the great arteries, and postoperatively in a large BT shunt), factors that cause pulmonary vasoconstriction need to be initiated to optimize the pulmonary blood flow. Such a strategy will improve systemic blood flow and decrease the ventilation-perfusion mismatch, and permit extubation. Promoting hypercarbia and a reduction in the FiO2 even down to 20% will increase PVR and improve the systemic blood flow. However, an arterial saturation of at least 80% should be maintained.

Bibliography 1. Balser JR, Butterworth J. Cardiovascular drugs. In: Hensley FA, Martin DE, Gravlee GEP, eds. A Practical Approach to Cardiac Anesthesia 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:46. 2. Beghetti M, Tissot C. Pulmonary hypertension in congenital shunts. Rev Esp Cardiol 2010; 63(10):1179–93. 3. Fischer LG, Van Aken H, Bürkle H. Management of pulmonary hypertension: physiological and pharmacological considerations for anesthesiologists. Anesth Analg 2003;96:1603–16. 4. Gorenflo M, Gu H, Xu Z. Peri-operative pulmonary hypertension in paediatric patients: current strategies in children with congenital heart disease. Cardiology 2010;116(1):10–7. 5. Huddleston AJ, Knoderer CA, Morris JL, Ebenroth ES. Sildenafil for the treatment of pulmonary hypertension in pediatric patients. Pediatr Cardiol 2009;30(7):871–82. 6. Lovell AT. Anaesthetic implications of grown-up congenital heart disease. Br J Anaesth 2004;93:129–39.

ERRNVPHGLFRVRUJ

86


7. Mossad E, Motta P, Sehmbey K, Toscana D. The hemodynamic effects of phenoxybenzamine in neonates, infants, and children. J Clin Anesth 2008;20(2):94–8. 8. Palma G, Giordano R, Russolillo V, et al. Sildenafil therapy for pulmonary hypertension before and after pediatric congenital heart surgery. Tex Heart Inst J 2011;38(3):238–42. 9. Peiravian F, Amirghofran AA, Borzouee M, et al. Oral sildenafil to control pulmonary hypertension after congenital heart surgery. Asian Cardiovasc Thorac Ann 2007;15(2):113–7. 10. Rich GF, Murphy GD Jr., Roos CM, Johns RA. Inhaled nitric oxide. Selective pulmonary vasodilation in cardiac surgical patients. Anesthesiology 1993;78(6):1028–35. 11. Rosenzweig EB, Widlitz AC, Barst RJ. Pulmonary arterial hypertension in children. Pediatr Pulmonol 2004;38:2–22. 12. Shiyanagi S, Okazaki T, Shoji H, et al. Management of pulmonary hypertension in congenital diaphragmatic hernia: nitric oxide with prostaglandin-E1 versus nitric oxide alone. Pediatr Surg Int 2008;24(10):1101–4. 13. Taylor MB, Laussen PC. Fundamentals of management of acute postoperative pulmonary hypertension. Pediatr Crit Care Med 2010;11(2 Suppl):S27–9. 14. Vlahakes GJ. Management of pulmonary hypertension and right ventricular failure: another step forward. Ann Thorac Surg 1996;61:1051–2.

ERRNVPHGLFRVRUJ

Cyanotic Spells

Management Drug/maneuver

Remarks

Oxygen is administered by face mask at 6 L/min.

Oxygen is a potent pulmonary vasodilator and systemic vasoconstrictor.

Knee-chest position

The knee-chest position increases the systemic vascular resistance and improves pulmonary blood flow.

Inj. sodium bicarbonate 8.4%, 1 mL/kg diluted in an equal quantity of sterile H2O, is given slow IV over 5–10 minutes. May be repeated after 10 minutes.

Sodium bicarbonate corrects the acidosis.

Inj. morphine 0.1–0.2 mg/kg IM or 0.05–0.1 mg/kg slow IV over 5–10 minutes. Alternative sedatives that can be given include: • Inj. midazolam 0.05–0.1 mg/kg IV • Inj. fentanyl 1–2 mcg/kg IV • Inj. ketamine 1–2 mg/kg IV

Sedation decreases irritability and controls hyperpnea. Possibly decreases infundibular spasm and increases pulmonary blood flow.

Inj. esmolol 0.5 mg/kg IV over 1–2 minutes, this may be followed by an IV infusion 50–300 mcg/kg/min up to 48 hours.

Esmolol is a short-acting β-blocker and decreases the heart rate and relieves infundibular spasm.

Alternative β-blockers that can be given are: Inj. metoprolol 0.1 mg/kg slow IV (over 5 minutes). May be repeated every 5 minutes for a maximum of 3 doses. Can be followed by infusion 1–2 mcg/kg/min.

The heart rate, blood pressure, and saturation is monitored. The aim is to maintain the heart rate below 100/min.

Inj. propranolol 0.1–0.2 mg/kg IV. Can be repeated if required up to 3–4 times/day.

ERRNVPHGLFRVRUJ

88


Drug/maneuver

Remarks

Phenylephrine 5–20 mcg/kg/dose slow IV bolus; can be repeated every 10–15 minutes (or noradrenaline 0.01–0.02 mcg/kg/min IV infusion).

α-adrenergic agents increase the systemic vascular resistance and thus increase pulmonary blood flow.

IV Normal saline/Ringers lactate 10–20 mL/kg bolus followed by maintenance fluids.

Isotonic IV fluids improve pulmonary blood flow by increasing venous return and reducing hyperviscosity.

Cyanotic spells occur in cyanotic children of 2 months–2 years age who have a congenital heart defect with associated subpulmonic obstruction, (tetralogy of Fallot, tricuspid atresia, transposition of the great arteries or single ventricle when associated with pulmonary stenosis). The spell may be initiated by crying, feeding, hypoxia, or any other stimulus. It is characterized by irritability and prolonged crying, which progresses to rapid and deep respiration (hyperpnea), an increase in the cyanosis, and on auscultation, a decrease in the intensity of the pulmonary outflow murmur. A cyanotic spell may result in seizures, coma, and death. Emergency management aims to improve pulmonary blood flow and correction of the acidosis. Continuous ECG, oxygen saturation, and blood pressure monitoring are initiated. In addition to the management listed above, any underlying cause such as arrhythmia, hypothermia, and hypoglycemia are corrected. In refractory spells, the child may need to be paralysed and ventilated. Tab propranolol 0.25–1 mg/kg/dose q6–8h PO may be given to prevent recurrences.

Bibliography 1. Bernstein D. Cyanotic congenital heart disease lesions: Lesions associated with decreased pulmonary blood flow. Chapter 423. In: Behrman, Kleigmen and Jenson eds. Nelson’s Textbook of Pediatrics 17th ed. Elsevier; 2004. 2. Kothari SS. Mechanism of cyanotic spells in tetralogy of Fallot—the missing link? Intl J Cardiol 1992;37(1):1–5. 3. Park M. Pathophysiology of cyanotic congenital heart disease. In: Park M, ed. Pediatric Cardiology for Practitioners 4th ed. Mosby; 2002:113–26. 4. Saxena A, Juneja R, Ramakrishnan S; Working Group on Management of Congenital Heart Diseases in India. Drug therapy of cardiac diseases in children. Indian Pediatr 2009;46:310–38. 5. Wood P. Attack of deeper cyanosis and loss of consciousness (syncope) in Fallot’s tetralogy. Br Heart J 1958;20:282.

ERRNVPHGLFRVRUJ

Pediatric Resuscitation “I made use of the opportunities that life offered to do some good” —Peter J Safar (1924–2003)*

Medications Used in Pediatric Resuscitation Drug

IV dose

Remarks

Adenosine

100 mcg/kg (maximum 6 mg); second dose: 200 mcg/kg (maximum 12 mg).

Monitor ECG. Rapid IV/IO bolus followed by 5 mL saline flush.

Adrenaline

10 mcg/kg (0.1 mL/kg, 1:10,000*) IV/IO. Max 1 mg. 100 mcg/kg (0.1 mL/kg, 1:1000*) ET. Max 2.5 mg.

Indicated in asystole, pulseless tachycardia, and severe bradycardia.

Amiodarone

5 mg/kg IV/IO; may repeat twice up Adjust administration rate to to 15 mg/kg. Maximum single dose urgency (IV push over several 300 mg. minutes during cardiac arrest; more slowly, over 20–60 minutes, with perfusing rhythm). Monitor ECG and blood pressure.

Atropine

0.02 mg/kg IV/IO 0.04–0.06 mg/kg ET (minimum dose IV/IO/ET 0.1 mg, maximum single dose in a child 0.5 mg, adolescent 1 mg). May be repeated once if needed

Indicated in bradycardia.

10% Calcium gluconate

20–30 mg/kg (0.2–0.3 mL/kg) slow IV/IO (adult 5–10 mL)

Correction of hypocalcemia.

Dextrose

0.5–1 g/kg, i.e., dextrose 10%: 5–10 mL/kg dextrose 25%: 2–4 mL/kg dextrose 50%: 1–2 mL/kg

Correction of hypoglycemia.

Lignocaine

Bolus: 1 mg/kg IV/IO Infusion: 20–50 mcg/kg/min

*Peter J Safar was the pioneer of cardiopulmonary resuscitation, author of “ABC of Resuscitation“.

ERRNVPHGLFRVRUJ

90


Drug

IV dose

Remarks

Magnesium sulfate

25–50 mg/kg IV/IO over 10–20 minutes, faster in torsades de pointes. Maximum dose 2 g.

Naloxone

Initial dose 10 mcg/kg. Then: < 5 yr or ≤ 20 kg: 100 mcg/kg IV/IO/ET. ≥ 5 yr or > 20 kg: 2 mg IV/IO/ET. May be repeated PRN every 2–3 minutes to maintain opioid reversal. If required start an IV infusion 5–20 mcg/kg/h.

Indicated for respiratory depression because of opioids. Use lower dose initially followed by a higher dose if there is no response.

Sodium bicarbonate

1 mmol/kg slow IV/IO (8.4% sodium bicarbonate 1 mL = 1 mmol; max 50 mL)

Correction of acidosis.

IV: intravenous, IO: intraosseous, ET: via endotracheal tube. Drug requires to be flushed with 5 mL normal saline, followed by 5 ventilations. *Adrenaline 1:10,000 implies 1 g in 10,000 mL, i.e., 10 mcg in 0.1mL; 1:1000 implies 1 g in 1000 mL, i.e., 100 mcg in 0.1 mL.

The following protocols are based on the American Heart Association guidelines for Pediatric cardiopulmonary resuscitation 2010.

Pediatric Basic Life Support The sequence of cardiopulmonary resuscitation (CPR) has previously been known by the initials “ABC”, i.e., Airway, Breathing, and Chest compressions (or Circulation). The 2010 AHA Guidelines for CPR and External Cardiac Compression now recommends a CAB sequence (chest compressions, airway, breathing) instead of ABC. For a single person available for rescue, a compression-ventilation ratio of 30:2 is recommended. Chest compressions are commenced first and after 30 compressions, two breaths are given. When two individuals are available for CPR, a ratio of 15:2 is recommended. One person performs chest compressions at a rate of 100–120/min, while the other provides 2 breaths after every 15 compressions.

Chest Compressions External chest compressions (ECC) for a newborn or infant can be performed with two fingers placed just below the intermammary line, alternatively, the chest is encircled with both hands, compressing the sternum anteriorly with the thumbs while stabilizing the vertebral column posteriorly with the fingers. The hands must encircle the chest freely and not restrict chest expansion.

ERRNVPHGLFRVRUJ


91

ECC for a child is performed with the heel of one or two hands compressing the lower half of the sternum. A cycle should allow complete chest recoil after each compression. Sufficient force is used to depress the chest at least one-third the anteriorposterior (AP) diameter (approximately 1½ inches/4 cm in infants and 2 inches/5 cm in children).

Airway and Breathing For the provision of effective ventilation during CPR, bag-mask ventilation with 100% supplemental O2 is needed. Two persons are required for bag-mask ventilation, and it is not recommended for a single individual providing CPR. The single person can possibly only use mouth-to-barrier device techniques (if available), mouth-to-mouth ventilation, or chest compressions alone (no ventilation). A self-inflating bag-mask is available in appropriate sizes for infants, children, and adults for ventilation. To deliver high oxygen concentrations (60–95%), an oxygen reservoir is attached to the self-inflating bag.

Pediatric Advanced Life Support (PALS) The term ALS covers various aspects of resuscitation including endotracheal intubation and mechanical ventilation, management of cardiac arrhythmias, and treatment of cardiorespiratory arrest and its complications.

Endotracheal Intubation and Ventilation Recommended endotracheal (ET) tube sizes for different age groups Age (years)

Internal diameter of uncuffed ET tube (in mm)

Internal diameter of cuffed ET tube (in mm)

Infant

3.5

3

1–2

4

3.5

>2

4 + (age ÷ 4)

3.5 + (age ÷ 4)

A patent airway is established with endotracheal (ET) intubation. This facilitates mechanical ventilation with 100% oxygen, minimizes pulmonary aspiration, and enables suctioning of the trachea. The position of the ET tube is confirmed clinically by bilateral chest movement and breath sounds and the absence of gastric insufflation sounds over the stomach. The position is subsequently assessed radiologically. Endtidal CO2 and pulse oximetry are additional monitoring aids.

ERRNVPHGLFRVRUJ

92


Cuffed ET tubes decrease the risk of aspiration and may be preferable. When a cuffed tube is used, an optimal cuff pressure is needed to be maintained (20–30 cm H2O). Laryngeal mask airway is an alternative to bag-mask ventilation when endotracheal intubation is not feasible.

Routes of Drug Administration IV access is secured with a peripheral venous, external jugular, or femoral vein cannulation. If cannulation is not immediately successful (>90 seconds), the intraosseous (IO) route or ET tube is utilized in an emergency for drug administration and later an IV cannula is placed. All drugs and resuscitative fluids may be given via the IO route, but only lignocaine, adrenaline, atropine, and naloxone (mnemonic LEAN) can be given via the ET tube. When drugs need to be administered via the ET tube, chest compressions are stopped briefly, medications are given into the ET tube and followed with a flush of at least 5 mL of normal saline and 5 consecutive positivepressure ventilations. Optimal endotracheal doses of medications are in general double or triple the IV doses for lidocaine, atropine, and naloxone.

Defibrillation The doses of drugs and DC shock are based on the patient’s body weight, which may be estimated from the age if the weight is unknown: Age

Estimated body weight

Newborn

3.5 kg

1 year

10 kg

1–10 years

(age in years + 4) × 2

Defibrillation is equally effective with manual or self adhesive pads. Adult size (8–10 cm) paddles or adhesive pads are used for children more than 10 kg weight and infant size (4.5 cm) for children under 10 kg. One paddle is firmly placed over the right side of the upper chest and the second on the left of the nipple over the lower ribs (cardiac apex), with preferably at least a 3 cm gap between the paddles. In infants and small children, paddles or pads may alternately be applied to the front and back of the chest. The initial dose in ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) is 2 or 4 J/kg, but the subsequent shocks recommended are 4 J/kg. Higher energy levels may be considered, not exceeding 10 J/kg in refractory cases. No synchronization with the ECG is required, and IV sedation or analgesia are not indicated.

ERRNVPHGLFRVRUJ


93

The initial adult dose (with a biphasic defibrillator) for VF is 120–200 J and subsequent shocks 200–360 J, depending upon the manufacturers recommendations.

Monitoring Arterial Pressure Line If the patient has an arterial monitoring line in place, the amplitude of the arterial pressure trace on the monitor can be used to evaluate the efficacy of the chest compressions and the return of spontaneous circulation (ROSC). End Tidal Carbon Dioxide Monitoring (ETCO2) ETCO2 monitoring (capnography or colorimetry) is recommended to confirm tracheal tube position and to help guide therapy, especially the effectiveness of chest compressions during CPR. Pulse Oximetry The systemic arterial oxygen saturation can only be recorded once a perfusing rhythm is present.

Drugs Adrenaline Adrenaline is a potent α, β1, and β2 agent and causes vasoconstriction in the dose recommended in CPR. It enhances the coronary perfusion pressure, stimulates spontaneous contractions, and increases the intensity of VF so increasing the likelihood of successful defibrillation. Amiodarone Amiodarone is a membrane stabilizing antiarrhythmic drug. It causes bradycardia and also has a mild negative inotropic effect. Hypotension is related to the rate of administration of the drug and is because of an α-blocking effect as well as a consequence of the histamine released by the solvent used (polysorbate 80 and benzyl alcohol). Amiodarone is preferably administered in a central line as it can cause thrombophlebitis when injected into a peripheral vein. Atropine Atropine is not a routine part of ALS algorithms as it has not shown improvement in the outcome of cardiac arrest. Atropine may increase myocardial oxygen demand and have its associated side effects. It is indicated when bradycardia is unresponsive to improved ventilation and circulatory support.

ERRNVPHGLFRVRUJ

94


The dose of atropine is 0.02 mg/kg, however, a minimum dose of 0.1 mg is given to avoid paradoxical bradycardia because of its central effect at low doses.

Calcium Calcium administration is not recommended for administration during CPR and should only be given when specifically indicated, e.g., for hypocalcemia, calcium channel blocker overdose, hypermagnesemia, or hyperkalemia. Sodium Bicarbonate Acidosis during cardiac arrest is best corrected by effective CPR. Administration of sodium bicarbonate increases CO2 production and intracellular acidosis. It has a negative inotropic effect, increases the sodium load and shifts the oxygen dissociation curve to the left impairing oxygen release to the tissues. Sodium bicarbonate administration may however be considered in special circumstances such as hyperkalemic cardiac arrest or in prolonged arrest. Catecholamines and sodium bicarbonate should not be administered through the same IV line simultaneously because alkaline solutions inactivate catecholamines. Magnesium Administration of magnesium is indicated in children only if there is known hypomagnesemia or for treatment of torsades de pointes. Lignocaine Lignocaine may be given in the acute management of ventricular tachycardia (including torsades) and multiple ventricular ectopics but is a less effective alternative to amiodarone. Toxic effects of lignocaine include myocardial depression, drowsiness, and seizures.

PALS Protocols Abnormal cardiac rhythms, which do not produce a cardiac output (i.e., cardiac arrest), can be categorized into (i) shockable rhythms (ii) nonshockable rhythms based upon whether the particular arrhythmia responds to defibrillation or not. The two shockable rhythms are ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT), while the two nonshockable rhythms are asystole and pulseless electrical activity (PEA).

ERRNVPHGLFRVRUJ


95

Protocol for shockable rhythm Cardiac arrest • Bag-mask ventilation (15:2; compressions:breaths) • Chest compression rate 100–120/min • Monitor cardiac rhythm (rhythm–shockable) • Tracheal intubation (ventilation rate 8–10/min) • Monitor ETCO2 • Establish vascular access (IV/IO) DC shock 2 J/kg • CPR × 2 minutes • Check rhythm DC shock 4 J/kg • Resume CPR • Amiodarone 5 mg/kg (after 3rd & 5th shock only) • CPR × 2 minutes

• Resume CPR • Adrenaline 10 mcg/kg, IV/IO • CPR × 2 minutes • Check rhythm DC shock 4 J/kg

During CPR • Adrenaline is administered after every alternate DC shock. • Reversible causes are corrected. • At any stage, if on rhythm check there is asystole, non shockable protocol is commenced instead. • At any stage, when there is ROSC, post resuscitation care is instituted.

Ventricular Fibrillation and Pulseless Ventricular Tachycardia The only effective treatment of VF or pulseless VT is DC shock: 1. CPR ECC is started at a rate of 100–120/min and with bag-mask ventilation, 2 breaths are given after every 15 chest compressions. The child is intubated as soon as feasible with minimal interruption to CPR, and chest compressions are then given continuously at a rate of 100–120/min and ventilation at 8–10 breaths/min. On return of spontaneous circulation, chest compressions are stopped and the ventilation rate is adjusted to 12–20/min (depending on the age of the patient).

ERRNVPHGLFRVRUJ

96


2. Defibrillation ●

As soon as the defibrillator is ready and it is confirmed that the rhythm is shockable, an initial DC shock of 2 J/kg is given and the CPR is resumed without reassessing the rhythm.

●

After every 2 minutes of CPR, the rhythm is assessed and if it remains shockable, a DC shock of 4 J/kg is repeated.

3. Adrenaline ●

Inj. adrenaline 10 mcg/kg IV (0.1 mL of 1:10,000 solution) is administered after the 2nd shock and repeated after the 4th and 6th shocks (i.e., after every 2 shocks).

●

In the Resuscitation Council, UK guidelines 2010, adrenaline is given first after 3 shocks and then after every 2 shocks.

4. Amiodarone ●

Refractory VF or VT is treated with amiodarone 5 mg/kg (or lignocaine 1 mg/kg IV, if amiodarone is NA) after the 3rd shock and if required after the 5th shock.

5. Asystole/PEA If asystole or PEA is noted anytime on rhythm assessment prior to giving a shock, non-shockable protocol is instituted. 6. Return of spontaneous circulation ●

If there is ROSC, CPR is discontinued and post-resuscitation care is commenced.

●

If VF/VT recurs after successful defibrillation, resumption of CPR sequence and defibrillation is indicated. Amiodarone bolus is given (unless 2 doses have previously been administered) and a continuous infusion is started.

Asystole and Pulseless Electrical Activity PEA (formerly known as electromechanical dissociation) is recognized by slow, wide QRS complexes, but there is no cardiac output; at times, the ECG is relatively normal but the pulses are absent. 1. CPR ECC is initiated at a rate of 100–120/min, and a compression:ventilation ratio of 15:2 is provided with bag-mask ventilation. The child is intubated with minimal interruption to CPR and then continuous chest compressions are given at a rate of 100–120/min and ventilation at 8–10 breaths/min. The chest compressions are discontinued only on ROSC and the ventilation rate is adjusted to 12–20/min (depending on the age of the patient).

ERRNVPHGLFRVRUJ


97

Protocol for non-shockable rhythm Cardiac arrest • Bag-mask ventilation (15:2; compressions:breaths) • Chest compression rate 100–120/min • Monitor cardiac rhythm (rhythm non-shockable) • Tracheal intubation (ventilation rate 8–10/min) • Monitor ETCO2 • Establish vascular access (IV/IO) Adrenaline 10 mcg/kg IV

• CPR × 2 minutes • Check rhythm • CPR × 2 minutes • Check rhythm During CPR • Adrenaline is administered after every alternate loop of CPR (i.e., every 3–5 minutes). • Reversible causes are corrected. • At any stage, if on rhythm check the rhythm becomes shockable, shockable protocol is commenced instead. • At any stage, when there is ROSC, post resuscitation care is instituted.

2. Adrenaline Inj. adrenaline 10 mcg/kg IV (0.1 mL/kg of 1:10,000 solution) is administered as soon as it is confirmed that the rhythm is nonshockable and CPR is continued. The rhythm is checked after every 2 minutes of CPR. Adrenaline is repeated after every two such cycles of CPR and cardiac rhythm check (i.e., every 3–5 minutes). 3. DC shock Whenever the rhythm converts to VF, a DC shock of 4 J/kg is administered and the shockable rhythm protocol followed. 4. Correct reversible causes Any evident cause of arrhythmia or associated metabolic disorder is treated. Hypovolemia is corrected with a bolus of 20 mL/kg of crystalloid. 5. Discontinuing CPR CPR is discontinued only when there is ROSC or it is decided to terminate the effort.

ERRNVPHGLFRVRUJ

98


Torsades de Pointes Torsades is a variant of polymorphic VT and deteriorates rapidly to VF or pulseless VT, so CPR is initiated as soon as possible. An IV infusion of magnesium sulfate (25–50 mg/kg; maximum single dose 2 g) is administered over several minutes and the heart is defibrillated.

Bradycardia If the heart rate is less than 60/min and is associated with signs of poor peripheral perfusion, CPR is urgently needed. 1. CPR All inotrope lines, stopcocks, and infusion pumps are checked to confirm these are functioning, and adequate oxygenation and ventilation is ensured. If bradycardia with signs of poor perfusion persists, CPR with ECC at the rate of 100–120/min is instituted. 2. Adrenaline Adrenaline 10 mcg/kg (0.1 mL/kg of 1:10,000 solution) IV bolus can be given to increase the HR. If IV/IO access not available, it may be administered via the ET tube in a dose of 100 mcg/kg (0.1 mL/kg of 1:1000 solution). 3. Atropine In bradycardia due to increased vagal tone or primary AV conduction block, atropine 0.02 mg/kg IV/IO bolus or an endotracheal dose of 0.04–0.06 mg/kg may be effective. 4. Cardiac pacing In complete heart block or sinus node dysfunction unresponsive to ventilation, chest compressions, or medications, some form of cardiac pacing will be needed.

Management After Resuscitation 1. Oxygen 100% oxygen is used for initial resuscitation. After ROSC, the FiO2 is reduced to achieve an oxygen saturation of 94–98%. However, in the single ventricle patient, who has undergone a bidirectional superior cavopulmonary shunt or a systemic to pulmonary artery shunt, following resuscitation from cardiac arrest, FiO2 should be adjusted

ERRNVPHGLFRVRUJ


99

to optimize the systemic and pulmonary blood flow and the arterial oxygen saturation maintained at around 80%. 2. Hypothermia Mild hypothermia may improve neurological outcomes, whereas fever may be detrimental following ROSC. A child who remains in coma following successful resuscitation may benefit from core cooling to 32–34°C for at least 24 hours. Following a period of hypothermia, the child is rewarmed slowly (0.25–0.50°C/h). 3. Blood glucose control Hypo- and hyperglycemia are avoided following resuscitation. Moderate glucose control (as against tight glucose control) has been advocated.

Bibliography 1. Biarent D, Bingham R, Eich C, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 6. Paediatric life support. Resuscitation 2010;81:1364–88. 2. Kleinman ME, Chameides L, Schexnayder SM, et al. American Heart Association. Pediatric advanced life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Pediatrics 2010;126:e1361–99. 3. Kleinman ME, de Caen AR, Chameides L, et al. Pediatric Basic and Advanced Life Support Chapter Collaborators. Pediatric basic and advanced life support: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science with Treatment Recommendations. Pediatrics 2010;126:e1261–318. 4. Kotur PF. An update on pediatric resuscitation. Indian J Anaesth 2004;48:330. 5. Part 12: Pediatric Advanced Life Support. Circulation 2005;112:IV-167–IV-187. Resuscitation Council (UK). [Updated: 2010 Dec; cited: 2011 Feb 22] Available at: http://www.resus.org.uk/ pages/pals.pdf 6. Burke DP, Bowden BF. Modified paediatric resuscitation chart. BMJ 1993;306:1096–8. 7. Pediatric Drug Lookup. CPR Pediatric Drug Dosages. Pediatriccareonline. [Updated: 2011 Mar 21; cited: 2011 Apr 29] Available at: http://www.pediatriccareonline.org/pco/ub/view/ Pediatric-Drug-Lookup/153899/all/cpr_pediatric_drug_dosages 8. Madden SCV. Paediatric drug doses. University Hospitals Coventry and Warwickshire N.H.S. Trust. [Updated: 2011 Mar 21; cited: 2011 Apr 29] Available at: http://www.esculape.com/ pediatrie/medicament_dose.html#index.

ERRNVPHGLFRVRUJ

Fluid and Electrolytes “A good heart and kidneys can survive all but the most willfully incompetent fluid regimen” —Mark M Ravitich (1910–1989)*

Fluid and electrolyte management can be divided into two components: (i) maintenance therapy and (ii) deficit therapy. Maintenance therapy comprises of replacement of the ongoing physiological losses of water and electrolytes, which occur in urine, sweat, respiration, and stool. Maintenance fluid requirements need to be increased if there are additional losses, as with fever, surgical drainage or ongoing gastrointestinal losses. The requirements are decreased in oliguric renal failure, edematous states and in the syndrome of inappropriate ADH secretion. Deficit therapy comprises of existing water and electrolyte deficits, which may be present as a result of gastrointestinal, urinary, skin or blood loss and third-space sequestration.

Maintenance Therapy Daily electrolyte requirements in children Electrolytes

Daily requirement (mmol/kg)

Normal blood levels

Sodium (Na)

2–4 mmol/kg

136–145 mmol/L

Potassium (K)

2–3 mmol/kg

3.5–5.0 mmol/L

Calcium (Ca)

0.2–0.4 mmol/kg

Total Ca: 2.2–2.8 mmol/L (8.8–11.2 mg/dL) Ionized Ca: 1.1–1.4 mmol/L (4.4–5.4 mg/dL)

Magnesium (Mg)

0.15–0.25 mmol/kg

1.8–3.0 mg/dL (1.5–2.5 meq/L or 0.75–1.25 mmol/L)

Chloride (Cl)

3 mmol/kg

95–105 mmol/L

*Mark M Ravitich was a renowned pediatric surgeon, teacher, author of medical textbooks, and editor of several medical journals.

ERRNVPHGLFRVRUJ


101

Daily maintenance fluid requirements in a newborn Age (days)

Daily requirement (mL/kg/day)

Hourly requirement (mL/kg/h)

Type of fluid

1

20–40

2–3

10% Dextrose

2

40–60

3–4

1/5

Saline + 10% dextrose

3

60–80

4–6

1/5


4

80–100

6–8

1/5


Daily maintenance fluid requirements in infants and children Weight (kg)

Daily requirement

Hourly requirement

Type of fluid

0–10

100 mL/kg

4 mL/kg

¼ Saline in 10% dextrose

11–20

1000 mL (for 10 kg) + 50 mL/kg (for wt >10 kg)


¼ Saline in 5% dextrose

21–30


60 mL (for 20 kg) + 1 mL/kg (for wt > 20 kg)

½ Saline in 5% dextrose

Maintenance Fluid Requirement Maintenance fluid requirements in infants and children can be calculated based on body weight or surface area. By the body weight method, 100 mL/kg is the requirement for the first 10 kg, 50 mL/kg for the next 10 kg, and 20 mL/kg for the remaining weight. By the surface area method (applicable to children >10 kg), the requirement is 1500–2000 mL/m2/day.

Type of Fluid The type of IV fluid required to be given is dependent on the electrolyte requirement of the child. One liter of normal saline (NS) contains 154 mmol of Na and an equal concentration of chloride. One liter of ¼ NS will contain about 38 mmol of sodium, which will meet the daily sodium requirement of children up to 20 kg. The maintenance regimen is changed to a more concentrated saline solution (e.g., ½ NS instead of ¼ NS) if the serum sodium drops, or to a more dilute solution if the serum sodium starts to rise. The daily potassium requirement calculated as per body weight is added to the days IV fluid unless the patient is hyperkalemic or in renal failure. 2 mmol of potassium added to every 100 mL of maintenance fluid will approximately provide the daily potassium requirement of 2 mmol/kg/day. The calcium requirement can be given as 1–2 mL/kg/day of 10% calcium gluconate by continuous IV infusion.

ERRNVPHGLFRVRUJ

102


Daily maintenance requirements of adult patients with normal renal function are met with two liters of half isotonic (½ N) saline, to which 20 mmol of potassium chloride (KCl) is added per liter. Patients with ongoing gastrointestinal or third-space losses may require a higher rate of saline (or blood) administration to maintain volume balance. Gastric aspiration fluids are replaced by N/2 saline and intestinal losses by NS. Guidelines for fluid therapy in postoperative open heart patients Post Op day

Hourly fluid maintenance requirement

Day of operation

1 mL/kg/h (for first 10 kg) + 0.5 mL/kg (for next 10 kg) + 0.25 mL (for remaining weight)

Day 1 Post Op

2 mL/kg/h (for first 10 kg) + 1 mL/kg/h (for next 10 kg) + 0.5 mL/kg/h (for remaining weight)

Day 2 Post Op

3 mL/kg/h (first 10 kg) + 1.5 mL/kg/h (for next 10 kg) + 0.75 mL/kg/h (for remaining weight)

Day 3 Post Op

Normal maintenance, i.e., 4 mL/kg/h (first 10 kg) + 2 mL/kg/h (for next 10 kg) + 1 mL/kg/h (for remaining weight)

In the immediate postoperative period following cardiac surgery, there is a need for fluid restriction because of cardiac dysfunction and fluid retention caused by cardiopulmonary bypass. The general guidelines for fluid administration following open heart surgery are enumerated in the table. The total fluid intake is restricted to 25–50% of normal maintenance on the day of surgery and increased each morning by 20–25% (provided systemic or pulmonary edema is not present) until normal requirement is reached. (Based on these guidelines, the calculated daily requirement in the immediate postoperative period for an open heart surgery patient is given in Appendix J.) After closed heart surgery one can commence with a higher intake, 50% of the normal daily requirement is given on the day of surgery and normal requirements can be given the following day or on day 2.

Deficit Therapy Analysis of the severity of dehydration by physical signs Clinical sign

Mild

Moderate

Severe

Pre-illness body wt

<5% loss

5–10% loss

>10% loss

Skin color

Pale

Ashen

Mottled

Skin turgor

↓

Tented

Tented

Dryness of mucous membranes

+

++

++

ERRNVPHGLFRVRUJ


Clinical sign

Mild

Moderate

Heart rate

Normal/↑

↑

↑↑

Blood pressure

Normal

Normal/↓

Shock

Urine output

↓

↓↓

Azotemic

103

Severe

Fontanelle (<7 months)

Flat

Soft

Sunken

CNS

Consolable

Irritable

Lethargic/coma

In adults and older children (post pubertal), same symptoms and signs are present in mild, moderate, and severe dehydration with 3%, 6%, and 9% loss of body weight, respectively.

In isotonic dehydration, volume deficit (mL) = % Dehydration × Wt (kg) × 1000 (g/kg) ÷ 100 The goal of deficit therapy is to correct existing abnormalities in volume status and serum electrolytes in 24–48 hours. The total fluid deficit can be estimated from pre- and post-deficit body weight and other clinical parameters. The rate of correction of volume depletion depends upon its severity. In children with severe volume depletion or hypovolemic shock (estimated 10–15% dehydration), initially fluid bolus of 20 mL/kg of crystalloid (e.g., normal saline) or 10 mL/kg colloid (e.g., 5% albumin) is administered rapidly and repeated until the circulation improves (warm skin, decreased heart rate, improved capillary refill time, increased urine output). Hyper-/hyponatremia should be corrected slowly, since overly rapid correction can be potentially harmful. The addition of sodium bicarbonate may be required in patients with metabolic acidosis.

Hypokalemia Hypokalemia (serum K+ <3.5 mmol/L) can be caused by: ■ ■

■

GI losses, i.e., vomiting, nasogastric aspiration, and diarrhea. Renal losses: Excessive diuretics lead to loss of both K+ and acid resulting in hypokalemia and metabolic alkalosis. Hypomagnesemia itself promotes urinary K+ loss and hypomagnesemia is therefore, often associated with hypokalemia. Transcellular shifts of potassium into the cells occur with respiratory or metabolic alkalosis, hypothermia, insulin therapy and other drugs (e.g., β-agonist bronchodilators). In general, for every 0.1 unit change in pH, the serum K+ level changes in the opposite direction by a value of 0.3–0.6 mmol/L.

ERRNVPHGLFRVRUJ

104


Clinical Features Hypokalemia may result in paresthesias, skeletal muscle weakness, hypoventilation, and ileus. It promotes rhythm disturbances (ventricular ectopics, bigeminy, supraventricular tachyarrhythmias, and atrial fibrillation) when associated with some electrolyte abnormalities (e.g., magnesium depletion) and administered drugs (e.g., digoxin). There is therefore an increased risk of digoxin toxicity with hypokalemia. ECG changes: Hypokalemia causes ST depression, shallow, flat or inverted T waves and prominent U waves. Cardiac arrhythmias (atrial and ventricular ectopics, tachycardia and fibrillation), prolongation of the QRS and increased P wave amplitude and duration occur less frequently.

Management 1. If serum K+ falls to <3.4 mmol/L, potassium chloride is given in a dose of 0.5–1 mmol/kg, at a rate of 0.5 mmol/kg/h. Higher rates up to 2 mmol/kg/h may be given in arrhythmia. It is administered in saline or dextrose in a maximum concentration of 20 mmol/100 mL for a central line and 4 mmol/100 mL for a peripheral line. K+ level is checked after the infusion, and the dose of potassium is repeated if required. (1 g KCl = 13.3 mmol K+; 7.5% KCl = 1 mmol/mL) 2. Associated conditions that cause transcellular K+ shift (e.g., alkalosis) are treated. 3. If the signs of hypokalemia or arrhythmias do not respond to potassium chloride, consider associated magnesium depletion. Check the blood level of magnesium.

Hyperkalemia Hyperkalemia (Se K >5 mmol/L) can be caused by: ■

■

■

Impaired renal excretion. Low cardiac output states and renal failure cause decreased renal excretion of potassium because of reduced urinary output. In addition, the associated acidosis induces a transcellular shift of K+ out of the cells. Hyperkalemia also occurs with various drugs that prevent renal elimination of K+, e.g., potassium sparing diuretics, ACE inhibitors, etc. Transcellular shift of potassium out of the cells as seen with acidosis, myonecrosis, and drugs (e.g., β-blockers, NSAIDs, digoxin, etc.). Hemolytic reactions and massive blood transfusions may be a cause of hyperkalemia.

ERRNVPHGLFRVRUJ


105

Clinical Features Clinical features include CNS features (irritability, paresthesias, and muscle weakness especially of the legs), GI symptoms (nausea, abdominal cramps, and diarrhea), and hypotension.

ECG Changes The first changes on the ECG are tall T waves, most evident in leads V2 and V3. These are followed by PR prolongation with decreasing P wave amplitude. Eventually, prolongation of QRS, ventricular fibrillation, and asystole occurs.

Management Treatment

Remark

10% Calcium gluconate 0.5 mL/kg (max dose 10 mL) over 10 minutes Dose can be repeated in 5 minutes.

Response lasts 20–30 minutes Contraindicated if the child is on digoxin.

Frusemide 1 mg/kg IV stat IV infusion 0.1–1 mg/kg/h.

The dose may be repeated in 30–60 minutes or an infusion started.

Insulin 0.1 U/kg IV with 0.5 g/kg dextrose (2 mL/kg of 25% D) over 30 minutes.

Insulin-dextrose should drop Se K+ by 1 mmol/L for 1–2 hour.

Sodium bicarbonate 1–2 mmol/kg IV given over 5–10 minutes (8.4% sodium bicarbonate 1 mL = 1 mmol).

Duration of action 2 h. Use controversial in the absence of acidosis. Sodium bicarbonate is not to be given immediately after calcium.

Kayexalate sodium or calcium resonium is given 1 g/kg PR as a retention enema or via an NG tube q4–6h. It is administered mixed with 20% sorbitol to prevent concretion.

Indicated after management of the acute phase or only if no ECG changes are present.

Hemodialysis or peritoneal dialysis.

Hemodialysis is the most effective method of controlling serum K+.

Hypocalcemia Calcium is present in the blood in two forms: (i) Bound to the plasma proteins (mainly albumin) and plasma anions (sulfates and phosphates) constitutes 50–60%; and (ii) Free ionized fraction, 40–50%. The ionized

ERRNVPHGLFRVRUJ

106


fraction constitutes the physiologically active form. A decrease in the serum albumin level results in a decrease in the bound form, but the ionized active fraction may remain unchanged. Total serum calcium level is 2.2–2.8 mmol/L (8.8–11.2 mg/dL), and the range of ionized calcium is 1.1–1.4 mmol/L (4.4–5.4 mg/dL). Hypocalcemia requires treatment if ionized serum calcium level is <1.0 mmol/L.

Causes of Hypocalcemia ■

Increased calcium binding to albumin, as occurs in alkalosis and sepsis, decreases the active ionized fraction.

■

Binding of the ionized fraction to drugs. Infusion of sodium bicarbonate can result in hypocalcemia because of calcium binding to the bicarbonate. Other drugs that bind ionized calcium include heparin and aminoglycosides.

■

Citrate in multiple blood transfusions chelates calcium and causes hypocalcemia.

■

Magnesium depletion inhibits parathormone secretion and thus promotes hypocalcemia. Hypocalcemia caused by hypomagnesemia is refractory to calcium therapy alone, and magnesium replacement is required in addition.

■

Renal failure causes hypocalcemia because of two reasons: conversion of Vitamin D to its active form needed for calcium absorption from the gut is impaired, and there is an increase in the level of serum phosphate which binds additional calcium.

Clinical Features Clinical features are related to enhanced neuromuscular irritability (hyperreflexia, seizures, and tetany) and cardiac depression (hypotension, decreased cardiac output, ventricular ectopics, and tachycardia). ECG changes: Hypocalcemia results in prolongation of the QT interval because of lengthening of the ST segment, which is directly proportional to the degree of hypocalcemia. T wave flattening and inversion are late changes and heart blocks and VF may rarely occur.

Management ■

Symptomatic hypocalcemia requires urgent management. 10% Calcium gluconate (i.e., 100 mg/mL or 0.23 mmol Ca/mL) is given in a dose of 10–20 mg/kg (0.1–0.2 mL/kg) slow IV bolus. Dilute to at least 1 in 5 with 5% dextrose or isotonic saline.

ERRNVPHGLFRVRUJ


107

■

Daily maintenance IV dose of calcium is 0.2–0.4 mmol/kg/day (100–200 mg/kg/day or 1–2 mL/kg/day) of 10% calcium gluconate.

■

To counteract citrate in transfused blood, 10% calcium gluconate is recommended in a dose of 50 mg (0.5 mL) per 50 mL of transfused blood.

■

Calcium gluconate is used as an inotrope in the dose of 10–40 mg/kg/h (0.1–0.4 mL/kg/h).

10% Calcium chloride (i.e., 100 mg/mL) has three times the content of calcium (0.68 mmol Ca/mL) compared to 10% calcium gluconate. It is therefore given in 1/3rd the dose of 10% calcium gluconate.

Hypomagnesemia Magnesium is largely an intracellular cation, like potassium. It is present in the plasma in a bound and a free ionic form. The physiologically active form is the ionic form but since the total plasma levels are low, the difference between the bound and ionic forms is not clinically relevant and generally total serum magnesium levels are measured. Normal total serum magnesium level is 1.8–3.0 mg/dL (1.5–2.5 meq/L or 0.75–1.25 mmol/L). Causes of hypomagnesemia are as follows: ■

Dietary deficiency or malabsorption are the commonest causes of hypomagnesemia.

■

Renal losses of magnesium are associated with diuretics and antibiotics like aminoglycosides and amphotericin.

■

Transcellular shift of magnesium into the cells, which promotes hypomagnesemia, is seen with a variety of drugs (e.g., digoxin, adrenergic agents, etc.).

Clinical Features The clinical features of hypomagnesemia are not specific but involve the following systems: CNS (altered level of consciousness, confusion); neuromuscular (muscular weakness, lower limb cramps, exaggerated reflexes and tetany); cardiovascular (tachycardia, hypertension), and GIT (dysphagia, anorexia, nausea, and vomiting). ECG changes: may be similar to the findings in hypokalemia, i.e., ST segment depression; flat or inverted T waves in the precordial leads and prominent U waves; other infrequent presentations include PR prolongation, widened QRS, torsades de pointes, and refractory atrial fibrillation. Since hypomagnesemia and hypokalemia occur from similar causes and hypomagnesemia promotes urinary potassium excretion, over 40% of patients with hypokalemia have associated hypomagnesemia. Patients

ERRNVPHGLFRVRUJ

108


with hypokalemia with rhythm disorders who do not respond to potassium administration require magnesium in addition. Magnesium depletion inhibits parathormone secretion and thus promotes hypocalcemia. Hypomagnesemia should therefore be suspected when tetany does not respond to calcium infusion. In hypomagnesemia, since most magnesium is intracellular, a total body deficit can be present with a normal plasma level. A finding of hypocalcemia, hypokalemia, and ECG changes is suggestive of associated hypomagnesemia.

Management Hypomagnesemia is treated with parenteral therapy. Inj. magnesium sulfate 50% (i.e., 500 mg/mL or 2 mmol mg/mL) is given in a dose of 25–50 mg/kg/dose (0.05–0.1 mL/kg/dose) IM/slow IV. (Max single dose 2 g). It is diluted to a concentration 1 in 10 with 0.9% saline or 5% dextrose for IV (1 in 5 with 0.9% saline for IM) and administered over 10 minutes.

Hyponatremia In hyponatremia, serum Na is <135 mmol/L, and in severe cases it is <120 mmol/L. Hyponatremia may be caused by: ■

Sodium loss more than water loss: As occurs in excessive use of diuretics, vomiting, diarrhea, and post cardiopulmonary bypass capillary leak syndrome (Hypovolemic hyponatremia).

■

Water retention: As in rapid infusion of hypotonic fluids and in postoperative syndrome of inappropriate antidiuretic hormone secretion (SIADH), which cause water retention (Isovolemic hyponatremia/Dilutional hyponatremia).

■

Water retention more than sodium retention: In congestive cardiac failure and renal failure, both water and sodium are retained but water gain is greater than sodium gain; edema occurs and the hyponatremia is mild (Hypervolemic hyponatremia).

Clinical Features The clinical features of hyponatremia are primarily neurological, because severe hyponatremia causes cerebral edema as a result of movement of water from hypo-osmolar plasma into the brain cells. Headache, vomiting, lethargy, seizure, and coma occur depending on the rate and severity of hyponatremia.

ERRNVPHGLFRVRUJ


109

Associated hypovolemia causes poor skin turgor, tachycardia, and hypotension, while hypervolemia is associated with edema, weight gain, tachycardia, and hypertension.

Management In hypovolemic hyponatremia, adequate volume and Na replacement is needed. In patients with neurological signs (seizure, coma), initially 2–3 mL/kg of 3% NaCl (contains 51.3 mmol of sodium per 100 mL) is given over 30–60 minutes. The increase in serum osmolality will reverse the cerebral edema. Thereafter, the serum sodium is corrected gradually over 48–72 hours by an infusion of appropriate maintenance fluid based on the sodium deficit. Rapid correction (an increase in serum Na level at a rate faster than 8–10 mmol/L/day) carries the risk of iatrogenic osmotic demyelination. The sodium deficit is determined by: Na deficit (mmol) = (Desired Na − Present Na) × Wt × 0.6 The management of dilutional hyponatremia is by fluid restriction. In SIADH, fluids are restricted to two-thirds the normal daily maintenance. Administration of full volumes of maintenance fluids (esp. hypotonic fluids e.g., ½ or ¼ NS) will exacerbate the hyponatremia. Additionally, a loop diuretic may be combined with IV 0.9% saline. Hypervolemic hyponatremia is managed with fluid restriction, diuretics, and treatment of the underlying disorder.

Hypernatremia In hypernatremia, serum Na is more than 145 mmol/L, and in severe cases it is more than 160 mmol/L. Hypernatremia is caused by: ■

Water loss more than Na loss, e.g., in vomiting, diarrhea. Pure water loss can occur secondary to nephrogenic diabetes insipidus. (Hypovolemic hypernatremia, hypernatremic dehydration.)

■

Sodium excess is unusual; it may be iatrogenic from excess bicarbonate or sodium chloride administration. (Hypervolemic hypernatremia.)

Clinical Features Hypernatremia causes CNS dysfunction by the movement of fluid from the brain to the ECF, resulting in lethargy, exaggerated reflexes, seizures, and coma. Rarely, intracerebral hemorrhage and central pontine myelinolysis

ERRNVPHGLFRVRUJ

110


(though classically associated with rapid correction) may occur. Volume loss of more than 10% will result in shock.

Management A patient with hypovolemic hypernatremia, who is in shock, is initially treated with repeated boluses of isotonic saline or Ringers solution 10–20 mL/kg IV over 20 minutes. Up to 60–100 mL/kg may need to be given before heart rate normalizes and urine output, capillary refill, and mental status improve. Then the remaining volume deficit is replaced by ½ or ¼ normal saline over 48–72 hours. Rapid correction (a fall in serum Na level at a rate faster than 8–10 mmol/L/day) can cause cerebral edema and central pontine myelinolysis because of movement of ECF water into the relatively hypertonic brain cells. The volume deficit is calculated by the following formula: Volume deficit (L) = 0.6 × Body weight (kg) × [1 − (140/serum Na)] In hypervolemic hypernatremia, 5% dextrose or hypotonic solutions are used as maintenance fluid. In addition, sodium excretion may be increased with a diuretic (e.g., furosemide). The diuresis will however aggravate the hypernatremia unless hypotonic solutions are used as maintenance fluid.

Blood Sugar Glucose homeostasis is frequently altered in infants and children during the postoperative period following cardiopulmonary bypass and circulatory arrest. Hyperglycemia may lead to osmotic diuresis, dehydration, and cerebral hemorrhage. Hypoglycemia manifests with seizures, generally when the blood sugar level falls to <30 mg%. The normal blood sugar level range in children is 70–150 mg/dL. However, in children undergoing complex congenital heart surgery, the suggested optimal postoperative glucose range is 110–126 mg/dL.

Management Hypoglycemia is treated with dextrose 0.5–1 g/kg (i.e., dextrose 10%: 5–10 mL/kg; dextrose 25%: 2–4 mL/kg; dextrose 50%: 1–2 mL/kg). If required, the maintenance fluid is changed to 10% dextrose IV to keep the blood sugar level in normal range. Hyperglycemia is treated with regular insulin 0.1–0.2 U/kg IV. The blood sugar level is checked (q6–12h), and the dose repeated as required. Alternatively, insulin 0.1 unit/kg/h IV infusion in 0.9% sodium chloride

ERRNVPHGLFRVRUJ


111

(prepared to a concentration of 1 unit/mL) is administered. The rate of infusion is adjusted according to the response.

Bibliography 1. Adrogué HJ, Madias NE. Changes in plasma potassium concentration during acute acid-base disturbances. Am J Med 1981;71:456–67. 2. Ambalavanan N. Fluid, electrolyte, and nutrition management of the newborn. [Updated: 2010 Jun 29; cited: 2012 Jan 4] Available at: http://emedicine.medscape.com/article/ 976386-overview. 3. Davis ID, Avner ED. Fluid, electrolytes, and acid-base homeostasis. In: Fanaroff AA, Martin RJ eds. Neonatal–Perinatal Medicine 7th ed. Mosby, St. Louis; 2002:619. 4. Elenberg E. Hypernatremia. [Updated: 2009 Nov 2; cited: 2011 Apr 11] Available at: http:// emedicine.medscape.com/article/907653-overview. 5. Fluid and electrolyte requirements in children. [Updated: 2011 Feb 16; cited: 2011 Apr 11] Available at: http://www.pediatriccareonline.org/pco/ub/view/Pediatric-Drug-Lookup/153910/0/ ub?cmd=cookiep. 6. Friis-Hansen B. Body water compartments in children: changes during growth and related changes in body composition. Pediatrics 1961;28:169–81. 7. Hypomagnesemia. [Updated: 2011 Mar 11; cited: 2011 Apr 11] Available at: http:// en.wikipedia.org/wiki/Hypomagnesemia. 8. Intravenous fluids. Clinical practice guideline: The Royal Children’s Hospital, Melbourne. [Updated: 2009 Oct 8; cited: 2011 Feb 22] Available at: http://www.rch.org.au/clinicalguide/ cpg.cfm?doc_id=5203. 9. James MB, Mario FV, Ben TU, Belding HS. The effect in humans of extracellular pH change on the relationship between serum potassium concentration and intracellular potassium. J Clin Invest 1956;35(9):935–9. 10. Marino PL. Fluid and electrolyte disorders. In: Marino PL ed. The ICU Book 2nd ed. Hong Kong: Williams & Wilkins Asia Pacific Ltd; 1997:631–72. 11. Nair SG, Balachandran R. Perioperative fluid and electrolyte management in pediatric patients. Indian J Anaesth 2008;48:355–64. 12. Polito A, Thiagarajan RR, Laussen PC, et al. Association between intraoperative and early postoperative glucose levels and adverse outcomes after complex congenital heart surgery. Circulation 2008;118:2235–42. 13. Reynolds RM, Padfield PL, Seckl JR. Disorders of sodium balance. BMJ 2006;332:702–5. 14. Roberts KB. Fluid and electrolytes: parenteral fluid therapy. Pediatr Rev 2001;22:380–6. 15. Rose BD, Post TW. Clinical Physiology of Acid-Base and Electrolyte Disorders 5th ed. New York: McGraw-Hill; 2001:285–7, 441. 16. RuDusky BM. ECG abnormalities associated with hypocalcemia. Chest 2001;119(2):668–9. 17. Shafiee MA, Bohn D, Hoorn EJ, Halperin ML. How to select optimal maintenance intravenous fluid therapy. QJM 2003;96:601–10. 18. Tam M. “Maintenance” IV fluids in euvolaemic children. [Updated: 2006 June 19; cited: 2011 Feb 25]. Available at: http://vitualis.wordpress.com/2006/05/02/maintenance-ivfluids-in-euvolaemic-children/. 19. Wiederseiner JM, Muser J, Lutz T, et al. Acute metabolic acidosis: characterization and diagnosis of the disorder and the plasma potassium response. J Am Soc Nephrol 2004;15:1589–96. 20. Yamamoto LG. Fluids and electrolytes. Case Based Pediatrics For Medical Students and Residents. University of Hawaii, Department of Pediatrics [Updated: 2003 March; cited: 2011 Feb 25]. Available at: http://www.hawaii.edu/medicine/pediatrics/pedtext/s02c04.html. 21. Yeates KE, Singer M, Morton AR. Salt and water: a simple approach to hyponatremia. CMAJ 2004;170(3):365–70.

ERRNVPHGLFRVRUJ

Arterial Blood Gas Analysis “Life is a struggle, not against sin, not against the money power, not against malicious animal magnetism, but against hydrogen ions” —HL Mencken (1880–1956)*

Normal Values Parameter

Normal range

pH

7.35–7.45

H+

35–45 nmol/L

PaO2

80–100 mmHg or 9.3–13.3 kPa

SpO2

97–100%

tO2

16–22 mL O2/dL

PaCO2

35–45 mmHg or 4.7–6.0 kPa

AaDO2

<10 mmHg

−

HCO3

22–26 mmol/L

SBC

21–27 mmol/L

Base excess

−3 to +3 mmol/L

tCO2

25–30 mmol/L

pH The pH indicates if a patient is acidotic (pH <7.35) or alkalemic (pH >7.45). The concentration of hydrogen ions in the blood determines the pH of the blood.

Hydrogen Ion The hydrogen ion (H+) concentration in the extracellular fluid is a direct measure of acidosis (H+ >45 nmol/L) or alkalosis (H+ <35 nmol/L).

*Henry Louis Mencken was an American author, journalist, magazine editor, and critic. He was known for his satirical writings on social and other controversial issues.

ERRNVPHGLFRVRUJ


113

Partial Pressure of Oxygen Oxygen is transported in the blood in the freely dissolved form and bound to the hemoglobin. The partial pressure of oxygen (PaO2) reflects only the free oxygen molecules dissolved in plasma and not which is bound to the hemoglobin. The PaO2 is determined by the partial pressure of alveolar oxygen and the state of the alveolar membrane. It is decreased in ventilation perfusion mismatch and right to left shunt. It is not affected by the hemoglobin level.

Systemic Arterial Oxygen Saturation The arterial oxygen saturation (SpO2) is the percentage of hemoglobin saturated with oxygen. The more the PaO2, the higher is the SpO2, but the relationship is not linear and is described by the sigmoid shape of oxygen dissociation curve (see Fig. 9 of Chapter 1). At the upper and lower end of the curve, significant changes in PaO2 cause little change in the SpO2, but in the steep part of the curve, changes in PaO2 are reflected by equivalent alterations in SpO2. The SpO2 depends not only on the PaO2 but also on the pH, PaCO2, and temperature. A rise in the pH, a fall in PaCO2 or a decrease in the temperature shifts the curve to the left increasing the affinity of hemoglobin for oxygen, and the same hemoglobin saturation implies a lower PaO2. A fall in pH and a rise in PaCO2 and temperature shifts the curve to the right. The affinity of hemoglobin for O2 is decreased, and with the same hemoglobin O2 saturation, the PaO2 is higher.

Oxygen Content The oxygen content (tO2) is the sum of the dissolved oxygen and the oxygen bound to hemoglobin. The dissolved fraction constitutes 0.003 mL per mmHg (PaO2) per dL, and each gram of hemoglobin (Hb) binds to 1.34 mL of oxygen. tO2 = (Hb in g/dL × 1.34 × SpO2) + (PaO2 × 0.003) Normal tO2 ranges from 16 to 22 mL O2/dL.

Partial Pressure of Carbon Dioxide Carbon dioxide is transported from the body cells back to the lungs in three forms—(i) dissolved in the plasma (10%); (ii) as carbohemoglobin (30%); and (iii) as bicarbonate (60%). Only a small amount of carbon dioxide that enters the blood remains in the dissolved form, the rest enters

ERRNVPHGLFRVRUJ

114


the RBCs. Some of the carbon dioxide combines with desaturated hemoglobin to form carbohemoglobin. In the RBCs, the remaining carbon dioxide is converted to carbonic acid, which dissociates into hydrogen ion and bicarbonate. This bicarbonate then diffuses back into the plasma and is transported to the lungs. On reaching the lungs, the bicarbonate and hydrogen ion combine to form CO2 and H2O, and the CO2 is exhaled.

Hb

CO2 Hb (Carbohemoglobin)

CO2

CO2

CO2

HCO3

H2CO3 Carbonic unhydrase

H+

H2O

Fig. 1: CO2 metabolism in RBC.

The partial pressure of carbon dioxide reflects the dissolved form. A normal PaCO2 of 37–42 mmHg indicates normal alveolar ventilation. Values above normal indicate respiratory acidosis and are present with hypoventilation. Values below normal are evidence of respiratory alkalosis and are present with hyperventilation.

Alveolar–Arterial Oxygen Gradient The alveolar–arterial oxygen gradient (AaDO2) depends on the state of the alveolar membrane. In cases with hypoxemia where the lungs are normal, the AaDO2 will be normal (e.g., low FiO2, right to left shunts, and central respiratory depression). In patients with parenchymal lung disease with impaired oxygen diffusion, hypoxemia will be associated with an increase in AaDO2.

Bicarbonate (HCO3-) Level Bicarbonate level reflects the metabolic component of an acid–base disturbance. A low HCO3− reflects metabolic acidosis and a high HCO3− metabolic alkalosis.

ERRNVPHGLFRVRUJ


115

HCO3− level, however, is varied by both components, respiratory and metabolic, since carbon dioxide itself is transported in the blood as sodium bicarbonate. However, in a patient with no respiratory abnormality, the bicarbonate will reflect the metabolic disturbance.

Standard Bicarbonate (SBC) It is defined as the bicarbonate concentration under standard conditions of PCO2 40 mmHg, temperature 37°C, and oxygen saturation 100%. It is a more accurate measure of the metabolic component of an acid–base disorder than the nonstandardized (actual) bicarbonate. The respiratory fraction of the sodium bicarbonate level in the blood is converted to a similar value in all samples by the standardized conditions.

Base Excess Base excess is a measure of all metabolites (not only HCO3−), which will alter the acid–base status. A base deficit indicates metabolic acidosis, and base excess indicates metabolic alkalosis.

Total CO2 Content (tCO2) Total CO2 content is the sum of the blood bicarbonate level and the dissolved carbon dioxide present in the blood. tCO2 = (HCO3−) + (α PaCO2), [where α = 0.226 mM/kPa, HCO3− is expressed in (mmol/L) and PaCO2 in kPa]

Acid–Base Balance Acid–base disorder

Primary disorder

Compensatory response

Respiratory acidosis

↑ PaCO2

↑ HCO3

Respiratory alkalosis

↓ PaCO2

↓ HCO3

Metabolic acidosis

↓ HCO3

↓ PaCO2

Metabolic alkalosis

↑ HCO3

↑ PaCO2

Same direction rule: A low PaCO2 is compensated by a low HCO3− and a high PaCO2 by a high HCO3−. Similarly, a low HCO3− is compensated by a low PaCO2 and a high HCO3− is by a high PaCO2.

In acidosis, the pH of the blood is <7.35 and in alkalosis it is more than 7.45. pH is a measure of hydrogen ion concentration of the blood.

ERRNVPHGLFRVRUJ

116


Furthermore, the concentration of the H+ is determined by the ratio of the partial pressure of carbon dioxide and the blood bicarbonate level. H+ (nmol/L) = 24 × PaCO2/HCO3− An alteration of this ratio results in an acid–base disorder. Respiratory acidosis results from an increase in the PaCO2 level (i.e., accumulation of carbonic acid) and alkalosis by a fall of the PaCO2 level. Metabolic acidosis is caused by an accumulation of acids or by a loss of bases and is reflected by a low bicarbonate level. Metabolic alkalosis is caused by accumulation of bases or a loss of acids and is reflected by a high bicarbonate level. When either component (PaCO2 or HCO3−) is altered, the other component is accordingly changed as a compensatory mechanism, in an attempt to keep the ratio constant. Thus, when a primary disorder is metabolic, the response is respiratory compensation; the lungs provide compensation by altering the rate of respiration by either retaining or washing off the carbon dioxide. When the primary disorder is respiratory, the response is metabolic compensation. The kidneys provide compensation for respiratory acid–base disorders by increasing or decreasing the reabsorption and production of bicarbonate. However, the adjustment by the kidneys is slow and takes 6–12 hours to start and increases over days.

Specimen Care Samples should be analyzed within 30 minutes of withdrawal (samples drawn in glass syringes can be kept longer in ice baths). Delay in analysis leads to inaccurately low PaO2 and high PaCO2 levels as a result of ongoing cellular respiration. Similarly, air bubbles that exceed 1–2% of the blood volume can cause a falsely high PaO2 and a falsely low PaCO2. The amount of heparin solution used should be minimized and at least 2 mL of blood should be obtained to ensure accuracy.

Interpretation of Blood Gas Analysis Interpretation of blood gases involves systematically checking the various parameters: Step 1—pH pH <7.35 = acidosis; pH >7.45 = alkalosis. Step 2—CO2 PaCO2 gives information about the respiratory component of acid–base balance.

ERRNVPHGLFRVRUJ


117

■

In respiratory acidosis, PaCO2 increases; in respiratory alkalosis, the PaCO2 decreases.

■

Respiratory acid–base disorders have been classified as acute or chronic depending upon whether renal compensation has taken place or not. For acute disturbances, a PaCO2 variation from normal by 10 mmHg is accompanied by a pH shift of approximately 0.08 units and in a chronic respiratory acid–base disorder by 0.03 units. A PaCO2 change of <10 mmHg will be associated with a smaller pH shift.

Step 3—HCO3-, SBC, and base excess These parameters provide information about the metabolic component of the acid–base disorder. ■

■

In metabolic acidosis, the pH is low, the HCO3− (and SBC) is low, and there is base deficit. In metabolic alkalosis, the pH is high, the HCO3− (and SBC) is high, and there is base excess.

Step 4—Compensation If a change is seen in both, PaCO2 and bicarbonate, the disorder consistent with the direction of change of pH, indicates the primary disorder and the disorder which is reversing this change in pH, is the compensatory disorder. Compensation does not return pH completely to normal (and never overshoots). Thus in: ■

Primary respiratory alkalosis and compensatory metabolic acidosis: pH ↑, PaCO2 ↓, HCO3− ↓

■

Primary respiratory acidosis and compensatory metabolic alkalosis: pH ↓, PaCO2 ↑, HCO3− ↑

■

Primary metabolic alkalosis and compensatory respiratory acidosis: pH ↑, HCO3− ↑, PaCO2 ↑

■

Primary metabolic acidosis and compensatory respiratory alkalosis: pH ↓, HCO3− ↓, PaCO2 ↓

A mixed disorder is suspected if the compensatory change in pH is more than expected or returns the pH to normal. Step 5—PaO2 and SaO2 PaO2 reflects ability of the lungs to oxygenate the blood. A low PaO2 and SaO2 (<95%) indicates inadequate oxygenation. Step 6—For metabolic acidosis, determine whether anion gap is present The anion gap is the calculated difference between the positively charged (cation) electrolytes (i.e., Na) and the negatively charged (anion) electrolytes (i.e., HCO3− and Cl−) in the blood. Anion gap = Na+ − (Cl− + HCO3−)

ERRNVPHGLFRVRUJ

118


The normal anion gap is 3–12 mmol/L. Anion gap acidosis (Gap >12 mmol/L) results from the accumulation of anions other than Cl− and HCO3− (organic acids, phosphates, sulfates, albumin, etc.) and these decrease the HCO3− level, thus increasing the gap. Causes of anion gap acidosis include uremia, diabetic ketoacidosis, and lactic acidosis. Non-anion gap acidosis (Gap <12 mmol/L), also called hyperchloremic acidosis, results from loss of HCO3, and causes include diarrhea, renal tubular acidosis, hyperalimentation, compensation for respiratory alkalosis, etc.

Respiratory Acidosis A decrease in the respiratory rate or tidal volume can result in accumulation of CO2 and respiratory acidosis. It occurs in brain stem lesions, airway obstruction, pulmonary disease, inadequate mechanical ventilation, splinting of the chest wall following surgery, drugs, etc.

Clinical Features It is manifested by restlessness, tremors, diaphoresis, dyspnea, tachycardia, a warm flushed skin, and decreased reflexes.

Blood Gas Analysis ■

Uncompensated respiratory acidosis: pH <7.35, PaCO2 >45 mmHg, and a normal HCO3−.

■

Compensated respiratory acidosis: pH <7.35 but approaching normal, PaCO2 >45 mmHg, and HCO3− >26 mmol/L.

Treatment In the ventilated patient, tracheal suctioning and increasing the respiratory rate and/or tidal volume may correct the disorder. The unventilated patient may need bronchodilators, chest physiotherapy to remove secretions and supplemental oxygen. Associated hyperkalemia needs to be corrected.

Respiratory Alkalosis Respiratory alkalosis results from hyperventilation, which may be because of pain, drugs (e.g., overdose of salicylate or aminophylline), hypermetabolic

ERRNVPHGLFRVRUJ


119

states, excessive mechanical ventilation or acute hypoxia (this may cause stimulation of the respiratory center).

Clinical Features The clinical features of respiratory alkalosis are restlessness, diaphoresis, dyspnea, tachycardia, exaggerated reflexes, paresthesias, tetany, and ECG changes of hypokalemia.


Uncompensated respiratory alkalosis: pH >7.45, PaCO2 <35 mmHg, and a normal HCO3−.

■

Compensated respiratory alkalosis: pH >7.45 but approaching normal, PaCO2 <35 mmHg, and HCO3− <22 mmol/L.

Treatment In the ventilated patient, the ventilator rate and/or tidal volume is reduced. The non-ventilated patient may require sedation and oxygen for associated hypoxemia. Rebreathing into a paper bag will increase the PaCO2.

Metabolic Acidosis Metabolic acidosis is characterized by accumulation of acid or loss of bicarbonate and has been classified into two types—(i) anion gap acidosis and (ii) non-anion gap acidosis. Anion gap acidosis can be because of (a) accumulation of lactic acid, which occurs secondary to shock, dehydration, low cardiac output, hypoxia, infection, seizures, renal failure, and hepatic failure or (b) formation of Ketone bodies, as in diabetes mellitus and starvation. Non-anion gap acidosis occurs in renal tubular acidosis from loss of bicarbonate, as a response to hyperkalemia and as a compensatory mechanism in respiratory alkalosis.

Clinical Features Clinical features of metabolic acidosis include confusion, lethargy, and headache. The skin is warm and dry. In later stages, there is hypotension, Kussmaul’s respiration (a deep and labored breathing pattern), and sluggish

ERRNVPHGLFRVRUJ

120


reflexes. There may be signs of hyperkalemia (abdominal cramps, diarrhea, muscle weakness, and ECG changes).


■

Uncompensated metabolic acidosis: pH <7.35, PaCO2 normal, HCO3− <22 mmol/L. Compensated metabolic acidosis: pH <7.35 but approaching normal, PaCO2 <35 mmHg, HCO3− <22 mmol/L.

Treatment IV sodium bicarbonate (NaHCO3) is given for rapid correction (sodium bicarbonate 8.4% : 1 mL = 1 mmol). Dose of NaHCO3 (in mL of 8.4% solution) = Base deficit × 0.3 × body wt. 50% of the amount is given initially, and the base excess is checked after 1 hour. Further correction is done if required. Fluid losses are corrected. Dialysis may be needed in extreme cases.

Metabolic Alkalosis Metabolic alkalosis is the more commonly encountered disorder in the intensive care unit and has also been classified into two types—(i) chlorideresponsive metabolic alkalosis and (ii) chloride-resistant metabolic alkalosis. Chloride-responsive metabolic alkalosis is caused by loss of hydrogen ions through the GI tract by vomiting or nasogastric suctioning. Excessive diuretic therapy results in renal losses of chloride, potassium and magnesium ions, which promote bicarbonate reabsorption and metabolic alkalosis. It can also be caused by excessive administration of organic anions such as HCO3− or because of citrate in multiple blood transfusions. It occurs as a compensatory response to respiratory acidosis and hypokalemia. Chloride-responsive metabolic alkalosis is characterized by urine chloride levels of <10 mmol/L, low serum chloride levels, and a decrease in the ECF volume. This type responds to administration of IV saline. Chloride-resistant metabolic alkalosis occurs in primary aldosteronism or with excessive corticosteroid therapy and is characterized by urine chloride levels of more than 20 mmol/L and an increased ECF volume rather than volume depletion. It is resistant to treatment by administration of IV sodium chloride.

ERRNVPHGLFRVRUJ


121

Clinical Features In the non-ventilated patient, metabolic alkalosis results in anorexia, nausea, apathy, and confusion. There is muscle weakness and loss of reflexes. It impairs myocardial contractility, reduces cardiac output, and causes hypotension. In the ventilated patient, it can be a cause of failed weaning and decreased tissue oxygenation.


Uncompensated metabolic alkalosis: pH >7.45, PaCO2 normal, HCO3 >26 mmol/L.

■

Compensated metabolic alkalosis: pH >7.45 but approaching normal, PaCO2 >45 mmHg, HCO3 >26 mmol/L.

Treatment Chloride-Responsive Metabolic Alkalosis Administration of isotonic saline Metabolic alkalosis is commonly associated with depletion of chloride and extracellular fluid volume, which are corrected by administration of isotonic saline. Chloride deficit and the volume of isotonic saline required can be calculated by the following formulae: Chloride deficit (mmol) = 0.3 × Wt (kg) × (100 − plasma Cl−) Volume of isotonic saline (L) = Chloride deficit ÷ 154 With correction of the chloride deficit, a brisk alkaline diuresis is initiated, which returns the plasma bicarbonate level towards normal. (Normal serum chloride level is 95–105 mmol/L and bicarbonate level 22–26 mmol/L).

Correction of hypokalemia Hypokalemia is corrected by concomitant potassium repletion. Potassium can be provided by adding KCl 1–2 mmol/kg to the fluid regimen. Hydrochloric acid Intravenous HCl is indicated in severe cases (pH > 7.55) when administration of NaCl or KCl is contraindicated (e.g., in hypervolemia, CCF, hyperkalemia). The volume of HCL to be given can be calculated by the following formula: H+ deficit (mmol) = 0.3 × Weight (kg) × (measured HCO3 − desired HCO3 [mmol/L])

ERRNVPHGLFRVRUJ

122


Volume of 0.1 N HCl (L) = H+ deficit (mmol) ÷ 100 (0.1 N HCl contains 100 mmol/L of H+) Rate of H+ replacement: 0.1–0.2 mmol/kg/h (i.e., 1–2 mL/kg/h of 0.1 N HCl).

Ammonium chloride Ammonium chloride (NH4Cl) is an alternative to IV HCl. The recommended dose for children is 75 g/kg/day in divided doses q6h PO or IV (max 6g/day) and for adults is 1.5 g q6h IV (max 6 g/day) or 2–3 g q6h PO (max 12 g/day). It is diluted to a concentration <1–2% and given at the rate of <50 mg/kg/h. NH4Cl is contraindicated in the presence of renal or hepatic insufficiency. Dialysis Hemodialysis or peritoneal dialysis will effectively correct metabolic alkalosis in unresponsive patients and in renal failure. The normal dialysis fluid for peritoneal or hemodialysis, which contains bicarbonate or its metabolic precursors, will however require to be modified. In an emergency, peritoneal dialysis can be performed using isotonic saline with appropriate maintenance of plasma potassium, calcium, and magnesium concentrations by intravenous infusion. Chloride-Resistant Metabolic Alkalosis It is associated with fluid retention and hypokalemia. The management involves correcting the potassium deficiency and appropriate diuretic therapy. Acetazolamide is a carbonic anhydrase inhibitor and promotes bicarbonate excretion. It is administered in a dose of 5 mg/kg/day in divided doses q8h.

Bibliography 1. Acid-Base Regulation and Disorders. The Merck Manuals 19th ed. Accessed 2011 Oct 26. Available at: http://www.merckmanuals.com/professional/endocrine_and_metabolic_disorders/ acid-base_regulation_and_disorders/acid-base_regulation.html. 2. Atkins EL. Assessment of acid-base disorders. A practical approach and review. Canad Med Ass 1969;100:992–6. 3. Baillie JK. Simple, easily memorised rules of thumb for the rapid assessment of physiological compensation for acid-base disorders. Thorax 2008;63:289–90. 4. Brackett NC Jr. An approach to clinical disorders of acid-base balance. South Med J 1974; 67(9):1084–101. 5. Breen PH. Arterial blood gas and pH analysis. Clinical approach and interpretation. Anesthesiol Clin North America 2001;19(4):885–906. 6. Doyle DJ. Synopsis of acid base analysis. [Updated: 2006 Jan; cited: 2011 Feb 25]. Available at: http://acidbase.homestead.com/ABG_Analysis_Rev_2.0.pdf

ERRNVPHGLFRVRUJ


123

7. DuBose TD Jr. Acidosis and alkalosis. In: Fauci AS, Braunwald E, Kasper DL, et al. eds. Harrison’s Principles of Internal Medicine 17th ed. Vol I. McGraw-Hill Companies Inc.; 2008:287–96. 8. Galla JH. Metabolic alkalosis. JASN 2000;11(2):369–75. 9. Huang LH, Priestly LA. Pediatric metabolic alkalosis. [Updated: 2010 May 5; cited: 2011 Feb 25]. Available at: http://emedicine.medscape.com/article/906819-diagnosis. 10. Kaehny WD. Respiratory acid-base disorders. Med Clin North Am 1983;67(4):915–28. 11. Lynch F. Arterial blood gas analysis: implications for nursing. Paediatr Nurs 2009;21(1):41–4. 12. Marino PL. Acid base disorders. In: Marino PL, ed. The ICU Book 2nd ed. Hong Kong: Williams & Wilkins Asia Pacific Ltd; 1997:581–616. 13. Reddy P, Mooradian AD. Clinical utility of anion gap in deciphering acid`base disorders. Int J Clin Pract 2009;63(10):1516–25. 14. Rowlands BJ, Tindall SF, Elliott DJ. The use of dilute hydrochloric acid and cimetidine to reverse severe metabolic alkalosis. Postgrad Med J 1978;54(628):118–23.

ERRNVPHGLFRVRUJ

Parenteral Nutrition “Manual skill has not appreciably improved in the last 50 years, and cannot improve much further. But manual skill is not the whole of surgery” —Sir William Heneage Ogilvie (1887–1971)*

Daily Nutritional Requirements (Based on Body Weight) 3–10 kg Fluids/day

10–30 kg

100–120 mL/kg

Fluids (mL/m2/day)

>30 kg st

1000 mL (1 10 kg) + 50 mL/kg (2nd 10 kg) + 20 mL/kg (3rd 10 kg) 1500–1800

1500

Caloric requirement (kcal/kg/day)

90–150

60–90

40–60

Ratio non-protein calories: Nitrogen

150–200:1

150–200:1

150–200:1

Carbohydrates (g/kg/day)

15–30

15–25

10–20

Proteins (mg/kg/day)

2.5–3.0

1.5–2.5

1.0–1.5

Fats (g/kg/day)

2–4

2–4

2–3

Sodium (mmol/kg/day)

2–4

2–4

2–3

Potassium (mmol/kg/day)

2–3

2–3

1.5–3

Calcium (mmol/kg/day)

0.2–0.4

0.2–0.4

0.2–0.4

Magnesium (mmol/kg/day)

0.15–0.25

0.15–0.25

0.15

Phosphorus (mmol/kg/day)

0.5–2.0

0.5–2.0

1.0–1.5

Guidelines for Initiation and Maintenance of Parenteral Nutrition Substrate

Initiation

Advancement

Goals

Amino acids

0.5–1 g/kg/day

↑ 0.5–1 g/kg/day

2–3 g/kg/day

20% Lipids

0.5–1 g/kg/day

↑ 0.5–1 g/kg/day

2–3 g/kg/day

Dextrose

6 mg/kg/min 8–9 g/kg/day

↑ 2 mg/kg/min ↑ 2–3 g/kg/day

10–12 mg/kg/min 14–18 g/kg/day

g/kg/day = mg/kg/min × 24 × 60 ÷ 1000.

*Sir William Heneage Ogilvie was a renowned British surgeon, who described the syndrome of acute colonic pseudo-obstruction (Ogilvie’s syndrome). He was appointed Knight of the British Empire in 1946 for his extra-ordinary military service.

ERRNVPHGLFRVRUJ


125

Parenteral Nutrition (PN) in Children The provision of nutrition to infants and children following surgery remains one of the most important aspects of postoperative care. IV nutritional therapy is indicated as a replacement for enteral nutrition when oral intake is not feasible or as a supplement to enteral feeding.

Caloric Requirements Caloric requirements of children are noted in the table above. In children aged 6 months–15 years, caloric requirements may also be estimated by the formula: kcal/kg/day = 95 − [3 × age (yr)] Small children (<3 kg) require 90 kcal/kg/day for growth, but 40 kcal/kg/day will prevent catabolism. Fever increases the requirement by 10–12% for every degree rise, surgery by 20–30%, and sepsis up to 50%. Caloric requirements are reduced in sedated ventilated patients.

Amino Acids Neonates and children are given only pediatric formulations due to the requirement of essential amino acids, cysteine, taurine, tyrosine, and histidine, which are added to these formulations. Amino acids are available in 6% and 10% concentration (Aminoven, Primene). These are started in a dose of 0.5–1 g/kg/day and increased up to 3 g/kg/day with daily increments of 0.5–1 g/kg/day. For efficient protein utilization for tissue building, 1 g nitrogen (1g N = 6.25 g protein) requires 150–200 non-protein calories (nPC), i.e., calories from carbohydrates and fats. The ratio of nPC:N in the PN is calculated by the formula: nPC:N =

CHO (kcal) + Fat (kcal) × 6.25 Protein (g)

1 g of protein provides 4 kcal; 1 g dextrose: 3.4 kcal; and 1g fat: 9 kcal. Thus, the amount of amino acids that can be given is restricted by the nonprotein calories being administered. Grams of nitrogen that can be given are calculated by the kcal provided by Carbohydrate (kcal) + Fat (kcal) ÷ 150. In other words, to prevent catabolism, calories from non-protein and protein sources are maintained at a ratio of more than 6:1.

Fat Fat is available as 10% and 20% intralipid. 20% lipid is preferable as it is isotonic, besides the higher phospholipid content of the 10% solution impedes plasma triglyceride clearance.

ERRNVPHGLFRVRUJ

126


Fats are started on day 2 or 3 in a dose of 0.5–1 g/kg/day and increased by 0.5 g/kg/day up to 3 g/kg/day. The dose of lipids needs to be reduced following sepsis, respiratory distress, thrombocytopenia, or hyperbilirubinemia. To maintain its stability, the intralipid is given as a separate infusion from other solutions, and is covered from light. The solution can, however, be joined with the amino acid containing solution with a Y-connector near the infusion point. The lipid infusion for the day is generally given over 20 hours to allow for blood sampling 4 hours after stopping lipid, prior to starting the next day’s requirement.

Dextrose The daily dextrose volume (in mL) is estimated by: Total fluid requirement – (Amino acid + Lipid + Supplements). The percentage of dextrose to be administered is tailored according to the calculated requirement. It is started at 6 mg/kg/min on day 1 and increased by 2 mg/kg/min daily to reach a target of 10–12 mg/kg/min. Maximum concentration of dextrose that can be given via peripheral line is 12.5%. Higher concentrations need to be given via a central line. Blood sugar level is monitored and maintained between 70 and 150 mg/dL. The intake of dextrose may need to be decreased to control the blood sugar level. In case the child still has persistent hyperglycemia, glycosuria, and osmotic diuresis, insulin is given as a continuous infusion starting at a rate of 0.05 units/kg/h, and increasing the dose as required. To calculate the rate of glucose administration, the following formula can be used: Glucose infusion rate (mg/kg/min) =

%Glucose × mL/kg/day 144

Electrolytes Electrolyte

Daily requirement (mmol/kg/day)

Supplement in PN providing daily requirement

Strength (mmol/mL)

Sodium

2–4 mmol/kg/day

0.9% saline or 3% saline

0.9% saline: 1 mL = 0.154 mmol 3% saline: 1 mL = 0.5 mmol

Potassium

2–3 mmol/kg/day

15% potassium chloride

1 mL = 2 mmol

Calcium

0.2–0.4 mmol/kg/day

10% calcium gluconate

1 mL = 0.23 mmol

Magnesium

0.15–0.25 mmol/kg/day

50% magnesium sulfate

1 mL = 2 mmol

ERRNVPHGLFRVRUJ


127

Isotonic saline is used to provide the daily sodium requirement. In case of volume restriction, 3% NaCl may be used instead of 0.9% saline to provide the daily sodium requirement.

Trace Elements Trace elements (Zn, Cu, Min, Se, etc.) are provided by giving 10 mL/kg of plasma over 4 hours every third day.

Vitamins Add MVI (multivitamin intravenous) 1 mL/kg/day to the TPN solution. Also give weekly doses of injection vitamin K (0.5–1 mg) and injection vitcofol (5 mcg vit B12 and 500 mcg folic acid).

Heparin Inj. heparin is indicated for central lines in a dose of 0.5–1 unit/mL of TPN.

Complications Complications as related to various aspects of PN are as follows: 1. Dextrose: Hypoglycemia, hyperglycemia, hyperosmolality, and dehydration. 2. Amino acids: Metabolic acidosis, azotemia, cholestatic jaundice. 3. Lipids: Hyperlipidemia, platelet dysfunction, abnormalities in pulmonary gas diffusion. 4. Mechanical: Thrombosis, embolism. 5. Sepsis: S. epidermidis, Candida.

Laboratory Monitoring All blood sampling should be done after 4 hours of stopping lipid infusion. 1. Urine specific gravity, glucose and protein—daily. 2. Blood glucose—initially 6 hourly; once glucose infusion rate is stable, 12 hourly.

ERRNVPHGLFRVRUJ

128


3. Serum Na+/K+—daily for 3–4 days, then twice weekly. 4. Blood pH—initially daily; once protein intake is stable, twice weekly. 5. Blood Hb and PCV—initially daily, later twice weekly. 6. Blood urea, serum creatinine, serum proteins, LFT, serum triglycerides—weekly.

Steps for Calculation of Parenteral Nutrition 1. The first step is to calculate the daily caloric requirement. 2. Note the daily fluid requirement, e.g., 100–120 mL/kg/day for a child 3–10 kg weight. 3. Volume of PN = Daily fluid requirement minus volume of other infusions (inotropes, blood products). 4. Volumes of lipid, amino acids, and supplements (saline, potassium chloride, calcium gluconate, magnesium sulfate, and vitamins) required is calculated. Volume of each = PN component

Daily requirement (mg or mmol/kg) × body wt Strength of solution (mg or mmol/mL)

5. Volume of dextrose that can be given = Volume of PN − (Volume of lipids + amino acids + supplements). Calculate the percentage of dextrose that will provide the daily requirement in this volume. 6. Calculate the non-protein:protein calorie ratio. Example (10 kg child on day 2) Component

Calculation

Amount

Total fluid requirement

110 mL/kg × 10

1100 mL

Volume of PN (total fluid requirement— other infusions)

1100–100

1000 mL

Fats (20% intralipid)

(1 g/kg × 10)/0.2

50 mL

Amino acids (6%)

(1 g/kg × 10)/0.06

167 mL

Sodium (0.9% saline), i.e., 0.154 mmol/mL

(3 mmol/kg × 10)/0.15

200 mL

KCl 15% (2 mmol/mL)

(2 mmol/kg × 10)/2

10 mL

Calcium (10% calcium gluconate), i.e., 0.23 mmol/mL

(0.3 mmol/kg × 10)/0.23

13 mL

ERRNVPHGLFRVRUJ


129

Component

Calculation

Amount

Magnesium (MgSO4 50%), i.e., 2 mmol/mL

(0.20 mmol/kg × 10)/2

1.0 mL

Multivitamins

1.5 mL

Lipid + amino acids + supplements (LAsp)

443 mL

Dextrose

Total volume of PN − LAsp = (1000 − 443)

557 mL

Percentage of dextrose: 20% (8 mg/kg/min = 115 g/day; 115 g/day ÷ 557 mL × 100). Ratio of non-protein calories:N = 300:1 [CHO kcal (115 × 3.4) + Fat kcal (10 × 9)] × 6.25 ÷ Protein g (10).

Classically, amino acids, dextrose, and other supplements are mixed together under aseptic conditions and given via the central line. Lipids can be given through a peripheral line or via a ‘Y’ connection in the central line.

Bibliography 1. Acra SA, Rollins C. Principles and guidelines for parenteral nutrition in children. Pediatr Ann 1999;28:13–120. 2. Chaudhari S, Kadam S. Total parenteral nutrition in neonates. Indian Pediatr 2006;43:953–64. 3. Fusch C, Bauer K, Böhles HJ, et al. Neonatology/Paediatrics – Guidelines on Parenteral Nutrition, Chapter 13. GMS Ger Med Sci 2009;7. 4. Herman R, Btaiche I, Teitelbaum DH. Nutrition support in the pediatric surgical patient. Surg Clin North Am 2011;91(3):511–41. 5. Intravenous fluids. Clinical practice guideline: The Royal Children’s Hospital, Melbourne. [Updated: 2009 Oct 8; cited: 2011 Oct 29] Available at: http://www.rch.org.au/clinicalguide/ cpg.cfm?doc_id=5203 6. Kraus DM. Pediatrics nutrition. PMPR 652 Pharmacotherapeutics. [Updated: 1997 Dec 19; cited: 2011 Oct 29]. Available at: http://www.uic.edu/classes/pmpr/pmpr652/Final/krauss/ pedsnutrition.html 7. Krohn K, Babl J, Reiter K, Koletzko B. Parenteral nutrition with standard solutions in paediatric intensive care patients. Clin Nutr 2005;24:274–80. 8. Kurkchubasche AG. Nutritional requirements. Pediatric Surgery Handbook: The Hasbro Children’s Hospital. [Cited: 2011 Oct 29]. Available at: http://med.brown.edu/pedisurg/Brown/ Handbook/Nutrition.html 9. Math Homepage. Pharmacy Tech Study. [Updated: 1997 Dec 19; cited: 2011 Oct 29]. Available at: http://www.pharmacy-tech-study.com/math.html 10. Mohandas KM, Shastri YM, Shirodkar M. Total parenteral nutrition. Natl Med J India 2003; 16:29–33. 11. Owens JL, Musa N. Nutrition support after neonatal cardiac surgery. Nutr Clin Pract 2009; 24(2):242–9. 12. Reimer SL, Michener WM, Steiger E. Nutritional support of the critically ill child. Pediatr Clin North Am 1980;27(3):647–60. 13. TPN solution requirements. [Cited: 2011 Apr11]. Available at: http://www.rxkinetics.com/ tpntutorial/3_1.html

ERRNVPHGLFRVRUJ

Enteral Feeding “The doctor of the future will no longer treat the human frame with drugs, but rather will cure and prevent disease with nutrition” —Thomas Edison (1847–1931)*

Indications for Enteral Tube Feeding Enteral tube feeding is indicated in children who have been on the ventilator for 3–5 days and may be started within 48 hours of surgery if a delay in weaning from ventilator and extubation is anticipated. It is, however, possible only in patients with stable hemodynamics and a functional gastrointestinal tract. It is not advised when high doses of adrenergic drugs and neuromuscular blockers are being used. Enteral feeding is well tolerated in critically ill children and is preferable to parenteral nutrition as it prevents intestinal atrophy and is not associated with the risk of infection and other complications. It is also indicated in patients after extubation who are malnourished and require additional caloric intake or whose documented energy intake is less than the required levels.

Route Nasogastric (NG) or orogastric (OG) tubes are usually placed for shortterm enteral feeding. Long-term use of NG or OG tubes is associated with esophagitis and gastroesophageal reflux (GER) and if tube feeding is required for >8–12 weeks, gastrostomy or gastrojejunostomy tube placement should be considered.

Fluid and Nutritional Requirements Daily fluid and nutritional requirements have been discussed earlier in the chapter on parenteral nutrition. *Thomas Edison was the inventor of the phonograph, motion picture camera, and electric light bulb.

ERRNVPHGLFRVRUJ

Enteral Feeding

131

Daily maintenance fluid requirements based on the body weight are as follows: ■

<10 kg: 100 mL/kg

■

10–20 kg: 1000 mL + 50 mL for each kg >10 kg

■

>20 kg: 1500 mL + 20 mL for each kg >20 kg

Method of Administration Tube feeding can be instituted by either of the following methods: (i) Bolus feedings are given using a syringe or gravity flow over a relatively short period of time at regular intervals during the day. Feeds are generally delivered 6–8 times per day; each feeding lasting about 5–15 minutes. (ii) Continuous feedings are given using an infusion pump over a number of hours. It may be a continuous infusion over 24 hours or as a cyclical infusion for a period of 8–20 hour per day. Continuous feeding is usually preferred for small bowel feedings and may be better tolerated for NG/OG feedings in critically ill patients, because of a slower infusion rate and volumes.

Types of Feed Infants should receive expressed breast milk (EBM) or standard infant formula feeds (e.g., Lactogen). For older children, standard pediatric formulas (which are an appropriate combination of proteins, carbohydrates, fats, vitamins, and minerals) are designed specifically to meet their nutrient

Table 1: Composition of human milk fortifier (per 2 g sachet) Protein (g)

0.2

Fat (g)

0.1

Carbohydrate (g)

1.2

Calcium (mg)

50

Phosphate (mg)

25

Sodium (mg)

1.75

Vitamin A (IU)

730

Vitamin D (IU)

250

Vitamin E (IU)

1.25

Energy (kcal)

6.5

ERRNVPHGLFRVRUJ

132


requirements. These formulae are isotonic with osmolality similar to various body fluids (300 mOsm/L). Diets for adult use have a higher osmolarity and concentration of electrolytes and are therefore not recommended in children, owing to the inherent risk of diarrhea and hypertonic dehydration. Supplements may be added to the EBM or to various formula feeds to increase the caloric content and provide additional nutrients, e.g., human milk fortifier (HMF) powder sachet of 2 g is added to 50 mL EBM to provide additional proteins, minerals, and vitamins. Elemental formulas (monomeric formulas) are made from amino acids or hydrolyzed proteins, carbohydrate, fat in the form of medium-chain triglycerides plus essential fatty acids and also contain appropriate vitamins and minerals. These diets are readily digestible, cause less stimulation of bile and pancreatic secretions, and result in a smaller amount of stool formation. Elemental diets are, however, hyperosmolar and need careful monitoring because of the risk of hyperosmolar dehydration. Indications for administration include various malabsorption disorders. Modular formulas provide carbohydrates, proteins, or fats, separately (as modules) for addition to diets and other formulas for specific nutrition needs (e.g., medium chain triglycerides in management of chylothorax).

Kitchen Based Feeds Kitchen based feeds may be used in older children, however, require care in preparation to prevent contamination and are likely to be thick and unsuitable for delivery through narrow NG tubes. The following feeds provide approximately 100 kcal/100 mL: ■

Milk (100 mL) + Sugar (1 tsp) + Oil (½ tsp)

■

Milk (100 mL) + Sugar (1 tsp) + Cereal flour (1½ tsp)

■

Curd (100 mL) + Sugar (2 tsp)

■

Orange (1) + Sugar (2 tsp) + Water (100 mL)

■

Egg (1) + Milk (150 mL) + Sugar (2 tsp)

Initiation and Progression Table 2: Guidelines for enteral feeding in neonates Weight (g)

Starting volume

Increased by

Full feed (mL/kg/day)

1500–2000

2–3 mL q3h

2 mL q6h

160–180

2000–2500

4–5 mL q3h

3 mL q6h

160–180

>2500

5–10 mL q4h q2–4h if demand fed

4–8 mL q8h

160–180

ERRNVPHGLFRVRUJ

Enteral Feeding

133

Table 3: Guidelines for 4 hourly bolus tube feeding in children Weight (kg)

Starting volume/ day (mL/day)

Starting volume of each feed (mL/4h)

Increase in volume of each feed q24h (mL/4h)

Final volume of each feed (mL/4h)

3–5

72–120

12–20

12–20

48–80

6–10

145–240

24–40

24–40

96–160

11–20

278–360

46–60

46–60

185–240

21–30

365–420

60–70

60–70

240–280

Table 4: Guidelines for continuous tube feeding in children Weight (kg) 3–5

Starting volume/ day (mL/day)

Starting rate of infusion (mL/h)

Rate of increase q8–24h (mL/h)

Goal (mL/h)

72–120

3–5

3–5

12–20

6–10

145–240

6–10

6–10

24–40

11–20

278–480

11–20

11–20

46–60

21–30

500–720

20–30

20–30

60–70

Tube feedings are initiated in low volumes, and if tolerated, the volume is increased every 8–24 hour to meet the child’s daily fluid requirements. While isotonic formulas are started at full strength, hypertonic formulas are initially given at half strength and subsequently increased in steps to full strength. Either the volume or the concentration is increased at any one time, so that the effect of the change can be monitored. Bolus feedings may be administered starting with 25% of the daily fluid requirement divided equally into the number of daily feedings. One method is to increase the administered volume every 24 hour by 25% of the daily requirement. Faster increments may be given if tolerated and full feeding is instituted in 48–72 hour. To prevent the feeding tube from becoming blocked, the tube may require to be flushed with water after every feed but not >3–5 mL water should be used, as infants may not tolerate large amounts of calorie-free fluid. Continuous feeding can be started at 1–2 mL/kg/h and advanced by 0.5–1 mL/kg/h every 8–24 hour until the goal volume is achieved. Preterm, critically ill children may require a lower initial volume of 0.5–1 mL/kg/h.

Complications of Tube Feeding Complication

Cause and possible intervention

Nausea/vomiting/large gastric residuals

● ● ●

Rapid administration of feeding Hyperosmolar formula ↓ gastric motility: consider prokinetic and acid inhibitory medication

ERRNVPHGLFRVRUJ

134


Complication

Cause and possible intervention ● ●

●

Diarrhea

● ● ● ●

● ● ●

Constipation

● ● ● ● ●

Metabolic disorders: dehydration, dyselectrolytemia, hyper/ hypoglycemia

● ● ● ●

Mechanical problems: blocked tube, tube displacement

● ●

●

Medication, e.g., antibiotics Gastric air collection: position child 30° head up. Vent NG tube High fat content of formula Medication, e.g., antibiotics Lactose intolerance Nutrient malabsorption Bacterial infection; check stools for Rotavirus, Lorovirus, C. difficile Inadequate fiber Rapid infusion Hyperosmolar formula Dehydration Fecal impaction: laxative, stool softner Inadequate fiber Electrolyte abnormalities Medications (narcotics, codeine) Inadequate fluid intake/excessive fluid loss High/low electrolyte content of formula Excess glucose intake/prolonged feeding interval Drug therapy Excessive residue in formula Inappropriate mixing of medication if administered via the tube Tube displacement: verify position by auscultation and pH testing of tube aspirate

Gastric Residue Abdominal girth and gastric residue are recorded before every bolus feed (or every 4 hours if continuous feeding is being given). In case of abdominal distension or if gastric residue is >50% of previous bolus feed (or >2 times the hourly volume for continuous drip feeding), either the volume or the strength of the next feed is reduced by one or two steps. The aspirated contents are returned and the feeds advanced more slowly. In severe cases of feed intolerance, the feeding is stopped and recommenced when the distension or vomiting settles down and the residue is no more than a few mL. Feeding the child in a 20–30° head up tilt and placing the child in the right lateral decubitus position after feeding has been helpful in preventing gastroesophageal reflux and decreasing the amount of gastric residue. If high residuals persist without associated clinical signs and symptoms, a promotility agent (e.g., erythromycin, metoclopramide) may be tried.

ERRNVPHGLFRVRUJ

Enteral Feeding

135

Bibliography 1.

2. 3.

4.

Aquilina A, Kelly J, Bisson R, et al. Guidelines for the administration of enteral and parenteral nutrition in paediatrics. SickKids, Toronto, Ontario, Canada [Cited: 2012 May 22]. Available at: www.sickkids.ca/pdfs/.../19499-Enteral_Parenteral_Nutrition.pdf Elizabeth KE. Nutrition in health and illness. In: Gupte S. Textbook of Pediatric Nutrition New Delhi: Peepee; 2006:354–5. Kurkchubasche AG. Nutritional requirements. Pediatric Surgery Handbook: The Hasbro Children’s Hospital. [Cited: 2011 Feb 22]. Available at: http://bms.brown.edu/pedisurg/Brown/ Handbook/Nutrition.html Seashore JH. Nutritional support of children in the intensive care unit. Yale J Biol Med 1984; 57(2):111–34.

ERRNVPHGLFRVRUJ


Anti-emetics Name

Dose

Remarks

Domperidone

Children: 250–500 mcg/kg q6–8h PO (max 2.4 mg/kg/day which should not exceed 80 mg) Adults: 10–20 mg q6–8h PO (max 80 mg/ day)

Side effects include extrapyramidal symptoms (anxiety, distress, slurred speech, tremor and various movement disorders).

Metoclopramide

Children Anti-emetic and GE reflux—0.1–0.2 mg/ kg/dose q6–8h PO/IM/IV >14 yr and adults Anti-emetic dose—10 mg q6–8h IV GE reflux—10–15 mg 30 min before meals and HS PO/IM/IV (4 doses)

Side effects include extrapyramidal symptoms.

Ondansetron hydrochloride

Children IV: 2–12 yr: 0.1 mg/kg/dose (max 4 mg). PO: 4–11 yr: 4 mg q8h >12 yr and adults 8 mg q8h PO/IV

Indicated in chemotherapy and radiotherapy induced emesis. Single dose used for the prevention and treatment of postoperative nausea and vomiting. Repeated after 4 hours if required.

Cisapride

Children >1 year—0.2–0.3 mg/kg/dose q6–8h PO Adults 10–20 mg 15 min before meals and HS (4 doses) PO

Indicated for GE reflux.

Prochlorperazine

Children >10 kg: PO—0.4 mg/kg/day in divided doses q6–8h or alternatively: 10–13 kg: 2.5 mg q12–24h (max 7.5 mg/day); 14–17 kg: 2.5 mg q8–12h (max 10 mg/ day); 18–39 kg: 2.5 mg q8h or 5 mg q12h (max 15 mg/day) IM—0.13 mg/kg single dose Adults PO: 5–10 mg q6–8h IM: 5–10 mg q3–4h (max 40 mg/day)

Side effects include extrapyramidal symptoms.

ERRNVPHGLFRVRUJ


Name

Dose

Remarks

Triflupromazine

Children PO: 0.5 mg/kg q8h. IM: 0.2–0.25 mg/kg (max 10 mg/day). Adults IM: 5–15 mg q4h (max 60 mg/day). IV: 1 mg (max 3 mg/day). PO: 10–25 mg q12h.

Side effects include extrapyramidal symptoms. Safety and efficacy not established for children <2.5 years of age

137

Prophylactic agents for GI hemorrhage Name

Dose

Ranitidine (150/300 mg Tab)

1 month–16 yr: 2–4 mg/kg in divided doses q12h PO. (For treatment max 300 mg/day; maintenance max 150 mg/day) Adult: 150 mg q12h or 300 mg HS PO; maintenance 150 mg HS. 1 month–12 yr: 3 mg/kg/day in divided doses q8h IV. >12 yr: 150 mg/day in divided doses q8h IV.

Inj. ranitidine (25 mg/mL amp)

Remarks

Dilute 10 times with 0.9% saline (over 2–5 minutes) or inject into running infusion. Use ½ dose in severe renal impairment and liver disease.

Omeprazole (20 mg capsule)

1 month–12 yr: 10–20 mg/day in divided doses q12–24h PO. >12 yr: 20–40 mg/day in divided doses q12–24h PO.

Reduce dose in severe liver disease.

Sucralfate suspension (1 g in 5 mL)

0–1 yr: 6 mL/day in divided doses q4h PO. 2–6 yr: 12 mL/day in divided doses q4h PO. 7–12 yr: 18 mL/day in divided doses q4h PO. >12 yr: 30 mL/day in divided doses q4h PO.

Contraindicated in severe renal impairment.

Stress Ulceration and Upper GI Bleeding Stress ulceration and upper gastrointestinal bleeding are well-known complications in the postoperative period in children operated for heart disease. Some of the factors which increase the risk of stress ulceration are as follows: ■ ■

Children on ventilator for >48 hours Coagulopathy

ERRNVPHGLFRVRUJ

138 ■

■ ■ ■


Unstable hemodynamic condition requiring high doses of intravenous catecholamines Re-thoracotomy Multiorgan dysfunction or sepsis Steroids

Various available prophylactic agents include H2-receptor blocking agents, proton pump inhibitors (PPIs), sucralfate, and antacids. H2-receptor antagonists (ranitidine, famotidine) decrease the acid secretion in the stomach and lower the incidence of stress ulceration and the occurrence of GI bleeding. PPIs however, provide a higher level of stomach pH control and are therefore more effective therapy for prophylaxis. At the same time, this elevation in the level of gastric pH has been implicated in an increase in bacterial colonization of the gut promoting bacterial translocation and an increased incidence of blood-borne sepsis and also an increased incidence of aspiration and ventilator-associated pneumonias. H2 blocking agents and PPIs are therefore not generally used for routine postoperative prophylaxis but in patients who are at a higher risk for GI bleeding and in the treatment of GI bleeding. Sucralfate has not been shown to be as effective as H2 blockers and PPIs in the control of stress ulceration but since it does not increase the gastric pH, it may be safer and has been recommended for routine use in postoperative protocols. It may also be used in combination with H2-receptor blocking agents, and PPIs in the treatment of GI bleeding. Antacids are associated with diarrhea and electrolyte disturbances and have not proven to be of any benefit in GI prophylaxis.

Bibliography 1. Allen ME, Kopp BJ, Erstad BL. Stress ulcer prophylaxis in the postoperative period. American Journal of Health-System Pharmacy 2004;61(6). Medscape. [Updated: 2004 Apr 16; cited: 2011 Apr 26] Available at: http://www.medscape.com/viewarticle/472701. 2. Araujo TE, Vieira SM, Carvalho PR. Stress ulcer prophylaxis in pediatric intensive care units. J Pediatr (Rio J) 2010;86(6):525–30. 3. Arora NK, Ganguly S, Mathur P, Ahuja A, Patwari A. Upper gastrointestinal bleeding: etiology and management. Indian J Pediatr 2002;69(2):155–68. 4. Behrens R, Hofbeck M, Singer H, Scharf J, Rupprecht T. Frequency of stress lesions of the upper gastrointestinal tract in paediatric patients after cardiac surgery: effects of prophylaxis. Br Heart J 1994;72:186–9. 5. Cook D, Guyatt G, Marshall J, et al. A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group. N Engl J Med 1998;338(12):791–7. 6. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med 1994;330:377–81. 7. Deorari AK. Rational drug therapy. In: Ghai OP, Paul VK, Bagga A, ed. Essential Paediatrics 7th ed. New Delhi: CBS Publishers & Distributors Pvt Ltd; 2009:729–30.

ERRNVPHGLFRVRUJ


139

8. Elliot MJ, Delius RE. Renal issues. In: Chang AC, Hanley FI, Wernovsky GU, Wessei DL, ed. Pediatric Cardiac Intensive Care Pennsylvania: Williams and Wilkins; 1998:388. 9. Ephgrave KS, Kleiman-Wexler R, Pfaller M, et al. Effects of sucralfate vs antacids on gastric pathogens: results of a double-blind clinical trial. Arch Surg 1998;133(3):251–7. 10. Fennerty MB. Pathophysiology of the upper gastrointestinal tract in the critically ill patient: rationale for the therapeutic benefits of acid suppression. Crit Care Med 2002;30:S351–5. 11. Prescription Drug Information, Interactions & Side Effects. [Cited: July 2012] Available at: http://www.drugs.com/ 12. Reveiz L, Guerrero-Lozano R, Camacho A, Yara L, Mosquera PA. Stress ulcer, gastritis, and gastrointestinal bleeding prophylaxis in critically ill pediatric patients: a systematic review. Pediatr Crit Care Med 2010;11:124–32. 13. Sean C. Sweetman. Gastrointestinal drugs. Martindale: The Complete Drug Reference 36th ed. 2009:1693–778.

ERRNVPHGLFRVRUJ

Postoperative Respiratory Complications “It is unsettling to find how little it takes to defeat success in medicine” —Atul Gawande* (In: Better: A Surgeon’s Notes on Performance)

Pulmonary Dysfunction Postoperative pulmonary dysfunction (PPD) refers to an impairment of blood gases and alteration of lung mechanics in the immediate post surgical period. The cause of the dysfunction is primarily because of the inflammatory response and microatelectasis initiated by cardiopulmonary bypass (CPB) resulting in abnormalities of oxygen and carbon dioxide transfer across the alveolar membrane. The AaDO2 is significantly higher, and there is a decrease in the vital capacity, functional residual capacity, and lung compliance following CPB. In the extubated patient, this may be clinically evident by tachypnea, respiratory distress, and tachycardia. The severity of dysfunction may range from hypoxemia (which is present to a variable degree in all patients following CPB) to acute respiratory distress syndrome (ARDS) (0.4–2%). Recovery from PPD requires a variable period of postoperative mechanical ventilation. Appropriate mode of ventilation, moderate PEEP, and repeated endotracheal suctioning gradually improves the oxygenation and increases the functional residual capacity permitting extubation. Thereafter, positioning, pain management, and chest physiotherapy further improves alveolar recruitment. Postoperative pain is certainly an important consideration in patient recovery, and failure to control postoperative pain may itself result in inadequate tidal volume with increasing areas of lung collapse and poor blood gases.

Pleural Effusion Causes of pleural effusion in the postoperative period include right heart failure, fluid overload, pulmonary edema, and extravasation from extracardiac *Atul Gawande is a practicing general surgeon and author of three best sellers, Complications, Better and The Checklist Manifesto which are based on his personal experience of surgical triumphs, errors, and controversies.

ERRNVPHGLFRVRUJ


141

shunts. The inflammatory response to CPB may also itself result in small, transient effusions. Small effusions will resolve with treatment of the cause, however, large effusions will require chest tube drainage. The most appropriate position for chest drains for fluid collections is the 5th or 6th intercostal space in the posterior axillary line.

Chylothorax Chylothorax may occur after injury to the thoracic duct or its tributaries either within the pericardium or more often after extrapericardial operations, e.g., Blalock–Taussig shunt or coarctation repair. It may also be seen after open heart procedures associated with high systemic venous pressure, especially the Fontan operation. Often, a chylothorax becomes evident only after 2–7 days of surgery. The reason for this is that lymph initially accumulates in the posterior mediastinum until the mediastinal pleura gives way, usually into the right pleural cavity.

Diagnosis Presence of a milky white effusion, which increases with the intake of dietary fat, is an indication of a chylothorax. Chyle is sterile and can be distinguished from other opalescent collections by the presence of chylomicrons, which are stained with Sudan III and estimation of the triglyceride content (>110 mg/dL). Chyle has a protein concentration of 2.2–6 g/dL and has a white blood cell count >1000/mL with a lymphocyte fraction >80%.

Management As a first step, conservative management is initiated with chest tube drainage and a fat-free formula consisting of only proteins and starch or a dietary intake of medium chain triglycerides instead of normal fats. Medium chain triglycerides are absorbed directly into the portal venous system and allow healing of the injured duct. Alternatively, the child is placed on IV hyperalimentation at the time of diagnosis or later after a trial of the above management. Inj. somatostatin (or its synthetic analog octreotide) has been effectively used to treat chylothorax in various dosing schedules. One recommended dose is 80–100 mcg/kg/day, which can be given in divided doses 8 hourly either IM or IV. An alternative dose protocol is 1–4 mcg/kg/h as a continuous infusion. It is tapered after cure and may need to be given up to 3 weeks. If the drainage persists, recommendations about the length of conservative management vary considerably. One opinion is to continue aggressive

ERRNVPHGLFRVRUJ

142


nonoperative management for 4 weeks before surgical intervention. Other authors have advocated surgical intervention at 1–2 weeks if there is no significant improvement in the drainage. Operative procedures include surgical ligation of the injured duct at the site of operation or above the right diaphragm. Alternatively, a pleurodesis or a pleuroperitoneal shunt may be performed.

Diaphragmatic Paralysis Phrenic nerve injury can occur during surgery, along the course of the nerve in the mediastinal pleura either by cold cardioplegia solution, diathermy, or direct surgical trauma. It is a cause of failure to wean from the ventilator. It may be difficult to diagnose, and an abnormal abdominal breathing pattern in the extubated child may be the pointer. Respiratory distress and CO2 retention after extubation may require that the child be put back on the ventilator. X-ray chest after extubation reveals a raised dome of diaphragm with atelectasis, which was not evident during ventilation. Ultrasound examination or fluoroscopy confirms the paradoxical diaphragmatic movements (upward diaphragmatic movement during inspiration). Plication of the affected diaphragm may be needed before the child can eventually be extubated.

Pneumothorax Intermittent positive pressure ventilation (IPPV) or vigorous hand bagging may result in barotrauma and pneumothorax. Entry of air from around a loosely fitting chest drain can also be a cause. Pneumothorax is suspected in the ventilated patient, if there is an increase in the peak inspiratory pressure, a fall in the oxygen saturation, and a decrease of breath sounds on the affected side. In the extubated patient, there may be tachypnea, cyanosis, tracheal deviation away from the affected side, and reduced respiratory breath sounds. In tension pneumothorax, there is in addition, sudden hemodynamic decompensation manifested by hypotension and bradycardia or tachycardia. X-ray chest will show pneumothorax. In the unstable patient, rather than waiting for the X-ray, the diagnosis can be confirmed with a needle and syringe aspiration, and the pneumothorax relieved by the introduction of a 20 gauge needle. A chest tube is inserted subsequently. For a pneumothorax, the appropriate position for the chest tube is the third intercostal space in the anterior axillary line.

ERRNVPHGLFRVRUJ


143

Atelectasis Atelectasis produces tachypnea, tachycardia, and impairment of blood gases, depending upon the extent of collapse. In case of a large collapse, there is a decrease in chest expansion, a mediastinal shift towards the affected side, and diminished breath sounds over the corresponding area of the chest. The patient may have fever 48–72 hours after a persistent collapse lung. Radiological findings show infiltration of the collapsed segment or lobe. Typically, the right upper or middle lobe collapse obscures the right heart border, left upper lobe atelectasis may be evident by a triangular infiltrate extending to the upper mediastinum, and a left lower collapse causes an increased density of the cardiac silhouette.

Causes Collapse of the lung may be caused by obstruction of the endotracheal tube, or bronchial airway with blood clot or secretions. Vascular structures such as dilated pulmonary arteries or enlarged cardiac chambers, because of their close association with the respiratory tract, can cause extrinsic compression of the airways. The trachea, the left bronchus, and the origin of the right middle lobe bronchus are the more common sites of compression. Significant airway compression presents with pulmonary collapse or persistent wheezing or rarely it is a cause of failure of extubation of the ventilated patient.

Management Postoperative management involves measures to assist complete lung expansion and prevention of atelectasis. The ventilated child needs humidification of inspired gases, institution of adequate PEEP (or CPAP) and regular endotracheal suction. Minimal negative pressure (−80 to −120 mmHg) is utilized to aspirate endotracheal secretions so as not to cause epithelial damage. After the child is extubated, chest physiotherapy and adequate analgesia prevents pain and splinting of the chest. A collapse segment or lobe may re-expand with chest physiotherapy alone. More often it may require tracheal aspiration with a flexible bronchoscope. Alternatively, endotracheal intubation is done to allow tracheal suctioning. This is followed by short-term IPPV with PEEP before extubation. Atelectasis may be difficult to distinguish from pneumonia and nonresolving atelectasis may progress to pneumonia. Endotracheal secretions

ERRNVPHGLFRVRUJ

144


should be Gram stained and cultured, and appropriate prophylactic antibiotics should be started in non-resolving atelectasis.

Aspiration Pneumonitis Aspiration pneumonitis (Mendelson syndrome) is caused by an episode of vomiting or reflux, with aspiration of the gastric contents. This can possibly occur in a sedated or neurologically obtundated child or in a ventilated child in whom a non-cuffed endotracheal tube has been used. The aspiration causes a chemical pneumonitis, which may be followed subsequently by a bacterial infection. The extent of damage to the tracheobronchial tree depends upon the amount and acidity of the material aspirated, and the pathological lesions can vary from mild bronchiolitis to acute pulmonary edema.

Clinical Features The child usually presents with clinical features of mild to severe respiratory distress 2–5 hours after the episode of aspiration. Severe cases may progress to ARDS. Radiological findings vary from segmental or lobar consolidation to bilateral perihilar or multifocal opacities. In the recumbent child, the posterior segments of the upper lobes and the superior segments of the lower lobes are more likely to be involved.

Treatment Oropharyngeal and tracheal suctioning is urgently required in a child who has aspirated following vomiting. Pulse oximetry is monitored and supplemental oxygenation is provided. The need for intubation is assessed depending on the oxygenation and the patient’s neurological status. Antibiotics are indicated if aspiration pneumonitis fails to resolve within 48 hours; Pseudomonas aeruginosa, Klebsiella pneumoniae, and methicillin-resistant Staphylococcus aureus must be covered.

Bibliography 1. Apostolakis EE, Koletsis EN, Baikoussis NG, Siminelakis SN, Papadopoulos GS. Strategies to prevent intraoperative lung injury during cardiopulmonary bypass. J Cardiothorac Surg 2010; 5:1. [Cited: 2011 Oct 8] Available at: http://www.cardiothoracicsurgery.org/content/5/1/1. 2. Bandla HPR, Hopkins RL, Beckerman RC, Gozal D. Pulmonary risk factors compromising postoperative recovery after surgical repair for congenital heart disease. Chest 1999;116:740–7.

ERRNVPHGLFRVRUJ


145

3. Bennet NR. Paediatric intensive care. Br J Anaesth 1999;83:139–56. 4. Büttiker V, Fanconi S, Burger R. Chylothorax in children: guidelines for diagnosis and management. Chest 1999;116:682–7. 5. Chakrabarti B, Calverley PMA. Management of acute ventilatory failure. Postgrad Med J 2006;82:438–45. doi: 10.1136/pgmj.2005.043208. 6. Engelherdt T, Webster NR. Pulmonary aspiration of gastric contents in anaesthesia. Br J Anaesth 1999;83:453–60. 7. Helin RD, Angeles STV, Bhat R. Octreotide therapy for chylothorax in infants and children: a brief review. Paediatr Crit Care Med 2006;7(6):576–9. 8. Nair SK, Petko M, Hayward MP. Aetiology and management of chylothorax in adults. Eur J Cardiothorac Surg 2007;32:362–9. 9. Ng CS, Wan S, Yim AP, Arifi AA. Pulmonary dysfunction after cardiac surgery. Chest 2002; 121:1269–77. 10. Oster JB, Sladen RN, Berkowitz DE. Cardiopulmonary bypass and the lung. In: Gravlee GP, Davis RF, Kurusz M, Utley JR, eds. Cardiopulmonary Bypass: 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2000:367. 11. Pratap U, Slavik Z, Ofoe VD, Onuzo O, Franklin RCG. Octreotide to treat postoperative chylothorax after cardiac operations in children. Ann Thorac Surg 2001;72:1740–2. 12. Sandora TJ, Harper MB. Pneumonia in hospitalized children. Pediatr Clin N Am 2005;52: 1059–81. 13. Wynne R, Botti M. Postoperative pulmonary dysfunction in adults after cardiac surgery with cardiopulmonary bypass: clinical significance and implications for practice. Am J Crit Care 2004;13:384–93.

ERRNVPHGLFRVRUJ


Diagnosis Parameter

ARDS

Onset

Acute

Clinical setting

Predisposing condition exists

Gas exchange

PaO2/FiO2 <200 mmHg regardless of PEEP level

Chest X-ray

Bilateral infiltrates

Wedge pressure

≤18 mmHg

Acute respiratory distress syndrome (ARDS) has been defined as a syndrome characterized by an acute onset of dyspnea, severe hypoxemia, bilateral lung infiltrates on X-ray chest, and a decreased compliance of the respiratory system in the absence of congestive cardiac failure. It is a complication that arises when other disease processes produce a diffuse inflammatory injury of the lungs. Predisposing conditions in the postoperative cardiac patient include sepsis, multiple transfusions, ventilatorassociated pulmonary contusion, aspiration pneumonia, and cardiopulmonary bypass itself. The term “acute lung injury” (ALI) has been used in order to identify patients who have not yet progressed to ARDS or have a milder form of ARDS and the ratio of PaO2:FiO2 defines the degree of severity of hypoxemia. The criteria for diagnosis that have been proposed by American-European Consensus Conference (1993) for ARDS and ALI are as follows: ■

Acute bilateral infiltrates on chest X-ray.

■

Ratio of the partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2): in ARDS is ≤200 and for ALI from 200–300.

■

A pulmonary artery wedge pressure of <18 mmHg, as evidence that the cause of the pulmonary edema is non-cardiogenic. In children, an echocardiogram may instead be used to assess the LA pressure.

ERRNVPHGLFRVRUJ


147

Presentation The clinical features of ARDS may develop over hours or days after the predisposing event. The first sign is tachypnea with associated hypoxemia, which shows no response to O2 therapy. The patient has progressive respiratory distress and may develop cyanosis and eventually require mechanical ventilation. In severe cases, in spite of IPPV, the clinical condition may continue to worsen and there may be an outpouring of intra-alveolar fluid of high protein content from the endotracheal tube. The peak inspiratory pressure is increased, and there may be a further deterioration in the oxygen saturation. Pneumothorax as a result of barotrauma is a frequent complication of ARDS because of high peak inspiratory pressures generated with mechanical ventilation. Blood gas analysis reveals a low PaO2 because of severe intrapulmonary shunting, and a high alveolar-arterial oxygen gradient (AaDO2). The left atrial pressure is normal and excludes cardiogenic pulmonary edema.

Differential Diagnosis Signs

ARDS

Left heart failure

Aspiration pneumonia

Fever and leukocytosis

Yes

Absent

Yes

Hypoxemia

Hypoxemia is more pronounced than X-ray findings

Chest X-ray findings more pronounced

Chest X-ray findings more pronounced

Chest X-ray

Diffuse bilateral infiltrates, ‘white out’ in severe cases

Bilateral hilar infiltrates

Infiltrate usually involves superior segments of lower lobes or posterior segments of upper lobes

Pleural effusion

Absent

Present

May be present

Wedge pressure

<18 mmHg

>18 mmHg

<18 mmHg

Predisposing cause Present

Associated cardiac defect Sepsis

Bronchoalveolar lavage

Polymorphonuclear cells <5%

Polymorphonuclear cells ↑ (>18%)

Polymorphonuclear cells ↑ (>18%)

X-ray chest shows bilateral, diffuse pulmonary infiltrates but is not specific for ARDS. Air bronchograms may be present but Kirley B lines, peribronchial cuffing and pleural effusions are uncommon. In left ventricular failure (cardiogenic pulmonary edema), there is a confluent alveolar shadowing spreading out from the hilum giving a “bats wing” appearance. Presence of Kirley B lines, pleural effusion, fluid in the

ERRNVPHGLFRVRUJ

148


fissures, and peribronchial cuffing is more common while air bronchograms are unusual. Kirley B lines are caused by edema of the interlobular septa and are seen perpendicular to the pleural surface at the lung bases. In the upright film, the upper lobe blood vessels may be wider than the lower lobe vessels. This “upper lobar diversion” occurs because of lower zone arteriolar vasoconstriction secondary to alveolar hypoxia. Upper lobe diversion is however, normal in the supine film. Associated LV enlargement may be additional evidence of LV failure.

Management Management strategy Ventilation 1. Tidal volume 2. PEEP 3. FiO2

Comments 5–7 mL/kg. The plateau pressure is maintained ≤30 cm H2O. CO2 retention (permissive hypercapnia) because of low TV is accepted. 5–10 cm is added to prevent atelectasis. 50–60% to minimize O2 toxicity. An arterial oxygen saturation of >90% is acceptable.

Diuretics

Diuretic may be used to reduce fluid overload but does not decrease the inflammation.

Volume infusion

Large amounts of colloid/crystalloid infusions may be required to maintain the CVP because of the capillary leak syndrome.

Dobutamine

Dobutamine ↑ cardiac output. Dobutamine is preferable to dopamine since dopamine in higher doses acts as a pulmonary vasoconstrictor. Pulmonary vasodilators are also avoided as they may increase the intrapulmonary shunting.

Blood products

Packed RBCs are given to maintain Hb >10 g%.

Steroids

Steroids have no specific role.

Surfactant

Aerosolized surfactant may be of benefit in neonates.

Various ventilatory strategies in the management of ARDS have been advocated with debatable outcomes. One of the prevalent methods (ARDS network trial 2000) aims at ventilatory settings that prevent any further lung injury by achieving the lowest peak inspiratory pressures (PIP) and tidal volumes (TV) that will allow gas exchange. Some degree of CO2 retention (permissive hypercapnia) because of low TV is accepted. End expiratory atelectasis is prevented by appropriate levels of PEEP. Volume or pressure preset ventilation can be used. The following protocol is appropriate in volume assist control mode: 1. The initial TV is set at 5–7 mL/kg. 2. A plateau pressure of ≤30 cm H2O is maintained by reducing the TV to 5 or 4 mL/kg if necessary.

ERRNVPHGLFRVRUJ


149

3. The ventilator rate is set at 12–35 breaths/min to provide appropriate minute ventilation. Hypercapnea is accepted as a protective lung strategy and an increase in PCO2 (pH >7.10 and PCO2 40–90 mmHg) is allowed to the extent that it does not result in significant hemodynamic instability. 4. A moderate prolongation of inspiratory time (IT) is used to improve oxygenation (1:1 to 1:3). Excessive IT (which shortens the expiratory time) is avoided as this can cause intrinsic PEEP and lung injury. 5. One method recommended for setting the appropriate PEEP and FiO2 is to titrate levels of “PEEP and FiO2 combinations” against increasing oxygen saturations. The following combinations of FiO2/PEEP are stepped up to achieve an oxygenation goal of PaO2 55–80 mmHg (SaO2 88–95%): FiO2 PEEP (cm H2O)

0.3 0.4 5

8

0.5

0.6

0.7

0.8

8–10

10

10–14

14

0.9

1.0

14–18 18–22

6. Attempts to wean by pressure support are indicated when FiO2/PEEP ≤0.40/8.

Bibliography 1. Corne J, Carrol M, Brown I, Delany D, eds. Chest X-ray Made Easy 2nd ed. Churchill Livingston; 2002:56–63. 2. Christie JD, Lanken PN. Acute lung injury and acute respiratory distress syndrome. In: Hall JB, Schmidt GA, Wood LDH, eds. Principles of Critical Care 3rd ed. New Delhi: McGraw-Hill 2005:515–47. 3. Feng AK, Steele DW. Pediatrics, respiratory distress syndrome: treatment and medication. [Updated: 2009 Sep 18; cited; 2011 Feb 22]. Available at: http://emedicine.medscape.com/ article/803573. 4. Fiore ML, Lieh-Lai MW. Acute respiratory distress syndrome [Cited: 2011 Feb 22]. Available at: http://www.scribd.com/doc/24857688/ARDS-Lecture. 5. Hess D. Mechanical ventilation of patients with ARDS [Cited: 2011 Feb 22]. Available at: http://www.rcsw.org/Download/2004_RCSW_conf/ARDS%20Dean%20Hess.pdf 6. O’Croinin D, Chonghaile MN, Higgins B, Laffey JG. Bench-to-bedside review: permissive hypercapnia. Crit Care 2005;9(1):51–9. 7. Prodhan P, Noviski N. Pediatric acute hypoxemic respiratory failure: management of oxygenation. J Intensive Care Med 2004;19:140–53. 8. The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 2000;342:1301–8. 9. Varon J, Wenker OC. The acute respiratory distress syndrome: myths and controversies. The Internet Journal of Emergency and Intensive Care Medicine 1997;1(1). [Updated: 2009 Feb 13; cited: 2011 Feb 22]. Available at: http://www.ispub.com/ostia/index.php?xmlFilePath=journals/ ijeicm/vol1n1/ards.xml.

ERRNVPHGLFRVRUJ


Postoperative Causes Bronchospasm or respiratory wheeze in the immediate postoperative period is not uncommon and may be caused by a number of potential factors: 1. Primarily, it may be a manifestation of preexisting bronchial asthma or airway hypersensitivity. Bronchial irritation by the endotracheal tube, anesthetic gases, or secretions in predisposed individuals may precipitate an acute episode. 2. Hypersensitivity reactions to various drugs, in particular protamine, β-adrenergic blockers, and drugs that cause histamine release (e.g., morphine or atracurium), may induce bronchospasm. Activation of inflammatory factors by the CPB (e.g., C5a anaphylatoxin) may itself be the cause. 3. Bronchospasm may be a manifestation of pulmonary edema, possibly the result of over transfusion in a child with poor LV function. 4. Other postoperative respiratory complications (e.g., respiratory infection, pneumothorax, or atelectasis) may present with bronchospasm.

Assessment of Severity of Acute Bronchial Asthma Clinical feature

Mild

Moderate

Severe

Breathlessness

Only on activity, e.g., walking

Becomes breathless on talking. In infants, cry is softer and shorter; difficulty in feeding

Is breathless even on rest, inability to feed

ERRNVPHGLFRVRUJ


151

Clinical feature

Mild

Moderate

Severe

Ability to talk

Is able to talk in sentences

Talks in phrases or words

Drowsy/confused

Use of accessory muscles of respiration/ suprasternal retraction

Not in evidence

Evident

Evident. Breathing may be thoracoabdominal

Wheeze

Moderate, may be only end expiratory

Loud

Loud/may be inaudible

Pulsus paradoxus

Absent <10 mmHg

May be present 10–25 mmHg

Often present 20–40 mmHg

PaO2 on air

Normal

>60 mmHg

<60 mmHg, possible cyanosis

PaCO2

<45 mmHg

>45 mmHg

>45 mmHg

SaO2%

>95%

91–95%

<90%

PEF after bronchodilator therapy; % of predicted

>80%

60–80%

<60% or response lasts <2 h

The respiratory rate and the heart rate are increased in proportion to the severity of bronchospasm (Normal heart rates—2 mths–1 yr: <160/min, 1–2 yr: <120/min, 2–8 yr: <110/min; Normal respiratory rates— up to 2 mths: <60/min, 2 mths–1 yr: <50/min, 1–5 yr: <40/min, 6–8 yr: <30/min).

Drug Therapy in Acute Bronchial Asthma Drugs given by nebulization Drugs

Dose

Comments

Salbutamol (albuterol)

Adults and children: 100–200 mcg/kg/dose every 4–6 h. (Max dose <20 kg: 2.5 mg q6h; >20 kg: 5 mg q4–6h) Initially, the dose can be repeated every 20 min × 3 times.

Inhaled short-acting β2agonists used in the treatment of acute bronchospasm include salbutamol, terbutaline, levalbuterol, and pirbuterol. Salbutamol can cause tachycardia and severe electrolyte disturbances. Inhaled, long-acting β2agonist salmeterol and formoterol are used for maintenance therapy, typically with inhaled corticosteroids.

ERRNVPHGLFRVRUJ

152


Drugs

Dose

Comments

Ipratropium

1–5 yr: 125–250 mcg/dose q4–6h >5 yr: 250–500 mcg/dose q4–6h

Ipratropium is an inhaled anticholinergic bronchodilator, chemically related to atropine. It has a delayed onset of action (20 minutes) and is used as adjuvant therapy in combination with salbutamol for acute episodes of bronchospasm.

Budesonide

>3 mo: 0.5–1 mg q12h (maintenance 0.25–0.5 mg q12h) Adults: 1–2 mg q12h Maintenance: 0.5–1 mg q12h.

Inhaled corticosteroids are used for their antiinflammatory effects, primarily for maintenance therapy in persistent asthma. Alternative drugs include beclomethasone, fluticasone, and triamcinolone.

L-adrenaline 1:1000 (1000 mcg/mL)

0. 5 mL/kg with 3 mL saline (max dose <4 yr: 2.5 mL; >4 yr: 5 mL)

May be tried in severe bronchospasm not responding to other drugs.

Drugs given IV Drug

Dose

Comments

Methylprednisolone

Children 1–2 mg/kg/day divided q6–12h Adults 60–500 mg/day divided q6–12h. (High dose is given for a few days and then tapered.)

Systemic steroid is indicated in severe cases not responding to nebulization therapy alone. Parenteral corticosteroids that may be given include methylprednisolone, hydrocortisone, or prednisone.

Hydrocortisone

Children 5 mg/kg q6h. Adults 100–500 mg q6h.

In severe bronchospasm, Inj. hydrocortisone may be used instead of methylprednisolone.

Theophylline

Children and adults Loading dose: 4–5 mg/kg IV over 20–30 minutes. Then— 1–9 yr: 800 mcg/kg/h. 9–12 yr: 600–700 mcg/ kg/h. Adults: 400–600 mcg/ kg/h.

May be given in addition to nebulization therapy in severe cases. Used with caution in infants as theophylline acts as a central stimulant and is metabolized slowly. Theophylline can cause tachycardia and tremors and has a narrow therapeutic index (therapeutic serum levels: 10–20 mcg/mL). Children have a more rapid theophylline clearance rate, thus the maintenance doses in them are higher than in adults.

ERRNVPHGLFRVRUJ


153

Drug

Dose

Comments

Terbutaline

Children >2 yr 10 mcg/kg (max 300 mcg) SC/IM/IV, followed by an infusion of 0.1–4 mcg/kg/min. Adults 250–500 mcg q6h SC/IM/IV.

Terbutaline is an IV short-acting β2agonist, which may be used in patients unresponsive to conventional therapy. Adverse effects include headache, tremor, tachycardia, hypertension, hyperglycemia, and hypokalemia.

Management of Acute Bronchial Asthma Oxygen Oxygen is administered by face mask at flow rates of 6–8 L/min to maintain oxygen saturation above 95%. Salbutamol Salbutamol nebulization (0.15 mg/kg) is administered every 20 minutes for the initial 1 hour. Thereafter, it is continued every 4–6 hourly, and once there is improvement in the bronchospasm, the interval is increased to 6–8 hourly and further 12 hourly before discontinuation. Ideally, nebulization should be followed by chest physiotherapy. Salbutamol may also be given in a dose of 0.5–1 mg/kg/h diluted to a minimum of 4 mL by continuous inhalation for the first hour along with the oxygen. Monitoring of the heart rate is required with continuous nebulization because of the possibility of severe tachycardia. Ipratropium In a patient with moderately severe bronchospasm or if the response to the above therapy is inadequate, inhaled ipratropium is administered in addition to the salbutamol. In case of severe bronchospasm, initially ipratropium nebulization is given every 20 minutes following each salbutamol nebulization by 5–10 minutes to maximize airway deposition. After 1 hour of therapy, salbutamol and ipratropium can be mixed in the recommended doses and nebulized 4–6 hourly. Systemic corticosteroids Systemic corticosteroids are indicated in all patients who do not respond promptly and completely to the initial bronchodilator therapy. Steroids also diminish the frequency and intensity of exacerbations. IV methylprednisolone is given in a dose of 1 mg/kg every 6 hourly for 24–48 hours before decreasing the dose.

ERRNVPHGLFRVRUJ

154


Oral corticosteroids are apparently equally effective, however, intravenous administration ensures optimal drug levels in severe cases and is also preferable because of the risk of intubation in these patients. Oral prednisolone may be given in a dose of 1–2 mg/kg/day in 1–3 divided doses for 5 days. Inhaled corticosteroids are not generally used in the management of acute bronchospasm but mainly for maintenance therapy. These are administered in daily 2–4 doses in addition to the β-agonist. Other drugs In case of severe bronchospasm which is refractory to conventional therapy, other drugs that may be tried include Inj. adrenaline, theophylline, terbutaline or magnesium sulfate. Inj. adrenaline is administered in a dose of 10 mcg/kg (i.e., 0.1 mL/kg of 1:10000) IM or SC. Dose may be repeated twice at an interval of 20–30 minutes. Ventilation Intubation and IPPV are indicated in unresponsive severe bronchospasm associated with a silent chest, drowsiness or confusion, and elevated PCO2 and hypoxemia. Inj. ketamine 1–3 mg/kg IV or vecuronium 0.1–0.3 mg/kg may be used for intubation. A volume preset mode is recommended with low set respiratory rate (8–12 per minute) and long expiratory time (I:E ratio of 1:4 or 1:3). A tidal volume of 10–12 mL/kg is set with plateau airway pressure limited to 30 cm H2O and PIP to < 45 cm H2O. If required, the TV is reduced to limit the PIP, and a high level of PCO2 is allowed. PEEP is not advocated or kept at a minimal to prevent further gas trapping. High inspiratory flow rates are achieved with sedation and muscle relaxants and help improve gas exchange. During the period of ventilation, β2-agonists are nebulized into the inspiratory circuit of ventilator.

Management of Bronchospasm in a Ventilated Patient 1. The cause of acute bronchospasm is confirmed as bronchial asthma or airway hypersensitivity. Other potential causes are excluded. Mechanical obstruction of the endotracheal tube is identified by endotracheal suction and if required by bronchoscopy. A chest X-ray is obtained to diagnose atelectasis, pneumothorax, or pulmonary edema. 2. The bronchospasm is managed with bronchodilators. Inhaled salbutamol is administered directly into the endotracheal tube either

ERRNVPHGLFRVRUJ


155

by a dose inhaler or by nebulization. Alternatively, an IV infusion of epinephrine or IV theophylline may relieve the bronchospasm. Systemic IV steroids are also indicated; however, these have a slow onset of action and do not immediately relieve acute bronchospasm. 3. In patients not responding to the above measures, bronchospasm can be treated by increasing the depth of anesthesia. Ketamine IV, isoflurane, sevoflurane, and halothane gas anesthesia, all have bronchodilator properties. 4. In a known case of bronchial asthma, Inj. hydrocortisone can be started prophylactically at the onset of surgery and tapered in 24–48 hours.

Bibliography 1. Herner SJ, Seaton TL, Mertens MK. Combined ipratropium and beta 2-adrenergic receptor agonist in acute asthma. J Am Board Fam Med 2000;13(1):55–65. 2. Mehta P. Asthma controller drugs. [Updated: 2010 Jul 30; cited: 2011 Feb 22]. Available at: http://www.mehtachildcare.com/asthma/controllers.htm#can. 3. New asthma management guidelines. Health Central: Myasthmacentral.com. [Updated: 2008 Mar 18; cited: 2011 Feb 22]. Available at: http://www.healthcentral.com/asthma/introduction000005_7-145.html?ic=506019. 4. Robinson P, Chang A. Differential diagnosis. Acute asthma exacerbation in children. [Updated: 2009 Nov 30; cited: 2011 Feb 22] Available at: https://online.epocrates.com/noFrame/showPage.domethod=diseases&MonographId=1098&ActiveSectionId=35. 5. Rudra A, Sengupta S, Chatterjee S, Ghosh S, Ahmed S, Sirohia S. Paediatric asthma and anaesthesia. Indian J Anaesth 2008;52(Suppl 5):713–24. 6. Sethi GR, Bajaj M, Sehgal V. Management of acute asthma. Indian Pediatr 1998;35:745–62. 7. Siwik JP, Nowak RM, Zoratti EM. The evaluation and management of acute, severe asthma. Med Clin N Am 2002;86:1049–71. 8. Sweetman SC, Blake S. Bronchodilators and anti-asthma drugs. In: Martindale: The Complete Drug Reference 34th ed. 2005:777–808. 9. Woods BD, Sladen RN. Perioperative considerations for the patient with asthma and bronchospasm. Br J Anaesth 2009;103 (Suppl 1):i57–i65.

ERRNVPHGLFRVRUJ

Ventilation “Nature heals—assist it” —Hippocrates (460 BC–370 BC)

Expiration

30

Inspiration

Airway pressure (cm H2O)

Normal Breathing

20 10 0 −10

Time (sec)

Fig. 1: Airway pressure changes during normal breathing.

Spontaneous breathing is initiated by outward movement of the rib cage and lowering of the diaphragm. This results in generation of a negative intrathoracic pressure (−4 to −7 cm H2O), relative to the atmospheric pressure and flow of air into the lungs (for the purpose of discussion, atmospheric pressure is taken as 0 cm H2O). Expiration is a passive phenomenon initiated by elastic recoil of the chest wall and upward movement of the diaphragm resulting in reversal of the pressure gradient and flow of air out of the lungs. In the graphical display of spontaneous breathing (Figs. 1 and 2), the negative pressure tracing of airway pressure is that of inspiration and the positive tracing of expiration. However, in positive pressure ventilation as gas is delivered under pressure, the airway and alveolar pressures are positive during inspiration and fall to zero (or the set PEEP value) during expiration (Fig. 3).

ERRNVPHGLFRVRUJ

157

Expiration

Inspiration

Ventilation

Flow (L/min)

Pressure (cm H2O)

Volume (mL) Time (sec) Fig. 2: Relationship of air flow and lung volume with pressure changes during spontaneous breathing.

Ventilatory Modes Ventilatory modes can primarily be classified on the basis of the method used to provide ventilation. ■

Volume preset ventilation: When the tidal volume (TV) delivered to the patient is decided by the set value of the TV and is constant with every breath. The alveolar pressure generated is variable and depends upon the lung compliance, resistance, and other ventilatory parameters.

■

Pressure preset ventilation: When the TV delivered to the patient is decided by the set peak inspiratory pressure (PIP) and may not be constant with every breath. The TV varies with the change in resistance and compliance of the lungs and other ventilatory parameters.

■

Combination or dual modes: Two or more modes are combined to provide ventilation.

Various modes of ventilation can be further defined by the method used for triggering, i.e., initiation of ventilation (time/pressure/flow triggered), the parameter which is limited in inspiration from rising beyond the set value (pressure/volume/flow limited) and the method used for cycling, i.e., changing over from inspiration to expiration (pressure/volume/flow/time cycled).

ERRNVPHGLFRVRUJ

158


Volume Preset Modes


Controlled Mechanical Ventilation (CMV) 60 40 20 0 −20

Time (sec)

Fig. 3: Controlled mechanical ventilation. Set tidal volume is given at a regular rate.

Flow (L/min)

Pressure (cm H2O)

Volume (mL) Time (sec) Fig. 4: Controlled mechanical ventilation (CMV). Relationship of air flow and lung volume with pressure changes. CMV is time triggered, flow limited, volume cycled.

The patient is given a set tidal volume at a set rate (the PIP generated may be variable) and he or she is not allowed to breath between ventilator breaths. The advantage of CMV is the ability to precisely manipulate ventilation and the partial pressure of carbon dioxide (PaCO2). It is used only when the patient is deeply sedated and paralyzed, as during surgery or at the time of initiation of ventilation.

ERRNVPHGLFRVRUJ

Ventilation

159

Intermittent Mandatory Ventilation (IMV)


The patient is given a set tidal volume at a set rate but can also initiate his own spontaneous breaths. The ventilator breaths are not synchronized with the patient’s breaths, and the ventilator may deliver a breath even when the patient is exhaling. Since the patient does not interact with the ventilator, there is an increased incidence of barotrauma and a greater need for sedatives. Other complications include low cardiac output and increased work of breathing. In order to make the mode more patient friendly and decrease the complication rate, synchronized IMV was introduced. The mechanical cycles, which were time controlled in IMV, are triggered by the patient’s inspiratory effort in SIMV, thus allowing for synchronization of the ventilated and patient breaths.

40 20 0 −20

Time (sec)

Fig. 5: Intermittent mandatory ventilation. Mandatory breaths are delivered at a set rate with no co-ordination with the patient’s breathing.


Synchronized Intermittent Mandatory Ventilation (SIMV)

40 20 0 −20

Time (sec)

Fig. 6: Synchronized intermittent mandatory ventilation. A set number of patient breaths are supplemented by the ventilator.

ERRNVPHGLFRVRUJ

160


Flow (L/min)

Pressure (cm H2O)

Volume (mL) Time (sec) Fig. 7: Volume preset, SIMV. Relationship of flow, pressure, and volume. The first breath is ventilator initiated, the second, third, and fifth breaths are patient breaths, and the fourth is a patient initiated ventilated breath (note the negative deflection in the pressure trace of the patient initiated ventilated breath).

The patient is given a set tidal volume at a set rate (the PIP generated may be variable) but the ventilator waits for the patient’s spontaneous breaths, which it uses as a trigger to deliver the machine set tidal volume. If the patient breathes at a rate faster than the machine set rate, only the set number of breaths every minute will be supplemented. If the patient breathes at a slower rate, all patient breaths are supplemented, and in addition, the patient receives machine breaths, so that the set number of breaths are delivered. The ventilator delivers a breath at the end of a time cycle, if there was no spontaneous breath during this period. The time cycle depends on the set rate. In SIMV mode, since all spontaneous breaths do not trigger a machine breath, the risk of respiratory alkalosis and hyperinflation is less than in other modes and changes in the patient’s spontaneous respiratory rate do not cause a large alteration in minute ventilation. The disadvantages of SIMV remain an increase in the work of breathing and a possible reduction in cardiac output. Spontaneous breathing during SIMV requires a ventilator valve to be opened and breathing through a high resistance ventilator circuit, which increases the work of breathing and respiratory muscle fatigue. Pressure support may be added to overcome this increase in respiratory work of spontaneous breaths. SIMV is the most commonly used mode of ventilation and is also utilized as a weaning mode. The mechanical breaths are gradually reduced in frequency until weaning is complete and the patient can be extubated.

ERRNVPHGLFRVRUJ

Ventilation

161


Assist Control (AC) 60 40 20 0 –10

Time (sec)

Fig. 8: Assist control mode. Every patient breath initiates a mechanical breath (note the negative deflection of the patient initiated ventilated breaths). Also in case, the patient fails to breathe in the set time period, a mechanical breath is given (breath 1 and 4).

Flow (L/min)

Pressure (cm H2O) Preset volume Volume (mL) Time (sec) Fig. 9: Assist control ventilation. Note the preset volume delivered to each breath.

Unlike SIMV, in this mode, the set tidal volume is delivered to all patient breaths even if the patient is breathing faster than the machine set rate. If the ventilator senses a patient respiratory effort, it will deliver the machine set tidal volume. But if the patient is breathing at a rate less than the set ventilator rate, the ventilator will deliver additional breaths so that the set number of breaths/min are given (as in SIMV). Thus, if the patient is breathing at a fast rate, the minute ventilation is likely to be large, since all breaths are being supplemented. A doubling of the patient respiratory rate will double the minute ventilation. This could cause hyperventilation and also generate high intrathoracic pressures, a decrease in venous return and hypotension. AC is used in patients with very weak respiratory effort. This mode is also selected in crises situations, e.g., cardiac arrest or early phases of resuscitation and in patients with high minute ventilation requirements (sepsis/ARDS).

ERRNVPHGLFRVRUJ

162


Pressure Preset Modes Pressure Controlled Ventilation (PCV)

Flow (L/min) Pressure limit Pressure (cm H2O)

Volume (mL)

Time (sec)

Fig. 10: Pressure controlled ventilation (PCV). Figure depicts time triggered, pressure limited, time cycled PCV.

Flow (L/min)

Pressure (cm H2O)

Volume (mL) Time (sec) Fig. 11: Pressure preset, SIMV. Relationship of flow, pressure, and volume. The first breath is ventilator initiated, the second, third, and fifth breaths are patient breaths, and the fourth is a patient initiated ventilated breath.

PCV is similar to CMV, a set number of breaths/min are delivered at a fixed interval but the difference is that the PIP setting controls the TV delivered to the patient and the TV is not set directly. (Technically, the term for this mode should be pressure preset CMV.) PCV may be “pressure limited and time cycled” or “pressure cycled”. Pressure limited, time cycled implies that once the pressure reaches the set

ERRNVPHGLFRVRUJ

Ventilation

163

value, it is maintained at this value for the specified inspiratory time, at the end of which the inspiration cycles to expiration. In pressure cycled ventilation, inspiration cycles to expiration, once PIP is reached. Limiting the rise of pressure decreases the risk of barotrauma. PCV is used in neonates, or in patients with high airway pressures (such as ARDS) to avoid barotrauma.

Pressure Preset SIMV Pressure preset SIMV is similar to volume preset SIMV except that the setting of PIP controls the TV delivered to the patient rather than the TV setting itself. If the patient’s respiratory rate is higher than the ventilator set rate, only the set number of patient breaths are supported. On the other hand if the patients respiratory rate is less than the ventilator set rate, additional breaths are delivered to achieve the set rate.

Pressure Assist Control Pressure assist control mode is the counterpart of the volume assist control mode. Irrespective of the patient respiratory rate, all patient breaths are supported. If the ventilator senses a patient respiratory effort, it will deliver the machine set breath. In case, the patient’s respiratory rate is less than the set ventilator rate, additional ventilator breaths will be given to achieve the set rate.

Pressure Support Ventilation (PSV)

Flow (L/min)

Pressure support level Pressure (cm H2O)

Volume (mL) Time (sec) Fig. 12: Pressure support ventilation. Spontaneously breathing patient; supplemental flow maintains set inspiratory pressure.

ERRNVPHGLFRVRUJ

164


The ventilator supports all spontaneous patient breaths with supplemental flow to achieve a set inspiratory pressure. Increasing the pressure support increases the tidal volume of the patient’s spontaneous breaths. This may be useful in patients who have an adequate spontaneous rate but a low TV. PSV may be used alone in intubated, spontaneously breathing patients with an adequate respiratory rate and used together with other volumepreset modes (e.g., SIMV + PS) to provide pressure support to the spontaneous breaths. A level of 5–20 cm is recommended depending upon the need of the patient.

Positive End-Expiratory Pressure (PEEP) PEEP is not a stand-alone mode but is applied in combination with other modes. During intermittent positive pressure ventilation, the airway pressure falls to 0 cm H2O (actually atmospheric pressure) at the end of expiration. With the application of PEEP, the baseline end expiratory pressure is not allowed to fall to zero and at the end of expiration, the patient exhales against this pressure. Application of PEEP prevents alveolar collapse at the end of expiration, thus increasing the functional residual capacity. Since more alveoli remain open, the V/Q mismatch and intrapulmonary shunting are decreased and oxygenation is improved. However, PEEP results in an increase of both PIP and mean airway pressure, and high values of PEEP may decrease venous return and cardiac output. In addition, a PEEP of >10 cm H2O is associated with a higher incidence of barotrauma, increased intracranial pressure, and decreased urine output.

CPAP It is the equivalent of the application of constant PEEP during all phases of respiration and is applicable only to patients with spontaneous respiration. It can be administered either through a tight fitting mask, nasopharyngeal catheter, nasal prongs, or through an endotracheal tube. CPAP is utilized either as a part of weaning protocols or as a modality to improve oxygenation in a conscious patient with hypoxemia or respiratory acidosis. It can be used in conjunction with bronchodilators and steroids in patients with bronchospasm to avoid intubation. CPAP may be started at 5 cm water and increased in increments of 2–3 cm up to 10–12 cm.

ERRNVPHGLFRVRUJ

165

Ventilation

With improvement in the blood gases, CPAP is gradually reduced in steps of 2–3 cm. A PaO2 of <50 mmHg, despite a FiO2 100% and a CPAP of 10–12 cm is an indication for assisted ventilation.

Flow (L/min)

CPAP

Pressure (cm H2O)

Volume (mL) Time (sec) Fig. 13: Spontaneously breathing patient. Application of CPAP. Relationship of flow, pressure, and volume.

BIPAP

Flow (L/min) Pressure support level CPAP

Pressure (cm H2O)

Volume (mL) Time (sec) Fig. 14: Spontaneously breathing patient; application of CPAP + pressure support. All patient breaths receive supplemental flow to achieve a set inspiratory pressure.

BIPAP is a noninvasive mode and is a combination of CPAP along with PS (5–20 cm H2O). It is used in spontaneously breathing adult patients in respiratory failure to improve oxygenation and avoid intubation.

ERRNVPHGLFRVRUJ

166


Dual/Combination Modes SIMV + PS

Flow (L/min) Pressure support level Pressure (cm H2O)

Volume (mL) Time (sec) Fig. 15: Volume preset SIMV + PS. Breaths one, three, and four are patient initiated ventilated breaths; breath two is a pressure supported patient breath.

Flow (L/min) Pressure support level

Pressure (cm H2O)

Volume (mL) Time (sec) Fig. 16: Pressure preset SIMV + PS. Breaths one, three, and four are patient initiated ventilated breaths; breath two is a pressure supported patient breath.

In SIMV mode, if the patient breathes at a rate faster than the set rate, only the machine set number of breaths are supplemented with additional TV. In SIMV + PS, the extra breaths, which did not receive supplementation with additional TV, are provided pressure support. SIMV + PS thus allows machine synchronization with the patients breathing and at the same time reduces the work of breathing.

ERRNVPHGLFRVRUJ

Ventilation

167

Pressure Regulated Volume Control (PRVC) It is a volume assist control mode, with an additional parameter setting for limiting maximum pressure. PRVC has a decelerating flow pattern, and the flow rates are adjusted by the ventilator to deliver the set tidal volume, below the set maximum pressure. PRVC is particularly suitable in patients with high airway pressures and is more friendly in awake patients.

Ventilator Settings Initially when the child is paralyzed or deeply sedated and has no respiratory effort, ventilation is started with 100% oxygen in the control mode (controlled mechanical ventilation). Once the child begins to breathe spontaneously, a suitable mode is selected (e.g., SIMV, SIMV with PS, etc). The initial settings primarily depend on the diagnosis and age of the patient. Positive pressure mechanical ventilation is produced through an interaction of five primary variables—respiratory rate (RR), tidal volume, peak inspiratory pressure, inspiratory–expiratory ratio (I:E ratio), and inspiratory flow rate—which are set differently in various modes and ventilators. Additional manually set or machine preset variables further define the type of ventilated breath that the patient receives.

Ventilator Settings in Volume Preset Modes Initial Ventilator Settings in SIMV Mode Neonate

Child

Adult

FiO2

1.0

1.0

1.0

TV

10–12 mL/kg

10–12 mL/kg

8–10 mL/kg

RR

20–30

15–25

10–14

IT

0.5–1.0 sec

0.5–1.0 sec

1.0–1.5 sec

PEEP

3–5 cm H2O

5 cm H2O

5 cm H2O

RR: respiratory rate, IT: inspiratory time.

The different parameters, which are required to be set directly or monitored, in different ventilators are somewhat variable.

Tidal Volume In volume preset ventilation, the ventilator delivers a set TV regardless of PIP generated. In children, a TV of 10–12 mL/kg is adjusted to achieve

ERRNVPHGLFRVRUJ

168


visible chest excursion and audible air entry. The lowest TV, which allows a SpO2 of >90% and PaO2 >60 mmHg, is set since lower tidal volumes avoid barotrauma. The goal is to adjust the TV so that plateau pressures are less than 30 cm H2O. Some ventilators may require the minute volume to be set instead of the TV.

Respiratory Rate Total respiratory rate is the sum of the patient’s respiratory rate and ventilator rate. Ideally, this combined rate should be 20–25 per minute for children under 2 years and 15–20 per minute for older children. PaCO2 has an inverse relationship with the minute ventilation (MV = TV × RR). In hypercarbia, since increasing the TV will result in a higher airway pressure, the minute ventilation can be increased by increasing the RR.

I:E Ratio The I:E ratio is usually kept in the range of 1:2–1:4. Incomplete exhalation because of a short expiratory time will result in auto PEEP. When the end expiratory pressure does not return to 0 cm H2O or the PEEP level, it is an indication of auto PEEP. Depending on the ventilator in use, the I:E ratio may be preset or determined by the ventilator from a combination of other controls: 1. Flow rate: Increasing the flow rate, shortens the inspiratory time (IT) and prolongs the expiratory time (ET). 2. Inspiratory time: Optimal inspiratory time is between 0.5–1.5 sec. 3. Respiratory rate: An increase in the respiratory rate has minimal effect on the inspiratory time but results in a decrease in the expiratory time. 4. Minute volume/tidal volume: An increase in the TV results in an increase in the inspiratory time and a decrease in the expiratory time.

Flow Rate The inspiratory flow rate is equal to the TV divided by the inspiratory time and may be controlled internally by the ventilator via the settings of TV, I:E ratio, and the respiratory rate. As an approximation, 3–4 times the minute ventilation is the flow rate required to be set on the ventilator to achieve the parameters of TV, I:E ratio, and respiratory rate (60–80 L/min in the adult). At lower flows, a longer inspiratory time is required for the TV to be delivered, which may result in inadequate expiratory time and auto PEEP. With higher flows, the tidal volume is delivered in shorter inspiratory time and expiratory time is longer.

ERRNVPHGLFRVRUJ

Ventilation

169

The set inspiratory flow rate also determines the level of peak inspiratory pressure, and higher flow rates result in higher PIP.

FiO2 FiO2 is initially kept at 0.9–1. It is gradually reduced to 0.5 provided a SaO2 of >90% can be maintained. FiO2 >60% for over 24 hours has been associated with oxygen toxicity.

PEEP PEEP increases functional residual capacity and decreases intrapulmonary shunting. It is initially set at 3–5 cm water and any subsequent increase is based on the patient’s PaO2 and FiO2 requirement. The need for a high FiO2 to maintain an adequate PO2 requires an increment in the level of PEEP. High levels of PEEP (>10–20 cm H2O) may, however, cause barotrauma and hypotension by a decrease in the cardiac preload.

Sensitivity This setting is provided on some ventilators for triggering a ventilator breath by a pressure change or flow alteration caused by the patient’s respiratory effort. It is usually adjusted by trial and error to the degree of the patient’s effort (in pressure triggered ventilators, −0.5 to −2.5 cm H2O). If the sensitivity is too high, the patient’s work of breathing is increased but too low a setting will allow the ventilator to initiate breaths spontaneously.

Sigh

Pressure (cm H2O)

Inspiratory pause

A sigh is a ventilator breath with a larger volume than the tidal volume. The hyperinflation caused was used to prevent atelectasis but currently considered of doubtful value. The usual sigh volume is 1.5–2 times the TV at a rate of 4–8 times/h.

PIP Plateau pressure Time (sec)

Fig. 17: Controlled mechanical ventilation with inspiratory pause. Note PIP and plateau pressure.

ERRNVPHGLFRVRUJ

170


Pressure Limit and Inspiratory Pause The pressure limit setting does not allow the peak pressure to rise beyond the set limit. If the pressure limit is reached, inspiration will be terminated, and a TV less than the set volume is then delivered to the patient. In volume preset ventilation, an inspiratory pause (usually 0.5–1 sec) may also be set to allow measurement of plateau pressure. Plateau pressure is the pressure recorded at the end of inspiratory flow and at the beginning of expiratory flow during the phase when there is no air flow taking place. Monitoring of pressures (PIP and plateau pressure) is essential in volume preset ventilation. PIP is a reflection of the airway pressure, while plateau pressure is the pressure at the alveolar level. Without lung disease, PIP is only slightly above the plateau pressure. The PIP and plateau pressures rise proportionately with an increase in TV or a decrease in pulmonary compliance. The peak pressure increases with no significant change in plateau pressure when the inspiratory gas flow rates or airway resistance is raised (e.g., obstruction to the ventilator tubing, airway secretions, bronchospasm, etc.). In children and adults, PIP should ideally be maintained under 25–30 cm H2O. Patients with lung disease may require a PIP of more than 30 cm for adequate TV to be delivered. PIP of more than 40 cm H2O and a plateau pressure of more than 30 cm H2O increase the risk of barotrauma and an alternative mode of ventilation should be considered.

Flow Waveforms

Flow (L/min)

Ventilators may allow four different types of flow waveforms to be set.

Square

Decelerating

Accelerating

Sine

Fig. 18: Flow waveforms.

■

Square waveform: The square flow waveform delivers a set flow rate (peak flow rate) through the entire inspiratory phase.

■

Decelerating waveform: The peak flow is delivered at the start of inspiration and decreases gradually until a percentage of the peak inspiratory flow rate is reached.

ERRNVPHGLFRVRUJ

Ventilation

171

■

Accelerating waveform: A fraction of the peak inspiratory flow is initially delivered and gradually increases until the peak flow is reached.

■

Sine/sinusoidal waveform: The waveform resembles a sinusoidal curve similar to the normal breathing pattern.

Ventilator Settings in Pressure Control Ventilation In PCV, instead of the tidal volume the PIP is set and the ventilator delivers gas at the set pressure for the duration of inspiration. The resulting tidal volume is variable, and the patient receives smaller tidal volumes when the compliance is low or the airway resistance is high. In children, the PIP may initially be set at 16–20 cm H2O (above PEEP) and adjusted to provide desirable TV. One guideline is starting with twothirds the PIP that was generated during the original CMV. In addition to the PIP, the RR, and IT or I:E ratio requires to be set. In PCV, the flow rate is determined by the patient’s airway resistance, compliance, inspiratory effort, and PIP. On some machines, the time taken for the PIP to be reached can be adjusted by altering the initial flow rate or rise time. On other ventilators, it is possible to manipulate the maximum flow rate allowing greater flow rates to be set when needed, e.g., during suctioning.

Alarm Settings 1. Volume alarm: Low volume alarm is set about 100 mL less than the expired TV. It detects circuit leaks or disconnection. 2. Pressure alarms: Low inspiratory pressure alarm is set 10–15 cm H2O below the PIP. This alarm also detects circuit leaks or disconnection. The high inspiratory pressure alarm is set 10–15 cm above the observed PIP. Causes of high PIP include airway obstruction, pneumothorax, and poor lung compliance. 3. Apnea alarm: This can be set at a delay of 10–20 sec or less depending on the respiratory rate. 4. Respiratory rate alarm: This may be set at 10–12 breaths above the observed respiratory rate. An increased rate may be indication of respiratory distress. 5. FiO2 alarm is set at 5–10% more and less than the set FiO2.

ERRNVPHGLFRVRUJ

172


Monitoring Oxygenation Cause of fall in O2 saturation

Treatment

Right-to-left intracardiac shunt

Improve oxygen delivery and pulmonary blood flow: ↑ Hemoglobin ↑ Cardiac output ↓ PVR ↑ RV function

Alveolar hypoventilation/ intrapulmonary shunt

↑ FiO2 ↑ PEEP ↑ VT or ↑ PIP ↑ Inspiratory time ↑ Rate

If no improvement

Change to pressure control ventilation. Consider high frequency jet ventilation (HFJV), ECMO

Inadequate oxygenation (SaO2 < 85% or inability to decrease FiO2 to <60%) may be either because of alveolar hypoventilation or an R-L intracardiac shunt. In alveolar hypoventilation, oxygenation may be improved by increasing the level of PEEP, the TV or PIP depending on the mode of ventilation in use. Changes in TV or PIP affect both PaO2 and PaCO2. An increase will improve oxygenation and decrease PaCO2. However, a high TV or PIP is associated with an increased risk of barotrauma. Improvement in PaO2 may also be achieved by increasing the inspiratory time. The I:E ratio is altered to 1:1 or even 2:1. Changes in the I:E ratio do not affect the TV but may result in auto PEEP because of a short expiratory time. Higher frequency, with smaller TV (6–8 mL/kg) may be tried if other methods are ineffective.

Hypercarbia Cause

Treatment

Bronchospasm

↓ Inspiratory time ↑ Expiratory time ↓ RR ↑ VT Bronchodilator therapy sedation/paralysis

Inadequate alveolar ventilation

↑ RR Increase sedation, add paralysis (to decrease CO2 production) ↑ VT until PIP 35–40 cm ↑ Expiratory time

ERRNVPHGLFRVRUJ

If no improvement

Change to PCV Consider HFJV

Ventilation

173

Hypercarbia (PaCO2 >45–50 mmHg) is caused by inadequate ventilation or sometimes bronchospasm. Hypercarbia causes the inadequately sedated patient to hyperventilate. In addition there may be tachycardia, hypertension, and sweating. The PCO2 is corrected by increasing the minute ventilation either by increasing the tidal volume or the respiratory rate.

Peak Airway Pressure As noted above, the PIP generated depends upon the preset TV and is more with high flow rates, high airway resistance caused by obstruction to the ventilator tubing or airway, and with pulmonary pathology affecting pulmonary compliance (pulmonary edema, pneumothorax, pulmonary collapse, etc.). If the PIP is persistently high in spite of adequate sedation, analgesia, and bronchodilators, it may be necessary to change to pressure control ventilation.

Asynchrony The patient is unable to breathe in synchrony with the ventilator, the airway resistance rises and inadequate TV is delivered, the PO2 falls and the PCO2 rises. The causes include: 1. Discomfort because of pain, coughing, full bladder, etc. 2. Decreased pulmonary compliance—pneumothorax, pulmonary edema, collapse, etc. 3. Increased airway resistance—bronchospasm, secretions, etc. 4. Hypoxia/hypotension itself may be the cause. Once the above causes have been ruled out, manual ventilation with 100% O2 is started for a while before putting the patient back on ventilator. Adequate chest expansion and bilateral air entry are confirmed. If required the mode of ventilation is changed to a better tolerated mode, e.g., SIMV, PSV. If all these measures fail, the patient is sedated and paralyzed.

Weaning Weaning from SIMV Parameter

Initial setting

Extubate when

FIO2

<0.60

<0.50 <5 cm H2O

PEEP SIMV rate

≤20 breaths per min

ERRNVPHGLFRVRUJ

<5–10 breaths per min

174


Parameter

Initial setting

Extubate when

Pressure support

10–15 cm H2O

5–10 cm H2O <25 cm H2O

PIP Tidal volume

15 mL/kg

4–6 mL/kg

SIMV Weaning The SIMV rate and TV is gradually decreased as the patient takes over more of the respiratory work. The patient is extubated when hemodynamically stable and is able to maintain normal blood gas values at an SIMV rate of <5–10 breaths/min with minimal TV.

Pressure Support Weaning The level of pressure support is gradually reduced to minimal levels (5–10 cm H2O above PEEP). The patient can then be extubated or CPAP instituted till he can maintain acceptable blood gas values (PaCO2 <45 and SaO2 >92%). If at any stage, there are signs of respiratory distress (increasing respiratory rate, use of accessory muscles of respiration, etc.) or deterioration of blood gases or evidence of hemodynamic compromise (in particular tachycardia and hypertension), then weaning is stopped and ventilation is returned to a higher level of support.

Bibliography 1. Abdallah A. Mechanical ventilation. [Cited: 2011 Jul 11] Available at: www.alexaic.com/alexaicfiles/presentation2010/day3/035002.pdf. 2. Amitai A, Kulkarni R. Ventilator management: introduction to ventilator management. [Updated: 2009 May 17; cited: 2011 Jul 11] Available at: http://emedicine.medscape.com/ article/810126-overview#aw2aab6b2. 3. Batiha A. Mechanical ventilation: critical care nursing theory. [Updated: 2004 Mar; cited: 2011 Jul 11] Available at: http://www.philadelphia.edu.jo/academics/abatiha/uploads/Mechanical% 20ventilation.doc. 4. Butcher R, Boyle M. Mechanical ventilation learning package. [Cited: 2011 Jul 11] Available at: http://update.anesthesiologists.org/wp-content/uploads/2009/09/Mechanical-Ventilation-inthe-ICU.pdf 5. Cantwell S, Hopkins F, Totaro R. Intensive care service: nursing policy and procedures. Royal Prince Alfred Hospital Intensive Care Service. [Updated: 2004 Mar; cited: 2011 Jul 11] Available at: http://intensivecare.hsnet.nsw.gov.au/five/doc/ventilation_modes_V_rpa.pdf. 6. Chang DW, Hiers JH. Operating modes of mechanical ventilation. In: Chang DW, ed. Clinical Application of Mechanical Ventilation New Delhi: Delmar Learning; 2006:80–122.

ERRNVPHGLFRVRUJ

Ventilation

175

7. Evans N. How to determine the initial settings for mechanical ventilation. [Updated: 2010 Jan 30; cited: 2011 Feb 22] Available at: http://www.helium.com/items/1726975-initialsettings-mechanical-ventilator-icu-patient. 8. Kuschel C. Basic principles of ventilation. Auckland district health board: Neborn services clinical guideline. [Updated: 2003 Dec; cited: 2011 Feb 22] Available at: http://www.adhb.govt.nz/ newborn/TeachingResources/ventilation/VentilationBasics.htm#BasicPrinciples. 9. Lumb AB. Elastic forces and lung volumes. Nunn’s Applied Respiratory Physiology 6th ed. Philadelphia: Elsevier; 2005:28–9. 10. Mariani GL, Carlo WA. Ventilatory management in neonates. Science or art? Clin Perinatol 1998;25:33–48. 11. Schmidt GA, Hall JB. Management of the ventilated patient. In: Hall JB, Schmidt GA, Wood LDH, eds. Principles of Critical Care 3rd ed. New Delhi: McGraw-Hill; 2005:481–98. 12. Stoelting RK, Hillier SC. The lung. Pharmacology & Physiology in Anaesthetic Practice 4th ed. Philadelphia: Lippincott Williams & Wilkins; 2006:771–2.

ERRNVPHGLFRVRUJ

Ventilator Associated Pneumonia “Every operation in surgery is an experiment in bacteriology” —Sir Berkeley Moynihan (1865–1936)*

Definition Ventilator associated pneumonia (VAP) is defined as pneumonia occurring more than 48 hours after a patient has been placed on ventilator. It has been further classified as early-onset VAP when it occurs between 2–4 days of ventilation and late-onset VAP, occurring more than 4 days after ventilation.

Pathogenesis Pneumonia can result from inhalation of small amounts of infected oropharyngeal contents, either by endotracheal aspiration or by passage around the endotracheal tube. Bacterial translocation from the GIT by reflux or hematogenous spread from various sites in the body may also be a possible means of bacterial spread to the lungs. Increased incidence of VAP has been correlated with a number of factors, which include duration of mechanical ventilation, re-intubation, frequency of endotracheal suctioning, depth of sedation, use of H2-receptor antagonists, and various interventions like placement of multiple central venous catheters, bronchoscopy, and thoracocentesis. Late-onset VAP is considered to be hospital acquired and in all probability caused by nosocomial strains of organisms including Pseudomonas aeruginosa, Staphylococcus aureus, and Acinetobacter baumannii. Early onset VAP is more likely to be the result of infection with community-acquired pathogens—Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and gram-negative enteric bacilli.

*Sir Berkeley Moynihan was a noted British surgeon. He was a recipient of numerous awards, and his book Abdominal Operations earned him international reputation.

ERRNVPHGLFRVRUJ


177

Diagnosis of VAP in Children Definitive diagnosis of VAP in children requires clinical, radiological, and microbiological evidence. The clinical features of VAP, other than respiratory signs, will be those of generalized sepsis. Radiological criteria include development of pulmonary infiltration, consolidation, or cavitation. X-ray features are however not specific for VAP and may well be difficult to differentiate from atelectasis, ARDS, or congestive cardiac failure. Microbiological evidence of pathogenic bacteria can help establish the diagnosis, and culture can guide antibiotic therapy. A number of different methods are available to obtain specimens from the lower respiratory tract. ■ Bronchoscopic bronchoalveolar lavage (BAL) can obtain specimens from the infected area with the least chance of contamination but may cause hypoxia. A small volume of saline (quantity of saline injection is not standardized—in children <20 kg, 1 mL/kg; >20 kg, 20 mL; repeated × 3 times is one recommendation) is injected and aspirated for culture. Quantitative bacterial cultures (>104 or 105 cfu/mL) are used to distinguish colonization from infection. Sensitivity of obtaining quantitative BAL fluid cultures ranges from about 40% to 90% and specificity varies from 45% to 100%. These techniques, however, require large endotracheal tubes and may not be routinely feasible in children. ■ Non-bronchoscopic bronchoalveolar lavage (NBL): In NBL, a suction catheter is inserted into the endotracheal tube and advanced until resistance is encountered. Warm sterile saline in a volume similar to BAL (<20 kg, 1 mL/kg; >20 kg, 20 mL; repeated × 3 times) is then injected and aspirated. Sensitivity and specificity are nearly the same as BAL. ■ Tracheal aspiration (TA) involves obtaining secretions by suctioning of the endotracheal tube and using these for Gram stain examination and culture. Even though the technique is sensitive, specimens obtained by TA have low specificity because of likelihood of contamination from upper respiratory tract and oropharyngeal flora. Initial antibiotic therapy can be guided by Gram stain of specimens obtained by either of the above procedures. Evidence of infection includes presence of polymorphonuclear and other inflammatory cells, and intracellular organisms. Center for Disease Control and Prevention (USA) has suggested clinical criteria for the diagnosis of VAP for various age groups of patients as reference standards to enable incidence and results of intervention and therapy to be compared between institutions. Clinical criteria for VAP in infants <12 months of age: Worsening gas exchange (e.g., SpO2 <94%, increased FiO2 requirement) with at least three of the following: ■ ■

Temperature instability with no other recognized cause White blood cell count <4000/mm3 or >15000/mm3 and band forms >10%

ERRNVPHGLFRVRUJ

178 ■ ■ ■ ■ ■


New-onset or change in character of sputum or increased respiratory secretions Apnea, tachypnea, increased work of breathing, grunting Wheezing, rales, or rhonchi Cough Heart rate <100 beats/min or >170 beats/min

Clinical criteria for VAP in children between 1 and 12 years of age: At least three of the following: ■ ■ ■ ■ ■ ■

Temperature >38.4°C or <37°C with no other recognized cause White blood cell count <4000/mm3 or >15000/mm3 New-onset or change in character of sputum or increased respiratory secretions New-onset or worsening of cough, dyspnea, or tachypnea Rales or bronchial breath sounds Worsening gas exchange (e.g., SpO2 <94%, increased FiO2 requirement)

In addition to the clinical criteria, the following radiological criteria must be met for any age group: Two or more serial chest X-rays showing at least one of the following: new or progressive infiltrates, consolidation, or cavitation. In patients without underlying pulmonary or cardiac disease (e.g., respiratory distress syndrome, bronchopulmonary dysplasia, pulmonary edema, or chronic obstructive pulmonary disease), one definitive chest radiograph is acceptable.

Care of the Ventilated Patient Various clinical guidelines (including the recommendations in the Pediatric Supplement of ‘Institute for Healthcare Improvement’s’ VAP bundle: 2008) for the optimum care of a ventilated patient are as follows: Hand hygiene: Frequent and meticulous hand washing by all care givers is perhaps the most significant factor in reducing the incidence of VAP. Elevation of the head end: Patients should be nursed in the head up position at an angle of 30–45 degree to prevent aspiration of secretions. In neonates, the incubator or radiant warmer is positioned in the reverse Trendelenburg position (legs raised) by 15–30 degrees. Incidence of VAP in neonates has also been reported to be less in the neonates nursed in lateral position than in the supine position. Endotracheal tube: Use of a sterile endotracheal tube is recommended for each intubation attempt. Adequate cuff pressure (20–30 cm H2O) must be maintained in cuffed endotracheal tubes to prevent passage of secretions alongside the tube. Endotracheal suction to aspirate secretions is done utilizing minimal negative pressure (60–80 mmHg in neonates and

ERRNVPHGLFRVRUJ


179

<120 mmHg in older children). It is preferable to use an in-line, closed ET tube suction system. Open suction catheters, if used, are disposed after single use. Oropharyngeal suction: Regular intermittent or continuous suction must be used to aspirate collected oropharyngeal secretions. The mouth should be suctioned before the nose, using an uncontaminated suction catheter. Multiuse oral and nasal suction catheters are stored in a clean non-sealed plastic bag when not in use. Oral hygiene: Oral care of the patient reduces the colonization of oral cavity with pathogenic bacteria. At least twice a day brushing of teeth and alcohol-free oral rinses (e.g., chlorhexidine in children >2 months of age) are advisable. Two hourly frequency of oral care for children at higher risk for VAP is recommended (IHI’s VAP prevention pediatric supplement). Level of sedation: The child should be permitted to breathe spontaneously rather than receive heavy sedation or paralysis. Increased sedatives and paralytic agents depress the cough reflex, prolong weaning, and predispose to aspiration of oropharyngeal secretions. Daily “sedation vacation”, which has been recommended for adults, is not recommended in children due to high risk of unplanned extubation, however, daily assessment of readiness to extubate is included. Care of ventilator: The ventilator circuit should be cleared of the condensed water on a regular basis every 2–4 hours, and every time the patient is repositioned to prevent the condensed water from passing into the patient’s airway. The circuit is changed only when it is visibly soiled or mechanically malfunctioning. Peptic ulcer prophylaxis: Peptic ulcer disease prophylaxis is recommended for all ventilated patients as appropriate for the age and condition of the child. Children at high risk for stress ulceration (ventilation >48 h, coagulopathy, unstable hemodynamics, sepsis, steroids, and following a rethoracotomy) should receive H2 blockers or proton pump inhibitors rather than sucralfate, as these drugs are more effective in decreasing the gastric pH. Feeding: Early enteral feeding preserves the integrity of the gut mucosa, promotes establishment of gut motility, and reduces bacterial translocation. Gastric residues and abdominal distension are monitored before every feed and 4 hourly to prevent aspiration. Educational interventions: Effective implementation of VAP preventive measures in a clinical setting is possible only by adequate education of healthcare staff.

ERRNVPHGLFRVRUJ

180


Treatment Hospital-Acquired and Ventilator Associated Pneumonia (HAP and VAP) 1. In HAP and VAP, a combination of drugs of different classes is initially indicated to provide coverage against Pseudomonas and multidrug-resistant gram −ve infections. A β-lactam (piperacillin/ tazobactam, ceftazidime, cefuroxime, or a carbapenem) with an aminoglycoside or fluoroquinolone is recommended. 2. In addition, a glycopeptide (vancomycin or tiecoplanin) or linezolid is added if the risk of MRSA is high. 3. Once the causative organism is isolated, antibiotic therapy is appropriately tailored. Combination therapy or single drug therapy to which the organism is sensitive is equally effective, and the decision is based on the clinical status of the patient.

Duration of Treatment In general, antibiotics are continued for a minimum of 7–14 days or for 3 days after resolution of clinical signs and findings of laboratory tests. If there is inadequate response after 48–72 hours of therapy, patients should be re-assessed for nosocomial organisms.

Bibliography 1. Akça O, Koltka K, Uzel S, et al. Risk factors for early-onset, ventilator-associated pneumonia in critical care patients: selected multiresistant versus nonresistant bacteria. Anesthesiology 2000;93:638–45. 2. Babcock HM, Zack JE, Garrison T, et al. An educational intervention to reduce ventilatorassociated pneumonia in an integrated health system: a comparison of effects. Chest 2004; 125:2224–31. 3. Centers for Disease Control and Prevention. Guidelines for preventing health-care-associated pneumonia, 2003: recommendations of CDC and the Healthcare Infection Control Practices Advisory Committee. MMWR 2004;53 (No. RR-3). [Updated: June 2011; cited: 2012 Jan 17] Available at: www.cdc.gov/nhsn/PDFs/pscManual/6pscVAPcurrent.pdf. 4. Foglia E, Meier MD, Elward A. Ventilator-associated pneumonia in neonatal and pediatric intensive care unit patients. Clin Microbiol Rev 2007;20:409–25. 5. Gillespie R. Prevention and management of ventilator-associated pneumonia – the Care Bundle approach. SAJCC 2009;25:44–51. 6. How-to Guide: Prevent ventilator-associated pneumonia (Pediatric Supplement). [Accessed: Jul 2012] Available at: http://www.ihi.org/knowledge/Pages/Tools/HowtoGuidePreventVAP PediatricSupplement.aspx

ERRNVPHGLFRVRUJ


181

7. Institute for Healthcare Improvement. Getting started kit: prevent ventilator-associated pneumonia. How-to guide. 2008. [Accessed: July 2012] Available at: http://www.premierinc.com/ safety/topics/bundling/downloads/03-vap-how-to-guide.pdf. 8. Morrow BM, Argent AC, Jeena PM, Green RJ. Guideline for the diagnosis, prevention and treatment of paediatric ventilator-associated pneumonia. S Afr Med J 2009;99:255–67. 9. Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: a statement for health professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Pediatrics 2004;114:1708–33. 10. Ratjen F, Bredendiek M, Brendel M, Meltzer J. Costabel JU. Differential cytology of bronchoalveolar lavage fluid in normal children. Eur Respir J 1994;7:1865–70. 11. Srinivasan R, Asselin J, Gildengorin G, Wiener-Kronish J, Flora HR. A prospective study of ventilator-associated pneumonia in children. Pediatrics 2009;123:1108–15. 12. Venkatachalam V, Hendley JO, Willson DF. The diagnostic dilemma of ventilator-associated pneumonia in critically ill children. Pediatr Crit Care Med 2011;12:286–96. 13. Wright ML, Romano MJ. Ventilator-associated pneumonia in children. Semin Pediatr Infect Dis 2006;17:58–64.

ERRNVPHGLFRVRUJ

Antibiotics “Even diseases have lost their prestige, there aren’t so many of them left. Think it over … no more syphilis, no more clap, no more typhoid … antibiotics have taken half the tragedy out of medicine” —Louis-Ferdinand Celine (1894–1961)*

Microbiology Gram-Positive Cocci Staphylococci are broadly divided into two groups based on the production of the enzyme coagulase. Clinically, the most significant coagulase-positive Staphylococcus is Staph. aureus, which is frequently part of the skin and nasal flora and causes a range of severe infections—skin, soft tissue, respiratory, bone, joint, endovascular, and wound infections. Coagulase-negative Staphylococcus are Staph. epidermidis and Staph. saprophyticus. Staph. epidermidis is a skin commensal in human beings. It becomes potentially pathogenic in the immune compromised individuals and is a cause of intravascular catheter related infections. Staph. saprophyticus causes urinary tract infection in women. All classes of staphylococci can produce an enzyme penicillinase (a type of β-lactamase), making them resistant to the antibiotics that have a susceptible β-lactam ring in their structure. The β-lactam ring has been modified in some synthetic antibiotics to make them effective against “penicillinase-producing Staph”. In other β-lactam antibiotics, the spectrum has been extended to include penicillinase-producing Staphylococcus by a combination with the β-lactamase inhibitors clavulanate, sulbactam, or tazobactam. (Note: the following antibiotics have a b-lactam ring in their structure and constitute the b-lactam group of antibiotics—penicillins, cephalosporins, carbapenems, and monobactams.) Currently, antibiotics that are specifically given for penicillinase-producing staphylococci infection include cloxacillin, piperacillin–tazobactam, first- and fourth-generation cephalosporins (e.g., cefazolin, cefpirome), glycopeptides (vancomycin and teicoplanin), linezolid, clindamycin, quinupristin–dalfopristin, daptomycin, and tigecycline (safety and effectiveness of daptomycin, and tigecycline has not been established in patients under 18 years of age). *Louis-Ferdinand Celine was a French physician and controversial author who became famous with his first novel Voyage au bout de la nuit (Journey to the End of the Night), 1932.

ERRNVPHGLFRVRUJ

Antibiotics

183

Methicillin-resistant Staph. aureus (MRSA): Staph. aureus can also acquire resistance against methicillin, and are designated methicillinresistant Staph. aureus (MRSA). MRSA are invariably also resistant to cloxacillin, cephalosporins (cephalexin, cefazolin), and the macrolide group (erythromycin, clarithromycin and azithromycin) of antibiotics. MRSA infections are susceptible to vancomycin and teicoplanin, but several strains of MRSA are now showing resistance even to vancomycin and teicoplanin (VRSA) and require linezolid, quinupristin–dalfopristin, daptomycin, or tigecycline for management. Streptococci are classified based on their hemolytic properties. α-hemolytic streptococci cause partial hemolysis with a green coloration on blood agar plates, β-hemolytic streptococci cause clear areas because of complete hemolysis, while other streptococci are labeled as gamma-hemolytic, when no hemolysis takes place. The two α-hemolytic streptococci are S. pneumoniae and S. viridans. S. pneumoniae causes bacterial pneumonia and occasionally otitis media, sinusitis, meningitis, and peritonitis. S. viridans is a group of streptococcal species found in the oral flora and can rarely cause endocarditis after release into the blood stream. β-hemolytic streptococci are further characterized by Lancefield serotyping, based on surface antigens. Clinically significant are group A and B. S. pyogenes is a Group A streptococci and causes streptococcal pharyngitis, acute rheumatic fever, scarlet fever, acute glomerulonephritis, and necrotizing fasciitis. Other organisms of group A do not cause human infections. S. agalactiae is a group B streptococci, which causes pneumonia and meningitis in neonates and the elderly, with occasional systemic bacteremia. Enterococci (E. faecalis, E. faecium) was previously part of streptococci (Group D) but now a separate genus, it causes urinary tract infection, intraabdominal infection, and septicemia.

Gram-Negative Bacilli The Enterobacteriaceae (Klebsiella, Proteus, E. coli, Enterobacter, Serratia, etc.) are a group of organisms that are primarily found in the colon and cause GIT infections, urinary tract infections, septicemia, and are associated with hospital-acquired pneumonias. H. influenzae is community acquired and is a causative agent for otitis media, conjunctivitis, meningitis, pneumonia, and sepsis. Pseudomonas is primarily an opportunistic organism causing nosocomial infection in the immunocompromised. In the treatment of Pseudomonas aeruginosa infections, a combination of two drugs from different chemical classes, β-lactam antibiotics (such as piperacillin, meropenem, ceftazidime, aztreonam) plus an aminoglycoside (such as amikacin) or fluoroquinolone is advocated to prevent emergence of resistance.

ERRNVPHGLFRVRUJ

184


Acinetobacters are environmental organisms that are present in the ICU premises on fomites and other equipment. The main species associated with human infection is Acinetobacter baumannii, which can cause wound infections, nosocomial pneumonia, and urinary infection in the immune suppressed patient and may be resistant to available antibiotics used to treat gram-negative infections. In general, for the treatment of severe gram-negative sepsis, because of the morbidity associated with endotoxin production, empirical coverage using two antibiotics of different classes effective against gram-negative organisms is initially recommended.

Anaerobic Pathogens The principal anaerobic gram-positive cocci that cause disease are peptococci and peptostreptococci and are part of the normal flora of the mouth, upper respiratory tract, and large intestine. The anaerobic gramnegative bacilli include Bacteroides fragilis, Prevotella, and Fusobacterium sp. The B. fragilis group is part of the normal bowel flora and is most frequently isolated from intra-abdominal infections, while the Prevotella and Fusobacterium sp. are part of the normal oral flora. The following drugs are effective against anaerobic organisms: metronidazole, carbapenems (imipenem, meropenem), combinations of β-lactam and β-lactamase-inhibiting agents (piperacillin–tazobactam, ampicillin– sulbactam, amoxicillin–clavulanate, ticarcillin–clavulanate), cephalosporins (e.g., cefotaxime), and clindamycin. GI or pelvic infections are likely to contain mixed infections, enterobacilli (e.g., E. coli) and anaerobes (e.g., B. fragilis), thus antibiotic regimens active against both must be used. All the above drugs (except clindamycin and metronidazole) have good activity against enterobacilli and can be used as monotherapy.

Antibacterial Spectrum of Various Antibiotics Natural penicillins Antibiotics

Penicillin G, benzathine penicillin, procaine penicillin

Gram +ve cocci Gram +ve bacilli

Staph. aureus, Strep. pneumoniae, Strep. pyogenes, Strep. viridans B. anthracis, C. diphtheriae, C. perfringens, Listeria monocytogenes, Treponema pallidum, Leptospira

Gram –ve cocci

Gram –ve cocci: N. gonorrhoeae, N. meningitidis

Comments

These penicillins have no effect on penicillinase-producing Staphylococcus, enterococci, and majority of gram –ve bacilli. B. fragilis is also resistant.

ERRNVPHGLFRVRUJ

Antibiotics

185

Penicillinase-resistant penicillins (anti-Staph. penicillins) Antibiotics

Methicillin (not used clinically), cloxacillin

Gram +ve cocci

Staph. aureus, Staph. epidermidis, Strep. pneumoniae

Gram –ve

–

Comments

Even though cloxacillin is active against penicillinase-producing staphylococci, some staphylococci are resistant (so called methicillinresistant Staph. aureus [MRSA] and methicillin-resistant Staph. epidermidis [MRSE]). These penicillins have no effect against gram –ve bacteria, enterococci, and B. fragilis. The penicillinase-resistant penicillins are used primarily for penicillinaseproducing staphylococci.

Aminopenicillins (extended-spectrum penicillins) Antibiotics

Ampicillin–sulbactam, amoxicillin–clavulanate

Gram +ve cocci

Gram +ve cocci: Strep. pneumoniae, Strep. pyogenes, Strep. viridans, enterococci Listeria monocytogenes

Gram +ve bacilli Gram –ve bacilli

Enterobacilli (E. coli, Proteus, Salmonella, and Shigella) Other (H. influenzae)

Comments

The aminopenicillins, ampicillin, and amoxicillin alone are effective against non–lactamase-producing enterobacilli, some gram +ve cocci, and Listeria. The aminopenicillins are not effective against Staph. aureus, Klebsiella, Serratia, Acinetobacter, Pseudomonas, and B. fragilis. The addition of β-lactamase inhibitors, ampicillin–sulbactam, and amoxicillin–clavulanate extends the spectrum to include methicillinsensitive staphylococci (but not MRSA) and some gram –ve organisms such as Serratia, Acinetobacter, and B. fragilis.

Ureidopenicillins (antipseudomonal penicillin) Antibiotics

Piperacillin–tazobactam

Gram +ve cocci

Staph. aureus (MSSA), Strep. pneumoniae, enterococci

Gram –ve bacilli

Enterobacilli (E. coli, Proteus, Klebsiella, Serratia, Enterobacter) Pseudomonas, anaerobic bacteria

Comments

Piperacillin is active against major gram –ve, some gram +ve (streptococci and enterococci), and anaerobic bacteria. Tazobactam adds to the activity by including β-lactamase producing Staph. aureus (MSSA) and additional strains of E. coli and Klebsiella. Piperacillin–tazobactam has largely supplanted the use of ampicillin– sulbactam, and amoxicillin–clavulanate because of its wider spectrum of activity. It is also more effective than ticarcillin–clavulanate for the treatment of Pseudomonas infection.

ERRNVPHGLFRVRUJ

186


Carboxypenicillin (antipseudomonal penicillins) Antibiotics

Ticarcillin–clavulanate

Gram +ve cocci

Staph. aureus (MSSA)

Gram –ve bacilli

Enterobacilli (E. coli, Proteus, Klebsiella, Serratia, Enterobacter), Pseudomonas, H. influenzae, B. fragilis

Comments

Clavulanic acid enhances the activity of ticarcillin against beta-lactamase producing bacteria. These include strains of Staph. aureus, enterobacilli (E. coli, Klebsiella, Proteus), H. influenzae, N. gonorrhoeae, and B. fragilis. The activity of ticarcillin against enteric aerobic gram-negative bacilli is similar to ampicillin and inferior to piperacillin, and in addition it may interfere more with platelet function. Piperacillin–tazobactam is preferable for gram-negative infections unless ticarcillin–clavulanate is specifically indicated.

Cephalosporins (first generation) Antibiotics

Cefazolin, cephalexin

Gram +ve cocci

Staph. aureus (MSSA), Strep. pneumoniae, Strep. viridans, Strep. pyogenes

Gram –ve bacilli

Enterobacilli (E. coli, Klebsiella), H. influenzae

Comments

Cefazolin is the only parenteral preparation still in use. Oral preparations are used in minor infections. It is effective against anaerobes (but not B. fragilis). Not active against MRSA, Proteus, Enterobacter, Serratia or Pseudomonas.

Cephalosporins (second generation) Antibiotics

Cefuroxime, cefaclor, cefoxitin

Gram +ve cocci

Staph. aureus (MSSA), Strep. pneumoniae

Gram –ve bacilli

Enterobacilli (E. coli, Klebsiella), H. influenzae, anaerobes including B. fragilis.

Comments

Less activity against gram +ve and better activity against β-lactamase producing gram –ve organisms compared to first generation.

Cephalosporins (third generation) Antibiotics

Ceftriaxone, cefotaxime, ceftazidime, cefoperazone

Gram +ve cocci

Staph. aureus (MSSA), Strep pneumoniae

Gram –ve bacilli

Enterobacilli (E. coli, Klebsiella, Proteus, Serratia, Enterobacter) H. influenzae

Comments

Third generation cephalosporins are mainly used for gram –ve infections. Gram +ve activity is variable. Ceftazidime and cefoperazone have additional anti-Pseudomonal and anaerobe coverage but are not effective against Staph. aureus.

ERRNVPHGLFRVRUJ

Antibiotics

187

Cephalosporins (fourth generation) Antibiotics

Cefepime, cefpirome

Gram +ve cocci

Staph. aureus (MSSA), Strep. pneumoniae

Gram –ve bacilli

Enterobacilli (E. coli, Klebsiella, and Proteus). Others (H. influenzae, Pseudomonas)

Comments

Similar to third generation but with activity against Staph. and also Pseudomonas.

Aminoglycosides Antibiotics

Gentamicin, tobramycin, amikacin, netilmicin

Gram +ve cocci

Staph. epidermidis, Staph. saprophyticus, Strep. pneumoniae, Strep. viridans, enterococci

Gram –ve bacilli

Enterobacilli (E. coli, Proteus, Klebsiella, Serratia, Enterobacter) Pseudomonas, V. cholerae

Comments

Broad spectrum of gram –ve coverage. Gram +ve organisms are resistant to gentamicin. No activity against anaerobes.

Fluoroquinolones Antibiotics

Ciprofloxacin, ofloxacin, levofloxacin

Gram +ve cocci

Staph. epidermidis, Staph. saprophyticus, Strep. pneumoniae, enterococci

Gram –ve bacilli

Enterobacilli (E. coli, Proteus, Klebsiella, Serratia, Enterobacter and Shigella), Pseudomonas, H. influenzae, Legionella N. gonorrhoeae

Gram –ve cocci Comments

Lack of activity against gram +ve organisms though levofloxacin has some activity against Strep. pneumoniae and Strep. pyogenes. Also effective against Chlamydia and Mycoplasma. Ofloxacin and levofloxacin (but not ciprofloxacin) have moderate activity against anaerobes.

Carbapenems Antibiotics

Imipenem–cilastatin, meropenem, ertapenem

Gram +ve cocci

Staph. aureus (MSSA), Strep. viridans, Strep. pyogenes, enterococci

Gram –ve bacilli

Enterobacilli (E. coli, Proteus, Klebsiella, Serratia, Enterobacter) Pseudomonas, H. influenzae, anaerobes including B. fragilis

Comments

Has one of the broadest spectrums. Meropenem is slightly more effective against gram –ve infections. Anaerobic organisms are very susceptible. Indicated as a second-line drug in severe infections and sepsis of unknown cause.

ERRNVPHGLFRVRUJ

188


Monobactams Antibiotics

Aztreonam

Gram +ve

–

Gram –ve bacilli

Enterobacilli (E. coli, Proteus, Klebsiella, Serratia, Enterobacter), Pseudomonas

Comments

It is an option for gram –ve coverage in penicillin allergic patients.

Glycopeptides Antibiotics

Vancomycin, teicoplanin

Gram +ve cocci

Methicillin-resistant Staph. aureus (MRSA), Staph. epidermidis, Strep. viridans, enterococci, C. diphtheriae

Gram –ve bacilli

Anaerobes

Comments

Vancomycin is used orally in pseudomembranous colitis caused by C. difficile and in enterocolitis caused by Staph. aureus. Teicoplanin has a spectrum similar to vancomycin but has a longer half life, so OD dose suffices. Teicoplanin can also be injected by the IM route.

Oxazolidinones Antibiotics

Linezolid


Staph. aureus (MRSA), Strep. pneumoniae, Strep. agalactiae, Strep. pyogenes, Strep. viridans, enterococci Listeria monocytogenes, Corynebacterium, Clostridia

Gram –ve bacilli

Anaerobes

Comments

Linezolid has no significant gram –ve activity, Pseudomonas and enterobacilli are not susceptible. The main indications of linezolid are gram +ve infections of the skin, soft tissues, osteomyelitis, pneumonia (particularly hospital-acquired), endophthalmitis, and infective endocarditis.

Lincosamides Antibiotics

Clindamycin

Gram +ve cocci

Active against most gram-positive cocci except enterococci and nosocomially-acquired MRSA. Active against most community-acquired MRSA, anaerobic bacilli and cocci

Gram –ve bacilli

Gram –ve anaerobic bacilli

Comments

No gram –ve activity other than anaerobes

ERRNVPHGLFRVRUJ

Antibiotics

189

Macrolides Antibiotics

Erythromycin, clarithromycin, azithromycin


Gram +ve cocci: Staph. aureus (MSSA), Strep. pyogenes, Strep. pneumoniae C. diphtheriae

Gram –ve bacilli

H. influenzae

Comments

Macrolides are also active against Chlamydia, Mycoplasma, and Treponema. Clarithromycin is more effective against gram +ve cocci, H. influenzae, and Chlamydia compared to erythromycin, while azithromycin is not as effective against gram +ve cocci.

Sensitivity Summary of Commonly Used IV Antibiotics Staph. Staph. Enterococcus Enteric gram Pseudomonas B. fragilis aureus aureus faecalis –ve bacilli aeruginosa (MSSA) (MRSA) Cloxacillin

+++

–

–

–

–

–

Amoxicillin– clavulanate

+

–

++

+++

–

+

Piperacillin– tazobactam

+

–

+++

+++

++

+

Cefotaxime/ ceftriaxone

++

–

–

+++

–

+

Ceftazidime

–

–

–

+++

+++

–

Cefpirome

++

–

–

+++

++

–

Imipenem/ meropenem

+++

–

++

+++

+++

+++

Vancomycin/ teicoplanin

+++

+++

–

–

–

++

Aminoglycoside

–

–

++

+++

+++

–

Fluoroquinolones –

–

–

+++

+++

+++

Linezolid

+++

+++

+++

–

–

++

Clindamycin

+++

+

–

–

–

++

MSSA: methicillin-susceptible Staph. aureus, MRSA: methicillin-resistant Staph. aureus.

ERRNVPHGLFRVRUJ

190


Antibiotic Doses Amikacin Oral dose

Parenteral dose

Adult

NA

15 mg/kg q24h or 7.5 mg/kg q12h

Pediatric

NA

5–7.5 mg/kg q12h

Neonatal

15 mg/kg q24h. Administer over 30 minutes

Blood levels—peak (30 minutes after dose) 20–30 mcg/mL, trough (12–24 hours after dose) 2–5 mcg/mL. In renal failure, increase interval between doses (creatinine clearance [CrCl] 10–50 mL/min: q12–18h, CrCl <10 mL/min: q24–48h). Supplemental doses are required for hemodialysis (HD) and peritoneal dialysis (PD). Aminoglycoside administration is associated with nephrotoxicity, ototoxicity, and neurotoxicity.

Amoxicillin Oral dose

Parenteral dose

Adult

0.25–0.5 g q8h

500 mg q8h

Pediatric

22.5–45 mg/kg q12h Or 80 mg/kg/day in divided doses q8h

50–100 mg/kg/day in divided doses q8h

Neonatal

Not indicated

In renal failure, increase interval between doses (CrCl 10–50 mL/min: q8–12h, CrCl <10 mL/min: q12–24h). Supplemental dose is required for HD but not for PD. Side effects include diarrhea and rashes. Amoxicillin and ampicillin have a common spectrum, but amoxicillin is better absorbed so diarrhea is less. Adverse effects of all penicillins include hypersensitivity and local irritation at the site of injection.

Amoxicillin–Clavulanate (1.2 g vial contains Amoxicillin 1 g + Clavulanate 200 mg)

ERRNVPHGLFRVRUJ

Antibiotics

191

Oral dose

Parenteral dose

Adult

0.25–0.5 g q8h or 0.875 g q12h (amoxicillin content)

1.2 g vial q6–8h

Pediatric

22.5–45 mg/kg/day in divided doses q8h (amoxicillin content)

30 mg/kg/day in divided doses q8h (amoxicillin content)

Neonatal

Not indicated

In renal failure, increase interval between doses (CrCl 10–50 mL/min: q8–12h, CrCl <10 mL/min: q12–24h). Supplemental dose is required for HD and PD.

Ampicillin Oral dose

Parenteral dose

Adult

250 mg–1g q6h

0.5–2.0 g q4–6h

Pediatric



Neonatal

0–7 days: 5–50 mg/kg q12h >7 days: 25–50 mg/kg q8h

In renal failure, increase interval between doses (CrCl 10–50 mL/min: q6–12h, CrCl <10 mL/min: q12–16h). Supplemental dose is required for HD but not PD.

Ampicillin–Sulbactam (1.5 g vial contains Ampicillin 1 g + Sulbactam 0.5 g) Oral dose

Parenteral dose

Adult

NA

1.5–3.0 g vial q6–8h

Pediatric

NA

Neonatal

25–50 mg/kg q6h (ampicillin content) 0–7 days: 25–50 mg/kg q12h >7 days: 25–50 mg/kg q8h

In renal failure, increase interval between doses (CrCl 10–50 mL/min: q12h, CrCl <10 mL/min: q24h). Supplemental dose is required for HD but not PD.

ERRNVPHGLFRVRUJ

192


Aztreonam Oral dose

Parenteral dose

Adult

NA

1 g q8h or 2 g q12h

Pediatric

NA

30 mg/kg q6–8h

Neonatal

0–7 days: 30 mg/kg q12h >7 days: 30 mg/kg q8h

In renal failure, reduce the dose (CrCl 10–50 mL/min: to 50%, CrCl <10 mL/min: to 25%). Supplemental dose is required in HD. Toxic effects are phlebitis, rash, and elevated liver function tests.

Cefaclor Oral dose

Parenteral dose

Adult

0.25–0.5 g q8h

NA

Pediatric

10–20 mg/kg/day in divided doses q12h Or 6.6–13.3 mg/kg q8h (in more severe infections)

NA

Neonatal

NA

In severe renal failure (CrCl <10 mL/min), reduce dose by 50%. In mild/ moderate renal failure (CrCl >10 mL/min), no dose reduction is required. Supplemental dose is needed in HD and PD. All cephalosporins can cause allergic reactions.

Cefazolin Oral dose

Parenteral dose

Adult

NA

1–2 g q8h

Pediatric

NA


Neonatal


In renal failure, increase interval between doses (CrCl 10–50 mL/min: q12h, CrCl <10 mL/min: q24h). Supplemental dose is required for HD but not PD.

ERRNVPHGLFRVRUJ

Antibiotics

193

Cefepime Oral dose

Parenteral dose

Adult

NA

1–2 g q8–12h

Pediatric

NA

50 mg/kg q8–12h

Neonatal

50 mg/kg q8–12h

In renal failure, the interval between doses is increased and the dose of the drug is also reduced. (In children, CrCl 10–50 mL/min: 25 mg/kg q12h, CrCl <10 mL/min: 12.5 mg/kg q24h). Supplementary dose is required in HD and PD.

Cefoperazone Oral dose

Parenteral dose

Adult

NA

1–3 g/day in divided doses q8–12h

Pediatric

NA

25–100 mg/kg q12h

Neonatal

NA

No change in dosing is required in renal failure.

Cefotaxime Oral dose

Parenteral dose

Adult

NA

1 g q12h to 2 g q4h (higher dose for life-threatening infections)

Pediatric

NA

25–50 mg/kg q6–8h

Neonatal


In creatinine clearance <20 mL/min, reduce dose by 50%. Supplemental dose is required for HD but not PD.

Ceftazidime Oral dose

Parenteral dose

Adult

NA

1 g q12h to 2 g q8h (higher dose for life-threatening infections)

Pediatric

NA

25–50 mg/kg q8h

Neonatal


ERRNVPHGLFRVRUJ

194


In renal failure, increase interval between doses (CrCl 10–50 mL/min: q12–24h, CrCl <10 mL/min: q24–48h). Supplemental dose is required for HD and PD.

Ceftriaxone Oral dose

Parenteral dose

Adult

NA

1–2 g q24h

Pediatric

NA

50–75 mg/kg q24h Or 25–37.5 mg/kg q12h

Neonatal

50 mg/kg q24h

No dose adjustment is required in mild/moderate renal failure.

Cefuroxime Oral dose

Parenteral dose

Adult

0.125–0.5 g q12h

0.75–1.5 g q6–8h

Pediatric

10–15 mg/kg suspension q12h; older children, 125–250 mg q12h

25–50 mg/kg q8h

Neonatal

50–100 mg/kg/day in divided doses q8–12h

In renal failure, increase interval between doses (CrCl 10–50 mL/min: q8–12h, CrCl <10 mL/min: q24h). Supplemental dose is required for HD but not PD.

Cephalexin Oral dose

Parenteral dose

Adult

0.25–0.5 g q6h

NA

Pediatric

6.25–12.5 mg/kg q6h or 8.0–16 mg/kg q8h

NA

Neonatal

NA


ERRNVPHGLFRVRUJ

Antibiotics

195

Ciprofloxacin Oral dose

Parenteral dose

Adult

0.5–0.75 g q12h

0.2–0.4 g q8–12h

Pediatric

10–15 mg/kg q12h (in select circumstances)

10–15 mg/kg q12h (in select circumstances)

Neonatal

Not indicated

In renal failure, reduce dose (CrCl 10–50 mL/min: to 50–75%, in CrCl <10 mL/min: to 50%). Supplementary dose is indicated in HD and PD. Adverse reactions of fluoroquinolones include nausea, dizziness, phototoxicity, and arthropathy.

Clarithromycin Oral dose

Parenteral dose

Adult

0.25–0.5 g q12h; Extended release 1 g q24h

500 mg q12h

Pediatric

7.5 mg/kg q12h

NA

Neonatal

NA

CrCl <30 mL/min reduce dose by 50% and administer q12h–24h.

Clindamycin Oral dose

Parenteral dose

Adult

150–300 mg q6h

200–600 mg q8h

Pediatric

10–30 mg/kg/day divided q6–8h

5–10 mg/kg q6–8h

Neonatal

0–7 days: 5–7.5 mg q8h >7 days: 5–7.5 mg q6h

0–7 days: 5–7.5 mg q8h >7 days: 5–7.5 mg q6h

No change of dosing is required in renal failure. Adverse effects include allergic rashes, neutropenia, thrombocytopenia, and anaphylaxis. Pseudomembranous colitis is caused by overgrowth of C. difficile, which responds to oral metronidazole or vancomycin.

ERRNVPHGLFRVRUJ

196


Erythromycin Oral dose

Parenteral dose

Adult

0.25–0.5 g q6h

50 mg/kg/day in divided doses q6h

Pediatric

10–16.6 mg/kg q8h or 7.5–12.5 mg/kg q6h

50 mg/kg/day in divided doses q6h

Neonatal

NA

Reduce dose with CrCl <10 mL/min to 50–75%. No change of dosing is indicated in CrCl >10 mL/min. Supplemental dose is not required in HD.

Gentamicin/Tobramycin Oral dose

Parenteral dose

Adult

NA

5–7 mg/kg q24h or 1–2 mg/kg q8h

Pediatric

NA

2–2.5 mg/kg q8h or 6–7.5 mg/kg q24h <1.5 kg: 3 mg/kg q18h >1.5 kg: 3 mg/kg q12h infuse over 30 minutes

Neonatal

Blood levels—peak: 5–12 mcg/mL (30 minutes after dose), trough: 0.5–1 mcg/mL (12–24 hours after dose). Once-daily dosing for aminoglycosides is now well accepted in children and adults. Treatment in patients with renal failure may be best continued with non-aminoglycoside antimicrobials. If an aminoglycoside is strongly indicated, careful monitoring of blood levels is required to determine frequency or dose of subsequent administration. (Empirically with a CrCl 10–50 mL/min: q12–18h; CrCl <10 mL/min: q24–48h). Supplemental dose is required in HD and PD.

Imipenem–Cilastatin Oral dose

Parenteral dose

Adult

NA

0.5–1.0 g q6h

Pediatric

NA

Infants 4 week to 3 months: 25 mg/kg q6h; children >3 months: 15–25 mg/kg q6h or 20–40 mg/kg q8h

Neonatal

20–25 mg/kg q12h

In renal failure, both dose and interval between dosing are altered (CrCl >50 mL/min: 50–100% of dose q6–8h; CrCl 10–50 mL/min: 25–50% q8h; CrCl <10 mL/min: 25% q12h). Supplemental dose is required in HD.

ERRNVPHGLFRVRUJ

Antibiotics

197

Adverse effects include nausea, vomiting, diarrhea, eosinophilia, neutropenia, and lowering of the seizure threshold. Imipenem is nephrotoxic.

Levofloxacin Oral dose

Parenteral dose

Adult

0.25–0.75 g q24h

0.25–0.75 g q24h

Pediatric

≥5 years: 10 mg/kg q24h 6 months to <5 years: 10 mg/kg q12h

≥5 years: 10 mg/kg q24h 6 months to <5 years: 10 mg/kg q12h

Neonatal

NA

NA

Use of levofloxacin in children is controversial because of the high incidence of arthralgia, tendinopathy, or arthritis.

Linezolid Oral dose

Parenteral dose

Adult

600 mg q12h

600 mg q12h

Pediatric

10 mg/kg q8h

10 mg/kg q8h Neonates <7 days: 10 mg/kg q12h >7 days: 10 mg/kg q8h

Neonatal

No change in dosing is required in renal failure. Common adverse effects of short-term use include headache, diarrhea, and nausea. Long-term use can cause bone marrow suppression, thrombocytopenia, peripheral neuropathy, optic nerve damage, and lactic acidosis.

Meropenem Oral dose

Parenteral dose

Adult

NA

0.5–2 g q8h

Pediatric

NA

20–40 mg/kg q8h

Neonatal

20 mg/kg q12h

In renal failure, the dosing interval is increased and the dose reduced. (In children, CrCl 10–50 mL/min: 50–100% of dose q12h; CrCl <10 mL/min: 50% of dose q24h.) Supplementary dose is required in HD and PD.

ERRNVPHGLFRVRUJ

198


Metronidazole (For Anaerobic Infection) Oral dose

Parenteral dose

Adult

7.5 mg/kg (250–750 mg) q6h (not to exceed 4 g/day)

7.5 mg/kg q6h (not to exceed 4 g/day)

Pediatric

7.5 mg/kg q8h

7.5 mg/kg q6h (1st dose 15 mg/kg may be given) 1st dose 15 mg/kg, then 7.5 mg/kg/dose 0–7 days: q24h >7 days: q12h

Neonatal

No change in dosing is required in mild/moderate renal failure. With a CrCl <10 mL/min, dose is reduced to 50%. Supplemental dose is required in hemodialysis but not peritoneal dialysis.

Piperacillin Oral dose Adult

Parenteral dose 100–150 mg/kg/day in divided doses q8h

Pediatric

NA

25–75 mg/kg q4–6h

Neonatal



Piperacillin–Tazobactam Oral dose Adult Pediatric

Neonatal

Parenteral dose 3.375 g (3 g of piperacillin and 0.375 g of tazobactam) q6h.

NA

100 mg/kg of piperacillin and 12.5 mg/kg of tazobactam given every 8 hours. Pediatric patients 2–9 months of age should receive 80 mg/kg of piperacillin and 10 mg/kg of tazobactam every 8 hours. Not indicated

In renal failure, the interval between doses is increased and the dose of drug is reduced. (In children, CrCl 10–50 mL/min: 70% of dose q6–8h; CrCl <10 mL/min: 70% of dose q8h.) Supplementary dose is required in HD but not PD.

ERRNVPHGLFRVRUJ

Antibiotics

199

Quinupristin–Dalfopristin Oral dose

Parenteral dose

Adult

NA

7.5 mg/kg q8h

Pediatric

NA

7.5 mg/kg q12h

Neonatal

NA

NA

Quinupristin–dalfopristin is a combination injectable streptogramin antibiotic that is active against most strains of VRSA. No dosing recommendations are available in pediatric patients less than 12 years of age. No dosage adjustment is required for use in patients with renal impairment.

Rifampin Oral dose

Parenteral dose

Adult

0.3 g q8h Or 0.6–0.9 g q24h

0.3 g q8h Or 0.6–0.9 g q24h

Pediatric

20 mg/kg q24h or 10 mg/kg q12h

10–20 mg/kg q12–24h

Neonatal

5–10 mg/kg q24h (Oral 10–20 mg/kg q24h)

In renal failure, CrCl 10–50 mL/min administer 50–100% dose, CrCl <10 mL/min administer 50% of dose. Supplementary dose is not indicated in HD or PD. Indicated for staphylococcal infections (in combination with a penicillin, cephalosporin, or vancomycin).

Ticarcillin (5.2 mEq Na/g) Oral dose

Parenteral dose

Adult

NA

3 g q4–6h

Pediatric

NA

25–75 mg/kg q6h

Neonatal



ERRNVPHGLFRVRUJ

200


Ticarcillin–Clavulanate (3.1 g vial containing 3 g Ticarcillin and 100 mg Clavulanic acid) Oral dose

Parenteral dose

Adult

NA

3.1 g vial q4–6h

Pediatric

NA

25–75 mg/kg (ticarcillin dose) q6h

Neonatal


In renal failure, increase interval between doses (CrCl 10–50 mL/min: q6–8h, CrCl <10–50 mL/min: q12h). Supplemental dose is required for HD but not PD.

Teicoplanin Oral dose

Parenteral dose

Adult

NA

400 mg q12h for 3 doses then 200–400 mg q24h.

Pediatric

NA

10 mg/kg q12h for 3 doses, then 6–10 mg/kg q24h. Administer IV bolus over 3–5 minutes

Neonatal

Loading dose 16 mg/kg, then 8 mg/kg q24h. Administer IV over 30 minutes

In renal failure, CrCl 10–50 mL/min reduce dose to 33% on 4th day; CrCl <10 mL/min, administer 50% of dose. Adverse effects include increased risk of ototoxicity and nephrotoxicity when given along with aminoglycosides; increased ototoxicity with loop diuretics.

Vancomycin Oral dose

Parenteral dose

Adult

125 mg q6h (only effective for C. difficile colitis)

15 mg/kg q12h (often 1–1.5 g q12h)

Pediatric

5 mg/kg q6h

10–15 mg/kg q6–8h

Neonatal

0–7 days: 10–15 mg/kg q12h >7 days: 10–15 mg/kg q8h Administer over 1 hour


ERRNVPHGLFRVRUJ

Antibiotics

201

Rapid IV infusion can cause severe hypotension (including shock, cardiac arrest), wheezing, dyspnea, urticaria, pruritus, flushing (Red man syndrome). Vancomycin has been associated with ototoxicity and nephrotoxicity, primarily when used in combination with an aminoglycoside.

Bibliography 1. Aoki FY. Principles of antimicrobial therapy and the clinical pharmacology of antimicrobial drugs. In: Hall JB, Schmidt GA, Woods LDH, eds. Principles of Critical Care McGraw-Hill; 2005:641–97. 2. Approach to infectious diseases. In: Apostolakas MJ, Papadakos PJ, eds. The Intensive Care Manual McGraw-Hill; 2001:156–65. 3. Beta-lactamase. [Updated: 2009 Jul; cited: 2011 Feb 26] Available at: http://www.medic8. com/medicines/Penicillinase.html. 4. Binkley S. Antibiotic dosing in renal impairment. University of Pennsylvania Medical Center Guidelines for Antibiotic Use. [Updated: 2008 Sep 23; cited: 2011 Feb 26] Available at: http:// www.uphs.upenn.edu/bugdrug/antibiotic_manual/renal.htm. 5. Bradley JS, Arguedas A, Blumer JL, et al. Comparative study of levofloxacin in the treatment of children with community-acquired pneumonia. Pediatr Infect Dis J 2007;26:868–78. 6. Chien S, Wells TG, Blumer JL, et al. Levofloxacin pharmacokinetics in children. J Clin Pharmacol 2005;45:153–60. 7. Cubicin (Daptomycin) [package insert]. Cubist Pharmaceuticals, Inc. Lexington, MA 02421 USA November 2010 (1004-11). [Updated: 2000 Jul 25; cited: 2011 Feb 26] Available at: http:// www.cubicin.com/pdf/PrescribingInformation.pdf. 8. Heritage J. The classification and identification of bacteria of medical importance. [Updated: 2006 Apr; cited: 2011 Feb 26] Available at: http://www.bmb.leeds.ac.uk/mbiology/ug/ugteach/ icu8/classification/gnb.html. 9. Krilov LR, McCracken GH. Pediatric infectious diseases. In: Cunha BA, ed. Antibiotic Essentials Michigan: Physician’s Press; 2005:294–322. 10. Levison ME. Usual doses of commonly prescribed antibiotics. The Merck manuals: online medical library. [Updated: 2009 Jul; cited: 2011 Feb 26] Available at: http://www.merckmanuals. com/media/professional/pdf/Table_170-3.pdf. 11. Levofloxacin information from drugs update. [Updated: 2011; cited: 2012 Jan 17] Available at: http://www.drugsupdate.com/generic/view/663. 12. Quinn FB, Rosen EJ. Microbiology, infections, and antibiotic therapy. Grand rounds presentation, UTMB, Dept of Otolaryngology. [Updated: 2000 Jul 25; cited: 2011 Feb 26] Available at: http://www.utmb.edu/otoref/Grnds/Infect-0003/Infect-0003.htm. 13. Suzuki MM. Drugs in renal failure. In: Siberry GK, Iannone R, eds. The Harriot Lane Handbook 15th ed. NOIDA, UP, India: Harcourt (India) Pvt Ltd; 2001:927–44. 14. Systemic anti-infectives. In: Kastrup EK, Meives CA, et al., eds. Drug Facts and Comparisons, Missouri, USA: Wolters Kluwer Health; 2010:1903–2103. 15. Tygacil (Tigecycline) [package insert]. Wyeth Pharmaceuticals Inc. Philadelphia, PA 19101. [Updated: 2011 Jan; cited: 2012 Jan 17] Available at: http://labeling.pfizer.com/ShowLabeling. aspx?id=491.

ERRNVPHGLFRVRUJ

Sepsis and Multiorgan Dysfunction “I do not expect my contemporaries to accept all my doctrines, but I look to the coming generation to adopt and perfect them” —Joseph Lister (1827–1912)*

Systemic inflammatory response syndrome (SIRS) is a non-specific, widespread inflammatory reaction, which takes place in response to a pathological event (ischemia, trauma, infection, etc.). This inflammatory process results in disorders of microcirculation, a decrease in organ perfusion, and finally organ dysfunction. In general, Sepsis is defined as SIRS caused by infection, and Severe sepsis is sepsis with evidence of organ dysfunction. Septic shock is sepsis associated with hypotension unresponsive to fluids or requires inotropes for its management. To make it possible to compare the results of various clinical trials in pediatric sepsis, the International Pediatric Sepsis Consensus conference (2005) has defined infection, SIRS, sepsis, severe sepsis, and septic shock in pediatrics.

Definitions Infection

A suspected or proven infection caused by any pathogen, or a clinical syndrome associated with a high probability of infection.

SIRS

The presence of at least two of the following four criteria, one of which must be abnormal temperature or leukocyte count: ■

Core temperature of >38.5°C or <36°C. (>101°F or <97°F).

■

Tachycardia (defined as a mean heart rate >2 SD above normal) or for children <1 year old, bradycardia (defined as a mean heart rate <10th percentile for age).

■

Mean respiratory rate >2 SD above normal for age or mechanical ventilation.

*Joseph Lister was the pioneer of antiseptic surgery. He introduced carbolic acid to sterilize surgical instruments and clean wounds.

ERRNVPHGLFRVRUJ

Sepsis and Multiorgan Dysfunction ■

203

Leukocyte count elevated or depressed for age or >10% immature neutrophils.

Sepsis

SIRS in the presence of or as a result of suspected or proven infection.

Severe Sepsis

Sepsis plus one of the following: (i) cardiovascular organ dysfunction or (ii) acute respiratory distress syndrome (ARDS) or (iii) at least two other organ dysfunction.

Septic Shock

Sepsis and cardiovascular organ dysfunction.

Organ Dysfunction Criteria Cardiovascular

Despite administration of isotonic intravenous fluid bolus ≥40 mL/kg in 1 hour: ■

Hypotension, i.e., blood pressure <5th percentile for age or systolic BP >2 SD below normal for age or

■

Need for vasoactive drug to maintain BP or

■

Two of the following signs of inadequate organ perfusion: ●

metabolic acidosis with a base deficit >5.0 mmol/L

●

increased arterial lactate >2 times upper normal limit

●

urine output <0.5 mL/kg/h

●

prolonged capillary refill >5 sec

●

core to peripheral temperature gap >3°C (>5.4°F)

Respiratory

PaO2/FiO2 ratio ≤300 or PaCO2 >65 mmHg or 20 mmHg over baseline PaCO2 or requirement of >50% FiO2 to maintain saturation >92%

CNS

Glasgow coma score <11 or a decrease in Glasgow coma score ≥3 points from abnormal baseline.

Hematology

Platelet count <80,000/mm3 or a decline of 50% in platelet count from highest value recorded over the past 3 days (for chronic hematology/oncology patients) or an international normalized ratio >2.

Renal

Serum creatinine ≥2 times upper normal limit for age or two-fold increase in baseline creatinine.

Hepatic

Total bilirubin ≥4 mg/dL (not applicable for newborn) or ALT (alanine transaminase) two times upper normal limit for age.

ERRNVPHGLFRVRUJ

204


Sources of Sepsis in the Postoperative Period ■

Wound infection

■

Urinary tract infection

■

Ventilator associated pneumonia (VAP)

■

Intravenous line related infection

■

Gastrointestinal infection

■

Sinusitis

■

Prosthesis infection

Clinical Manifestations of Sepsis Features of Organ System Dysfunction Organ system

Features of dysfunction

Cardiovascular

Hypotension, poor peripheral perfusion, capillary leak syndrome, metabolic acidosis

Pulmonary

Hypoxia, hypercarbia, ARDS

CNS

Altered sensorium, coma

Hematology

Fall in platelet count, abnormal INR, DIC

Renal

Oliguria, increasing Se/creatinine

Hepatic

Abnormal LFT, jaundice

Gastrointestinal

Abdominal distension, intolerance to feeds, stress ulceration

Peripheral nervous system

Sensory neuropathy or neuropathy

Cutaneous manifestations

Petechiae, diffuse erythema, ecchymoses, ecthyma gangrenosum, and symmetric peripheral gangrene

Early clinical features of sepsis include tachycardia (newborns may have bradycardia) and tachypnea associated with temperature abnormalities (fever or hypothermia). The initial phases of septic shock are associated with vasodilation and capillary leak, and an elevated cardiac output. This is evident by the presence of strong pulses, warm extremities, good capillary refill, and tachycardia (warm/vasodilatory shock). Relative or absolute hypovolemia and impaired cardiac function ultimately result in poor cardiac output and vasoconstriction. This is clinically manifested by delayed capillary refill, diminished peripheral pulses, cool extremities, and decreased urine output (cold shock).

ERRNVPHGLFRVRUJ


205

Vasoconstriction maintains the blood pressure for a while, and hypotension may be a late sign in infants and children and is therefore not a criterion for the diagnosis of shock. Clinical manifestations of various organ dysfunction progressively appear (multiple organ dysfunction).

Investigations of Suspected Sepsis

Hematology

Biochemistry

Microbiology

Investigation

Remark

Hemoglobin

To assess the need for blood transfusion

Platelet count

Decreases with persistent sepsis

WBC count

WBC >15000 cells/dL or polymorphonuclear cells >1500 cells/dL is highly significant

Prothrombin time

To assess coagulation status

aPTT


INR


CRP

Raised

Glucose

Hyperglycemia/hypoglycemia

Serum lactate

Raised in severe sepsis

Serum electrolytes

Electrolyte abnormalities are common in sepsis

Culture of catheter tips Blood culture Urine culture Throat swab

Other investigations X-ray chest Blood gases Other imaging; Echo/ CT/ultrasound/MRI

Diagnosis The diagnosis of sepsis requires SIRS in the presence of proven infection or a clinical picture consistent with infection. Methods to identify the source of infection include physical examination, imaging (chest radiograph etc.), and cytology and culture of clinically appropriate specimens. Hematologic investigations may show anemia, thrombocytopenia, elevated neutrophils, and increased immature forms (bands, myelocytes, promyelocytes), vacuolation of neutrophils, and toxic granulations. Neutropenia is sometimes present in overwhelming sepsis. The erythrocyte sedimentation

ERRNVPHGLFRVRUJ

206


rate is increased. The coagulation profile may be abnormal with prolonged prothrombin and partial thromboplastin times, reduced serum fibrinogen levels, and elevated fibrin degradation products. Metabolic abnormalities include hyperglycemia as a stress response or hypoglycemia if glycogen reserves are exhausted. Electrolyte abnormalities such as hypocalcemia and metabolic acidosis may be present. Lactic acidosis can occur if there is significant anaerobic metabolism. Elevated C-reactive protein, interleukin-6, and procalcitonin levels have been reported as potential biochemical markers of sepsis. Renal and liver function tests are abnormal in the presence of renal and liver dysfunction. Patients with acute respiratory distress syndrome or pneumonia will have impaired oxygenation (decreased PaO2) and ventilation (increased PaCO2).

Management of Sepsis Antimicrobial therapy

Appropriate antibiotics

Volume resuscitation

Crystalloids/colloids 10–20 mL/kg IV boluses, up to 60 mL/kg or more may need to be given in 30–60 minutes in children presenting with septic shock. CVP is monitored, and an arterial line is placed.

Inotropes

In case of inadequate response to fluids, dopamine 10–20 mcg/kg/min is commenced. Children who are unresponsive to volume infusion and dopamine are given epinephrine 0.05–1 mcg/kg/min if they are vasoconstricted, or norepinephrine 0.05–2 mcg/kg/min if they are vasodilated. In patients on epinephrine, a vasodilator (nitroglycerin/dobutamine/milrinone) may also be required. In children unresponsive to norepinephrine, vasopressin may be effective.

Corticosteroids

In catecholamine-resistant shock, hydrocortisone is given in a dose of 50 mg/kg.

Glycemic control

Hypoglycemia is treated with 0.5–1 mg/kg of dextrose. Blood sugar levels are maintained between 70 and 110 g/dL.

Calcium gluconate

Hypocalcemia is corrected.

Supportive therapy

Ventilation, nutrition, and control of fever (antipyretic drugs and cold sponge/cooling blanket).

ERRNVPHGLFRVRUJ


207

Choice of Antibiotics Empirical antibiotic therapy based on site of infection Site of infection

Usual pathogens

Alternate drug combinations

Intraabdominal sepsis

Enterobacteriaceae (Klebsiella, Proteus, E. coli, Enterobacter, Serratia) Enterococci (E. faecalis), B. fragilis

●

●

● ●

Ventilator associated pneumonia

P. aeruginosa, S. aureus. Enterobacteriaceae (E. coli, K. pneumoniae), Acinetobacter.

●

●

IV line sepsis

S. aureus, S. epidermidis, enterococci, Candida species.

●

●

●

Urosepsis

P. aeruginosa, enterobacilli (Enterobacter, Klebsiella, Serratia)

●

Metronidazole + fluoroquinolone (ciprofloxacin). Metronidazole + 3rd/4th-generation cephalosporin. Carbapenem (imipenem/meropenem) Piperacillin–tazobactam β-lactam (piperacillin–tazobactam/ ceftazidime/cefuroxime/ carbapenem) + aminoglycoside or fluoroquinolone. In addition, a glycopeptide (vancomycin/ teicoplanin) or linezolid is added if the risk of MRSA is high. Cloxacillin for MSSA or glycopeptide (vancomycin/teicoplanin) for suspected MRSA. Add 3rd/4th generation cephalosporin/ aminoglycoside/carbapenem for gram −ve organisms in immunocompromised patients. Add amphotericin/fluconazole for suspected fungal infection. β-lactam (piperacillin–tazobactam/ ceftazidime/cefuroxime/ carbapenem) + aminoglycoside or fluoroquinolone.

Published consensus statements can provide a broad basis for empirical antibiotic therapy. Initial antibiotic therapy should include agents from different classes in order to increase the likelihood of coverage of multidrug-resistant organisms. Gram-negative organisms are covered with two antibiotics from either of these groups: β-lactams, fluoroquinolones, or aminoglycosides. There is evidence supporting increased survival with aminoglycoside-containing regimens and therefore an aminoglycoside is generally included. Nosocomial sepsis or an immunocompromised patient should empirically be treated with either an extended-spectrum penicillin (e.g., piperacillin– tazobactam), carbapenem (imipenem, meropenem), or cephalosporin which is effective against pseudomonas (e.g., ceftazidime, cefpirome) plus an aminoglycoside.

ERRNVPHGLFRVRUJ

208


If MRSA is suspected or the patient has an indwelling medical device, in addition to the drug combinations noted above, a glycopeptide (vancomycin or teicoplanin) or linezolid is also indicated. Antifungal therapy: Empirical use of amphotericin B to treat fungal infections should be considered for selected immunocompromised patients. Combination versus monotherapy: Once the microbial agent has been isolated and the antibiotic sensitivity is known, the antibiotics can be appropriately modified. There is no consensus on efficacy of combination therapy versus monotherapy. Synergy of drug actions increasing effectiveness against pseudomonas or any other gram-negative organism has not been conclusively demonstrated. Drug toxicity and cost of treatment are less with monotherapy. In view of this, consideration of continuing management with a combination of drugs as against monotherapy must be based on clinical judgement.

Fluid Resuscitation Rapid, aggressive resuscitation with fluids (crystalloids or colloids) is initially required. Fluid boluses of 10–20 mL/kg are titrated to normalize heart rate, urine output (to at least 1 mL/kg/h), capillary refill (<2 sec), and mental status. Fluid resuscitation may sometimes require as much as 100–120 mL/kg over 30–60 minutes. Since hypotension may be a late sign of shock in children, it is not a reliable end-point for assessing resuscitation. There is no clearly defined end point in fluid resuscitation other than measurement of CVP (8–12 mmHg) or signs of fluid overload. Blood transfusion is needed to maintain hemoglobin of 10 g/dL. Coagulopathy is corrected with fresh frozen plasma and cryoprecipitate, and if the patient has active bleeding, platelet transfusions may also be needed.

Inotropes In infants and children, management of sepsis often requires use of inotropic agents to maintain a normal cardiac output. Dopamine (10–20 mcg/kg/min) is the initial choice for fluid-refractory shock. In dopamineresistant shock, epinephrine (in the patient with high systemic vascular resistance) or norepinephrine (in the patient with low systemic vascular resistance) is started and the dopamine gradually weaned. Further, in patients with high systemic vascular resistance with a normal BP but superior vena cava oxygen saturation (SvO2) of <70%, the addition of a vasodilator such as nitroprusside, nitroglycerin, or milrinone may help reverse the shock.

ERRNVPHGLFRVRUJ


209

In patients who do not respond to norepinephrine (norepinephrineresistant shock), vasopressin may be a useful alternative, as its mechanism of action is not mediated through α-receptors.

Electrolytes Electrolytes are corrected as needed. Hypoglycemia is treated with 0.5–1.0 g/kg of glucose. Hypocalcemia, which can contribute to cardiac dysfunction, is corrected with 10% calcium gluconate 10–20 mg/kg.

Steroids Up to 50% of children have a relative or absolute adrenal insufficiency, thus if shock is not responsive to catecholamines and fluid resuscitation, IV hydrocortisone 50 mg/kg bolus should be considered (the normal stress dose of hydrocortisone is 2 mg/kg).

Ventilation Children requiring ventilation are managed as for acute respiratory distress syndrome, with low tidal volume ventilation (5–7 mL/kg), plateau pressures of <30 cm of water, FiO2 of <60%, and a PEEP of 5–10 cm.

Renal Replacement Therapy Renal replacement therapy is indicated in children with anuria or oliguria and a severe fluid overload. Extracorporeal membrane oxygenation may be considered in selected patients with refractory septic shock.

Monitoring Monitoring patients with septic shock should ideally include central venous pressure, continuous invasive arterial blood pressure, pulse oximetry, systemic venous oxygen saturation and hourly urine output in addition to heart rate, capillary refill, and mental status. Resuscitation goals include capillary refill <2 sec, normal pulses, warm extremities, urine output of >1 mL/kg/h, normal mental status, and normal blood pressure for age.

ERRNVPHGLFRVRUJ

210


Bibliography 1. Al-Khafaji AH, Sharma S. Multisystem organ failure of sepsis. [Updated: 2010 Jan 29; cited: 2011 Nov 02] Available at: http://emedicine.medscape.com/article/169640-overview. 2. Bugano DD, Camargo LF, Bastos JF, Silva E. Antibiotic management of sepsis: current concepts. Expert Opin Pharmacother 2008;9:2817–28. 3. Cunha BA, Nicols RL, Rex JH. Sepsis, septic shock and febrile neutropenia. In: Cunha BA, ed. Antibiotic Essential Michigan: Physician’s Press; 2005:117–22. 4. Davidson JE, Powers K, Hedayat KM, et al; American College of Critical Care Medicine Task Force 2004-2005, Society of Critical Care Medicine. Clinical practice guidelines for support of the family in the patient-centered intensive care unit: American College of Critical Care Medicine Task Force 2004-2005. Crit Care Med 2007;35:605–22. 5. Empiric antibiotic use in critically ill patients. [Update: 2007 August; Accessed: 2012 Jan 17] Available at: http://www.surgicalcriticalcare.net/Guidelines/empiric_antibiotics.pdf. 6. International Liaison Committee on Resuscitation. The International Liaison Committee on Resuscitation (ILCOR) consensus on science with treatment recommendations for pediatric and neonatal patients: pediatric basic and advanced life support. Pediatrics 2006;117(5): e955–77. 7. Khilnani P, Deopujari S, Carcillo J. Recent advances in sepsis and septic shock. Indian J Pediatr 2008;75(8):821–30. 8. Lentino JR. Mixed anaerobic infection. The Merck Manuals: Online medical library. [Updated: 2009 Aug; cited: 2011 Feb 22] Available at: http://www.merckmanuals.com/professional/ infectious_diseases/anaerobic_bacteria/mixed_anaerobic_infections.html?qt=&sc=&alt=. 9. Maccioli GA, Dorman T, Brown BR, et al. American College of Critical Care Medicine, Society of Critical Care Medicine. Clinical practice guidelines for the maintenance of patient physical safety in the intensive care unit: use of restraining therapies—American College of Critical Care Medicine Task Force 2001-2002. Crit Care Med 2003;31(11):2665–76. 10. Management for suspected sepsis for children receiving Parenteral Nutrition (PN) via a central venous catheter (Hickman type). The Newcastle Upon Tyne Hospitals: NHS Foundation Trust [Updated: 2008 Nov; cited: 2011 Feb 22]. Available at: http://www.newcastle-hospitals.org.uk/ downloads/clinical-guidelines/Childrens%20Services/CVC_infection_management.pdf. 11. Munford RS. Severe sepsis and septic shock. In: Longo DL, Kasper DL, Jameson JL, et al., eds. Harrison’s Principles of Internal Medicine 18th ed. McGraw-Hill Companies, Inc.; 2012:2223–32. 12. Russel JA. The current management of septic shock. Minerva Med 2008;99:431–58. 13. Silva E, Passos Rda H, Ferri MB, de Figueiredo LF. Sepsis: from bench to bedside. Clinics (Sao Paulo) 2008;63:109–20. 14. Skippen P, Kissoon N, Waller D, Northway T, Krahn G. Sepsis and septic shock: progress and future considerations. Indian J Pediatr 2008;75:599–607. 15. Tantaleán JA, León RJ, Santos AA, Sánchez E. Multiple organ dysfunction syndrome in children. Pediatr Crit Care Med 2003;4:181–5. 16. Watson NA, Denton M, Antibiotic prescribing in critical care: specific indications. JICS 2008; 9:30–6. 17. Weber DJ, Rutala WA. Central line-associated bloodstream infections: prevention and management. Infect Dis Clin North Am 2011;25(1):77–102.

ERRNVPHGLFRVRUJ


Systemic Fungal Infections Patients who are immunocompromised or have undergone surgery are susceptible to opportunistic fungal infections; the more common ones being candidiasis (50%), aspergillosis, and cryptococcosis, with the organism gaining entry through the lungs, gastrointestinal tract, or through intravenous lines. Infection occurring in previously healthy persons usually arises through the respiratory route, and examples include histoplasmosis, blastomycosis, and coccidiomycosis. Candidiasis: C. albicans is part of the normal oral flora and is the most common cause of disseminated fungal infection in the immunocompromised patient. Aspergillosis: A. fumigatus can infect the lungs, inner ear, sinuses, and eyes of previously healthy persons. In the immunosuppressed host, Aspergillus can cause disseminated infection. Cryptococcosis: This is a systemic infection caused by Cryptococcus neoformans. The commonest manifestation is a subacute or chronic form of meningitis resulting from the inhalation of the organism. Pulmonary infection can also occur. The disease affects both healthy and immunosuppressed individuals. Histoplasmosis: This is caused by Histoplasma capsulatum. The lungs are the main site of infection with symptoms resembling tuberculosis but dissemination to the liver, heart, and central nervous system can also occur.

Drug Doses Amphotericin B deoxycholate Route

IV

Dose

Children and adults: 0.5–1.5 mg/kg/day infused as a single dose over 2–6 hours for 10–14 days. (Total dose for disseminated mycosis is 1–4 g.)

ERRNVPHGLFRVRUJ

212


Dose for empiric therapy: 0.5 mg/kg/day. Dose for invasive candidiasis or aspergillosis: 1 mg/kg/day. Dose for pulmonary coccidiomycosis: 1.5 mg/kg/day. A dose reduction is required with a serum creatinine of >3 mg%. No change in dosing is indicated in hemodialysis or liver failure. Adverse reactions

Amphotericin B is highly nephrotoxic, and up to 80% of patients will have an increase in serum creatinine within 2 weeks of therapy. Other adverse effects include hypotension, chills, nausea, vomiting, drug fever, hypokalemia, musculoskeletal adverse effects (myalgia, arthralgia), blood disorders (anemia, leukopenia, thrombocytopenia) and various neurological disorders (hearing loss, diplopia, convulsions). To minimize nephrotoxicity, 10–15 mL/kg of normal saline is infused IV before amphotericin administration. In addition, premedication with antihistaminics (chlorpheniramine 200 mcg/kg) and corticosteroids (hydrocortisone 4 mg/kg) given 30 min before may decrease adverse effects. Amphotericin 0.1 mg/kg (max 1 mg) is first administered as a test dose over 1 hour followed by the remaining dose.

Amphotericin B lipid complex Route

IV

Dose

Children and adults: 2.5–5 mg/kg/day administered q24h, infused over 2 hours for at least 14 days.

Adverse reactions

Drug reactions and adverse effects are similar to amphotericin B deoxycholate but less nephrotoxic.

Route

IV

Dose

Children and adults: 3–5 mg/kg/day repeat q24h infused over 1–2 hours.

Adverse reactions

Drug reactions and adverse effects are similar to amphotericin B deoxycholate but less nephrotoxic.

Amphotericin B liposomal

Anidulafungin Route

IV

Dose

Children: 1.5–3 mg/kg loading dose, then 0.75–1.5 mg/kg/day. Adults: 100–200 mg loading dose, then 50–100 mg q24h.

Adverse reactions

Fever, headache, nausea, vomiting, diarrhea, hypokalemia, leukopenia, hepatotoxicity, and phlebitis. Rarely bronchospasm and hypotension.

ERRNVPHGLFRVRUJ


213

Caspofungin Route

IV

Dose

Children: 70 mg/m2 loading dose, then 50 mg/m2 q24h is infused over 1h. Adults: 70 mg loading dose, then 50 mg q24h infused over 1h.

Adverse reactions

Adverse reactions are mild and transient. Fever, rash, pruritus, phlebitis, headache, gastrointestinal tract symptoms, anemia.

Fluconazole Route

IV/PO

Dose

Neonate: <2 weeks: 3 mg/kg q72h. 2–4 weeks: 3 mg/kg q48h. Children: Prophylaxis and oropharyngeal or esophageal candidiasis: 6 mg/kg once, then 3 mg/kg/day. Invasive fungal infections: 6–12 mg/kg/day. Adults: Prophylaxis and oropharyngeal or esophageal candidiasis: 200 mg once, then 100 mg/day. Other invasive fungal infections: 400–800 mg/day. Though not nephrotoxic, the drug dose is reduced in renal dysfunction (50% if CrCl 21–50 mL/min and 25% of dose in CrCl <20 mL/min) because it is cleared unchanged by renal excretion.

Adverse reactions

Rash, gastrointestinal tract symptoms, hepatotoxicity, Stevens–Johnson syndrome, anaphylaxis, alopecia, leukopenia, and thrombocytopenia. Fluconazole is generally well-tolerated with few GIT effects (vomiting) and rashes.

Micafungin Route

IV

Dose

Children: 4–12 mg/kg/day administered q24h (higher dose needed for patients <8 years of age) Adults: 50–150 mg once daily.

Adverse reactions

Fever, headache, nausea, vomiting, diarrhea, leukopenia, hepatotoxicity, and phlebitis.

Posaconazole Route

PO

Dose

Children: Not recommended (Off label use in 3–13 yr: 300–800 mg/day in divided doses q8–12h). Children ³13 yr and Adults: 400 mg q12h with meals (or liquid nutritional supplement). Prophylaxis: 200 mg q8h.

Adverse reactions

Gastrointestinal tract symptoms, rash, edema, headache, anemia, neutropenia, thrombocytopenia, fatigue, arthralgia, myalgia, fever, and visual changes.

ERRNVPHGLFRVRUJ

214


Voriconazole Route

IV/PO

Dose IV

Children and adults: 6 mg/kg q12h for first 24 hours, then 4 mg/kg q12h. Given IV over 1–2 h (max rate 3 mg/kg/h and concentration <5 mg/mL).

Dose PO

Children: 10 mg/kg q12h for first 24 hours, then 7 mg/kg q12h. Adults: <40 kg: 200 mg q12h for first 24 hours, then 100 mg q12h; >40 kg: 400 mg q12h for first 24 hours, then 200 mg q12h.

Adverse reactions

Visual disturbance, photosensitive rash, hepatotoxicity, and GI symptoms.

Treatment Options Clinical condition

Drug of choice

Alternative drug

Prophylactic therapy Neutropenic/ post transplant patient

Caspofungin

Voriconazole

Oropharyngeal/ esophageal candidiasis

Fluconazole

Caspofungin, amphotericin B, voriconazole

Invasive candidiasis

Fluconazole, caspofungin

Amphotericin B, voriconazole

Aspergillosis

Voriconazole

Amphotericin B, caspofungin

Cryptococcal meningitis

Liposomal amphotericin B (can be combined with flucytosine in severe cases)

Fluconazole

Mucormycosis

Posaconazole

Amphotericin B

Fungal infection should be suspected in seriously ill patients who have been receiving antibiotics for a prolonged period of time and have persistent fever and elevated WBC. Voriconazole or caspofungin (caspofungin is preferable in the presence of neutropenia) can be started empirically in such patients even though fungal serologic studies are negative.

Amphotericin B Amphotericin B is effective against most systemic fungal infections and penetrates the CNS; however, it is one of the most toxic antifungals and is therefore not the first choice except in cryptococcal meningitis. Liposomal amphotericin B is preferable to amphotericin B deoxycholate because of less nephrotoxicity.

ERRNVPHGLFRVRUJ


215

Fluconazole Fluconazole is effective against Candida but not Aspergillus. It enters the CSF and is effective against Cryptococcus and is used as chronic suppressive therapy of cryptococcal infections after these have been initially treated with liposomal amphotericin B or voriconazole.

Voriconazole Voriconazole is effective against aspergillosis and candidiasis. It has a wide antifungal spectrum but does not enter the CSF.

Caspofungin Caspofungin is used for antifungal prophylaxis in febrile neutropenic patients or in patients with invasive candidiasis or aspergillosis who have not responded to other drugs. It has no effect against Cryptococcus and so is not used for CNS infections.

Posaconazole Posaconazole is the drug of choice for mucormycosis. Even though posaconazole has not been widely used in children younger than 13 years of age, it is considered safe and effective.

Other Antifungal Drugs Itraconazole is a systemic antifungal agent, not generally used because of its highly variable bioavailability, and Anidulafungin and Micafungin are active only against Candida. Griseofulvin and Terbinafine are drugs used for dermatophytosis. Clotrimazole and Ketoconazole are now mainly used in topical preparations, and Nystatin is used as lozenges, mouth paints, or as vaginal tablets (vaginal candidiasis).

Bibliography 1. Ananthanarayan R, Paniker CKJ. Medical Mycology. In: Textbook of Microbiology 8th ed. Hyderabad, India: University Press (India) Pvt Ltd; 2009:600–17. 2. Bennett JE. Antifungal agents. In: Brunton LL, Chabner BA, Knollmann BC, eds. Goodman & Gilman’s. The Pharmacological Basic of Therapeutics 12th ed. USA: McGraw Hill Inc; 2011: 1571–91.

ERRNVPHGLFRVRUJ

216


3. Blyth CC, Palasanthiran P, O’Brien TA. Antifungal therapy in children with invasive fungal infections: a systematic review. Pediatrics 2007;119:772–84. 4. British National Formulary. Antifungal drugs 2009:332–9. 5. Das S, Shivaprakash MR, Chakrabarti A. New antifungal agents in pediatric practice. Indian Pediatr 2009;46:225–31. 6. Galgiani JN, Ampel NM, Catanzaro A, Johnson RH, Stevens DA, Williams PL. Practice guidelines for the treatment of coccidioidomycosis. Clin Infect Dis 2000;30:658–61. 7. Mitchell TG. Medical mycology. In: Brooks GF, Carroll KC, Butel JS, et al, eds. Jawetz, Melnick & Adelberg’s Medical Microbiology 25th ed. USA: McGraw Hill Inc; 2010:625–44. 8. Sheppard D, Lampiris HW. Antifungal agents. In: Katzung BG, Masters SB, Trevor AJ, eds. Basic and Clinical Pharmacology 11th ed. USA: McGraw Hill Inc; 2009:835–44. 9. Systemic anti-infectives. In: Kastrup EK, Meives CA, et al, eds. Drug Facts and Comparisons. Missouri, USA: Wolters Kluwer Health; 2010;2096–150. 10. Wolkowiez MC, Moran C, Daniel K, Benjamin Jr, Smith PB. Pediatric antifungal agents. Curr Opin Infect Dis 2009;22:553–8.

ERRNVPHGLFRVRUJ

Sedatives, Analgesics, and Muscle Relaxants “A man who cannot work without his hypodermic needle is a poor doctor. The amount of narcotic you use is inversely proportional to your skill” —Martin H Fischer (1879–1962)*

Sedatives Drug

Dose

Onset

Duration of action

Chloral hydrate

Children: Sedation: 8 mg/kg or 250 mg/m2 q8h PO (max 500 mg q8h). Sedation for procedures: 25–50 mg/kg PO. Adult: Sedation: 250 mg q8h PO; hypnotic dose: 0.5–1 g PO.

15–30 min

60–120 min

Dexmedetomidine

Children: Loading dose of 0.25–0.5 mcg/ kg over 10 min, followed by IV infusion of 0.25–0.5 mcg/kg/h, titrated to response Adults: Loading dose of 1mcg/kg over 10 min, followed by IV infusion of 0.2–0.7 mcg/kg/h

Diazepam

Children: PO: 0.12–0.8 mg/kg/day in divided doses q6–8h PRN. IM/IV: 0.04–0.3 mg/kg/dose q2–4h PRN (max of 0.6 mg/kg in an 8 h period). Adults: PO: 2–10 mg/dose q6–12h PRN. IM/IV: 2–10 mg/dose q3–4h PRN.

2–5 min (IV dose)

60–120 min

Lorazepam

Children: PO/IM/IV: 0.05 mg/kg/dose q4–8h (range: 0.02–0.1 mg/kg/dose; max 2 mg/dose). Adults: PO: 1–2 mg/dose q8–12h (up to a max of 10 mg/day). IV: 2 mg (or 0.044 mg/kg, whichever is less) single dose.

PO: 20–30 min IM: 30–60 min IV: 1–5 min

6–8 h

*Martin H Fischer was a German physiologist, chemist, and author.

ERRNVPHGLFRVRUJ

218


Drug

Dose

Onset

Duration of action

Midazolam

Sedation with mechanical ventilation: Children: 0.05–0.2 mg/kg IV bolus followed by 0.06–0.12 mg/kg/h IV infusion Adults: 0.15–0.35 mg/kg IV bolus followed by 0.02–0.10 mg/kg/h IV infusion

2–3 min

45–60 min

30–45 min

4–6 h

Conscious sedation: Children: IV: < 6 mo: titrate in small increments 6 mo–5 yr: 0.05 to 0.1 mg/kg IV (may increase up to 0.6 mg/kg; max dose 6 mg). 6–12 yr: 0.025–0.05 mg/kg IV (may increase up to 0.4 mg/kg; max dose 10 mg). IM: 0.1 to 0.15 mg/kg IM (may increase up to 0.5 mg/kg; max dose 10 mg) Adults IV: 1–2.5 mg. (May increase up to 5 mg) Triclofos

Children: 25–30 mg/kg PO (1–5 yr: 250– 500 mg PO; >5 yr: 500 mg–1 g PO) Adults: 1–2 g PO

Sedation and analgesia are separate entities; although some agents (e.g., morphine, ketamine) have both sedative and analgesic properties, others are almost exclusively analgesics (e.g., fentanyl, paracetamol) or sedatives (e.g., benzodiazepines, propofol, chloral hydrate). Dexmedetomidine is an a2-agonist with both sedative and analgesic properties. It is used as an IV infusion for ventilated and nonventilated patients and provides a moderate level of sedation without causing notable respiratory depression. It, however, can cause clinically significant bradycardia and hypotension because of peripheral a2-receptor stimulation. Midazolam is a benzodiazepine derivative. It is a sedative and an anxiolytic agent with a short duration of action. May cause hypotension especially if the patient has hypovolemia. Tolerance and dependence are known to occur after prolonged use of morphine, fentanyl, or midazolam. Abrupt discontinuation of these drugs may precipitate withdrawal syndrome. Clinical features of withdrawal usually occur within a few hours of stopping the drug and include manifestations associated with the following systems: (i) CNS (e.g., agitation, seizures, hallucinations, and psychosis),

ERRNVPHGLFRVRUJ


219

(ii) autonomic system (e.g., vomiting, tachycardia, hypertension, and fever), and (iii) CVS (e.g., arterial desaturation). Narcotic analgesics Drug

Dose

Onset

Duration of action

Fentanyl

Children: 1–2 mcg/kg IV bolus; may be repeated q30 min–1 h or followed by IV infusion 4–10 mcg/kg/h Adults: 50–100 mcg IV q1–2h or 0.5–1.5 mcg/kg/h IV infusion

1 min

15–60 min

Morphine

Children IV— 1–3 mo: 25 mcg/kg; may be repeated q6h 3–6 mo: 50 mcg/kg; may be repeated q6h 6–12 mo: 100 mcg/kg; may be repeated q4h >1 yr: 100–200 mcg/kg may be repeated q4h Followed by IV infusion— 1–6 mo: 5 mcg/kg/h 6–12 mo: 10 mcg/kg/h >1 yr: 10–50 mcg/kg/h IM— 6–12 mo: 150 mcg/kg >1 yr: 250 mcg/kg Adult IV—2.5–10 mg; may be repeated q4h, followed by IV infusion 0.8–80 mg/h IM—5–20 mg q4h

2–3 min

30–60 min

Fentanyl is a synthetic opioid, having a relatively short half-life of 30–60 minutes and causes less histamine release than morphine, and therefore less hypotension. Like morphine, it can also cause nausea, constipation, and respiratory depression. A reduction in dose is required in renal failure. Respiratory depression caused by an overdose of morphine or fentanyl is counteracted by Inj. naloxone 10 mcg/kg IV bolus (can be given IM/SC/IO). This is followed by a higher dose if there is no response (<20 kg: 100 mcg/ kg, >20 kg: 2 mg). The dose may be repeated if required to maintain opioid reversal or administered as an IV infusion in a dose of 5–20 mcg/kg/h in a concentration of 4 mcg/mL. Morphine is a strong opioid analgesic administered for relief of severe pain and sedation. It may cause hypotension, because of histamine release, particularly after bolus administration. Its other adverse effects include respiratory depression, nausea, and constipation. Dose reduction (by 25–50%) is required in moderate renal failure.

ERRNVPHGLFRVRUJ

220


IV anesthetic agents Drug

Dose

Onset

Duration of action

Etomidate

Children >10 yr and adults: 0.2–0.6 mg/kg IV.

1 min

3–5 min

Ketamine

Children IV: 1.0–2.75 mg/kg. IM: 3–4 mg/kg. IV infusion: 5–20 mcg/kg/min. Adults IV: 1–4.5 mg/kg; repeat 50% of induction dose as required. IM: 6.5–13 mg/kg. IV infusion: 0.1–0.5 mg/min.

3–5 min

15–150 min (2 mg/kg provides 5–10 min of surgical anesthesia and analgesia)

Propofol

Dose for GA: Children: Induction—2.5–3.5 mg/kg; maintenance—125–300 mcg/kg/min. Adult: Induction—2–2.5 mg/kg; maintenance—100–200 mcg/kg/min. ICU sedation 5–50 mcg/kg/min (0.3–3 mg/kg/h).

1 min

10 min

Thiopental sodium

Children: 2–6 mg/kg IV (1–2 mg/kg IV in hemodynamic instability). Adults: 100–150 mg IV (can be repeated if required), maximum dose 500 mg.

30–60 seconds

5–30 min

Etomidate has a rapid onset and short duration of anesthetic action without analgesia. It may be used for short interventional procedures and induction of anesthesia. The drug is useful in patients with hemodynamic instability as it has no effect on the myocardium, peripheral circulation, or the pulmonary circulation. IV injection causes transient pain and may be associated with skeletal muscle movements, including myoclonus. Ketamine in lower doses primarily causes anxiolytic and analgesic effects. With higher doses, it produces sedation and dissociative anesthesia and is used as an anesthetic agent for short painful procedures. Recovery from ketamine anesthesia may be associated with restlessness, agitation, and disorientation. Propofol is a short-acting IV anesthetic agent with no analgesic activity and can be used as an IV infusion for sedation. It has a rapid onset of action, and the effect lasts for 10–15 minutes. Propofol is a negative inotrope, vasodilator and a potent respiratory depressant. It can cause hypotension, respiratory acidosis and apnea. Thiopental sodium is a short-acting barbiturate, which induces hypnosis and anesthesia but not analgesia. It has been used for induction of anesthesia, control of status epilepticus, and to reduce increased intracranial

ERRNVPHGLFRVRUJ


221

pressure in neurosurgical patients. Its adverse effects include pulmonary (apnea, laryngospasm, coughing), cardiovascular (hypotension progressing to shock), and CNS (muscle twitching) manifestations. Muscle relaxants Drug

IV dose

Duration of action

Atracurium

Children (>1 mo) and adults: 300–600 mcg/kg IV followed by 100–200 mcg/kg as required q15–25min or 5–10 mcg/kg/min IV infusion

20–30 min

Pancuronium

Neonates: 30–40 mcg/kg IV bolus, then 10–20 mcg/kg as required q1–1.5h Adults and children >1 month: 50–100 mcg/kg IV bolus, then 10–20 mcg/kg as required q1–1.5h

50–60 min

Rocuronium

Children and adults: 0.6–1.2 mg/kg IV bolus followed by 150 mcg/kg as required. IV infusion: 7–12 mcg/kg/min.

30–50 min

Succinylcholine (suxamethonium chloride)

Children: 1–2 mg/kg IV bolus (3–5 mg/kg IM). Repeat 0.3–0.6 mg/kg IV as required q5–10min. Adults: 0.3–1.1 mg/kg (average 0.6 mg/kg) IV bolus (3–5 mg/kg IM). Repeat 0.04–0.07 mg/kg IV as required q5–10min. IV infusion: 2.5–4.3 mg/min.

3–5 min (IV onset of action: 30 sec; IM: 2–3 min).

Vecuronium

<1 mo: 50–100 mcg/kg IV bolus >1 mo and adults: 100–150 mcg/kg IV bolus, repeat as required IV infusion: 50–80 mcg/kg/h

25–35 min

Pancuronium produces pharmacologic effects similar to those of other non-depolarizing neuromuscular blocking agents. In pharmacological doses, it has a duration of action of 50–60 minutes. The drug may produce an increase in heart rate as a result of its blocking effect on the acetylcholine receptors of the heart. It does not cause hypotension or bronchospasm. Rocuronium is an analogue of vecuronium with a rapid onset and intermediate duration of action. It is used as an adjunct to general anesthesia to facilitate both rapid sequence and routine tracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation. The most common adverse reactions are transient hypotension or hypertension (in 2%) and rarely, nausea, vomiting, arrhythmias, and bronchospasm may occur. Succinylcholine is a short-acting depolarizing muscle relaxant, which is used in general anesthesia to facilitate tracheal intubation and to provide a short period of skeletal muscle relaxation during surgery. Its depolarizing action is observed as muscle fasciculations, which can be a cause

ERRNVPHGLFRVRUJ

222


of hyperkalemia and postoperative myalgia. Injection may result in bradycardia especially in children. This may be prevented by giving atropine 20 mcg/kg (minimum dose, 0.1 mg) or glycopyrrolate 10 mcg/kg preceding the dose of succinylcholine. Despite its adverse effects, this agent remains the drug of choice in an emergency or in patients with anticipated difficult airway because of its rapid onset and short duration of action. Vecuronium is a non-depolarizing muscle relaxant indicated in general anesthesia to facilitate endotracheal intubation and to provide skeletal muscle relaxation during surgery or mechanical ventilation. The drug does not alter the level of consciousness or provide analgesia or amnesia. Its advantage is that it has no clinically significant effects on hemodynamic parameters. Non-depolarizing neuromuscular blockade is readily reversed with neostigmine (50–70 mcg/kg; in age >12 yr: 5 mg) which is given in conjunction with an anticholinergic agent (atropine 10–20 mcg/kg or glycopyrrolate 10 mcg/kg). Nonsteroidal anti-inflammatory drugs Drug

Dose

Remarks

Aspirin

Children: 30–60 mg/kg/day divided q4–6h PO Adult: 300–900 mg q4–6h PO (maximum 4 g/day)

Should be avoided in children <12 years due to risk of Reye syndrome

Ibuprofen

Children: 20–30 mg/kg/day divided q4–6h PO Adults: 1.2–2.4 g/day divided q4–6h PO

Avoid in infants <6 months

Nimesulide

Children: 5 mg/kg/day divided q8–12h PO Adults: 100–200 mg q12h PO

Banned in many countries, but available in India

Paracetamol Children: 40–60 mg/kg q4–6h PO or 5 mg/kg q4–6h IV (maximum 30 mg/kg/day IV) Adult: 0.5–1g q4–6h PO (maximum 4 g/day)

Sedation and Analgesia on Ventilator Muscle Relaxants At the commencement of ventilation, the patient receives muscle relaxants, sedation and analgesia. Whenever muscle relaxants are used, sedation and analgesia must invariably be given. Once the patient has been stabilized, muscle relaxants may be discontinued because of the risks and complications associated with their prolonged use. Ventilation is then maintained with optimum levels of sedation and analgesia. Muscle relaxants may however, be continued in children who are hemodynamically unstable or when it is difficult to achieve compliance with the ventilator.

ERRNVPHGLFRVRUJ


223

Analgesics Analgesia should be administered to any child who has undergone a surgical procedure and is likely to have some degree of pain or discomfort. Adequacy of analgesia may be assessed by noting pain related behavior and physiological responses to pain. The use of a pain scoring system appropriate to the age of the child is advocated for accurate assessment and pain management (Appendix M). Morphine or fentanyl administered as a continuous IV infusion have been the drugs of choice for relief of severe postoperative pain. NSAIDs are used as adjuncts to opioids in certain patients and have been shown to reduce opioid requirements by around 15–30%. Local/regional anesthetic techniques (e.g., epidural) are also beneficial for the relief of pain.

Sedatives Modified Ramsay sedation scale Level response 1 - Awake and anxious, agitated, or restless. 2 - Awake, cooperative, and settled on minimal ventilation. 3 - Awake; responds to commands. Moves spontaneously. 4 - Asleep; brisk response to light glabellar tap or loud noise. No spontaneous movement. 5 - Asleep; sluggish response to light glabellar tap or loud noise stimulus. 6 - Asleep; no response to light glabellar tap or loud noise. The Ramsay is a simple scale, scored from 1 to 6 for assessment of the level of sedation.

Sedation is given in order to reduce anxiety and stress responses and maintain secure placement of tubes and lines in the postoperative patient. All sedation can cause some degree of hypotension, and reduction in the ability to clear secretions. There may also be paradoxical agitation, dependence, and a withdrawal phenomenon. In addition, opiates cause impaired gastric emptying and constipation. All sedatives therefore need to be reviewed periodically and administered in the lowest effective doses. The level of sedation should be regularly assessed and documented against a scale, such as the Ramsay sedation scale, and doses of sedative agents titrated to produce the desired level of sedation (a score of 2–4 is appropriate in most situations). Before increasing the degree of sedation in an agitated child, one needs to exclude all irritant factors viz. pain, hypoxia, hypercarbia, secretions, full bladder, hunger, thirst, ambient temperature too hot/cold, noise, lighting, position, nausea, constipation, colic, soiled nappy, pruritus, or inappropriate ventilator settings. After exclusion of irritant factors in the unsettled

ERRNVPHGLFRVRUJ

224


child, methods of restraint such as swaddling, arm splinting, and wrist and ankle ties may be effectively employed so that the lowest required doses of sedation are administered. Sedation is gradually terminated when the blood gases are normal, and the patient is hemodynamically stable on minimal inotropes and ready for extubation. Midazolam or dexmedetomidine given by continuous IV infusion are recommended agents of choice for the majority of critically ill children requiring intravenous sedation. Children may be changed over to enteral sedation (e.g., chloral hydrate) once enteral (nasogastric or nasojejunal) feeding is established.

Sedation for Short Procedures Children on IV sedation can have a bolus (up to 1 hour of infusion given as a bolus) a couple of minutes prior to physiotherapy, chest tube removal, catheterization, etc. More painful procedures can be done under ketamine (IV or IM) alone or a combination of propofol or midazolam plus an analgesic agent (ketamine/ fentanyl). Propofol alone may be used for nonpainful procedures.

Rapid Sequence Intubation Normal induction of general anesthesia involves administration of a shortacting opioid analgesic agent (fentanyl/morphine) followed by a slow injection of an intravenous anesthetic agent (thiopentone/propofol/etomidate) with simultaneous assessment of the patient’s verbal response or eyelash reflex. Once the patient is unconscious, a muscle relaxant (succinyl choline/ rocuronium/vecuronium) is administered and the patient is intubated. In rapid sequence intubation (RSI), a predetermined dose of intravenous anesthetic agent or sedative (thiopentone/propofol/etomidate/ketamine/ midazolam) is first given and this is immediately followed by a quick acting muscle relaxant (succinyl choline/rocuronium) to allow tracheal intubation. RSI may be indicated in the cardiac surgical patient because of sudden cardiac arrest, hemodynamic instability with impending arrest, or loss of airway due to dislodgement or obstruction of endotracheal tube. Step wise approach to RSI is as follows: (i)

Assist spontaneous ventilation with bag mask ventilation and pre-oxygenate with 100% oxygen.

(ii) Routine use of anticholinergics is not necessary but atropine 10–20 mcg/kg or glycopyrrolate 10 mcg/kg may be administered in presence of bradycardia.

ERRNVPHGLFRVRUJ


225

(iii) To prevent aspiration, consider cricoid pressure till airway is definitely secured. (iv) If the patient is awake and hemodynamic parameters permit, an induction agent or sedative is administered to prevent recall. Etomidate (0.2–0.3 mg/kg) is the drug of choice as it provides maximum hemodynamic stability and has minimal direct cardiac depressant action. Ketamine (1–2 mg/kg), midazolam (0.2–0.3 mg/kg), thiopentone (2–6 mg/kg), or propofol (2–3 mg/kg) are other alternative drugs. In severe hemodynamic compromise, an induction agent is avoided for fear of cardiovascular collapse though a muscle relaxant may be given. No induction agent or muscle relaxant is required in case of cardiac arrest. (v) IV muscle relaxant is next given to assist intubation and maintain ventilation. Succinylcholine (1–2 mg/kg) is indicated in difficult airway as it has a rapid onset and short duration of action. It may cause bradycardia and is contraindicated in hyperkalemia. Rocuronium bromide (0.6–1.2 mg/kg) is an alternative with equally rapid onset but prolonged duration of action. (vi) In case intubation is not accomplished, the patient is managed with an appropriate size supraglottic device (laryngeal mask airway or cuffed oropharyngeal airway).

Preparation and Administration Midazolam 2.5 mg/kg made up to 50 mL with 5% dextrose or 0.9% saline. With this concentration, 1 mL/h = 50 mcg/kg/h. Morphine 1 mg/kg made up to 50 mL with 5% dextrose. With this concentration, 1 mL/h = 20 mcg/kg/h. Fentanyl 0.25 mg/kg made up to 50 mL with 5% dextrose. With this concentration, 1 mL/h = 5 mcg/kg/h. Dexmedetomidine 10 mcg/kg made up to 50 mL with 5% dextrose. With this concentration, 1 mL/h = 0.2 mcg/kg/h.

ERRNVPHGLFRVRUJ

226


Bibliography 1. Arnold HM, Hollands JM, Skrupky LP, Mice ST. Optimizing sustained use of sedation in mechanically ventilated patients: focus on safety. Curr Drug Saf 2010;5:6–12. 2. Buck ML. Dexmedetomidine for sedation in the pediatric intensive care setting. Pediatric Pharmacotherapy 2006;12(1). © 2006 Children’s Medical Center, University of Virginia. Last accessed on 31th Jul 2011. Available at: http://www.medscape.com/viewarticle/524752. 3. Chrysostomou C, Di Filippo S, Manrique AM, et al. Use of dexmedetomidine in children after cardiac and thoracic surgery. Pediatr Crit Care Med 2006;7:126–31. 4. Darowski M. Sedation for ventilated children. [Updated: 2009 Aug; cited: 2011 Apr 26]. Available at: http://www.leedspicu.org/Documents/Mark%20D%20-%20Sedation%20for%20 Ventilated%20Children7.09%282%29.pdf 5. Deorari AK. Rational drug therapy. In: Ghai OP, Paul VK, Bagga A, ed. Essential Paediatrics 7th ed. New Delhi, India: CBS Publishers & Distributors Pvt Ltd; 2009:721–2. 6. Guinter JR, Kristeller JL. Prolonged infusions of dexmedetomidine in critically ill patients. Am J Health Syst Pharm 2010;67(15):1246–53. 7. Hall RI, Sandham D, Cardinal P, et al; Study Investigators. Propofol vs midazolam for ICU sedation: a Canadian multicenter randomized trial. Chest 2001;119:1151–9. 8. Khilnani P, Kaur J. Sedation and analgesia in pediatric intensive care unit. Indian J Crit Care Med 2003;7:42–9. 9. Newth CJ, Venkataraman S, Willson DF, et al; Eunice Shriver Kennedy National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network. Weaning and extubation readiness in pediatric patients. Pediatr Crit Care Med 2009;10:1–11. 10. Playfor SD. Analgesia and sedation in critically ill children. Cont Educ Anaesth Crit Care Pain 2008;8:90–4. 11. Precedex (dexmedetomidine hydrochloride) [package insert]. Lake Forest, IL: Hospira, Inc; 2008. Revised September 2010. 12. Prescription Drug Information, Interactions & Side Effects. [Cited: July 2012] Available at: http://www.drugs.com. 13. Ramsay MA, Savege TM, Simpson BR, Goodwin R. Controlled sedation with alphaxalonealphadolone. Br Med J 1974;2:656–9. 14. Ranjit S. Pharmacology of sedative and analgesic agents. In: Ranjit S, ed. Manual of Pediatric Emergencies and Critical Care Hyderabad, AP, India: Paras Medical Publisher; 2010:438–43. 15. Scherrer PD. Safe and sound: pediatric procedural sedation and analgesia [internet]. [Updated: 2011 Mar; cited: 2011 Apr 26]. Available at: http://www.minnesotamedicine.com/ PastIssues/March2011/PediatricProceduralSedationandAnalgesia2011/tabid/3691/Default. aspx. 16. Srouji R, Ratnapalan S, Schneeweiss S. Pain in children: assessment and nonpharmacological management. Int J Pediatr 2010; doi:10.1155/2010/474838. 17. Stawicki SP. Sedation scales: very useful, very underused. OPUS12 Scientist 2007;1(2):10–2. 18. Sweetman SC, Blake S. Anxiolytic sedatives hypnotics and antipsychotics. In: Martindale: The Complete Drug Reference 34th ed. 2005:663–731.

ERRNVPHGLFRVRUJ

Seizures

Drugs for Rapid Control of Seizures Drug

Initial dose (mg/kg)

Onset of action

Remarks

Diazepam

0.1–0.3 mg/kg slow IV.

Immediate

Dose is repeated after 10 minutes if seizure continues. Must be followed by an immediate loading dose of phenytoin, as the duration of action of diazepam is 20 minutes.

0.2–0.5 mg/kg rectal. Adults: 5–10 mg IV. 0.2–0.5 mg/kg rectal. Lorazepam

Rectal dose may be repeated after 4–12 hours.

0.05–0.1 mg/kg slow IV (max 2 mg)

Immediate

0.1–0.4 mg/kg rectal

Has a longer duration of action (6–8 hours), and is less respiratory depressant than diazepam.

Adults: 4 mg IV stat Midazolam

Dose for sedation: 6 mo–5 yr: 0.05–0.1 mg/kg slow IV/IM. Repeat in increments q2min till effect (up to 0.6 mg/kg; max 6 mg). 6–12 yr: 0.025–0.05 mg/kg. Repeat q2min PRN (up to 0.4 mg/kg; max 10 mg). Adult: 1–2.5 mg. Repeat in increments q2min PRN (max 5 mg).

Dose is repeated after 10 minutes if seizure continues.

Immediate

ERRNVPHGLFRVRUJ

228


Subsequent Therapy Drug

Initial dose

Maintenance dose Remarks

Phenytoin

Children: 15–20 mg/kg slow IV over 20–30 minutes.

5–10 mg/kg/day in divided doses q8–12h PO/IV.

Adults: 10–15 mg/kg Adults: 100 mg slow IV infusion over q6–8h PO/IV. 20–30 minutes.

It is infused at not >1 mg/kg/min at a maximum concentration of 10 mg/mL in normal saline only. Extravasation causes tissue necrosis. Therapeutic levels are reached in 20–30 min. Phenytoin causes minimal sedation. Immediate sideeffects are hypotension, arrhythmia, and phlebitis. Long-term side effects include gingival hyperplasia, ataxia, and megaloblastic anemia.

Fosphenytoin (Fosphenytoin sodium injection is dispensed in phenytoin sodium equivalent units [PE])

Children and adults: 4–5 PE/kg/day 10–15 phenytoin in divided doses equivalent units q12–24h PO/IV. (PE)/kg IV; it is administered at a rate of 100–150 PE/min.

The advantages over phenytoin are: it can be administered rapidly IV/ IM, in saline or dextrose, and therapeutic levels are achieved faster. Produces less venous irritation. Arrhythmias and hypotension can occur as with phenytoin.

Phenobarbitone

Children: 10–20 mg/kg slow IV.

5–10 mg/kg/day repeated q24h PO/IV.

Immediate side effects include hypotension, respiratory depression, and sedation.

Adults: 10 mg/kg slow IV (max 1 g).

Adults: 60–180 mg/day q24h PO HS (may be increased to 300 mg).

Long-term side effects include drowsiness and hyperkinesias.

ERRNVPHGLFRVRUJ

If seizures are refractory to phenytoin, phenobarbitone is given in addition. It is the drug of first choice in neonates, but not in older children.

Seizures

Drug

Initial dose

229


Sodium valproate Children: PO—10 mg/kg in divided doses q12h. IV—10 mg/kg bolus over 3–5 minutes. The dose is increased weekly to maintenance level.

20–50 mg/kg/day in divided doses q12h PO/IV. Adults: 20–50 mg/kg/day in divided doses q12h PO/IV (max 2.5 g/day).

Side effects include nausea, vomiting, impaired liver function, increased appetite, and weight gain. Less commonly, tremors and motor in-coordination, pancreatitis, and blood disorders.

Adults: PO—600 mg in divided doses q12h. IV—10 mg/kg bolus over 3–5 minutes. Carbamazepine

Children: 5–10 mg/ kg/day q24h PO (at night) and increased weekly by 2.5–5 mg/ kg/day to 10–30 mg/ kg/day in divided doses q8–12h PO. Adults: 100–200 mg q24h PO (at night) increased weekly by 100–200 mg/day to 800–1200 mg/ day in divided doses q8–12h PO.

Levetiracetam

20 mg/kg/day in divided doses q12h PO, double every 2 weeks to 60 mg/kg/day in divided doses q12h PO. Adults: 1 g/day in divided doses q12h PO double every 2 weeks to a max of 3 g/day in divided doses q12h PO.

10–30 mg/kg/day Adverse effects include divided q8–12h PO. drowsiness, headaches, motor in-coordination, and GIT Adults: 800–1200 symptoms. mg/day in divided doses q8–12h PO. Less common side effects are cardiac arrhythmias, diplopia, aplastic anemia, thrombocytopenia, and dermatological reactions.

60 mg/kg/day in Indicated as adjunctive divided doses q12h therapy in adults and children PO. over 4 years age. Adults: 3 g/day in May cause sleepiness, divided doses q12h weakness, and dizziness. In PO. children, the most common side effects are sleepiness, hostility, irritability, and weakness.

ERRNVPHGLFRVRUJ

230


Control of Refractory Seizures Drug

Initial dose


Midazolam

0.05–0.1 mg/kg IV bolus. May repeat dose q2–3 min up to max 6 mg (6 mo–5 yr) and 10 mg (>5 yr).

Children: 60–120 mcg/kg/h IV infusion.

Titrate drip to control seizures. Monitor respiration and ventilation.

Adults: 20–100 mcg/kg/h.

Adults: 1–2.5 dose over 2 minutes. Repeat q2–3 min until desired effect (max 10 mg). Thiopental sodium

2–6 mg/kg IV (1–2 mg/kg IV in hemodynamic instability).

0.5–5 mg/kg/h IV infusion.

Titrate drip to control seizures. Monitor respiration and ventilation.

Adults: 100–150 mg IV (can be repeated if required, to a max of 500 mg). Propofol

Diazepam

Dose for sedation: 25–75 mcg/kg/min Children and adults: (1.5–4.5 mg/kg/h) 0.5–1 mg/kg IV infusion. IV bolus then 0.1–0.5 mg/kg IV every 3–10 minutes for maintenance.

Titrate drip to control seizures.

0.1–0.3 mg/kg IV.

Titrate drip to control seizures.

100–400 mcg/kg/h IV infusion.

Monitor respiration and ventilation. Keep for 12 hours after seizure activity.

Adults: 10–20 mg IV. Monitor respiration and ventilation.

Management of Acute Seizures Airway, breathing and circulation In a child having seizures, the airway needs to be first secured by correct positioning of the head and neck. Oxygen is administered by a nasal cannula, facemask, or endotracheal intubation. Heart rate and respiration are monitored.

ERRNVPHGLFRVRUJ

Seizures

231

IV dextrose Blood sugar and serum electrolytes are checked. 0.25–0.5 g/kg of dextrose may be given empirically (i.e., 2.5–5 mL/kg of 10% dextrose or 1–2 mL/kg of 25% dextrose). IV sedation Rapid control of seizures is obtained by any one of the following injections: diazepam, lorazepam, or midazolam. Anti-epileptic drug therapy A loading dose of phenytoin or fosphenytoin is administered to prevent subsequent seizures. Because of the risk of hypotension and arrhythmias, phenytoin and fosphenytoin are administered slowly with continuous ECG, blood pressure, and respiratory monitoring. Ideally if 2 hours after administration, the plasma level of phenytoin is <10 mg/L, an additional IV dose of 5 mg/kg is administered. The full anti-epileptic effect of phenytoin, or fosphenytoin, is not immediate, and adjunctive benzodiazepines may be needed to interrupt convulsions if they occur during phenytoin infusion. Oral or parenteral phenytoin for long-term maintenance medication is started 12 hours after the loading dose. In case seizures recur despite single drug therapy, a combination of anti-epileptic drugs may be required. Paralysis and Intermittent positive pressure ventilation Refractory seizures (status) that do not respond to repeated doses of diazepam, lorazepam, or midazolam are managed by intubation, ventilation, and an infusion of short-acting muscle relaxants or complete paralysis.

Causes of Postoperative Seizures Disorder

Causes

Comment

Drugs

Lignocaine, tranexamic acid

High doses of Inj. lignocaine or tranexamic acid given in the cardiopulmonary bypass (CPB) may be a cause.

Hypoxia

Hypoxic brain injury may follow total circulatory arrest, cardiac arrest, or prolonged hypotension

Embolization

Gaseous and particulate embolization

Cerebral hemorrhage

Anticoagulation, hypertension

ERRNVPHGLFRVRUJ

232


Disorder

Causes

Comment

Metabolic disturbances

Commonly, hypocalcemia, hypoglycemia, hyponatremia

Less commonly, aminoacidurias, hepatic or uremic encephalopathy, hyperglycemia, hypomagnesemia, hypernatremia. In neonates, vitamin B6 (pyridoxine) deficiency.

Febrile convulsion

Neurological injury may result from ischemia, cerebral hemorrhage, hypoxia, or embolization. Under deep hypothermia, a duration of circulatory arrest of >40 minutes is associated with an increased risk of neurologic injury. Other variables that may influence the risk of brain injury include the duration of CPB, depth of hypothermia, the rate and duration of core cooling, and the degree of hemodilution. Dissemination of both macroemboli and microemboli (gaseous or particulate) during cardiopulmonary bypass may also cause brain injury. Febrile seizures usually occur in children between the ages of 3 months and 5 years, and are associated with a rise in the body temperature to >38°C (100.4°F). It is a generalized tonic-clonic seizure lasting between a few seconds to 15 minutes, followed by a brief period of drowsiness and is diagnosed when no other cause of the convulsion can be identified. Complex febrile seizures are defined as febrile seizures that are multiple, focal and last >15 minutes or have postfocal paresis. In general, treatment of a febrile convulsion is supportive (cold sponge, antipyretic agents) while seizures of longer duration are treated with IV diazepam, lorazepam, or midazolam. Prophylaxis by means of medications is controversial. Prompt treatment of fever alone has been shown to be effective in preventing recurrences of febrile convulsions.

Bibliography 1. Drislane FW. Status epilepticus. In: Schachter SC, Schomer DL, eds. The Comprehensive Evaluation and Treatment of Epilepsy San Diego, CA: Academic Press; 1997:149–72. [Cited: 2011 Feb 22] Available at: http://professionals.epilepsy.com/page/managing_phenfos.html. 2. Kalra V. Central nervous system. In: Ghai OP, Paul VK, Bagga A, ed. Essential Paediatrics 7th ed. New Delhi, India: CBS Publishers & Distributors Pvt Ltd; 2009:523–33. 3. Kutty MN, Kumar S. Seizures and epilepsy. Journal of Postgraduate Medical Education, Training & Research 2008;3:9–12. 4. Prescription Drug Information, Interactions & Side Effects. [Cited: July 2012] Available at: http://www.drugs.com. 5. Saleh F. Al-Ajlouni, Kodah I. Febrile convulsions in children. Neurosciences 2000;5:151–5.

ERRNVPHGLFRVRUJ

Management of the Comatose Child “I am a brain, Watson. The rest of me is a mere appendix” —Arthur Conan Doyle (1859–1930)*

Assessment of the Level of Consciousness Glasgow Coma Scale (GCS) Eye opening Response

Score

Spontaneously

4

To verbal stimuli (command, speech, or shout)

3

To pain

2

No response

1

Best verbal response Adult response

Equivalent response in non-verbal children

Score

Oriented and converses

Smiles, oriented to sounds. Older children use appropriate words

5

Disoriented, but able to answer questions

Cries and consolable

4

Inappropriate words

Persistent inappropriate crying or screaming

3

Incomprehensible speech

Grunts or is agitated or restless

2

No response

No response

1

Best motor response Response

Score

Obeys commands

6

Purposeful movement to painful stimulus

5

Flexion/withdrawal to painful stimulus

4

Abnormal flexion, decorticate posture

3

Extensor response, decerebrate rigidity

2

No response

1

*Excerpt from The Adventure of the Mazarin Stone by Sir Arthur Ignatius Conan Doyle—a Scottish physician, novelist, short story writer and poet. He became famous for the character of detective Sherlock Holmes in his stories.

ERRNVPHGLFRVRUJ

234


The best verbal response category of the adult Glasgow coma scale has been modified so that the scale becomes applicable to children who are as yet not of the age to be able to speak (Adelaide coma scale). The total score is the sum of the scores of three categories. The score may range from 3 to 15. Patients with scores of 3–8 are said to be in coma.

AVPU Scale AVPU scale is another simple method of recording the level of consciousness. A – Alert V – Responds to verbal commands P – Responds only to pain U – Unresponsive

Descriptive Terms that Define Levels of Consciousness ■

Delirium: Delirium is characterized by a state of fluctuating consciousness associated with agitation, drowsiness, incoherent speech, and disorientation.

■

Stupor is a state of unawareness in which the patient responds only to shouts or painful stimuli.

■

Coma: The comatose patient is unresponsive to ordinary stimuli and may have a non-purposeful response to painful stimuli. The Glasgow coma scale is generally <8.

■

Vegetative state: The patient is awake, eyes are open, and give the appearance of wakefulness but does not respond to command. Yawning, grunting, swallowing, as well as limb and head movements may be present.

■

Brain death: Brain death represents a complete and irreversible loss of brain and brainstem function. It is recognized clinically by absence of consciousness, cranial nerve function, motor reflexes, and spontaneous breathing. EEG shows no activity. Patients who are brain dead and maintained on mechanical ventilation and other life support systems may continue to have cardiovascular, renal, hepatic, and respiratory functions.

Causes The causes of coma in the postoperative period can broadly be classified into two groups: 1. Coma with no focal neurological deficit ■

Hypoxic encephalopathy

■

Drugs: sedatives, anesthetics, opioids, etc.

ERRNVPHGLFRVRUJ


235

■

Epilepsy: status epilepticus, post-ictal states.

■

Metabolic derangements: hypoglycemia, hyperglycemia, hypoxemia, hypercarbia, hyponatremia, hypernatremia, hypercalcemia, hypothermia, hyperpyrexia, uremia, etc.

■

Infection: meningitis, encephalitis.

2. Coma with focal neurological deficit ■

Particulate/air embolism

■

Vascular: embolism, hemorrhage (extradural, subdural, subarachnoid, intracerebral)

■

Infection: brain abscess, subdural empyema

■

Herniation syndromes

Neurological Examination Clinical signs of transtentorial herniation ●

Coma

●

Pupils dilated/constricted/unequal

●

Lateral gaze palsy

●

Hemiparesis

●

Decerebrate posture

●

Hypertension, bradycardia, Cheyne–Stokes respiration (Cushing’s triad)

Neurological examination of a comatose patient involves the examination of the following: 1. State of consciousness: The level of consciousness is recorded after evaluation by the GCS. 2. Respiratory pattern: Cheyne–Stokes respiration is present in lesions involving bilateral cerebral hemispheres (metabolic disorders, hypoxia, etc.), midbrain or upper pons (as in impending transtentorial herniation). Cushing’s triad is a late feature of cerebral injury and occurs when transtentorial herniation and brain stem compression take place. The components of the triad are (i) increased systolic blood pressure, (ii) bradycardia, and (iii) Cheyne–Stokes respiration. 3. Pupillary size and reactivity: Pupils are pinpoint (<2 mm) and non-reactive in pontine lesions, and small (2–3 mm) and reactive with an overdose of some drugs (opiates, barbiturates, phenothiazines).

ERRNVPHGLFRVRUJ

236


Bilateral dilated and non-reactive pupils are seen after atropine use, hypothermia and central herniation. A unilateral dilated non-reactive pupil is caused by compression of the oculomotor nerve and is seen in uncal herniation and lesions affecting the coronary sinus. 4. Ocular motility and papilledema: Normally, the eyes at rest are in mid position and looking ahead. Conjugate deviation of the eyes suggests either an ipsilateral cerebral hemispheric lesion or a contralateral pontine lesion. 5. Ocular reflexes: The oculocephalic reflex (Doll’s eyes movement) is present when the eyes do not follow the movements of the head and move in the direction opposite to head movement. It indicates an intact brain stem. The reflex is absent when the eyes follow the direction of head movement, and is an indication of a brain stem lesion. The oculovestibular reflex is elicited by injecting cold or warm saline (30 mL in the adult) into the external auditory meatus. If the brain stem is intact, both eyes deviate towards the irrigated ear. This movement is lost if the brain stem is damaged. 6. Papilledema: Raised intracranial pressure over a period of hours results in papilledema with or without hemorrhages. 7. Motor response: The motor system is evaluated by noting the child’s posture and response to painful stimuli. The muscle tone and reflexes are evaluated. Purposeful withdrawal from painful stimuli is a sign of cortical function and hence cortical preservation. Hemiparesis may occur in internal capsule lesions and midbrain compression due to uncal herniation. Decorticate posturing signifies diffuse damage to the cerebral cortex or basal ganglia, and decerebrate rigidity is a sign of more extensive damage to the midbrain. Decorticate posture consists of flexion at the elbows and wrists with shoulder adduction and internal rotation. The lower limbs are extended. Decerebrate rigidity is characterized by bilateral extension of the elbows with shoulder adduction and internal rotation and extension of the lower limbs. Flaccidity and the absence of any motor response are suggestive of a severe brainstem lesion. 8. Involuntary movements: Hypoxic brain damage may be a cause of epilepsy or myoclonus. Myoclonus is sudden, brief and jerky, involuntary movements which may be triggered by attempts at voluntary movement, sensory stimulation, or startle in a child. It occurs because of sudden contraction or relaxation of a muscle group and may be associated with hypoxic brain injury and various other neurological disorders (infection, injury, tumor, epilepsy, etc.).

ERRNVPHGLFRVRUJ


237

Investigations Investigations should include evaluation of blood gases, serum electrolytes, blood glucose, liver enzymes, complete and differential blood cell count, and peripheral blood smear. Prothrombin time, INR, and activated partial thromboplastin time are used to assess coagulation abnormalities. Fundoscopy detects papilledema and hemorrhages.

CT Scan A CT scan is often needed as an emergency investigation, particularly in children with signs of raised intracranial pressure or focal neurological deficits. CT has high sensitivity for diagnosis of acute intracranial hemorrhage, cerebral edema, and hydrocephalus; and moderate sensitivity for abscess or tumor. CT may not demonstrate any findings in hypoxic encephalopathy, ischemic stroke, or a metabolic disorder.

MRI Patients with equivocal CT findings should undergo MRI. MRI is more likely to detect diffuse hypoxic injury and acute ischemic stroke in addition to cerebral edema, tumor, abscess, and other inflammatory processes. MRI has a higher sensitivity for lesions not diagnosed clinically or by CT scan.

Lumbar Puncture Lumbar puncture (LP) is rarely indicated in the postoperative patient. It is needed to make an early diagnosis of CNS infection and identification of the pathogen or in suspected subarachnoid hemorrhage. Contraindications for LP include a low GCS, focal neurological signs, presence of signs of cerebral herniation or cardiorespiratory compromise.

Care of a Child in Coma Cerebral perfusion pressure (CPP) is the pressure at which the brain tissue is perfused and is denoted by the difference between the mean arterial pressure (MAP) and the intracranial pressure (ICP), i.e., CPP = MAP − ICP. Normal value of CPP in adults is >70 mmHg; children >50–60 mmHg;

ERRNVPHGLFRVRUJ

238


and infants >40–50 mmHg. The normal ICP values are estimated in adults <20 mmHg; children <18 mmHg; and infants <15 mmHg. Hypoxia, hypercarbia, lactic acidosis, or cerebral edema from any cause results in elevation of ICP. ICP normally also increases with activities such as suctioning, painful stimuli, and coughing, but returns to baseline values in a couple of minutes. The primary goal of treatment in adult patients is to maintain CPP >70 mmHg (or age appropriate in children) and ICP <20 mmHg (or age appropriate in children). Various devices that allow continuous intracranial pressure monitoring and therapeutic CSF drainage for control of ICP are available (intraventricular, subarachnoid, epidural and intraparenchymal devices).

Airway, Breathing, and Circulation The patient is ventilated if the GCS is <8 or if there is respiratory failure. A PaO2 >60 mmHg (oxygen saturation >90%) is maintained and mild hyperventilation (PaCO2 30–35 mmHg) is used to decrease the intracranial pressure by causing vasoconstriction and a decrease in cerebral blood flow. Excessive hyperventilation (PaCO2 <30 mmHg) is not advisable as it may cause severe vasoconstriction and exacerbation of the cerebral ischemia. It may however be utilized as a therapeutic measure in case of refractory intracranial hypertension or impending herniation. Ageappropriate blood pressure must is maintained with vasodilators/vasopressors so that the CPP is adequate and further ischemia is avoided.

Positioning The head end of the bed is elevated 15 to 30 degrees to encourage jugular venous drainage. Flexion, extension or rotation of the head and neck are avoided as these increase the ICP. Passive limb exercises and frequent change of position to relieve pressure areas are instituted.

Analgesia and Sedation Children in coma who are mechanically ventilated should receive appropriate analgesia and sedation to prevent pain and anxiety, which will increase the ICP. Additional sedation and analgesia is administered prior to any procedure (e.g., endotracheal suction) that may cause stimulation. If the child presents with a seizure, initial treatment with a benzodiazepine (e.g., lorazepam) should be followed by appropriate antiepileptic medication (e.g., phenytoin, fosphenytoin).

ERRNVPHGLFRVRUJ


239

Fluids, Electrolytes, and Nutrition The aims of fluid therapy are to maintain euvolemia and normoglycemia, and prevent hyponatremia. Maintenance fluid consists of normal saline with the addition of the daily requirement of potassium chloride based on body weight. All fluids administered must be isotonic. Hypotonic fluids and hyponatremia will cause fluid shifts into the brain and worsen the cerebral edema. Dextrose is not administered for the first 48–72 hours unless the patient is hypoglycemic, due to the increased risk of lactic acidosis. Hyperglycemia is treated with insulin therapy, and early nasogastric enteral feeding is started.

Osmotic Diuresis Mannitol decreases ICP by two mechanisms; firstly, it decreases blood viscosity thus increasing cerebral blood flow, and secondly, by increasing the osmolality of blood it draws fluid from the brain tissue into the vascular space, to be excreted by diuresis. Mannitol is administered in a dose of 0.25–0.5 g/kg IV over 20 minutes and is repeated every 2–6 hours. A higher initial dose (0.5–1 g/kg) may be administered for a more rapid reduction of ICP. Its onset of action is after 15–30 minutes, and the effect lasts 4–6 hours. CVP, serum electrolytes, and osmolality are monitored during therapy, and IV maintenance fluids are administered to maintain CVP and prevent a rise in serum osmolality to unacceptable levels (<320 mOsm/L for mannitol). Mannitol is discontinued after a period of 48–72 hours and on termination of therapy, the dose is gradually reduced because of the inherent danger of rebound rise of ICP. Other complications of mannitol include hypotension, hypokalemia, hemolysis, and renal failure. 3% hypertonic saline (HS) has been used as an alternative to mannitol for osmotic therapy in children. It is administered as a continuous infusion, in a dose of 0.1–1.0 mL/kg/h. The dose is titrated to achieve a serum sodium level of 145–155 mmol/L. Serum sodium and serum osmolality are monitored q2–4h till target sodium level is reached and then q12h. The maximum acceptable level of serum osmolality for HS is 360 mOsm/L. Hypertonic saline has been continued for up to 7 days, and therapy is discontinued gradually so that the rate of decrease of serum sodium level is <0.5 mmol/h because of the danger of pontine demyelination. Other complications of hypertonic saline include volume overload and pulmonary edema, cardiac failure, renal failure, hypokalemia, hyperchloremic acidosis and rebound increase in ICP. Other agents: ■ Inj. furosemide (1 mg/kg q8h) has sometimes been administered empirically by itself or in combination with mannitol.

ERRNVPHGLFRVRUJ

240 ■


Steroids are not indicated in ischemic and hemorrhagic brain lesions, and its use remains debatable in head injury. Dexamethasone is administered in meningitis, brain tumors, and following neurosurgery to reduce cerebral edema. It is the preferred steroid due to its low mineralocorticoid activity. (Dose: 1 mg single dose is followed by 1–1.5 mg/kg/day in divided doses q6h IV/IM/PO (max 16 mg/day) for 5 days and then tapered over a period of 5 days).

Supportive Care Fever is associated with a rise in ICP and is managed with antipyretics and cooling. Regular eye and oral care is instituted.

Bibliography 1. Hopp RL, Ford WJA, O’Connor SJ. The care and nutrition of patient in prolonged coma. Am J Clin Nutr 1956;4:625. 2. James H, Trauner D. The Glasgow coma scale. In: James H, Anas N, Perkin R, eds. Brain Insults in Infants and Children: Pathophysiology and Management Orlando: Grune and Stratton; 1985:179–82. 3. Khanna S, Davis D, Peterson B, et al. Use of hypertonic saline in the treatment of severe refractory posttraumatic intracranial hypertension in pediatric traumatic brain injury. Crit Care Med 2000;28:1144–51. 4. Maiese K. Stupor and coma. The Merck Manuals: Online medical library. [Updated: 2008 Feb; cited: 2011 Apr 29] Available at: http://www.merckmanuals.com/home/au/sec06/ch084/ ch084a.html# 5. Marcoux KK, LeFlore J. Management of increased intracranial pressure in the critically ill child with an acute neurological injury. AACN Advanced Critical Care 2005;16:212–31. Available at: http://www.nursingcenter.com/library/JournalArticle.asp?Article_ID=594176. 6. Ramesh S. Paediatric intensive care – update. Indian J Anaesth 2003;47:338–44. 7. Sankhyan N, Vykunta Raju KN, Sharma S, Gulati S. Management of raised intracranial pressure. Indian J Pediatr 2010;77:1409–16. 8. Tang A. Approach to a child with altered consciousness. [Cited: 2011 Apr 29] Available at: http://www.kairos2.com/50_Child%20with%20altered%20consciousness.pdf. 9. Yildizdas D, Altunbasak S, Celik U, Herguner O. Hypertonic saline treatment in children with cerebral edema. Indian Pediatr 2006;43:771–9.

ERRNVPHGLFRVRUJ

Acute Kidney Injury “These circumstances are wholly exceptional. Desperate diseases, they say, call for desperate remedies” —Anthony Wynne (1882–1963)*

The term “acute renal failure” (ARF) has now been replaced by the term “acute kidney injury” (AKI) and involves the entire spectrum of renal disease associated with decreasing renal function. The spectrum extends from less severe forms of injury to the point of renal failure when the patient requires renal replacement therapy.

Predisposing Factors ■

Low cardiac output is the foremost predisposing cause. In the event of systemic hypotension, children on drug therapy with ACE inhibitors, indomethacin, aminoglycosides, and NSAIDs are more susceptible to AKI.

■

Hypoxemia, acidosis, sepsis, and hypothermia are all associated with renal vasoconstriction, a decrease in the glomerular filtration rate (GFR), and a fall in urine output.

■

Additional risk factors include young age, complex cardiac lesions, and prolonged cardiopulmonary bypass and circulatory arrest times.

The mechanism of AKI because of ischemia comprises of two phases: (i) prerenal failure when the GFR is depressed by renal vasoconstriction but the tubular structure is normal and restoration of renal blood flow will return renal function to normal, and (ii) the stage of acute tubular necrosis (ATN).

Urinary Indices to Distinguish Established ARF from Prerenal Azotemia Laboratory test

Prerenal azotemia

ARF

Urinary osmolality (mosm/kg)

>500

<400

Urinary sodium level (mmol/L)

<20

>40

*Anthony Wynne was an English physician and author. This excerpt is taken from his Toll House Murder, published by J. B. Lippincott Company (1935).

ERRNVPHGLFRVRUJ

242


Laboratory test

Prerenal azotemia

Urine/serum creatinine ratio

>40

ARF <20

BUN/serum creatinine ratio

>20

<10

Fractional excretion of sodium (FENa)

<1%

>2%

Fractional excretion of urea (FEUN)

<35%

>35%

Urinary sediment

Normal occasional hyaline or fine granular casts

Renal tubular epithelial cells, granular and muddy brown casts.

FENa is calculated as: [(urine sodium/plasma sodium)/(urine creatinine/plasma creatinine)] ´ 100. FEUN is calculated as: [(urine urea nitrogen/blood urea nitrogen)/(urine creatinine/plasma creatinine)] ´ 100.

ARF (AKI) Biomarkers Currently, a number of urinary and serum biomarkers that reflect AKI are under investigation. These predict the onset of AKI 24–48 hours before the elevation of serum creatinine becomes evident. Increased levels of cystatin C (normal blood level in age >1 yr: 0.8–1 mg/L) are present in serum; elevated levels of interleukin-18 (IL-18) and kidney injury molecule-1 (KIM-1) are found in the urine; and elevated levels of neutrophil gelatinase associated lipocalin (NGAL) are present in the serum and urine of patients with AKI.

Estimation of Glomerular Filtration Rate in Children Glomerular filtration rate is the amount of water filtered by the kidney every minute and is the most physiological indicator of renal function. It is estimated by the fact that if a substance ‘x’ is removed from the blood only by renal filtration and is neither secreted nor reabsorbed then the volume of blood plasma that is cleared of this substance ‘x’ per minute is a reflection of the GFR. A number of substances have been used to measure the GFR, viz. inulin, creatinine, iohexol, cystatin C, etc. Creatinine clearance is the volume of blood plasma that is cleared of creatinine per minute. It is about 10–15% more than inulin clearance because creatinine is filtered and secreted in the urinary tubules unlike inulin, which is only filtered. Cx = Ux V/Px Cx is the renal clearance (mL/min) of substance x, V is the rate of urine flow (mL/min), Ux is the concentration of substance x in urine, and Px is the concentration of substance x in plasma.

ERRNVPHGLFRVRUJ

Acute Kidney Injury

243

Normal range of creatinine clearance in males is 90–130 mL/min/1.73 m2; in females it is 80–125 mL/min/1.73 m2. (Adult values of GFR are reached by about 2 years of age and decrease by 6.5 mL/min for every 10 years after the age of 20). Since these methods for the measurement of GFR are not clinically feasible, various formulae based on the serum creatinine levels are utilized to give an estimate of the GFR. As an approximation, changes in serum creatinine (Se creatinine) level correlate with changes in GFR as follows: ■

Se creatinine of 1 mg/dL is normal for an individual with a GFR of 100 mL/min.

■

Se creatinine of 2 mg/dL reflects a 50% reduction in GFR (50 mL/min).

■

Se creatinine of 4 mg/dL reflects a 75% reduction in GFR (25 mL/min).

■

Se creatinine of 8 mg/dL reflects a 90–95% reduction in GFR (12.5 mL/min).

Various formulae based on serum creatinine levels have been devised to estimate the GFR. The Schwartz and Counahan–Barratt formula for estimating the GFR in children use height in the estimate, as height is proportional to muscle mass. (a) Schwartz equation (Patient population: 1 week to 18 year old): CrCl (mL/min/1.73 m2) = [Height (cm) × K]/Se creatinine K = 0.45 for infants 1–52 weeks old; K = 0.55 for infants 1–13 year old; K = 0.55 for adolescent females 13–18 year old; K = 0.70 for adolescent males 13–18 year old. (b) Counahan–Barratt equation: GFR (mL/min/1.73 m2) = [0.43 × Length (cm)]/Se creatinine (c) Cockcroft–Gault equation (Applicable to adult patients): GFR (mL/min) = (140 − Age [yr]) (Weight [kg])/(72 × Se creatinine [mmol/L]) (For female patients, the calculated GFR is multiplied by a factor of 0.85).

Stratification of AKI International consensus panel described the RIFLE criteria for AKI in 2002, which were later modified in 2007 using the Acute Kidney Injury Network (AKIN) criteria. RIFLE criteria defined three levels of increasing severity

ERRNVPHGLFRVRUJ

244


(Risk, Injury, and Failure) and two outcomes (Loss and End-stage kidney disease based on changes in serum creatinine or urine output). RIFLE

Creatinine criteria

Urine output criteria

R - Risk I - Injury F - Failure

Creat ↑ >1.5 × or GFR loss >25% Creat ↑ >2 × or GFR loss >50% Creat ↑ >3 × or GFR loss >75% Creat ↑ >4 mg/dL Persistent failure >4 weeks Persistent failure >3 months

<0.5 mL/kg/h for 6 hours <0.5 mL/kg/h for 12 hours <0.3 mL/kg/h for 24 hours or anuria for 12 hours

eCCl loss >25% eCCl loss >50% eCCl loss >75% or eCCl <35 mL/min/1.73 m2 Persistent failure >4 weeks Persistent failure >3 months

<0.5 mL/kg/h for 8 hours <0.5 mL/kg/h for 16 hours <0.3 mL/kg/h for 24 hours or anuria for 12 hours

Creat ↑ >1.5 × or >0.3 mg/dL from baseline Creat ↑ >2 × Creat ↑ >3 × or Creat ↑ >4 mg/dL with an acute ↑ >0.5 mg/dL

<0.5 mL/kg/h for 6 hours

L - Loss E - End stage p RIFLE* R - Risk I - Injury F - Failure L - Loss E - End stage AKIN modification Stage 1 Stage 2 Stage 3

<0.5 mL/kg/h for 12 hours <0.3 mL/kg/h for 24 hours or anuria for 12 hours

*pRIFLE: pediatric RIFLE criteria. GFR: glomerular filtration rate, Creat: serum creatinine, eCCl: estimated creatinine clearance by the Schwartz formula.

Presentation Acute kidney injury may present as either one of these two types: (i) oliguric form when there is an increasing blood urea nitrogen (BUN) and serum creatinine with oliguria (urine output <0.5 mL/kg/h); or (ii) nonoliguric form where the rise in BUN and serum creatinine is not associated with a fall in urine output. With an increasing BUN, symptoms of uremia become evident, viz., anorexia, nausea, vomiting, confusion, lethargy, somnolence, seizures, and pruritus. Fluid overload and electrolyte abnormalities make these AKI patients more susceptible to cardiovascular (e.g., CHF, arrhythmias, cardiac arrest) and pulmonary (pulmonary edema and hypoxia) complications. Other complications that may occur include GI bleeding, jaundice, coagulopathies, and sepsis.

ERRNVPHGLFRVRUJ

Acute Kidney Injury

245

Laboratory Investigations in AKI Urinalysis Microscopic examination of urine is essential in the differential diagnosis of AKI. Normal urinary sediment without casts or cells is generally consistent with prerenal and postrenal causes of AKI. Granular casts are present in ATN, glomerulonephritis, and interstitial nephritis, while RBC casts are present in glomerulonephritis, and WBC casts indicate pyelonephritis.

BUN The normal level of BUN in children and adults is in the range of 5–20 mg/dL (<2 yr, 4–15 mg/dL). BUN correlates poorly with the GFR. In prerenal conditions (e.g., low cardiac output), low urine flow rates allow increased BUN reabsorption, which results in a disproportionate rise of BUN relative to creatinine, resulting in a serum BUN/creatinine ratio >20. Plasma BUN/ creatinine ratio <10–15 is suggestive of ATN (normal BUN:creatinine ratio 10–20:1). BUN may also rise significantly as a result of increase in urea production with steroids, trauma, or GI bleeding.

Serum Creatinine Serum creatinine reflects the creatinine clearance and is a good measure for approximating the GFR. Normal serum creatinine level is 0.5–1.5 mg/dL (children and adults). Creatinine levels are lower in young children and the elderly because of less muscle mass.

Serum Electrolytes The electrolyte findings that may be present in AKI include metabolic acidosis, hyperkalemia, hyperphosphatemia, hypocalcemia, hypermagnesemia, and hyperurecemia.

Hematology AKI may be associated with anemia and abnormal coagulation studies.

Imaging Renal ultrasound in established ATN shows increased echotexture and loss of corticomedullary differentiation.

ERRNVPHGLFRVRUJ

246


Treatment of Prerenal Failure Accurate measurement of volume state with CVP monitoring is mandatory. During the stage of prerenal failure, i.e., prior to the onset of ATN, urine output may be restored by correction of the volume status and administration of diuretics. ■

Fluid challenge: 5–10 mL/kg of colloid or crystalloid is given over 30–60 minutes to correct the CVP. Careful monitoring is mandatory as administration of excessive volume in a patient who is unable to excrete the extra fluid may result in volume overload and pulmonary edema.

■

Frusemide: Inj. frusemide 1–3 mg/kg IV stat is administered and can be repeated after 2–4 hours to a maximum dose of 5–10 mg/kg. A continuous frusemide infusion (0.1–0.2 mg/kg/h) may be preferred as an alternative to the bolus injection.

■

Dopamine: A dopamine infusion may be started in a low dose primarily for its dopaminergic effect or in higher doses as an inotrope (5–10 mcg/kg/min) to increase the mean arterial pressure.

■

Mannitol: Mannitol causes an osmotic diuresis and is also capable of scavenging free radicals. It is administered in a dose of 0.5 g/kg (2 mL/kg of 25% solution) over 20–30 minutes (adult dose: 100 mL of 25% mannitol). Mannitol needs to be administered with caution as it can precipitate pulmonary edema in a patient with established ATN.

Peritoneal Dialysis and Renal Replacement Therapy Indications Peritoneal dialysis (PD) or renal replacement therapy (RRT) is required in patients with severe kidney injury to remove excess fluid and correct or prevent various associated electrolyte and metabolic abnormalities. Indications include the following: 1. Increasing Se creatinine levels with clinical signs of fluid overload, hyperkalemia (serum potassium >5.5 meq/L), persistent metabolic acidosis or low cardiac output syndrome. 2. Prophylactic peritoneal dialysis has been used as a measure to prevent fluid overload in postoperative children with oliguria (e.g., urine output <1 mL/kg/h for a couple of hours). It may also be considered with long CPB (>90 min) or circulatory arrest time (>60 min) or if there has been a persistent intraoperative oliguria/anuria.

ERRNVPHGLFRVRUJ

Acute Kidney Injury

247

Peritoneal Dialysis Initial PD Prescription Parameter

Recommended prescription

Remarks

Dextrose concentration

1.7%

Increasing dextrose concentration increases ultrafiltration of fluids and clearance of urea and creatinine.

Volume

10 mL/kg (10–30 mL/kg)

Increasing fill volumes also improves ultrafiltration and clearance of urea and creatinine.

Dwell time

45 minutes

Decreasing the dwell time (rapid cycles) improves potassium removal, while longer dwell times improve urea and creatinine clearance.

The advantages of PD compared to various modalities of RRT include ease of application, avoidance of anticoagulation, and there is no requirement of vascular access for administration.

Initial Prescription Peritoneal dialysis is commenced with a dextrose concentration of 1.7% (standard dialysis fluid), dwell volume 10 mL/kg and continuous 1 hour cycles (inflow time: 5 minutes, dwell time: 45 minutes, and outflow time: 10 minutes). To start with, three or more rapid in and out runs are carried out to establish a free flow in the catheter and to clear the dialysate of any blood. If the drain is still blood stained, 500 U/L of heparin is added to the dialysis fluid to prevent clotting till the drain clears. Potassium is also added to the PD fluid (2–4 meq/L) once hyperkalemia has been corrected. Dextrose Concentration To improve fluid output, the dextrose concentration of the dialysis fluid may be increased. Initially, alternate hypertonic glucose exchanges (1.7% and 3%) can be used and then if required a higher concentration of dextrose is used for all exchanges. A 3% dialysis solution is prepared by adding 26 mL of 50% dextrose to 1 liter of 1.7% dextrose. The general principle is to start with the lowest concentration of glucose with stepwise increments if required. Dwell Time Short dwell time cycles remove electrolytes (K, Na, etc.) more rapidly. Short cycles (30 minutes) are considered initially if hyperkalemia needs

ERRNVPHGLFRVRUJ

248


urgent treatment. Longer dwell times (up to 2 hours) improve clearance of urea and creatinine.

Volume Higher inflow volumes increase the amount of fluid removed and also the clearance of urea and creatinine. Larger volumes may, however, cause respiratory distress by pushing the diaphragm up and also alter the cardiac filling pressures resulting in hemodynamic compromise. PD is initially started with an inflow volume of 10 mL/kg, which is increased only if this is well tolerated and there is need to remove higher volumes. Hyperglycemia Frequent cycles of 3% solution or presence of sepsis may cause hyperglycemia leading to hyperosmolarity and loss of effective ultrafiltration. An elevated BSL should be treated with IV insulin (0.1–0.2 U/kg IV). The blood sugar level is checked regularly (q6–12h), and the dose repeated as required. Feeding Patients on dialysis can continue with oral or nasogastric tube feeding. If enteral feeding is not tolerated, TPN is employed and a nasogastric tube is left in situ to prevent vomiting. Monitoring Peritoneal dialysis is generally discontinued after 45–72 cycles and if indicated, it is restarted after 48 hours. Adequacy of PD is assessed by the clinical status of the patient, the fluid output achieved (a net output of 50 mL/kg/day may be adequate), and regular monitoring of the urea, creatinine, and bicarbonate levels. Low cardiac output states and oxygenation needs to be managed appropriately as commercially available dialysis fluids contain lactate, and hypoxic babies may be unable to metabolize lactate resulting in a worsening of the acidosis.

Renal Replacement Therapy Renal replacement therapy is a more efficient method of fluid removal and urea and creatinine clearance compared to PD. Intermittent or continuous methods of RRT may be employed.

Intermittent Hemodialysis Intermittent hemodialysis is the standard form of intermittent renal replacement therapy. Solute removal in dialysis is by process of diffusion

ERRNVPHGLFRVRUJ

Acute Kidney Injury

249

of solutes from blood to dialysis fluid across a semipermeable membrane of a low permeability dialysis filter. This effectively removes small (e.g., electrolytes) and small to mid size molecular weight solutes (e.g., glucose, urea, creatinine). The pore size limits the ability to diffuse larger molecules. The major disadvantage of the procedure in the cardiac patient is the associated hemodynamic instability because of rapid fluid shifts over a short period of time.

Continuous Renal Replacement Therapy Continuous renal replacement therapy (CRRT) is thought to be more physiological and allows greater control over the amount of fluid or electrolytes to be removed. There are a number of modalities of instituting continuous renal replacement therapy, which include (i) arterio-venous or veno-venous SCUF (slow continuous ultrafiltration), (ii) CAVH (continuous arterio-venous hemofiltration), (iii) CVVH (continuous veno-venous hemofiltration), (iv) CVVHD (continuous veno-venous hemodialysis), (v) CVVHDF (continuous veno-venous hemodiafiltration).

Replacement

Access

Return

Hemofilter

Pump

Effluent Fig. 1: Circuit for CAVH.

ERRNVPHGLFRVRUJ

250


When arterio-venous cannulation is used (arterio-venous SCUF, CAVH), the mean arterial pressure provides the pressure for the blood to be driven through the filter, and no external pump is required. In a veno-venous circuit (veno-venous SCUF, CVVH, CVVHD, CVVHDF), an external pump is required to drive the blood through the filter. A controlled veno-venous circuit permits better control of blood flow and allows more hemodynamic stability.

CAVH (Fig. 1) CAVH is a form of CRRT in which an extracorporeal circuit originates from an artery and terminates in a vein, and the arterial pressure drives the blood through a highly permeable filter. A pump in the effluent line of the circuit is used to control the amount of fluid removal. High rate of fluid removal permits removal of solutes by the associated process of convection. The ultrafiltrate produced is replaced in part or completely with an appropriate replacement solution to achieve the optimum quantity of fluid and solute removal.

Replacement

Access

Return

Hemofilter

Effluent Fig. 2: Circuit in CVVH.

ERRNVPHGLFRVRUJ

Acute Kidney Injury

251

CVVH (Fig. 2) In CVVH, the extracorporeal circuit originates from a vein and terminates in a vein, and the blood is driven through a highly permeable filter by means of a pump on the inflow side of the filter, which permits filtration of high fluid volumes. In CVVH, like in CAVH, solutes are removed by the process of convection, associated with high rate of fluid removal. The ultrafiltrate produced is replaced in part or completely with an appropriate replacement solution in order to maintain hemodynamics and electrolyte balance. SCUF (Fig. 3) SCUF is a form of CAVH or CVVH in which a very slow rate of fluid removal is permitted, and this process removes only excess water. Slow ultrafiltration in SCUF does not result in removal of solutes and no replacement of fluid is done as in CAVH or CVVH. SCUF is often used in the management of refractory edema with or without renal failure. CVVHD (Fig. 4) In CVVHD, the extracorporeal circuit originates in a vein and terminates in a vein and is driven by a pump. The assembly utilizes a low permeability dialyzer with a countercurrent dialyzer flow, which results in clearance of

Access

Return

Hemofilter

Pump

Effluent Fig. 3: Circuit for arterio-venous SCUF. Veno-venous SCUF requires a pump in the inflow limb of the filter.

ERRNVPHGLFRVRUJ

252


Dialysate Access

Return

Hemofilter

Effluent Fig. 4: Circuit in CVVHD.

solute by diffusion as in intermittent hemodialysis. No fluid replacement is done.

CVVHDF (Fig. 5) CVVHDF is a form of CRRT in which the CVVH circuit is modified by the addition of slow, countercurrent dialysate flow into the ultrafiltratedialysate compartment of the hemofilter. The high permeability filter results in the removal of high volumes of fluids by filtration and elimination of solutes by convection and diffusion. Fluid replacement is administered as clinically indicated in part or completely to replace fluid losses. The modalities of CRRT most frequently used in infants and children with post heart surgery AKI are CVVH and CVVHDF. Guidelines for CVVH <10 kg

10–20 kg

>20 kg

Blood flow (mL/min)

50

80

150

Predilution flow (mL/h)*

200–400

300–650

600–1000

Maximum ultrafiltrate removal (mL/h)

750

1200

2250

*Replacement fluid administered in the inflow limb of the filter.

ERRNVPHGLFRVRUJ

Acute Kidney Injury

Replacement Access

253

Dialysate

Return

Hemofilter

Effluent Fig. 5: Circuit for CVVHDF.

The extracorporeal circuit requires adequate central venous access (femoral, internal jugular, subclavian), usually via a double lumen catheter, to allow high blood flows. Recommended catheter sizes in French gauge (F) are: Patient size (kg) Neonate 2.5–10 10–20 >20

Vascular access (double lumen) 5F 6.5 F (10 cm) 8 F (15 cm) 10.8 F or larger (20 cm)

Blood is removed from the patient through the distal port of a double lumen venous catheter and returned through the proximal port. Depending upon the negative balance required and at the same time to prevent sudden volume depletion, the filtration rate is controlled and some fluid is replaced. The replacement fluid is isotonic, and bicarbonate or potassium may be added depending on the biochemical profile of the patient. To decrease blood viscosity and prevent the filter from blocking, replacement fluids are generally infused on the inflow side of the filter (predilution flow). Heparinization is needed and is infused into the inflow port of the filter. The recommended dose of non-fractioned heparin is 30–50 U/kg

ERRNVPHGLFRVRUJ

254


(0.3–0.5 mg/kg) bolus followed by continuous infusion of 10–20 U/kg/h (0.1–0.2 mg/kg/h). Activated coagulation time is maintained in a range of 170–200 s. In patients at the risk of bleeding, the heparinization should be reduced or omitted. Platelet count needs to be monitored twice a day because of the high risk of thrombocytopenia in patients on CVVH, and the electrolyte status is monitored 4–6 hourly.

Bibliography 1. Acute dialysis. Braun Melsungen AG. [Updated: 2011 Jan 27; cited: 2011 Feb 21] Available at: http://www.bbraun.com/cps/rde/xchg/bbraun-com/hs.xsl/therapy-treatment-01.html. 2. Alkan T, Akçevin A, Türkoglu H, et al. Postoperative prophylactic peritoneal dialysis in neonates and infants after complex congenital cardiac surgery. ASAIO J 2006;52:693–7. 3. Baxter P, Rigby ML, Jones OD, Lincoln C, Shinebourne EA. Acute renal failure following cardiopulmonary bypass in children: results of treatment. Int J Cardiol 1985;7:235–43. 4. BUN-to-creatinine ratio. Wikipedia: the free encyclopedia. [Updated: 2011 Jan 3; cited: 2011 Jun 13] Available at: http://en.wikipedia.org/wiki/BUN-to-creatinine_ratio. 5. DiCarlo JV. Continuous hemofiltration. Wikipedia: the free encyclopedia. [Updated: 2011 May 5; cited: 2011 Jun 13] Available at: http://www.drugswell.com/wow/index.php. 6. Dittrich S, Vogel M, Dähnert I, Haas NA, Alexi-Meskishvili V, Lange PE. Acute hemodynamic effects of post cardiotomy peritoneal dialysis in neonates and infants. Intensive Care Med 2000;26:101–4. 7. Dwinnell BG, Anderson RJ. Diagnostic evaluation of the patient with acute renal failure. In: Schrier RW, ed. Atlas of Diseases of the Kidney Philadelphia: Blackwell Science; 1999:12.1–12.12. 8. Fleming F, Bohn D, Edwards H, et al. Renal replacement therapy after repair of congenital heart disease in children. A comparison of hemofiltration and peritoneal dialysis. J Thorac Cardiovasc Surg 1995;109:322–31. 9. Gomez-Campdera FJ, Maroto-alvaro E, Galinanaes M, Garcin E, Durate J, Rengel-Aranda M. Acute renal failure associated with cardiac surgery. Child Nephrol Urol 1988;9:138–43. 10. Halfman CJ. Laboratory evaluation of renal function. In: Halfman CJ, ed. Laboratory Medicine and Pathophysiology. [Updated: 2000 Mar 9; Accessed: 2011 Mar 10]. Available at: http:// pro2services.com/Lectures/Contents.htm. 11. Hanson J, Loftness S, Clarke D, Campbell D. Peritoneal dialysis following open heart surgery in children. Pediatr Cardiol 1989;10:125–8. 12. Mego S, Bartlett M. Establishing a normal range for paediatric glomerular filtration rate (GFR). [Cited: 2011 Jun 13] Available at: http://www.icms.com.au/anzsnm2006/ 13. Meyer TW, Hostetter TH. Uremia. N Engl J Med 2007;357:1316–25. 14. Peacock PR, Sinert RH. Renal failure, acute: treatment & medication. [Updated: 2010 Jun 17; cited: 2011 Feb 21] Available at: http://emedicine.medscape.com/article/777845-treatment. 15. Petroni KC, Cohen NH. Continuous renal replacement therapy: anesthetic implications. Anesth Analg 2002;94:1288–97. 16. Pica S, Principato E, Mazzera E, et al. Risks of acute renal failure after cardiopulmonary bypass surgery in children. A retrospective 10 year case control study. Nephrol Dial Transplant 1995; 10:630–36. 17. Renal function. Wikipedia: the free encyclopedia. [Updated: 2011 Jan 27; cited: 2011 Feb 21] Available at: http://en.wikipedia.org/wiki/Renal_function. 18. Rosner MH, Okusa MD. Acute kidney injury associated with cardiac surgery. Clin J Am Soc Nephrol 2006;1:19–32.

ERRNVPHGLFRVRUJ

Acute Kidney Injury

255

19. Schwartz GJ, Work DF. Measurement and estimation of GFR in children and adolescents. Clin J Am Soc Nephrol 2009;4:1832–43. 20. Stewart CL, Barnet R, Acute renal failure in infants, children and adults. Cri Care Clinic 1997; 13:575–90. 21. Strazdins V, Watson AR, Harvey B. Renal replacement therapy for acute renal failure in children: European Guidelines. Pediatr Nephrol 2004;19:199–207. 22. Washburn KK, Zappitelli M, Arikan AA, et al. Urinary interleukin-18 is an acute kidney injury biomarker in critically ill children. Nephrol Dial Transplant 2008;23:566–72. 23. Werner HA, Wensley DF, Lirenman DS, LeBlanc JG. Peritoneal dialysis in children after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1997;113:64–8.

ERRNVPHGLFRVRUJ

Coagulation Disorders in the Postoperative Period “The only weapon with which the unconscious patient can immediately retaliate upon the incompetent surgeon is hemorrhage” —William Stewart Halsted (1852–1922)*

Normal Hemostasis Intrinsic pathway Factor XII

XIIa

Factor XI

XIa

Factor IX

IXa

Extrinsic pathway Factor VII + tissue factor

Factor VIIIa Phospholipid Calcium ions Factor X

Xa Factor Va Phospholipid Calcium ions Prothrombin

Fibrinogen

Factor X

Thrombin

Fibrin

Fig. 1: Coagulation pathway.

The mechanism of normal coagulation involves three processes: 1. Primary hemostasis: When a vessel is injured, platelets aggregate at the injured site to form a platelet plug. 2. Secondary hemostasis: During secondary hemostasis, a fibrin clot forms and stabilizes the platelet plug. This fibrin clot is formed via two *William Stewart Halsted was an American surgeon, and an early advocate of aseptic surgical technique. He introduced several new operations in surgery, including radical mastectomy for breast cancer.

ERRNVPHGLFRVRUJ


257

concurrent pathways, which converge into a common pathway that leads to the formation of the fibrin clot. (a) The intrinsic coagulation pathway involves sequential activation of factors XII, XI, IX and VIII. (b) The extrinsic coagulation pathway requires the interaction of factor VII and tissue factor released from injured endothelial tissues, which in turn activate factor X in the common pathway. (c) Common pathway: The intrinsic and the extrinsic pathways converge into a common pathway of factors X, V and II (prothrombin), which leads to the formation of factor IIa (thrombin). This thrombin then cleaves fibrinogen (factor I) to form fibrin monomers, which get cross-linked via the action of factor XIIa to bind into a fibrin clot. 3. Fibrinolysis (degradation of the fibrin clot and restoration of normal blood flow): The role of the fibrinolytic system is to restore blood flow through the healed vessel by lyses of the fibrin clot. Plasminogen is activated to plasmin by (i) kallikrein generated by the intrinsic coagulation pathway, (ii) tissue plasminogen activator released from the injured endothelial cells, and (iii) urokinase produced by kidney endothelial cells. Plasmin then degrades the fibrin clot and fibrinogen into fibrinogen degradation products (FDPs). Whether fibrin or fibrinogen is degraded by plasmin, the FDPs are the same, with the exception of D-dimer, which is produced only with the degradation of fibrin.

Coagulation Studies Activated Partial Thromboplastin Time Activated partial thromboplastin time (APTT) identifies abnormalities of the intrinsic system and the common pathway and is utilized to monitor the level of anticoagulation in patients on heparin. Prothrombin time detects abnormalities of the extrinsic and common pathway and is used to monitor the effect of oral anticoagulants. In normal doses, heparin causes a prolongation of the APTT because of its action on the intrinsic pathway, but has no significant effect on the prothrombin time (PT). In larger doses, heparin however, does cause a prolongation of the PT by its effect on the common and extrinsic pathways. When a patient receives heparin, the target APTT is generally kept 1.5–2.5 times the control APTT. During initiation of anticoagulation, when the patient is concurrently receiving heparin and warfarin, the effect of heparin can be monitored with APTT and that of warfarin by PT.

ERRNVPHGLFRVRUJ

258


Prothrombin Time Prothrombin time detects abnormalities of the extrinsic and common pathways (factors VII, X, V, II and I). It is used to monitor the level of anticoagulation in patients prescribed warfarin for anticoagulation. Warfarin initiates anticoagulation by inhibition of vitamin K dependent clotting factors (factors II, VII, IX, and X) by its action on vitamin K. Warfarin also prolongs the APTT in higher doses, but in patients stabilized on long-term warfarin therapy, the APTT may be prolonged only by a few seconds.

International Normalized Ratio International normalized ratio (INR) is the ratio of patient’s PT divided by control PT to which a correction factor called International Sensitivity Index (ISI) has been applied. The ISI is supplied with each batch of reagent for doing the PT, as the sensitivity of different batches of commercial thromboplastin reagents is variable and the PT value changes with every batch of reagent used for the test. The INR overcomes this problem and allows comparison of the level of anticoagulation irrespective of the performance of the reagent used. INR = (PT patient/PT normal)ISI PT patient = patient’s prothrombin time (seconds) PT normal = mean value for normal patients (seconds) ISI = International Sensitivity Index An INR of 1 implies normal clotting, and an INR of 3 means the blood takes about three times as long to clot compared to the control. An INR of 2.5–3.5 is recommended for normal mechanical valves. The therapeutic range of INR for various disorders represents the level at which therapy should be effective with the least risk of bleeding.

Thrombin Time The thrombin time (TT) tests the ability of thrombin to convert fibrinogen to fibrin. A prolonged TT is caused by hypofibrinogenemia, accumulation of FDPs, or the presence of heparin. However, it is a relatively insensitive test (detectable prolongation requires fibrinogen level <75 mg/dL or FDPs >200 mcg/mL), and with availability of other tests to measure FDPs and D-Dimer, this test is of little practical utility.

ERRNVPHGLFRVRUJ


259

Platelet Count Normal platelet count in children is 150,000–450,000/mm3. Thrombocytopenia is defined as a platelet count of <150,000/mm3. With normal platelet function, thrombocytopenia is unlikely to cause bleeding unless the count is <50,000/mm3. A number of drugs cause platelet dysfunction and include aspirin, clopidogrel, non-steroidal anti-inflammatory drugs, and IIb/IIIa inhibitors. Aspirin needs to be discontinued for 5–7 days for recovery of normal platelet function.

Bleeding Time Bleeding time checks the efficiency of the vascular and platelet phases of hemostasis. The normal bleeding time is 1–9 minutes depending on the method used (1–3 minutes with Dukes needle prick method on the fingertip or earlobe). Prolongation of bleeding time occurs in severe thrombocytopenia or in functional platelet disorders.

Fibrinogen Degradation Products Fibrinogen degradation products are the breakdown fragments of fibrin and fibrinogen by the action of plasmin on the blood clot. Normal serum level of FDPs is 2.1–2.7 mcg/mL and values of >10 mcg/mL are significant. False positives are observed after exercise, in individuals under stress, in patients with liver disease or infection, and during pregnancy.

D-dimer D-dimer is the breakdown fragment of fibrin by the action of plasmin. Normal values are <0.5 mcg/mL, and a positive D-dimer (values >1.0 mcg/mL) can be seen in patients with DIC, deep venous thrombosis, pulmonary embolism, neoplasms, liver disease, inflammatory disorders, as well as after surgery.

Fibrinogen Normal blood fibrinogen level is 200–400 mg/dL. Patients who have dysfibrinogenemia or hypofibrinogenemia (<150 mg/dL) with active bleeding require cryoprecipitate to restore the fibrinogen level.

ERRNVPHGLFRVRUJ

260


Activated Clotting Time The activated clotting time (ACT) is a modification of the whole blood coagulation time. It qualitatively assesses the anticoagulation effect of heparin and is used to titrate the dose of heparin on cardiopulmonary bypass (CPB). The normal ACT value is 100–140s and increases in a linear fashion with increasing heparin concentration. ACT is also influenced by many other factors besides heparin, such as hypothermia, hemodilution, thrombocytopenia, aprotinin, and depletion of coagulation factors (especially fibrinogen). Thus, additional protamine to reverse the effect of heparin may not necessarily return the ACT to its baseline value. The initial heparin dose for bypass is 300–400 U/kg body wt, and the ACT target value is 480s. The ACT is checked every half hour and maintained between 450s and 500s by repeated doses of heparin.

Causes of Post CPB Bleeding Postoperative bleeding following CPB can be a result of a number of hemostatic derangements. The important causes of this bleeding are: ■

Inadequate heparin reversal

■

Thrombocytopenia or platelet dysfunction because of hemodilution, activation by the CPB surfaces, or hypothermia

■

Decrease in plasma coagulation factors

■

Isolated primary fibrinolysis

■

Disseminated intravascular coagulation.

Disseminated Intravascular Coagulation Disseminated intravascular coagulation (DIC) is an uncontrolled activation of the coagulation system with widespread formation of microthrombi. This is associated with an accelerated plasmin degradation of fibrin clots and circulating fibrinogen. The consumption of the coagulation factors and platelets results in generalized bleeding from needle puncture, surgical and wound sites. In addition to the bleeding, the patient presents with acute features of various organ dysfunction including fever, hypoxia, hypotension, acidosis, and acute kidney injury because of thrombi formation in the microvascular circulation. The most common cause of DIC is sepsis, but it can be triggered by a multitude of factors including prolonged CPB and massive blood transfusion.

ERRNVPHGLFRVRUJ


261

A slow chronic form of DIC can also occur and is associated with microthrombi formation but not generalized bleeding, as there is time for regeneration of coagulation factors.

Investigations The recommended coagulation profile of patients with DIC includes D-dimer (ELISA), antithrombin III, and alpha-2-plasmin inhibitor levels. These tests are early indicators of consumption and increased fibrinolysis, while PT, APTT, and fibrinogen levels usually change more slowly: ■

The PT, APTT, and TT will all be prolonged.

■

The platelet count is low.

■

Fibrinogen level is decreased and FDPs and D-dimer are elevated because of increased fibrinolysis and fibrinogenlysis.

■

Plasma level of antithrombin III and α2-antiplasmin are decreased.

■

Plasma levels of thrombin-antithrombin complexes (TAT) and plasminantiplasmin complexes (PAP) are increased. Elevated TAT levels are a marker of increased thrombin formation and PAP levels of fibrinolysis.

■

Schistocytes and microspherocytes may be present in the peripheral blood due to microangiopathic hemolysis in 10–20% of patients with DIC.

Serial results of coagulation studies more reliably indicate a consumptive process than does a random result.

Management Patients are treated with appropriate antibiotic therapy for sepsis or managed for any other precipitating event. Replacement therapy is required for coagulation factors (fresh frozen plasma or cryoprecipitate), platelets (platelet concentrate), and red cells (packed cells) to restore all consumed blood components. The use of heparin therapy remains controversial. Low-dose subcutaneous or IV heparin (5–10 U/kg/h) is indicated in the more chronic form of DIC where clinical features of thrombosis predominate and generalized bleeding is not a feature.

Primary Fibrinolysis Primary fibrinolysis has a clinical presentation similar to acute DIC, but the pathophysiology is different. Primary fibrinolysis results from primary activation of the fibrinolytic pathway and formation of plasmin, while DIC is associated with intravascular coagulation and secondary fibrinolysis.

ERRNVPHGLFRVRUJ

262


A number of pathological conditions including cardiopulmonary bypass, liver disease, and disseminated malignancy result in the release of proteolytic enzymes (tissue plasminogen activator and urokinase), which activate plasminogen to form plasmin. This circulating plasmin then degrades fibrinogen, fibrin, and factors V and VIII causing multiple coagulation factor deficiencies and bleeding.

Investigations The coagulation profiles in patients with primary fibrinolysis shows: ■

PT and APTT are normal or slightly prolonged.

■

Platelet count is normal since platelets are not being consumed in primary fibrinolysis.

■

Fibrinogen levels are decreased and plasma level of FDP is increased with normal level of D-dimer.

■

The plasma level of antithrombin III is normal and of α2-antiplasmin is decreased.

■

Levels of TAT complexes are within normal limits, but the levels of PAP complexes are increased.

■

Peripheral blood smear shows normal erythrocyte morphology, as no microvascular hemolysis occurs.

Management In addition to blood component replacement therapy, antifibrinolytic drugs (such as aprotinin, aminocaproic acid, or tranexamic acid) are used to treat primary fibrinolysis. The diagnosis of DIC should be conclusively ruled out before administration of antifibrinolytic drugs.

Therapeutic Approach in Postoperative Bleeding Cause

PT

PTTK TT

Platelet Fibrinogen FDP Treatment count

Heparin excess

↑

↑

↑

N

N

N

Protamine titrated with ACT

Thrombocytopenia N or platelet dysfunction*

N

N

↓/N

N

N

Platelet transfusion

↑

↑

N (except in marked N hypofibrinogenemia)

N

N

FFP/Cryo

Coagulation factor deficiency

ERRNVPHGLFRVRUJ


263

Cause

PT

PTTK TT

Platelet Fibrinogen FDP Treatment count

Primary fibrinolysis

↑

↑

↑

N

↓

↑

EACA/FFP

DIC**

↑

↑

↑

↓

↓++

↑

FFP, Cryo, platelets

*Platelet dysfunction is suggested by a normal platelet count but a prolonged bleeding time. **D-dimers are increased only in DIC and are normal in all the above bleeding disorders. N: normal, ↑: increased, ↓: decreased, FFP: fresh frozen plasma, Cryo: cryoprecipitate, DIC: disseminated intravascular coagulation, EACA: epsilon-aminocaproic acid.

Indications for Re-exploration In children, general guidelines for re-exploration for excessive blood loss can be based on the total blood volume. If after neutralization of heparin, blood loss exceeds 5% of estimated blood volume per hour for 3 consecutive hours or 10% in any hour, it is an indication for re-exploration. Coagulation tests are not as valuable in children as in adults for guiding transfusion therapy. (Blood volume: Neonates 85–90 mL/kg, children 80 mL/kg, adults 70 mL/kg).

Packed RBCs Packed red cells are indicated in anemia and hemorrhage to maintain an optimum hemoglobin level (12–14 g% in cyanotics and 10–12 g% in non-cyanotics).

Fresh Frozen Plasma Fresh frozen plasma (FFP) contains approximately 1 unit of each coagulation factor per mL, and is given prophylactically as part of colloid replacement. Thereafter, if bleeding is continuing, it is given in aliquots of 10 mL/kg so that it does not cause volume overload.

Platelet Transfusion It is the first blood fraction indicated for postoperative bleeding following CPB, since CPB causes platelet dysfunction. Platelet transfusion is also considered under the following circumstances: (i) Prophylactically post CPB in cyanotic children undergoing open heart surgery;

ERRNVPHGLFRVRUJ

264


(ii) In all cases when the duration of CPB is prolonged; and (iii) Following deep hypothermic circulatory arrest. 5–10 mL/kg of single donor platelets are recommended. Subsequent transfusions are given if bleeding is continuing and the platelet count <100,000/mm3.

Cryoprecipitate If bleeding persists, deficiency of clotting factors is the next consideration. Cryoprecipitate contains high levels of fibrinogen (1 unit of cryoprecipitate is 10–20 mL and contains about 150 mg of fibrinogen) and factor VIII. Cryoprecipitate is given in an amount that will restore plasma fibrinogen levels to >100 mg/dL.

Recombinant Factor VII Generates thrombin at the bleeding sites with the aid of tissue factor, and factors IX and X. It also activates platelets and stabilizes the clot. It is recommended in persistent life-threatening bleeding in intravenous doses of 60–90 mcg/kg every 2–3 hours until hemostasis is achieved.

Antifibrinolytic Agents The antifibrinolytic agents, epsilon-aminocaproic acid (EACA), tranexamic acid, and aprotinin have been used intraoperatively and postoperatively to reduce bleeding following cardiac surgery. EACA and tranexamic acid have lesser adverse effects and are currently preferred alternatives to aprotinin, which has been associated with an increased risk of renal failure, cardiac failure, and encephalopathy.

Dose EACA has been recommended as an IV infusion in a loading dose of 75–150 mg/kg given at induction followed by an infusion of 15–30 mg/ kg/h or alternatively, as an intermittent therapy in a dose of 100 mg/kg each given at induction, in the CPB prime and at the time of weaning from CPB. Tranexamic acid is administered in a dose of 10 mg/kg IV after induction followed by an infusion of 1 mg/kg/h for 10 hours or alternatively as three intermittent doses of 10 mg/kg each as was given for EACA. Complications of anti-fibrinolytic therapy include thrombosis, pulmonary embolism, bradycardia, hypotension, and hypersensitivity reactions.

ERRNVPHGLFRVRUJ


265

Contents of Blood Components Blood components

Contents

Volume

Shelf life

Whole blood

Content is RBC and plasma. WBC and platelets are not viable after 24 hours, and factors V and VIII are significantly decreased after 48 hours. 1 unit of 450 mL blood contains 63 mL of the anticoagulant CPDA-1 (citrate, phosphate, dextrose, adenine) and has a hematocrit (Hct) of 35% (depending on the donor).

450 mL ± 10%

35 days at 1–6°C in CPDA-1

Packed Red cells (PRBC)

Content is RBC with about 25 mL of plasma. In addition, the preservative SAGM (saline, adenine, glucose, mannitol) may be added to the PRBC to increase its shelf life. 1 unit of 280 mL of PRBC contains 100 mL of SAGM and has an Hct of 65–75%.

280 ± 50 mL

42 days at 1–6°C in bags containing SAGM. (35 days at 1–6°C in bags without SAGM)

Platelet concentrates from Whole Blood— Random Donor Platelets (RDP)

Platelets ≥5.5 × 1010. One unit gives an increment of 5,000–10,000/μL in a 70 kg adult or 150/μL/kg in pediatric patients.

50–70 mL

5 days at 20–24°C, in a platelet agitator

Single donor platelet (SDP) (obtained by apheresis)

Platelets ≥3 × 1011. One unit gives an increment of 30,000–60,000/μL in a 70 kg adult or 700/μL/kg in pediatric patients.

200–250 mL

5 days at 20–24oC, in a platelet agitator

Fresh frozen plasma (FFP)

1 unit contains factor VIII 0.7 IU/mL, Fibrinogen 200–400 mg, 200 units of each of the other coagulation factors, plasma proteins, and complement.

150–250 mL

1 year at ≤ −18°C & 7 years at −65°C

ERRNVPHGLFRVRUJ

266


Blood components

Contents

Volume

Shelf life

Cryoprecipitate

150 mg of fibrinogen, at least 80 IU of factor VIII, IX (von Willebrand factor), factor XIII, and fibronectin.

10–20 mL

1 year at ≤ −18°C

Bibliography 1. Cherian MN, Emmanuel JC. Clinical use of blood. World anaesthesia 2002;14:1. [Updated: 2002; accessed: 31 Jan 2012]. Available at: http://www.nda.ox.ac.uk/wfsa/html/u14/u1406_01.htm. 2. Cunnigham VL. A review of disseminated intravascular coagulation: presentation, laboratory diagnosis and treatment. Medical Laboratory Observer. [Updated: Jul 1999; cited: 2011 Feb 21] Available at: http://findarticles.com/p/articles/mi_m3230/is_7_31/ai_55343376/?tag= content;col1. 3. DeLoughery TG. Blood component therapy. Multiprofessional Critical Care Rev 2007:379–92. [Cited: 2011 Feb 21]. Available at: www.ohsu.edu/xd/health/services/.../Blood-component-therapy.doc. 4. Despotis GJ, Goodnough LT. Management approaches to platelet-related microvascular bleeding in cardiothoracic surgery. Ann Thorac Surg 2000;70:S20–32. 5. Despotis GJ, Joist JH, Goodnough LT. Monitoring of hemostasis in cardiac surgical patients: impact of point-of-care testing on blood loss and transfusion outcomes. Clin Chem 1997;43: 1684–96. 6. Hartstein G, Janssens M. Treatment of excessive mediastinal bleeding after cardiopulmonary bypass. Ann Thorac Surg 1996;62:1951–4. 7. Harvey GK, David JA. Immunology of leucocytes, platelets, plasma components. In: Klein HG, Mollison PL, Anstee DJ, eds. Mollison’s Blood Transfusion in Clinical Medicine11th ed. Massachussettes: Wiley-Blackwell; 2005:547–611. 8. Kusuma B, Schulz TK. Acute disseminated intravascular coagulation. Hospital Physician 2009;45:35–40. 9. Laffan MA, Manning RA. Investigation of hemostatsis. In: Lewis SM, Bains BJ, Bates I, ed. Dacie and Lewis: Practical Haematology 9th ed. Philadelphia: Churchill Livingstone; 2001:339–90. 10. Novoseven RT: highlights of prescribing information. [Update: 2010 Jan; Accessed: 2012 Jan 31]. Available at: http://www.fda.gov/downloads/biologicsbloodvaccines/bloodbloodproducts/approvedproducts/licensedproductsblas/fractionatedplasmaproducts/ucm056954.pdf. 11. Roback JD, Grossman BJ, Harris T, Hillyer CD. Technical Manual 17th ed. Bethesda, MD: American Association of Blood Banks; 2011:217–21. 12. Ross F, Luban NL. Blood component therapy. Pediatr Clin N Am 2008;55:421–45. 13. Saba HI, Morelli GA. The pathogenesis and management of disseminated intravascular coagulation. Clin Adv Hematol Oncol 2006;4:919–26. 14. Salenger RI, Gammie JS, Vander Salm TJ. Postoperative care of cardiac surgical patients. In: Cohn LH, Edmunds LH Jr, eds. Cardiac Surgery in the Adult 3rd ed. New York: McGraw-Hill; 2003:439–69.

ERRNVPHGLFRVRUJ


Drug

Dose

Remarks

Aspirin

Antiplatelet dose: Children: 5–10 mg/kg/day q24h PO or for under 10 kg: 37.5 mg q24h PO. Over 10 kg: 75 mg q24h PO. Adults: 20–50 mg/kg/day or 150–300 mg/day PO. Anti-inflammatory dose: Children: 30–60 mg/kg/day divided q4–6h PO Adult: 300–900 mg q4–6h PO (max 4 g/day)

Nonopioid analgesic, anti-inflammatory and antipyretic. Increased risk of bleeding with anticoagulants. Enhances effect of phenytoin sodium and sodium valproate. Risk of Reye’s syndrome* in children under 12 years of age.

Dipyridamole

Children: 2–5 mg/kg/day in divided doses q8h PO. Adult: 300–600 mg/day in divided doses q8h PO.

Enhances the effects of adenosine and anticoagulants.

Clopidogrel

Children: 0.2–1 mg/kg q24h PO. Adult: 300 mg initially, then 75 mg q24h PO.

A pediatric dose of 0.2–0.3 mg/kg/day has an equivalent antiplatelet effect of an adult dose of 75 mg/day.

Warfarin

Children: An initial loading dose of 200 mcg/kg PO can be given on day 1, which can be repeated on day 2 if the INR is between 1 and 1.3, then maintenance dose 50–200 mcg/kg q24h PO (depending on INR). Adults: 5–10 mg on day 1, then 3–9 mg q24h PO (depending on INR).

Monitor INR and adjust dose to nearest 500 mcg (0.5 mg). The goal is to maintain the INR between 2 and 3. Young children need more oral anticoagulation per kg body wt than do older children and adults.

Unfractionated heparin

Children and adults: Loading dose: 50–100 units/kg IV/SC followed by an IV infusion of 10–25 units/kg/h. Infused in 5% dextrose or isotonic saline. Or 50–100 units/kg IV/SC q4h.

Monitor APTT q4h till therapeutic range is achieved (2–2.5 × control), thereafter q12h. Alternatively, target is to achieve anti-Xa assay activity of 0.35–0.7 U/mL.

ERRNVPHGLFRVRUJ

268


Drug

Dose

Remarks

Low-molecularweight heparin (LMWH): enoxaparin

Children: <2 mo: 1.5 mg/kg (150 U/kg) q12h SC. >2 mo: 1 mg/kg (100 U/kg) q12h SC. Adults: 40 mg (4000 U) q24h or 30 mg (3000 U) q12h SC.

LMWH has the advantages of subcutaneous administration, less frequent monitoring, and predictable pharmacokinetics. Target is to achieve an anti-Xa assay activity of 0.5–1.0 U/mL.

Tissue plasminogen activator (tPA)

0.03–0.5 mg/kg/h IV infusion.

Lower doses 0.03–0.1 mg/kg/h are associated with a lower incidence of bleeding.

Streptokinase

Children: 2500–4000 units/kg loading dose over 30–60 minutes then 500–1000 units/kg/h IV infusion for 12–24 hours. Adults: 250,000 U/kg IV then 100,000 U/h IV infusion for 24–72 hours.

*Reye’s syndrome: The classic features are a rash, vomiting, liver derangement, and encephalopathy. It has been associated with aspirin consumption in children with a viral illness.

There are three primary classes of medications that may be used in the treatment of patients with a thrombophilic disorder: (i) antiplatelet drugs, (ii) anticoagulants, and (iii) thrombolytic agents. With all these drugs, bleeding is a possible side effect. The risk of bleeding is increased when two of these drugs are given at the same time. Antiplatelet therapy or anticoagulation is needed in pediatric surgical patients to either prevent or treat a thrombotic episode. Prophylactic therapy is indicated during cardiac catheterization and after the placement of endovascular stents or in patients in atrial fibrillation. Surgical procedures that require prophylaxis include prosthetic valve replacements, the Blalock–Taussig shunt and the Glen and Fontan operations. Conditions where definitive treatment is required are venous or arterial thromboembolism and their complications. Aspirin is the most commonly used antiplatelet agent in children. Dipyridamole or clopidogrel are adjuncts that may be recommended to be given in addition to aspirin or warfarin. When there is need for immediate anticoagulation, therapy with unfractionated heparin or low-molecular-weight heparin (LMWH) is initiated till the desired effect of warfarin is apparent (INR 2–3). Treatment with LMWH rather than warfarin is preferable in infants under 1 year of age because of a variable effect of heparin at this age.

ERRNVPHGLFRVRUJ


269

Antiplatelet Agents Aspirin and NSAIDs Aspirin inhibits the enzyme COX1 present in platelets. COX1 is involved in platelet aggregation, and its inhibition results in a decreased ability of the platelets to form clots. Once aspirin is discontinued, it takes 5–7 days for normal platelets to replace the affected platelets. Other nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, similarly inhibit platelet aggregation, but the effect is not of the same duration. NSAIDs may also cause thrombocytopenia in addition to platelet dysfunction and increase the susceptibility for acute kidney injury during an episode of hypotension.

Dipyridamole Dipyridamole is an antiplatelet agent and a vasodilator. It inhibits platelet aggregation by increasing platelet cAMP. This drug has primarily been used in combination with aspirin for anticoagulation prophylaxis for vascular grafts or an intravascular device and in combination with warfarin in patients with prosthetic heart valves. Side effects of dipyridamole, besides the increased risk of bleeding, include dizziness, hypotension, headache, nausea, abdominal discomfort, and rashes.

Clopidogrel The mechanism by which clopidogrel works is different from that of aspirin and other NSAIDs. Platelets require adenosine diphosphate (ADP) binding to platelet receptor sites to facilitate aggregation and clopidogrel inhibits this ADP binding. Clopidogrel is indicated for antithrombotic prophylaxis as an adjunct to therapy with either aspirin, warfarin, heparin, or low-molecular-weight heparin. Side effects of clopidogrel include bleeding, dyspepsia and diarrhea, rash, fatigue, headache, dizziness, and flu-like symptoms. Rarely, thrombotic thrombocytopenic purpura can occur.

ERRNVPHGLFRVRUJ

270


Anticoagulants Warfarin Warfarin is a vitamin K antagonist and provides anticoagulation by inhibiting the effects of vitamin K on clotting factors II, VII, IX, and X. In general, after administration, warfarin takes about 48 hours before it has a measurable effect on coagulation. Side effects of warfarin include rash, dyspepsia, diarrhea, alopecia, and hepatitis. Warfarin interacts with a large number of medications including many antibiotics. Dietary intake of vitamin K (e.g., spinach) can lower the anticoagulant effect of warfarin. Bleeding or a raised INR beyond the therapeutic range as a result of warfarin is managed by administration of fresh frozen plasma (FFP) and Inj. vitamin K. (Inj. vit K dose: 300 mcg/kg is given as IV bolus over 15–30 minutes q24h. It is diluted in 5% dextrose to a concentration of 0.2 mg/mL for administration. Dose in >12 yr age and adults,: 10 mg IV q24h. An IM preparation is also available.)

Unfractionated Heparin The main anticoagulant action of heparin is mediated through its interaction with antithrombin. The heparin–antithrombin complex inactivates factor IIa (thrombin), Xa, IXa, XIa, and XIIa. Of these, thrombin and factor Xa are most responsive to inhibition. Heparin reduces the procoagulant activity of factor VIIa and tissue factor and also interacts with platelets to cause bleeding by a mechanism independent of its anticoagulant effect. Upon initiating heparin, APTT monitoring is required every 4 hours and generally maintained at 2–2.5 × control values. Once the proper dose has been established, sampling is reduced to once or twice a day. APTT is sensitive to the inhibitory effects of heparin on thrombin, factor Xa, and IXa. Monitoring of therapy may be more accurately done by anti-Xa assay (target 0.35–0.7 × control). Side effects of heparin include irritation at the site of infusion, fever, chills, nasal congestion, osteoporosis (with prolonged use), and thrombocytopenia.

Low-Molecular-Weight Heparin LMWH (e.g., enoxaparin, dalteparin) enhances the inhibition of factor Xa, but not IIa and has actions similar to heparin on tissue factor, factor VIIa, and platelets.

ERRNVPHGLFRVRUJ


271

The anticoagulant effect of LMWH varies in direct proportion to the dose calculated by body weight. Dose alteration is required in renal disease. Its dose effect does not correlate with the APTT but can be monitored by anti-Xa assay (target value 0.5–1.0 U/mL; sample is collected 4 h after administration of dose). Side effects for the low-molecular-weight heparins are similar to those of heparin including the ability of LMWH to cause thrombocytopenia.

Thrombolytic Therapy Systemic thrombolytic therapy may be considered for arterial occlusions, venous thrombosis, pulmonary embolism not responding to heparin therapy, clotted valves, or blocked BT shunts. Tissue plasminogen activator (tPA) has been the recommended thrombolytic agent of choice in children because of higher fibrin specificity and lower antigenicity. It acts on circulating plasminogen to generate plasmin, which cause clot lyses. It is administered as in the following guidelines (Thrombosis Interest Group): 1. Baseline blood count, platelet count, PT, APTT, and fibrinogen levels are done prior to initiation of thrombolytic therapy. 2. FFP 10–20 mL/kg IV is administered q8–12h. It is a plasminogen source and is commenced either before starting thrombolytic therapy or simultaneously. 3. tPA is administered at the rate of 0.3–0.5 mg/kg/h IV initially for 6 hours (dose varies from 0.3–9 mg/kg/h in various reports). If required, tPA therapy may be repeated again after 24 hours along with FFP. 4. Unfractionated heparin is started at the same time as the tPA in a dose of 10 units/kg/h without an initial bolus dose. It is continued in therapeutic doses (20–30 U/kg/h), monitored by APTT for a period of 24 h, even after tPA has been discontinued.

Monitoring The PT, APTT, and fibrinogen levels are monitored at 4 hours and every 6–8 hours thereafter. The fibrinogen concentration is likely to drop by 20–50%. If the fibrinogen concentration falls to <100 mg/dL, tPA is discontinued till the fibrinogen level is restored by the administration of cryoprecipitate (1U/5–10 kg). A platelet count >100 × 109/L is also maintained.

ERRNVPHGLFRVRUJ

272


Contraindications Active bleeding or surgery in the previous 10 days are contraindications to thrombolytic therapy. During therapy, warfarin and antiplatelet agents are withheld and IM injections are avoided.

Complications In case of severe bleeding, the tPA and heparin are stopped and the effects of heparin may be reversed with protamine. Packed cells, FFP, and cryoprecipitate (1U/5–10 kg) are administered and may be repeated as required. Recombinant factor VII is considered for persistent bleeding in spite of above therapy.

Bibliography 1. Buck ML. Clopidogrel for platelet inhibition in pediatric patients: pediatric clinical trials. Pediatr Pharm 2010;16(5). [Updated: 2010 June 22; accessed: 2012 Jan 31]. Available at: http:// www.medscape.com/viewarticle/723239. 2. Buck ML. Use of aminocaproic acid in children undergoing cardiac surgery or ECMO. Pediatr Pharm 2006:12. [Updated: 2007 May 01; accessed: 2012 Jan 31]. Available at: http://www. medscape.com/viewarticle/549277. 3. Chen CC, You JY, Ho CH. The aPTT assay as a monitor of heparin anticoagulation efficacy in clinical settings. Adv Ther 2003;20:231–6. 4. Clopidogrel. Drugs update. [Updated: 2011; accessed: 2012 Jan 31]. Available at: http://www. drugsupdate.com/generic/view/594. 5. Eaton MP. Antifibrinolytic therapy in surgery for congenital heart disease. Anesth Analg 2008;106:1087–100. 6. Harker LA, Kadatz RA. Mechanism of action of dipyridamole. Thromb Res Suppl 1983;4:39–46. 7. Hirsh J, Warkentin TE, Shaughnessy SG, et al. Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety. Chest 2001;119:64S–94S. 8. Jennifer S, Yow E, Berezny KY, et al. Dosing of clopidogrel for platelet inhibition in infants and young children. Circulation 2008;117:553–9. 9. Massicot P, David M, Chan A. Thrombolytic therapy in children. Thrombosis interest group of Canada. [Cited: July 2012] Available at: http://www.tigc.org/clinical-guides/ThrombolyticTherapy-in-Children.aspx. 10. Monagle P, Chan A, Massicotte P, Chalmers E, Michelson AD. Antithrombotic therapy in children: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004;126:645S–87S. 11. Veldman A, Nold MF, Michel-Behnke I. Thrombosis in the critically ill neonate: incidence, diagnosis, and management. Vasc Health Risk Manag 2008;4:1337–48.

ERRNVPHGLFRVRUJ

Management of Anaphylaxis “Medicine sometimes snatches away health, sometimes gives it” —Ovid (43 BC–AD 17/18)*

Dose guide <6 mo

6 mo–6 yr

6–12 yr

>12 yr

Adrenaline IM (1:1000)

150 mcg (0.15 mL)

150 mcg (0.15 mL)

300 mcg (0.3 mL)

500 mcg (0.5 mL); 300 mcg (0.3 mL) if child is small or prepubertal.

Hydrocortisone IM/slow IV

25 mg

50 mg

100 mg

200 mg

Chlorpheniramine IM/slow IV

250 mcg/kg

2.5 mg

5 mg

10 mg

Crystalloid bolus 20 mL/kg IV

200 mL

400 mL

500 mL

500 mL

Presentation The characteristic presentation of anaphylactic reaction involves two or more systems, though it may also present with symptoms attributable only to respiratory or circulatory systems, or the skin. ■

Sudden onset and rapid progression of symptoms following exposure to an allergen.

■

Signs of airway obstruction (stridor, hoarseness, laryngeal or pharyngeal edema) or breathing difficulty (wheeze).

■

Signs of circulatory collapse (tachycardia, hypotension, cardiac arrest).

■

Skin and/or mucosal changes (flushing, urticaria, angioedema).

■

May have associated GIT symptoms (e.g., vomiting, abdominal pain, incontinence).

*Excerpt from Tristia. Tristia (“Sorrows” or “Lamentations”) is a collection of letters written by the Augustan poet Ovid during his exile from Rome.

ERRNVPHGLFRVRUJ

274


Laboratory Diagnosis Serum Tryptase Measurement of serum tryptase is a specific test to help confirm the diagnosis of anaphylactic reaction. Levels of serum tryptase peak 60–90 minutes after the onset of anaphylaxis and last about 6–8 hour. Ideally, the measurement should be obtained between 1 and 2 hour after start of symptoms.

Emergency Management of Anaphylaxis Adrenaline Adrenaline reverses peripheral vasodilation (α1 action) and increases the force of myocardial contraction and cardiac output (β1 action). It dilates the bronchial airways, suppresses histamine and leukotriene release, and attenuates the severity of IgE-mediated allergic reactions (β2 actions). In the first instance, adrenaline is given IM because of ease of administration and high incidence of arrhythmias associated with an inappropriate IV dose. Intravenous administration is indicated with ECG and arterial pressure monitoring in patients who respond poorly to IM adrenaline. ■

IM dose (Adrenaline 1:1000 contains 1000 mcg/mL; and 1:10,000 contains 100 mcg/mL) Children: 10 mcg/kg (0.01 mL of 1:1000/kg). Adults: 300–500 mcg (0.3–0.5 mL of 1:1000). It is preferably administered on the lateral aspect of the thigh and may be repeated every 5–10 min.

■

IV dose Children: 1 mcg/kg (0.01 mL of 1:10.000/kg). Adults: 50 mcg (0.5 mL of 1:10,000). Dose is repeated according to response. IV adrenaline infusion in the standard concentration (0.5 mg in 50 mL) may be started at a rate titrated to response.

Positioning of Patient The patient is placed in a supine position with elevation of the lower limbs, particularly when there is hemodynamic compromise. It may be preferable

ERRNVPHGLFRVRUJ

Management of Anaphylaxis

275

Stop allergen High flow oxygen

Adrenaline 10 mcg/kg IM or 1 mcg/kg IV

Hydrocortisone 4 mg/kg IM/IV

Chlorpheniramine 0.2 mg/kg IM/IV

Adrenaline 10 mcg/kg IM or 1 mcg/kg IV

5–10 minutes

Crystalloid 20 mL/kg Fig. 1: Flow diagram for treatment of anaphylaxis in children.

to allow patients with airway and breathing problems to sit up, provided there is no hemodynamic instability, as this will make breathing easier.

Oxygen High flow oxygen (>10 L/min) is administered by face mask and reservoir.

Fluids Hypotension because of vasodilatation and capillary leak may often require large volumes of fluid infusion. Saline is generally preferred to dextrose, because it stays in the intravascular compartment longer and does not contain lactate, which may increase metabolic acidosis. Saline bolus of 20 mL/kg in a child or 500–1000 mL in an adult is given initially and repeated depending on the response. If intravenous access is delayed, the intra-osseous route can be used for fluids or drugs.

Antihistaminics Antihistamines (H1) help counter histamine-mediated vasodilatation and bronchoconstriction. Inj. chlorpheniramine is administered slow IV/IM (Dose: 1 mo–1 yr, 0.25 mg/kg; >1 yr to adults, 0.20 mg/kg).

ERRNVPHGLFRVRUJ

276


Steroids Inj. hydrocortisone 4 mg/kg IM/slow IV.

Other Drugs IV glucagon is indicated in patients on β-blockers who are unresponsive to adrenaline and fluids. Glucagon increases heart rate and myocardial contractility, and improves atrioventricular conduction via non-adrenergic pathways. The dose of glucagon required to reverse severe beta-blockade is 50–150 mcg/kg IV (adults: 3–10 mg) followed by a continuous infusion of 50–150 mcg/kg/h (adults: 3–10 mg/h), titrated to maintain the reversal. Glucagon-treated patients should be monitored for side effects (nausea, vomiting, hypokalemia, and hyperglycemia). IV atropine may be required in patients who develop severe bradycardia after an anaphylactic reaction. 0.02 mg/kg IV/IO (minimum 0.1 mg, maximum single dose in a child 0.5 mg, adult 1 mg). The dose may be repeated once if needed. Vasopressors such as dopamine, vasopressin, noradrenaline are indicated if the hypotension is unresponsive to epinephrine and volume expansion. Bronchodilators (salbutamol, ipratropium) may benefit patients who develop bronchospasm that is not relieved by adrenaline.

Bibliography 1. Emergency treatment for anaphylactic reactions. Guidelines for healthcare providers. London: Resuscitation Council (UK). [Updated: 2008 Oct; cited: 2012 May 31]. Available at: http://www.resus.org.uk/pages/reaction.pdf. 2. Kerns W. Management of beta-adrenergic blocker and calcium channel antagonist toxicity. Emerg Med Clin N Am 2007;25:309–31. 3. Lieberman P, Nicklas RA, Oppenheimer J. The diagnosis and management of anaphylaxis practice parameter: 2010 Update. J Allergy Clin Immunol 2010;126:477–80.

ERRNVPHGLFRVRUJ

SI Units of Measure Prefix

Symbol

Factor

Peta

P

1015

Name

Tera

T

1012

Giga

G

109

Mega

M

6

10

Million

Kilo

k

103

Thousand

Hecto

H

2

10

Hundred

Deka

D

101

Ten

d

10−1

One tenth

−2

Billion

Liter: L Base unit

Meter: m Gram: g

Deci Centi

c

10

One hundredth

Milli

m

10−3

One thousandth

Micro

μ*

−6

10

One millionth

Nano

n

10−9

One billionth

−12

Pico

p

10

Femto

f

10−15

*In drug prescriptions, to avoid confusing μ (micro) with m (milli), it is recommended that μg should be written as mcg.

The basic metric units are meters (for length), grams (for mass), and liters (for volume). Higher and lower sized values are all multiples of ten of each other and are indicated by the prefixes kilo-, hecto-, deka-, deci-, centi-, milli- and so on. Therefore, 1 kg = 1000 g; 1 g = 1000 mg; 1 mg = 1000 mcg; 1 mcg = 1000 ng (10−6 g). Similarly, 1 L = 10 dL; 1 dL = 10 cL; 1 cL = 10 mL (i.e., 1 L = 1000 mL).

ERRNVPHGLFRVRUJ

Appendix A

International System of Units (SI Units) and Conversion Factors

278


Relationship among Units ■

1 L = 1 dm3, i.e., one liter has a volume equal to one cubic decimeter.

■

1 mL = 1 cm3, i.e., the milliliter is the same as a cubic centimeter.

■

1 μL = 1 mm3 (= 0.001 mL = 0.001 cm3), i.e., a microliter has a volume of one cubic millimeter.

■

1 L of water has a mass of approximately 1 kg.

■

1 mL of water has a mass of approximately 1 g.

■

1 μL of water has a mass of 1 mg.

Thus, the range of normal platelet count may be written as: ■

150,000–450,000/μL (microliter) or

■

150,000–450,000 × 106/L or

■

150,000–450,000/mm3 or

■

150–450 × 109/L

■

150–450 × 103/mm3 or

Pressure Scales cm H2O

1–2 3 4 5–6 7 8 9–10 11 12 13–14 15 16 17–18 19 20–21 22

mmHg* 1

2 3 4

5 6 7

8

9

10

11 12 13

14 15

16

*Pressures in mmHg are the nearest whole numbers.

For converting values in centimeters of water to millimeters of mercury, the value given in centimeters of water is divided by the factor 1.36 (1 mmHg = 1.36 cm H2O). 1 kilopascal (kPa) = 7.5 mmHg (10.2 cm H2O).

Temperature Scales Celsius

33

34

35

36

37

38

39

40

41

42

Fahrenheit

91.4

93.2

95

96.8

98.6

100.4

102.2

104

105.8

107.6

Conversion of Fahrenheit to Celsius: °C = (°F − 32) × (5/9) e.g., to convert 98.6°F to °C: (98.6 − 32) × 5/9 = 37°C Conversion of Celsius to Fahrenheit: °F = (°C × 9/5) + 32 e.g., to convert 100°C to °F: (100 × 9/5) + 32 = 212°F

ERRNVPHGLFRVRUJ

SI Units and Conversion Factors

279

French Gauge Catheter Scale French

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

mm

2

2.3

2.7

3

3.3

3.7

4

4.3

4.7

5

5.3

5.7

6

6.3

6.7

The French gauge (Fr) system is used as a measure of the sizes of the external diameter of catheters. 1 Fr = 0.33 mm, and therefore the diameter in mm is equal to Fr divided by 3, e.g., if the Fr size is 12, the diameter is 4 mm. An increasing Fr gauge corresponds to a larger diameter catheter.

IV Cannula and Needle Gauge Gauge

8

10

12

14

16

18

20

22

24

Outer diameter (mm)

4.19

3.40

2.77

2.11

1.65

1.27

0.91

0.72

0.57

The outer diameter of IV cannula and needles is commonly indicated in gauge (Birmingham wire gauge, also referred to as the Stub’s needle gauge). There is an inverse relationship between size and gauge, and an increasing gauge corresponds to a smaller outer diameter (gauge 14 has a larger diameter than gauge 20). Inner diameter depends on both gauge and wall thickness. ■

12–14 gauge are large cannulae, which may be used for rapid infusions during resuscitation.

■

16 gauge is midsize and can be used for blood transfusion.

■

18–20 gauge are used for IV infusions and taking blood samples.

■

22 gauge lines are used in pediatric patients.

ERRNVPHGLFRVRUJ

Appendix B

Vital Signs

Vital Signs at Various Ages (at Rest) Age

Heart rate (beats/min)

Respiratory rate (breaths/min)

Blood pressure (mmHg)

Premature

120–170*

40–70†

55–75/35–45†

0–3 mo

100–150*

35–55

65–85/45–55

3–6 mo

90–120

30–45

70–90/50–65

6–12 mo

80–120

25–40

80–100/55–65

1–3 yr

70–110

20–30

90–105/55–70

3–6 yr

65–110

20–25

95–110/60–75

6–12 yr

60–95

14–22

100–120/60–75

>12 yr*

55–85

12–18

110–135/65–85

th

Source: Kliegman RM, et al., eds. Nelson’s Textbook of Pediatrics 19 ed. Philadelphia: Saunders Elsevier; 2011:279–80. *From Dieckmann R, Brownstein D, Gausche-Hill M, eds. Pediatric Education for Prehospital Professionals. Sudbury, Mass, Jones & Bartlett, American Academy of Pediatrics; 2000:43–45. † From American Heart Association ECC Guidelines, 2000.

Hypotension* For purposes of resuscitation, hypotension has been defined as: ■

Age <1 mo: Systolic blood pressure <60 mmHg

■

1 mo–1 yr: <70 mmHg

■

1–10 yr: <(2 × age in yr) + 70 in mmHg

■

>10 yr: <90 mmHg

*Sources: Kleinman ME, Chameides L. et al. Pediatric Advanced Life Support 2010. American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S876–S908.

ERRNVPHGLFRVRUJ

Age Groups in Children Neonate

Birth to 4 weeks

Infant

1 month to 1 year

Toddler

1–3 years

Pre-school

3–6 years

School

6–12 years

Age – Weight – Height/Length – Surface Area Age (years)

Weight boys (kg)

Weight girls (kg)

Height/length boys (cm)

Height/length girls (cm)

BSA boys m2

At birth

3.3

3.2

49.9

49.1

0.21

1

9.6

8.9

75.7

74.0

0.45

2

12.2

11.5

87.1

85.7

0.54

3

14.3

13.9

96.6

95.1

0.62

4

16.3

16.1

103.3

102.7

0.68

5

18.3

18.2

110.0

109.4

0.75

Adult

68

56

173

163

1.80

WHO growth standards, 50th percentile values for weight and height/length are shown in this table. BSA calculated by Mostellar’s formula.

Calculation of Predicted Weight from Age The following formulas can be used to provide an approximation of median weight from age. 1–10 yr: Wt (kg) = (Age in yr + 4) × 2 7–12 yr: Wt (kg) = (Age in yr × 3) + 7

ERRNVPHGLFRVRUJ

Appendix C

Anthropometric Measurements and Major Motor Milestones

282


In the first few days after birth, children lose 10% of their birth weight, and regain this weight by the 7–10th day. In the first 3 months of age, the rate of weight gain is 25–30 g/day. Children double their birth weight by 5 months age, triple the birth weight by 1 year, and become 4 times their birth weight by 2 years age.

Calculation of Body Surface Area from Weight and Height/Length Mostellar’s formula: BSA (m 2 ) =

Ht (cm) × Wt (kg) 60

Pediatric prescriptions based on body surface area: Percentage of the adult dose based on body surface area may be used for calculation of pediatric doses for drugs having a wide margin between the therapeutic and toxic doses. Approximate pediatric dose =

Surface area of patient (m2 ) × Adult dose 1.8

Major Motor Development Milestones Milestone

1st percentile (in months)

99th percentile (in months)

Sitting without support

3.8

9.2

Standing with assistance

4.8

11.4

Hands and knees crawling

5.2

13.5

Walking with assistance

5.9

13.7

Standing alone

6.9

16.9

Walking alone

8.2

17.6

The 1st to 99th percentiles reflect normal variation in age of milestone achievement in healthy children.

Sources 1. WHO child growth standards. [Updated: 2012; accessed: 2012 Mar 21). Available at: www. who.int/childgrowth/standards/en/ 2. Luscombe MD, Owens BD, Burke D. Weight estimation in paediatrics: a comparison of the APLS formula and the formula ‘Weight = 3 (age) + 7’. Emerg Med J 2011;28:590–3. 3. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987;317:1098. 4. WHO Multicentre Growth Reference Study Group. WHO Motor Development Study: windows of achievement for six gross motor development milestones. Acta Paediatr Suppl 2006;450:86–95.

ERRNVPHGLFRVRUJ

Normal Hematology Values Age

Hb (g/dL)

PCV (%)

RBC (mill/ mm3)

MCV (fL)

MCH (pg)

MCHC PLTS (%) (×103/ mm3)

WBC (×103/ mm3)

Lymphs (%)

0–3 day

15.0–20.0 45–61 4.0–5.9 95–115 31–37 29–37 250–450 9.0–35.0 19–29

1–2 wk

12.5–18.5 39–57 3.6–5.5 86–110 28–36 28–38 250–450 5.0–20.0 36–45

1–6 mo

10.0–13.0 29–42 3.1–4.3 74–96

25–35 30–36 300–700 6.0–17.5 41–71

7 mo to 2 yr 10.5–13.0 33–38 3.7–4.9 70–84

23–30 31–37 250–600 6.0–17.0 45–76

2–5 yr

11.5–13.0 34–39 3.9–5.0 75–87

24–30 31–37 250–550 5.5–15.5 35–65

5–8 yr

11.5–14.5 35–42 4.0–4.9 77–95

25–33 31–37 250–550 5.0–14.5 28–48

13–18 yr

12.0–15.2 36–47 4.5–5.1 78–96

25–35 31–37 150–450 4.5–13.0 25–45

Adult male

13.5–16.5 41–50 4.5–5.5 80–100 26–34 31–37 150–450 4.5–11.0 24–44

Adult female

12.0–15.0 36–44 4.0–4.9 80–100 26–34 31–37 150–450 4.5–11.0 24–44

Mean corpuscular volume (MCV) is expressed in femtoliters (fL, or 10−15 L), the following formula is used: MCV =

10 × hematocrit (%) RBC count (millions/mm3 )

Mean corpuscular hemoglobin (MCH) is the average mass of hemoglobin per red blood cell in a sample of blood. MCH =

10 × Hb (g%) RBC count (millions/mm3 )

Mean corpuscular hemoglobin concentration (MCHC) is a measure of the concentration of hemoglobin in a given volume of packed red blood cells. It is calculated by dividing the hemoglobin by the hematocrit.

Erythrocyte sedimentation rate (ESR) is <20 mm/h by Westergren’s method (<13 by Wintrobe’s method) provided the PCV is >35%. Reticulocyte count: Newborns: 2–6%; 1–6 months: 0–2.8%; Adults: 0.5–1.55. Differential counts: ■ In general, in age <7 days: Neutrophils > lymphocytes; ■

7 days – 4 yr: Lymphocytes > neutrophils;

ERRNVPHGLFRVRUJ

Appendix D

Hematological Parameters

284


■

4–7 yr: Neutrophils = lymphocytes;

■

7 yr: Neutrophils > lymphocytes;

■

Eosinophils: 2–3%;

■

Monocytes: 6–9%.

Source Paediatric care online; American Academy Of Pediatrics (2012). Available at: www.pediatriccareonline.org

ERRNVPHGLFRVRUJ

Biochemistry Albumin Ammonia

Amylase Bilirubin, conjugated, direct

Bilirubin, total

0–1 yr

2.0–4.0 g/dL

1 yr to adult

3.5–5.5 g/dL

Newborns

90–150 mcg/dL

Children

40–120 mcg/dL

Adults

18–54 mcg/dL

Newborns

0–60 units/L

Adults

30–110 units/L

Newborns

<1.5 mg/dL

1 mo to adult

0–0.5 mg/dL

0–3 day

2.0–10.0 mg/dL

1 mo to adult

0–1.5 mg/dL

Bilirubin, unconjugated, indirect Calcium

0.6–10.5 mg/dL Newborns

7.0–12.0 mg/dL

0–2 yr

8.8–11.2 mg/dL

2 yr to adult

9.0–11.0 mg/dL

Calcium, ionized, whole blood

4.4–5.4 mg/dL

Chloride

95–105 mmol/L

Cholesterol

Creatinine Glucose

Newborns

45–170 mg/dL

0–1 yr

65–175 mg/dL

1–20 yr

120–230 mg/dL

0–1 yr

≤0.6 mg/dL

1 yr to adult

0.5–1.5 mg/dL

Newborns

30–90 mg/dL

0–2 yr

60–105 mg/dL

Children to adults

70–110 mg/dL

Children

20–140 units/L

Adults

0–190 units/L

Lactic acid, lactate Lipase

2–20 mg/dL

Magnesium

0.5–1.0 mmol/L

ERRNVPHGLFRVRUJ

Appendix E

Normal Laboratory Values for Children

286


Osmolality, serum

275–296 mOsm/kg

Osmolality, urine

50–1400 mOsm/kg

Phosphorus

Potassium, plasma

Protein, total

Newborns

4.2–9.0 mg/dL

6 wk to 19 mo

3.8–6.7 mg/dL

19 mo to 3 yr

2.9–5.9 mg/dL

3–15 yr

3.6–5.6 mg/dL

>15 yr

2.5–5.0 mg/dL

Newborns

4.5–7.2 mmol/L

2 day to 3 mo

4.0–6.2 mmol/L

3 mo to 1 yr

3.7–5.6 mmol/L

1–16 yr

3.5–5.0 mmol/L

0–2 yr

4.2–7.4 g/dL

>2 yr

6.0–8.0 g/dL

Sodium

136–145 mmol/L

Triglycerides

Urea nitrogen, blood Uric acid

Infants

0–171 mg/dL

Children

20–130 mg/dL

Adults

30–200 mg/dL

0–2 yr

4–15 mg/dL

2 yr to adult

5–20 mg/dL

Adult

3.0–7.0 mg/dL (M), 2.0–6.0 mg/dL (F)

Enzymes Alanine aminotransferase (ALT) (SGPT) Alkaline phosphatase (ALKP)

0–2 mo

8–78 units/L

>2 mo

8–36 units/L

Newborns

60–130 units/L

0–16 yr

85–400 units/L

>16 yr

30–115 units/L

Aspartate aminotransferase (AST)(SGOT)

Infants

18–74 units/L

Children

15–46 units/L

Adults

5–35 units/L

Creatine kinase (CK)

Infants

20–200 units/L

Children

10–90 units/L

Adults

0–206 units/L (M), 0–175 units/L (F)

Lactate dehydrogenase (LDH)

Newborns

290–501 units/L

1 mo to 2 yr

110–144 units/L

>16 yr

60–170 units/L

Source: Pediatric Care Online; the American Academy of Pediatrics. Available at: www.pediatriccareonline.org.

ERRNVPHGLFRVRUJ

Crystalloids Fluid

Na K Ca Cl HCO3 Comments (mmol/L) (mmol/L) (mmol/L) (mmol/L) (mmol/L) (pH/tonicity [mOsm/L])

Plasma

140

4.5

2.3

100

26

pH 7.4, Osm 290

5% Dextrose

Dextrose 50 g/L Osm 277

10% Dextrose

Dextrose 100 g/L Osm 556

Normal saline (0.9% NaCl)

154

154

pH 5, Osm 308

½ Normal 77 saline (0.45 NaCl)

77

pH 5, Osm 154

Glucose 5% + saline 0.45%

77

77

Glucose 50 g/L Osm 431

Ringer lactate

130

4

Plasmalyte 148

140

5

1.5

109

28

Contains lactate 28 mmol/L; pH 6.5, Osm 273

98

29

Contains acetate 27 mmol/L, gluconate 23 mmol/L; pH 5, Osm 294

Colloids Fluid

Na K Ca Cl Other (g/L) (mmol/L) (mmol/L) (mmol/L) (mmol/L)

Comments (pH/tonicity)

Haemaccel

145

5

6.25

145

Gelatin 35 g

7.4

Gelofusine

154

<0.4

<0.4

125

Gelatin 40 g

7.4

Hetastarch

154

–

–

154

Starch 60 g

5.5

Pentastarch

154

–

–

154

Starch 100 g

5.0

Albumin 5%

<160

<2

–

136

Albumin 50 g

7.4

ERRNVPHGLFRVRUJ

Appendix F

Composition of Frequently Used Parenteral Fluids

288


Fluid

Na K Ca Cl Other (g/L) (mmol/L) (mmol/L) (mmol/L) (mmol/L)

Dextran 70 (and 40) 6%

Comments (pH/tonicity)

Dextran (longchain glucose polysaccharides) 60 g + dextrose 50 g in water.

Intravenous fluids are of two types: ■ Crystalloids are volume expanders of the intra- and extravascular compartment and are further classified as Isotonic (D5W, 0.9% NaCl, or Lactated Ringers), Hypotonic (0.45% NaCl), or Hypertonic (D5/0.9% NaCl, D5/0.45% NaCl). ■

Colloids are a suspension of large molecules, usually in water or saline, with a tonicity of 270–300 mOsm/L, and tend to remain in the intravascular compartment after infusion thus expanding the circulating blood volume. These may be physiological (5% albumin, dextran 40/70), semi-synthetic (succinylated gelatin) or synthetic (hydroxyethyl starch). Dextran 70, when given in large amounts, also prevents platelet aggregation and facilitates fibrinolysis.

Sources 1. Intravenous fluids. Ganfyd. [Updated: 2011 Mar 11; accessed: 2012 Mar 21]. Available at: www.ganfyd.org/index.php?title=Intravenous_fluids. 2. Anaesthesia UK. Summary of IV fluids composition. [Updated: 2004 Oct 26; accessed: 2012 Mar 21]. Available at: www.frca.co.uk/article.aspx?articleid=295.

ERRNVPHGLFRVRUJ

Age

Weight (kg)

Internal diameter (mm)

Length (cm) Oral

Nasal

Suction catheter (Fr)

Premature

1.5

2.5–3.0

10.5

9.0–13.0

6

Newborn

3.0

3.0

10.5

13.0

6–8

2–3 mo

5.0–5.5

3.5

11.0

14.0

8

3–6 mo

6.0

4.0

12.0

14.5

8

1 yr

10.0

4.0

13.5

15.0

8

2 yr

14.0

4.5

14.0

16.0

8

2–4 yr

14.0–17.0

5.0

15.0

17.0

10

4–5 yr

17.0–20.0

5.5

16.0

18.0

10

5–7 yr

20.0–23.0

6.0

17.0

19.0

10

7–8 yr

23.0–30.0

6.5

19.0

21.0

10

8–12 yr

30.0–45.0

7.0

21.0

22.0

10

12–14 yr

45.0–70.0

7.0–7.5

22.0

23.0

12–14

The following formula may be used for assessment of size of required ET tube and suction catheter. ET tubes are measured in sizes by internal diameter in mm. Internal diameter (mm) of ET tube = (age/4) + 4 Length (cm) of oral ET tube = (age/2) + 12 Length (cm) of nasal ET tube = (age/2) + 15 The above calculation is applicable after 1 year of age. Neonates generally require a tube of internal diameter 3–3.5 mm. For tracheal suction catheters, in general, the suitable size in French gauge is twice the internal diameter of the ET tube, e.g., for an ET tube of 4 mm diameter the suction catheter should be 8 F size. Same size of suction catheter can be used as a feeding tube.

Source Mackway-Jones K, et al. Advanced Paediatric Life Support: The Practical Approach 3rd ed. London: BMJ books; 2001:37–8.

ERRNVPHGLFRVRUJ

Appendix G

Size and Length of Pediatric Endotracheal Tubes and Suction Catheters

Appendix H

Postoperative Checklist on Arrival in ICU

■

■

■

■

■

■

Ventilation ●

Select initial ventilator settings.

●

Transfer patient to ventilator and check bilateral breath sounds.

●

Fix endotracheal tube in position. Mark the position.

ICU monitor ●

Transfer ECG, pressure lines (LA/RA/PA), pulse oximeter, end-tidal CO2, rectal/skin temperature to ICU monitor.

●

Zero transducers and secure the lines.

Intracardiac and IV lines ●

Transfer all infusion pumps to bedside.

●

Check all IV lines for patency and secure.

●

Review, recalculate, and note all infusion doses.

Other lines and tubes ●

Connect thoracic drains to appropriate suction.

●

Aspirate nasogastric tube and place on gravity drainage.

●

Secure the urinary catheter and record the initial urinary output.

Pacemaker ●

Check pacing wires/pacemaker leads.

●

Note pacemaker settings.

Physical examination ●

Check all vital signs, and perform a physical examination.

●

Record level of consciousness, liver size, and fontanelles (in infants).

■

Arterial blood gases and lab samples

■

Portable chest X-ray ●

Note the position of the endotracheal tube, bilateral lung fields (pneumothorax, opacities, etc.), location of intracardiac lines, position of nasogastric tube, and configuration of cardiac silhouette.

ERRNVPHGLFRVRUJ

Date of surgery: Procedure done: Preoperative weight: Preoperative medications: Allergies: 1. Vital signs q30min 2. Elevate head of bed 30° 3. NPO 4. N/G tube open to gravity drainage 5. Chest drain negative suction: −10 to −20 cm H2O 6. Hourly intake-output 7. Milk chest drains q15min × 2 h, then q1h and PRN 8. Weight q AM if hemodynamically stable 9. Portable X-ray chest stat and in the morning 10. ECG stat and in the morning 11. Serum electrolytes, acid/base, and blood gases q4h (or PRN) × 12 hours, then q6h × 12 hours 12. Blood glucose q4h (or q1h if required) 13. Laboratory studies Total blood count, PT, PTT, platelet count, BUN, Se creatinine, stat and in the morning. 14. Respiratory care ■

Turn side to side and chest physiotherapy after 4 hours and thereafter every 2 hours if hemodynamically stable.

■

Endotracheal suction gently and irrigation with ½–1 mL normal saline q1-3h and PRN.

ERRNVPHGLFRVRUJ

Appendix I

Postoperative Instructions

292


15. IV fluids ■

¼ normal saline in 5% dextrose (¼ saline in 10% dextrose, in neonates) mL/h. Calculated as ¼–½ maintenance (including all drips) on the day of surgery; increased by 25% every subsequent day till full maintenance. Alternatively, plain 5 or 10% dextrose is administered for the first 48 hours and dextrose saline instituted only if the plasma sodium is low.

■

Potassium chloride

mmol in 50 mL of maintenance fluid.

The concentration of potassium is calculated for 50 mL of maintenance fluid based on the daily requirement (2 mmol/kg/day). The amount added is altered depending upon the serum potassium level and urinary output. If serum K+ falls to <3.4 mmol/L, potassium chloride 0.5–1 mmol/kg is administered in a saline or dextrose infusion at a rate of 0.5 mmol/h via infusion pump. Higher rates up to 2 mmol/kg/h IV may be given in arrhythmias. Maximum recommended concentration for a central line is 20 mmol/100 mL and peripheral line 4 mmol/100 mL. K+ levels are checked after the infusion, and the dose is repeated if required. ■

Inj. calcium gluconate 10%

mL in 50 mL of maintenance fluid.

Daily requirement of calcium is 0.2–0.4 mmol/kg (100–200 mg/kg) of calcium gluconate, which may be added to the maintenance fluid or administered intermittently. (1 mL/100 mg of 10% calcium gluconate provides 0.23 mmol of Ca++) ■

Arterial flushing fluid: Normal saline with heparin 1 unit/mL, at 1 mL/h.

16. Antibiotics ■

Inj. teicoplanin 10 mg/kg q12h for 3 doses, then 6–10 mg/kg q24h. Administer IV bolus over 3–5 minutes.

■

Inj. amikacin 5–7.5 mg/kg q12h IV.

17. Analgesics and sedatives ■

Inj. dexmedetomidine 100 mcg in 50 mL 5% dextrose; IV infusion at mL/h. With this concentration 0.25 × body wt (in mL/h) = 0.5 mcg/kg/h; Dose: 0.25–0.5 mcg/kg/h, titrated to response.

■

Inj. fentanyl IV infusion at

(250 mcg/kg) mcg in 50 mL 5% dextrose. mL/h.

With this concentration 1 mL/h = 5 mcg/kg/h; Dose: 2–5 mcg/kg/h IV infusion. ■

Inj. midazolam IV infusion at

(2.5 mg/kg) mg in 50 mL 5% dextrose. mL/h.

ERRNVPHGLFRVRUJ

Postoperative Instructions

293

With this concentration 1 mL/h = 50 mcg/kg/h. Dose: 60–120 mcg/kg/h.

18. Gut prophylaxis ■

Sucralfate suspension (1 g in 5 mL)

mL q4h PO.

Dose: 0–1 yr: 6 mL/day in divided doses q4h PO. 2–6 yr: 12 mL/day in divided doses q4h PO. 7–12 yr: 18 mL/day in divided doses q4h PO. >12 yr: 30 mL/day in divided doses q4h PO.

19. Inotropes and vasodilators ■

Dopamine/dobutamine 100 mg in 50 mL 5% dextrose; IV infusion at mL/h.

■

Sodium nitroprusside/NTG/milrinone 10 mg in 50 mL 5% dextrose; IV infusion at mL/h.

■

Adrenaline/isoprenaline/noradrenaline 1 mg in 50 mL 5% dextrose; IV infusion at mL/h.

■

Vasopressin 10 units in 50 mL 5% dextrose; IV infusion at units/h.

20. Other medication as indicated ■

IV furosemide 100 mg in 50 mL 0.9% saline (not 5% dextrose) IV infusion at mL/h. Dose: 0.05–2.0 mg/kg/h IV infusion.

■

Inj. magnesium sulfate 50% mL in mL of 0.9% isotonic saline or 5% dextrose (diluted 1 in 10) given at a rate of <1 mL/min (max 2 g of magnesium sulfate). Daily requirement of magnesium is 0.2 mmol/kg/day (50 mg/kg/day of magnesium sulfate). (1 mL/500 mg of 50% magnesium sulfate provides 2 mmol of Mg++)

■

Hypoglycemia (<70 mg%): dextrose 0.5–1 g/kg (dextrose 25%: 2–4 mL/kg) slow IV.

■

Hyperglycemia (>150 mg%): Inj. insulin 0.1–0.2 U/kg IV.

21. Blood products ■

Packed cell at mL/h to replace drainage and achieve desired hematocrit (e.g., 4 mL/kg/h × 3 hours).

■

Thereafter, FFP PRN to maintain LAP/CVP (e.g., 10 mL/kg over 2 hours).

22. Ventilator settings ■

FiO2

(initial setting 100%)

ERRNVPHGLFRVRUJ

294

Manual of Pediatric Cardiac Intensive Care ■

Respiratory rate

(15–25/min)

■

Inspiratory time

(0.5–1.0 sec)

■

Peak inspiratory pressure

■

Tidal volume mL

■

PEEP

cm H2O (<25) (10–12 mL/kg)

cm H2O (3–5)

ERRNVPHGLFRVRUJ

Weight (kg)

Op day

1st Post op day mL/h

mL/day

2nd Post op day mL/h

mL/day

3rd Post op day

mL/h

mL/day

mL/h

mL/day

2

2.0

48

4.0

96.0

6.0

144.0

8.0

190.0

3

3.0

72

6.0

144

9.0

216

12.0

290

4

4.0

96

8.0

192

12.0

288

16.0

380

5

5.0

120

10.0

240

15.0

360

20.0

480

6

6.0

144

12.0

288

18.0

432

24.0

580

7

7.0

168

14.0

366

21.0

504

28.0

670

8

8.0

192

16.0

384

24.0

576

32.0

770

9

9.0

216

18.0

432

27.0

648

36.0

860

10

10.0

240

20.0

480

30.0

720

40.0

960

11

10.5

252

21.0

504

31.5

756

42.0

1010

12

11.0

264

22.0

528

32.0

792

44.0

1060

13

11.5

276

23.0

552

34.5

328

46.0

1100

14

12.0

288

24.0

576

36.0

864

48.0

1150

15

12.5

300

25.0

600

37.5

900

50.0

1200

16

13.0

312

26.0

624

39.0

936

52.0

1250

17

13.5

324

27.0

648

40.5

972

54.0

1300

18

14.0

336

28.0

672

42.0

1008

56.0

1340

19

14.5

348

29.0

696

43.5

1044

58.0

1390

20

15.0

360

30.0

720

45.0

1080

60.0

1440

21

15.3

367

30.3

727

45.7

1097

61.0

1460

22

15.6

374

30.6

734

46.4

1114

62.0

1510

23

15.9

381

30.9

742

47.0

1130

63.0

1560

ERRNVPHGLFRVRUJ

Appendix J

Fluid Prescription after Open Heart Surgery

296


Weight (kg)

Op day

1st Post op day

2nd Post op day

3rd Post op day

mL/h

mL/day

mL/h

mL/day

mL/h

mL/day

mL/h

mL/day

24

16.2

388

31.2

749

47.8

1147

64.0

1540

25

16.5

396

31.5

756

48.8

1164

65.0

1560

26

16.8

408

31.7

763

49.2

1181

66.0

1580

27

17.1

410

32.0

770

49.9

1198

67.0

1610

28

17.4

418

32.4

778

50.6

1214

68.0

1630

29

17.7

424

32.7

785

51.3

1231

69.0

1660

30

18.0

432

33.0

792

52.0

1248

70.0

1680

Day of surgery:

1st day: 2nd day: 3rd day:

1/4th of the daily maintenance requirement: 1 mL/ kg/h (for 1st 10 kg) + 0.5 mL/kg/h (for weight >10 kg); in infants, one may start with 2 mL/kg/h and increase daily. Half maintenance requirement: 2 mL/kg/h (for 1st 10 kg) + 1 mL/kg/h : (next 10 kg) + ½ mL/kg/h (for weight >20 kg). 3/4th maintenance requirement: 3 mL/kg/h (for 1st 10 kg) + 1.5 mL/kg/h : (next 10 kg) + 0.75 mL/kg/h (for weight >20 kg). Full maintenance requirement: 4 mL/kg/h (for 1st 10 kg) + 2 mL/kg/h (next 10 kg) + 1 mL/kg/h (for weight >20 kg).

ERRNVPHGLFRVRUJ

To Calculate the Dose for a Given Infusion Rate 1. Convert drug into required measurement if necessary (mg into mcg) 2. Calculate how much of the drug is in one mL (mcg/mL) 3. Divide by patient’s weight (mcg/kg/mL) 4. Multiply by the rate of the infusion to obtain dose (mcg/kg/h) Dose (mcg/kg/h) = Concentration (mcg/mL) ÷ Weight (kg) × Rate (mL/h). Example: 12 kg Child—Fentanyl made up as 1 mg in 50 mL 5% glucose. Infusion running at 1.8 mL/h. Calculate the dose in mcg/kg/h. 1. Convert mg to mcg (1 × 1000 = 1000 mcg) 2. 1000 mcg in the 50 mL syringe (1000 ÷ 50 = 20 mcg/mL) 3. Patient weight 12 kg (20 ÷ 12 = 1.67 mcg/kg/mL) 4. Infusion rate 1.8 mL/h (1.67 × 1.8 = 3 mcg/kg/h) 1.8 mL/h gives 3 mcg/kg/h.

Dose (mg/kg/h) = Concentration (mg/mL) ÷ Weight (kg) × Rate (mL/h) Example: 14 kg Child—Midazolam syringe made up as 50 mg in 50 mL water for injection. Infusion running at 3 mL/h. Calculate the dose in mg/kg/h. 1. Midazolam IV expressed as mg/kg/h. No need to convert mg to mcg 2. 50 mg in the 50 mL syringe (50 ÷ 50 = 1 mg/mL) 3. Patient weight 14 kg (1 ÷ 14 = 0.071 mg/kg/mL) 4. Infusion rate 3 mL/h (0.071 × 3 = 0.2 mg/kg/h) 3 mL/h gives 0.2 mg/kg/h.

Dose (mcg/kg/min) = Concentration (mcg/mL) ÷ Weight (kg) × Rate (mL/h) ÷ 60

ERRNVPHGLFRVRUJ

Appendix K

Calculations of Drug Infusions

298


To Calculate the Infusion Rate for a Specific Dose Infusion rate (mL/h) =

Dose (mcg/kg/h) × Weight (kg) Concentration (mcg/mL)

Infusion rate (mL/h) =

Dose (mg/kg/h) × Weight (kg) Concentration (mg/mL)

Infusion rate (mL/h) =

Dose (mcg/kg/min) × Weight (kg) Concentration (mcg/mL) × 60

ERRNVPHGLFRVRUJ

Dilution of Solutions A concentrated solution must often be diluted before administration. To determine the volume of water required to be added for dilution to achieve the desired concentration can be calculated by the formula: C1 × V1 = C2 × V2 where, C1, concentration of the primary solution; V1, volume of the primary solution; C2, concentration of the final solution; V2, volume of the final solution. Example: How many mL of water must be added to 250 mL of a 3% sodium chloride to prepare a 0.9% w/v sodium chloride solution? C1 × V1 = C2 × V2 C1 = 3% V1 = 250 mL 3 × 250 = 0.9 × V2

C2 = 0.9% w/v V2 = ?

Therefore, V2 = (3 × 250) ÷ 0.9 = 833 mL. However, to carry out the dilution (833 − 250) 583 mL must be added.

Mixing of Solution When a particular concentration of a solution is required to be prepared from available solutions, the quantities needed to be mixed are determined by the formula: C1V1 + C2V2 = C3V3 where, C1, Concentration of 1st solution; V1, Volume of 1st solution; C2, Concentration of 2nd solution; V2, Volume of 2nd solution; C3, Percentage of solution to be prepared; V3, Volume of solution to be prepared.

ERRNVPHGLFRVRUJ

Appendix L

Preparation of Various Concentrations of Solutions

300


Example 1: How many mL of 50% dextrose solution and how many mL of 5% dextrose solution are required to prepare 510 mL of a 10% dextrose solution? When two solutions are combined to make a third one, the following formula is used: C1V1 + C2V2 = C3V3 C1 = 5% V1 = ?

C2 = 50% V2 = ?

C3 = 10% V3 = 510 mL

It is evident that V2 = V3 − V1, then from the above formula, the following can be derived: V1 =

(C2 − C3) × V3 (C2 − C1)

First V1 is calculated

(50 − 10) × 510 = 453 mL (50 − 5)

V2 = V3 − V1, i.e., (510 − 453) = 57 mL 453 mL of 5% dextrose and 57 mL of 50% dextrose are required to make 510 mL of 10% dextrose. Example 2: How many mL of 50% dextrose solution needs to be added to 1 L of dialysis fluid (1.7% dextrose) to make a 3% solution. C1V1 + C2V2 = C3V3 C1 = 1.7% V1 = 1000 mL

C2 = 50% V2 = ?

C3 = 3% V3 = ?

Knowing that V3 = (V1 + V2) mL The following formula for V2 can be derived: V2 =

V1(C3 − C1) 1000(3 − 1.7) = 27.6 mL i.e., (C2 − C3) (50 − 3)

27.6 mL of 50% dextrose needs to be added to 1 L of 1.7% dialysis fluid to make a 3% concentration.

ERRNVPHGLFRVRUJ

Crying

Characteristic cry of pain is high pitched

0 - No cry or cry that is not high-pitched 1 - Cry high pitched but baby is easily consolable 2 - Cry high pitched and baby is inconsolable Requires O2 for SaO2 <95%

Babies experiencing pain manifest decreasing oxygenation. Consider other causes of hypoxemia (e.g., oversedation, atelectasis, pneumothorax)

Increased vital signs (BP and HR)

Take BP last as this may awaken child making other assessments difficult

Expression

The facial expression most often associated with pain is a grimace. A grimace may be characterized by brow lowering, eyes squeezed shut, deepening nasolabial furrow, or open lips and mouth

0 - No oxygen required 1 - <30% oxygen required 2 - >30% oxygen required 0 - Both HR and BP unchanged or less than baseline 1 - HR or BP increased but increase is <20% of baseline 2 - HR or BP is increased >20% over baseline

0 - No grimace present 1 - Grimace alone is present 2 - Grimace and non-cry vocalization grunt is present Sleepless

Scored based upon the infant’s state during the hour preceding this recorded score

0 - Child has been continuously asleep 1 - Child has awakened at frequent intervals 2 - Child has been awake constantly The CRIES Pain Scale is a pain assessment scale generally used for infants <6 months age. Each of the five (5) categories—crying oxygenation, vital signs, facial expression, and sleeplessness—in relation to pain is scored from 0 to 2, which results in a total score between 0 and 10. For assessment of HR and BP multiply the baseline HR and mean BP by 0.2 then add to baseline HR/BP to determine the HR/BP that is 20% over baseline.

Source Krechel SW, Bildner J. CRIES: a new neonatal postoperative pain measurement score—initial testing of validity and reliability. Paediatric Anaesthesia 1995;5:53.

ERRNVPHGLFRVRUJ

Appendix M

Cries Pain Scale

Appendix N

Drug Prescription in Renal Failure

Cardiac Drugs and Diuretics Drug/dose in children

Change in dose (I/D)

GFR >50

10–50

<10

Supplemental dose for dialysis (HD/PD/CRRT)

Acetazolamide 5–10 mg/kg/day PO/IV in divided doses q6–12h (max 750 mg/day)

I

q6h

q12h

NR

HD/PD/CRRT–

Atenolol 1–1.2 mg/kg q24h PO

D, I

100% or q24h

50% or q48h

30–50% or q96h

HD+ PD– CRRT + (dose for GFR 10–50)

Captopril 0.3–3.0 mg/kg/day in divided doses q8h PO. (dose in CCF)

D, I

100% or q8–12h

75% or q12–18h

50% or q24h

HD + (25–30% of dose) PD– CRRT + (dose for GFR 10–50)

Digoxin Neonate–10 yr: 5 mcg/kg q12h PO >10 yr: 2.5 mcg/kg q12h PO

D, I

100% or q24h

25–75% or q36h

10–25% or q48h

HD– PD– CRRT + (dose for GFR 10–50)

Enalapril 0.1–0.5 mg/kg/day divided q12h–24h PO

D

100%

75–100%

50%

HD + (25–30% dose) PD– CRRT + (dose for GFR 10–50)

Hydrochlorothiazide 2–4 mg/kg/day divided q6–12h PO.

D

100%

100%

NR

ERRNVPHGLFRVRUJ


Drug/dose in children


Spironolactone 1.5–3.5 mg/kg/day divided q6–24h PO

I

Verapamil 3–6 mg/kg/day in divided doses q8h PO

GFR >50

10–50

<10

6–12 hours

12–24 hours

NR

100%

100%

50–75%

303



NR: not recommended, +: additional dose is indicated, –: additional dose is not indicated, PD: peritoneal dialysis, HD: hemodialysis, CRRT: continuous renal replacement therapy. D: method of dose reduction by administration of a percentage of the usual dose. I: method of dose reduction by increase in the dosing interval. D, I: Either the dose or the interval can be changed.

Noncardiac Drugs Drug/dose in children


>50

10–50

GFR <10

Aspirin 30–60 mg/kg/day PO divided q4–6h (anti-inflammatory dose)

I

q4h

q4–6h

NR

HD+ PD+ CRRT + (dose for GFR 10–50)

Cisapride 0.2–0.3 mg/kg q6–8h PO

D

100%

100%

50%

HD/PD not known CRRT + (50–100% dose)

Famotidine 0.5 mg/kg/day in divided doses q12–24h PO

D, I

100% or q12–24h

50% or q24h

25% or q36–48h


Fentanyl 1–2 mcg/kg IV bolus. May be repeated every 30 minutes–1 hour

D

100%

75%

50%

HD/PD/CRRT: not known

Insulin 0.1 U/kg/h IV infusion or 0.1–0.2 U/kg IV stat PRN

D

100%

75%

50%


ERRNVPHGLFRVRUJ


304


Drug/dose in children


GFR


>50

10–50

<10

Metoclopramide 0.1–0.2 mg/kg/dose q6–8h PO/IM/IV (anti-emetic dose).

D

100%

50–75%

25–50%

HD – PD: not known CRRT + (dose for GFR 10–50)

Midazolam 0.05–0.1 mg/kg IV bolus

D

100%

100%

50%


Morphine 1–6 mo: 0.25–50 mg/kg may repeat up to q6h IV. 6 mo–1 yr: 0.1–0.2 mg/kg may repeat up to q4h IV.

D

100%

75%

50%

HD – PD: not known CRRT + (dose for GFR 10–50)

Paracetamol (Acetaminophen) 40–60 mg/kg q4–6h PO or 5 mg/kg q4–6h IV

I

q4h

q4–6h

NR

HD – PD – CRRT + (dose for GFR 10–50)

Phenobarbitone 10–20 mg/kg slow IV. Maintenance 5–10 mg/kg/day in divided doses q8–12h PO/IV

I

q8–12h

q8–12h

q12–16h

HD+ PD + (50% of dose) CRRT + (dose for GFR 10–50)

Ranitidine IV (<12 yr): 3 mg/ kg/day in divided doses q8h PO: 2–4 mg/kg in divided doses q12h

D

100%

75%

50%

HD – PD – CRRT + (dose for GFR 10–50)

Thiopental sodium 2–6 mg/kg IV bolus

D

100%

100%

75%


Normal glomerular filtration rate is approximately 100 mL/min/1.73 m2. For prescribing purposes, renal impairment is usually divided into three categories: (i) Mild impairment: GFR 50–20 mL/min (serum creatinine approximately 2–5 mg/dL); (ii) Moderate: GFR 10–20 mL/min (serum creatinine approximately 5–10 mg/dL); and (iii) Severe: GFR <10 mL/min (serum creatinine >10 mg/dL).

ERRNVPHGLFRVRUJ


305

Patients with a GFR above 50 mL/min do not usually require any dosage adjustment; however, nephrotoxic drugs (e.g., many antibiotics, NSAIDs) are best avoided in patients with acute kidney injury. Drugs that are excreted by the kidneys but are in themselves not nephrotoxic require dose reduction to prevent dose related side effects. The total daily maintenance dose of a drug can be reduced either by reducing the individual dose or by increasing the interval between doses. It is however important to give a normal initial dose if an immediate effect is required. No change in dose in renal dysfunction is required for the following drugs: ■

Analgesics, sedatives, muscle relaxants: Diazepam, diclofenac, ibuprofen, ketamine, lorazepam, propofol, or vecuronium.

■

Steroids and antihistaminics: Dexamethasone, hydrocortisone, prednisolone, methyl prednisolone (additional dose required following HD), and chlorpheniramine.

■

Anti-convulsants: Carbamazepine, phenytoin or sodium valproate, however, drug levels need careful monitoring.

■

Drugs used in GI disorders: Omeprazole and ondansetron.

■

Anticoagulants: Heparin (dose of LMW heparin however requires reduction to 50% with GFR <10, no change is required with a GFR >10) and warfarin.

■

Cardiac drugs and diuretics: Adenosine, amiodarone, diltiazem, labetalol, metoprolol, nifedipine, xylocard, and furosemide.

Sources 1. Arnoff GR, Brier ME. Prescribing drugs in renal disease. Brenner and Rector’s The Kidney 7 ed. Philadelphia: Saunders; 2004:2849–70. 2. Robertson J, Shilkofski N. Drugs in renal failure. The Harriet Lane Handbook 17 ed. Philadelphia: Mosby; 2005:1053–68.

ERRNVPHGLFRVRUJ

Appendix O

Pediatric Blood Levels of Commonly Used Drugs

Drug

Optimal range

Remarks

Amikacin

Peak: 15–25 mcg/mL Trough: 2–5 mcg/mL

Suggested sampling time at 3rd dose or later. Peak 30 min after end of infusion. Trough levels are estimated before next dose.

Amiodarone

0.5–2.5 mcg/mL

Trough level after steady state has been achieved.

Carbamazepine

6–12 mcg/mL

Trough level after 1–2 weeks

Digoxin

0.8–1.2 ng/mL

Oral trough level after 1 week

Gentamicin

Peak: 5–10 mcg/mL Trough: <2 mcg/mL

Peak 60 minutes after IV or IM dose

Netilmicin

Peak: 4–12 mcg/mL Trough: <2 mcg/mL

Peak 60 minutes after IV or IM dose

Lignocaine

1.5–5 mcg/mL

Sample for drug level can be drawn at any time during infusion

Phenobarbitone

15–25 mcg/mL

Trough level after 1–2 weeks of oral therapy.

Phenytoin

10–20 mcg/mL

Trough level after 1 week of oral therapy. IV 2–4 hours after loading dose

Salicylate

100–300 mcg/mL

Suggested sampling time at 5th dose. Peak level 1–2 hours after dose.

Theophylline (for asthma)

10–20 mcg/mL

Peak level 1–2 hours after dose following 1–2 days of oral drug therapy; IV, 30 minutes after completion of loading dose and anytime during continuous infusion.

Valproic acid

50–100 mcg/mL

Trough level after 2–3 days of oral therapy.

Vancomycin

Peak: 18–26 mcg/mL Trough: 5–10 mcg/mL

Peak level at 4th dose, 2 hours after completion of infusion. (2 hours after start of infusion level 25–40 mcg/mL).

Sources: Rylance GW, Moreland TA. Review article: Drug level monitoring in paediatric practice. Archives of Disease in Childhood 1980;55:89–98. AND Therapeautic drug level monitoring. Alder Hey Book of Children’s Doses 6th ed. Liverpool: Royal Liverpool Children’s Hospital; 1994:252–3.

ERRNVPHGLFRVRUJ

Index

A AAI mode 66 Accelerated idioventricular rhythm 50 Acid–base disorder 115 Acinetobacters 184 Activated clotting time 260 Activated partial thromboplastin time 257 Acute kidney injury 241 Acute lung injury 146 Acute renal failure 241 Acute respiratory distress syndrome 146 Adenosine 52, 57, 61, 89 Adrenaline 25, 26, 89, 93, 273, 274 Adrenergic receptors 24 Afterload 20 Age groups in children 281 Alpha-2-antiplasmin 262 Alpha-2-plasmin inhibitor 261 Alprostadil 26, 28 Alveolar–arterial oxygen gradient 114 Amikacin 187, 190 Amino acids 125 Aminopenicillins 185 Amiodarone 53, 58, 89, 93 Amlodipine 79 Amoxicillin 190 Amoxicillin–clavulanate 185, 190 Amphotericin B 214 Amphotericin B deoxycholate 211 Amphotericin B lipid complex 212 Amphotericin B liposomal 212 Ampicillin 191 Ampicillin–sulbactam 185, 191

Anaerobic pathogens 184 Analgesics 223 Anidulafungin 212, 215 Anion gap acidosis 119 Anthropometric measurements 281 Anti-emetics 136 Antidromic AVRT 45 Antifibrinolytic agents 264 Antithrombin III 261, 262 AOO mode 66 Approximate pediatric dose 282 Aspergillosis 211 Aspiration pneumonia 147 Aspiration pneumonitis 144 Aspirin 222, 267 Assist control 161 Asynchrony 173 Asystole 96 Atelectasis 143 Atenolol 79 Atrial demand pacing 71 Atrial ectopics 42 Atrial ectopic tachycardia 43 Atrial electrocardiograms 38 Atrial fibrillation 44, 59 Atrial flutter 44 Atrioventricular interval 69 Atrioventricular reentrant (or reciprocating) tachycardia 45 Atropine 89, 93, 276 AV nodal reentrant tachycardia 46 A–V sequential pacing 70 AVPU scale 234 Azithromycin 189 Aztreonam 188, 192

ERRNVPHGLFRVRUJ

308

Index

B Bacteroides fragilis 184 Base excess 115 Benzathine penicillin 184 Beta-blockers 58 Beta-lactamase 182 Beta-lactamase inhibitors 182 Bicarbonate (HCO3−) level 114 BIPAP 165 Bisferiens pulse 4 Bleeding time 259 Blood components 265 Blood gas analysis 116 Blood glucose control 103 Blood sugar 110 Bolus feedings 131 Bradycardia 98 Brain death 234 Broad QRS complex tachycardia 60, 61 Bronchial asthma 150 Bronchospasm 150 Budesonide 152

C Calcium 94 Calcium channel blockers 58 Calcium gluconate 89 Calculation of body surface area from weight and height/length 282 Calculation of predicted weight from age 281 Calculations of drug infusions 297 Caloric requirements 125 Candidiasis 211 Capnography 93 Captopril 35, 80 Carbamazepine 229 Carboxypenicillin 186 Cardiac index 10 Cardiac output 10 Cardiopulmonary resuscitation 90 Cardioversion 61 Care of the ventilated patient 178 Carvedilol 36 Caspofungin 213, 215

CAVH 250 Cefaclor 186, 192 Cefazolin 186, 192 Cefepime 187, 193 Cefoperazone 186, 193 Cefotaxime 186, 193 Cefoxitin 186 Cefpirome 187 Ceftazidime 186, 193 Ceftriaxone 186, 194 Cefuroxime 186, 194 Central venous pressure 6 Cephalexin 186, 194 Cephalosporins 186 Cerebral perfusion pressure 237 Cheyne–stokes respiration 235 Chloral hydrate 217 Chloride-resistant metabolic alkalosis 120 Chloride-responsive metabolic alkalosis 120 Chlorpheniramine 273, 275 Chylothorax 141 Ciprofloxacin 187, 195 Cisapride 136 Clarithromycin 189, 195 Clindamycin 188, 195 Clinical criteria for VAP 177 Clopidogrel 267 Clotrimazole 215 Cloxacillin 185 Cockcroft–Gault equation 243 Collapsing pulse 4 Colloids 287 Colorimetry 93 Coma 234 Combination or dual modes 157 Common pathway 257 Compensation 117 Compensatory pause 42, 46, 48 Competition 72, 74 Complete heart block 64 Complications of tube feeding 133 Composition of frequently used parenteral fluids 287 Congestive heart failure 32

ERRNVPHGLFRVRUJ

Index

Continuous feedings 131 Controlled mechanical ventilation 158 Control of seizures 227 Conversion of Celsius to Fahrenheit 278 Conversion of Fahrenheit to Celsius 278 Counahan–Barratt equation 243 CPAP 164 Creatinine clearance 242 Cries pain scale 301 Cryoprecipitate 264, 266 Cryptococcosis 211 Crystalloids 287 CT scan 237 Cushing’s triad 235 CVVH 251 CVVHD 251 CVVHDF 252 Cyanide toxicity 27–31 Cyanotic spells 88

D D-dimer 259 Damping 3 DC cardioversion 57 DDD device 66 Decerebrate rigidity 236 Decorticate posture 236 Defibrillation 92 Deficit therapy 100, 102 Dehydration 102 Delirium 234 Dexamethasone 240 Dexmedetomidine 217, 225 Dextrose 89, 126 Diaphragmatic paralysis 142 Diazepam 217, 227, 230 Diazoxide 78 Differential counts 283 Digoxin 33, 58 Diltiazem 54, 80 Dilution of solutions 299 Dipyridamole 267 Disseminated intravascular coagulation 260 Dobutamine 25, 26

309

Doll’s eyes movement 236 Domperidone 136 Dopamine 25, 26 Drug prescription in renal failure 302 Dual/combination modes 166 DVI pacing 66

E E. coli 183 Ejection fraction 11 Electrolyte requirements 100 Electrolytes 126 Elemental formulas (monomeric formulas) 132 Enalapril 35, 78, 80 End tidal carbon dioxide monitoring 93 Enteral tube feeding 130 Enterobacter 183 Enterobacteriaceae 183 Enterococci 183 Epicardial pacing 67 Epoprostenol 26, 28 Ertapenem 187 Erythrocyte sedimentation rate 283 Erythromycin 189, 196 Esmolol 54, 78, 87 Established ARF 241 Etomidate 220 Expressed breast milk 131 External chest compressions 90 Extrinsic coagulation pathway 257

F Failure to capture 71, 72 Failure to pace 71, 74 Failure to sense 71, 73 Fat 125 Febrile seizures 232 Fentanyl 87, 219, 225 Fibrinogen 259, 261, 262 Fibrinogen degradation products 259 Fibrinolysis 257 FiO2 169 First-degree AV block 64 First-degree heart block 63 Flow rate 168

ERRNVPHGLFRVRUJ

310

Index

Flow waveforms 170 Fluconazole 213, 215 Fluid prescription after open heart surgery 295 Fluid therapy 102 Fluoroquinolones 187 Fosphenytoin 228 Frank–Starling law 18 French gauge catheter scale 279 Fresh frozen plasma 263, 265 Furosemide 34 Fusobacterium 184

G Gastric residue 134 Generic code for pacemakers 65 Gentamicin/tobramycin 196 Gentamicin 187 Glasgow coma scale 233 Glomerular filtration rate 242 Glucagon 276 Glucose homeostasis 110 Glycopeptides 188 Gram-negative bacilli 183 Gram-positive cocci 182 Griseofulvin 215

Hyponatremia 108 Hypothermia 99

I I:E ratio 168 Ibuprofen 222 Idioventricular rhythm 50 Imipenem–Cilastatin 187, 196 Infection 202 Inj. ranitidine 137 Inspiratory pause 170 Intermittent mandatory ventilation 159 International normalized ratio 258 Intracranial pressure 237 Intrinsic coagulation pathway 257 Ipratropium 152 Isoproterenol 25, 26 Itraconazole 215 IV cannula and needle gauge 279

J JET 59 Junctional ectopics 46 Junctional ectopic tachycardia Junctional rhythm 46

H

K

H. influenzae 183 Heart blocks 63 Hematological parameters 283 Heparin 127 Histoplasmosis 211 Human milk fortifier 132 Hydralazine 78, 80 Hydrochlorothiazide 34 Hydrocortisone 152, 273, 276 Hydrogen ion 112 Hypercarbia 172 Hyperkalemia 104 Hypernatremia 109 Hypertensive crisis 81, 84 Hypertensive emergency 81 Hypertensive urgency 81 Hypertonic saline 239 Hypocalcemia 105 Hypokalemia 103 Hypomagnesemia 107

Ketamine 87, 220 Ketoconazole 215 Kitchen based feeds Klebsiella 183

132

L L-adrenaline 152 Labetalol 79, 80 Laryngeal mask airway 92 Left atrial pressure 8 Left heart failure 147 Left ventricular end diastolic pressure 8 Levetiracetam 229 Levofloxacin 187, 197 Lignocaine 54, 89, 94 Lincosamides 188 Linezolid 188, 197 Lorazepam 217, 227 Losartan 35

ERRNVPHGLFRVRUJ

46

Index

Low cardiac output 15 Lumbar puncture 237

311

N

M Macrolides 189 Magnesium 90, 94 Magnesium sulfate 54, 90 Maintenance fluid requirement 101 Maintenance therapy 100 Management of sepsis 206 Mannitol 239 Mean arterial pressure 1 Mean corpuscular hemoglobin 283 Mean corpuscular hemoglobin concentration 283 Mean corpuscular volume 283 Meropenem 187, 197 Metabolic acidosis 119 Metabolic alkalosis 120 Methicillin-resistant Staph. aureus 183 Methicillin 185 Methylprednisolone 152 Metoclopramide 136 Metolazone 34 Metoprolol 35, 55, 80, 87 Metronidazole 198 Micafungin 213, 215 Midazolam 87, 218, 225, 227, 230 Milrinone 26, 27 Mixing of solution 299 Mobitz type 1 second-degree heart block 63 Mobitz type 2 second-degree heart block 63 Modified Ramsay sedation scale 223 Modular formulas 132 Monobactams 188 Monomorphic VT 49, 61 Morphine 87, 219, 225 Mostellar’s formula 282 Motor milestones 281 MRI 237 MRI in patients with pacing wires 76 Multifocal atrial tachycardia 43 Muscle relaxants 222 Myoclonus 236

Naloxone 90 Narrow QRS complex arrhythmias 52 Narrow QRS complex tachycardias 57 Natural penicillins 184 Netilmicin 187 Nicardipine 79 Nifedipine 80 Nimesulide 222 Nitroglycerin 25 Non-anion gap acidosis 119 Nonsustained VT 50 Noradrenaline 25, 27 Normal breathing 156 Normal ECG 37 Normal hemostasis 256 Normal laboratory values for children 285 Normal sinus rhythm 39 NTG 27 Nutritional requirements 124 Nystatin 215

O Oculocepahalic reflex (Doll’s eyes movement) 236 Oculovestibular reflex 236 Ofloxacin 187 Omeprazole 137 Ondansetron hydrochloride 136 Organ dysfunction criteria 203 Orthodromic AVRT 45 Osmotic diuresis 239 Overdrive pacing 59 Oxazolidinones 188 Oxygen 98 Oxygenation 172 Oxygen content 113

P Pacemaker mediated tachycardia 72, 75 Pacemaker output 67 Pacemaker parameters 67 Pacemaker settings 69 Pacing modes 65 Pacing rate 68

ERRNVPHGLFRVRUJ

312

Index

Packed RBCs 263 Packed red cells 265 PALS protocols 94 Pancuronium 221 PAP complexes 262 Paracetamol 222 Partial pressure of carbon dioxide 113 Partial pressure of oxygen 113 Peak airway pressure 173 Pediatric advanced life support 91 Pediatric basic life support 90 Pediatric blood levels of commonly used drugs 306 PEEP 169 Penicillinase-resistant penicillins 185 Penicillin G 184 Peritoneal dialysis 246 pH 112 Phenobarbitone 228 Phenylephrine 25, 27, 88 Phenytoin 228 Phenytoin sodium equivalent units 228 PIP 170 Piperacillin 198 Piperacillin–tazobactam 185, 198 Plasmin-antiplasmin complex 261 Plateau pressure 170 Platelet count 259 Platelet transfusion 263 Pleural effusion 140 Pneumonia 176 Pneumothorax 142 Polymorphic VT 49 Posaconazole 213, 215 Positive end-expiratory pressure 164 Post CPB bleeding 260 Postoperative bleeding 262 Postoperative checklist on arrival in ICU 290 Postoperative instructions 291 Postoperative seizures 231 Post ventricular atrial refractory period 69 Preload 19 Preparation of various concentrations of solutions 299 Prerenal azotemia 241

Prerenal failure 246 Pressure assist control 163 Pressure controlled ventilation 162 Pressure control ventilation 171 Pressure limit 170 Pressure preset modes 162 Pressure preset SIMV 163 Pressure preset ventilation 157 Pressure regulated volume control 167 Pressure scales 278 Pressure support ventilation 163 Pressure support weaning 174 Prevotella 184 Primary fibrinolysis 261 PR interval 37 Procainamide 55 Procaine penicillin 184 Prochlorperazine 136 Propofol 220, 230 Propranolol 81, 87 Prostacyclin 28 Proteus 183 Prothrombin time 258 Pseudomonas 183 Pulmonary arterial hypertension 83 Pulmonary artery (PA) pressure 83 Pulmonary artery pressure 8 Pulmonary blood flow 85 Pulmonary capillary wedge pressure 8 Pulmonary dysfunction 140 Pulmonary hypertensive crisis 84 Pulmonary vascular resistance 10, 83 Pulmonary vasoconstrictors 83 Pulmonary vasodilators 83 Pulseless electrical activity 51, 96 Pulseless ventricular tachycardia 95 Pulseless VT 50 Pulse pressure 2 Pulsus alternans 4 Pulsus paradoxus 5 Pulsus tardus et parvus 4 P wave 37

Q QRS complex 38 QT interval 38 Quinupristin–dalfopristin 199

ERRNVPHGLFRVRUJ

Index

R Random donor platelets 265 Ranitidine 137 Rapid sequence intubation 224 Re-exploration 263 Recombinant factor VII 264 Refractory seizures 230 Relationship among units 278 Removal of pacing wires 76 Renal replacement therapy 246 Respiratory acidosis 118 Respiratory alkalosis 118 Respiratory rate 168 Reticulocyte count 283 Rifampin 199 RIFLE criteria 243 Right ventricular end diastolic pressure 8 Rocuronium 221

S Salbutamol 151 Same direction rule 115 Schwartz equation 243 SCUF 251 Second-degree AV block 64 Sedation for short procedures 224 Sedatives 217, 223 Sensing threshold 68 Sensitivity 169 Sepsis 202, 203 Septic shock 17, 202, 203 Serratia 183 Serum tryptase 274 Severe sepsis 202, 203 Sigh 169 SIMV 167 SIMV + PS 166 SIMV weaning 174 Single donor platelet 265 Sinus arrest 41 Sinus arrhythmia 41 Sinus bradycardia 40 Sinus tachycardia 40 SIRS 200, 202 SI units and conversion factors 277

313

Size and length of pediatric endotracheal tubes and suction catheters 289 Sodium bicarbonate 87, 90, 94 Sodium nitroprusside 25, 27, 79 Sodium valproate 229 Sources of sepsis 204 Spironolactone 35 Standard bicarbonate 115 Standard infant formula 131 Staphylococci 182 Streptococci 183 Stress ulceration 137 Stroke volume 11, 18 Stupor 234 Succinylcholine 221 Sucralfate suspension 137 Supraventricular tachycardia 51, 60 Sustained VT 50 Synchronized intermittent mandatory ventilation 159 Synchronized ventricular pacing 70 Systemic arterial oxygen saturation 8, 113 Systemic inflammatory response syndrome 202 Systemic vascular resistance 10 Systemic venous oxygen saturation 10 Systolic overshoot 3

T TAT complexes 261, 262 Teicoplanin 188, 200 Temperature scales 278 Terbinafine 215 Terbutaline 153 Theophylline 152 Therapeutic overdrive pacing 75 Thiocyanate toxicity 27–31 Thiopental sodium 220, 230 Third-degree AV block 64 Thrombin time 258 Thrombin-antithrombin complex 261, 262 Ticarcillin 199 Ticarcillin–clavulanate 186, 200 Tidal volume 167 Tobramycin 187

ERRNVPHGLFRVRUJ

Manual of Pediatric Cardiac Intensive Care (1)

Recommend Documents