CLINICAL DECISION MAKING TOOLKIT
2018 edition
Instant guidance for diagnosis, risk management and treatment
The Clinical Decision Making Toolkit is produced by the Acute Cardiovascular Care Association (ACCA), (ACCA), developed and distributed through an educational grant from AstraZeneca. AstraZeneca AstraZ eneca was not involv involved ed in the development of this publication and in no way influenced its content. content.
The Clinical Decision Making Toolkit is produced by the Acute Cardiovascular Care Association (ACCA), (ACCA), developed and distributed through an educational grant from AstraZeneca. AstraZeneca AstraZ eneca was not involv involved ed in the development of this publication and in no way influenced its content. content.
The Acute Cardiovascular Care Associa Association tion Clinical Decision-Making TOOLKIT
Héctor Bueno, M.D., Bueno, M.D., PhD., FESC Editor in Chief Pascal Vranckx, M.D., Vranckx, M.D., PhD Associate Editor
ISBN: 978-2-9537898-7-4
Preface The best care of patients with acute cardiovascular syndromes relies not only on specialists but also on systems of care that involve many non-cardiologists. Several of these syndromes require immediate diagnosis and decisions on treatment, some of them life-saving. Critical decisions must often be made quickly by professionals with different backgrounds and levels of expertise with limited resources. This poses a significant clinical challenge. Against this background, the ACCA Clinical DecisionMaking Toolkit was created as a comprehensive resource encompassing all aspects of acute cardiovascular care but structured as an easy-to-use instrument in environments where initial acute cardiovascular care is typically initiated. Comprehensive tables, clear diagrams and algorithms, based on the ESC clinical practice guidelines as well as in clinical experience should provide diagnostic and therapeutic guidance at a glance. This 2018 Edition of the Clinical Decision Making Toolkit has been updated with the 2016 and 2017 ESC Guidelines, a chapter on secondary prevention was added and the chapter cha pter on acute heart failure benefited a major update. However, it does not replace textbooks and other sources of information that need to be consulted to reach an optimal management of these patients.
II
The ACCA Toolkit is available through different platforms: • Printed booklet, available at congresses where ESC-ACCA ESC-ACCA is i s represented • Web-based pdf file downloadable at: www.escardio.org/ACCA • Mobile application for smartphones/tablets available in both Apple & Googleplay stores
Héctor Bueno M.D., PhD., FESC Editor in Chief
7 DAYS F R O M U N T I L
C A R D I A C
P AT I E N T
E V E N T
S TA B I L I S AT I O N
CARDIAC ARREST, STEMI, ACS, AHF, CARDIOGENIC SHOCK, ARRHYTHMIAS, VASCULAR SYNDROMES
EMERGENCY ROOM PRE-HOSPITAL CARE
GENERAL HOSPITAL
CCU
CORONARY CARE UNIT
ICCU
INTENSIVE CARDIAC CARE UNIT
Contents IV List of Authors __________________________________________________________________________________________________________________________ VI CHAPTER 1: KEY SYMPTOMS
Chest Pain - M. Lettino, F. Schiele __________________________________________________________________________________________________ P. 2 Dyspnea - C. Müller _____________________________________________________________________________________________________________________ P. 9 Syncope - R. Sutton ___________________________________________________________________________________________________________________ P. 16 CHAPTER 2: ACUTE CORONARY SYNDROMES
General concepts - H. Bueno ______________________________________________________________________________________________________ P. 24 Non ST-segment elevation ACS - H. Bueno __________________________________________________________________________________ P. 29 STEMI - P. Vranckx, B. Ibañez ______________________________________________________________________________________________________ P. 34 CHAPTER 3: SECONDARY PREVENTION AFTER ACS
General secondary prevention strategies and lipid lowering - H. Bueno, S. Halvorsen _______________________ P. 38 Antithrombotic treatment - F. Costa, S. Halvorsen ________________________________________________________________________ P. 41 CHAPT ER 4: ACUTE HEART FAILURE
Wet-and-warm heart failure patient - V.P. Harjola, O. Miró _____________________________________________________________ P. 52 Cardiogenic shock (wet-and-cold) - P. Vranckx, U. Zeymer _____________________________________________________________ P. 61
Contents (Cont.) V CHAPTER 5: CARDIAC ARREST AND CPR - N. Nikolaou, L. Bossaert
P. 71
____________________________________
CHAPTER 6: RHYTHM DISTURBANCES
Supraventricular tachycardias and atrial fibrillation - J. Brugada __________________________________________________ P. 80 Ventricular tachycardias - M. Santini, C. Lavalle, S. Lanzara __________________________________________________________ P. 84 Bradyarrhythmias - B. Gorenek __________________________________________________________________________________________________ P. 87 CHAPTER 7: ACUTE VASCULAR SYNDROMES
Acute aortic syndromes - A. Evangelista ______________________________________________________________________________________ P. 92 Acute pulmonary embolism - A. Torbicki _____________________________________________________________________________________ P. 102 CHAPTER 8: ACUTE MYOCARDIAL/PERICARDIA L SYNDROMES
Acute myocarditis - A. Keren, A. Caforio ______________________________________________________________________________________ P. 112 Acute pericarditis and cardiac tamponade - C. Vrints, S. Price _______________________________________________________ P. 117 CHAPTER 9: DRUGS IN ACUTE CARDIOVASCULAR CARE - A. de Lorenzo ______________________ P. 121
Abbreviations ______________________________________________________________________________________________________________________ P. 191 References and copyright acknowledgments __________________________________________________________________ P. 199
List of Authors VI Leo Bossaert Josep Brugada Héctor Bueno Alida Caforio Francesco Costa Artur Evangelista Bulent Gorenek Sigrun Halvorsen Veli-Pekka Harjola Borja Ibañez Andre Keren
Department of Medicine, University and University Hospital Antwerp, Antwerp, Belgium Department of Cardiology, Hospital Clinic Universitat de Barcelona, Barcelona, Spain Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), and Department of Cardiology, Hospital Universitario 12 de Octubre, Madrid, Spain Department of Cardiology, Padua University Medical School, Padua, Italy Cardiovascular institute, Hospital Clínic, University of Barcelona, Barcelona, Spain Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy Department of Cardiology, Hospital Universitario Vall d’Hebrón, Barcelona, Spain Department of Cardiology, Eskisehir Osmangazy University, Eskisehir, Turkey Department of Cardiology, Oslo University Hospital Ulleval and University of Oslo, Oslo, Norway Division of Emergency Medicine, Department of Emergency Care and Services, Helsinki University Hospital, Finland Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), and Department of Cardiology, University Hospital Fundación Jiménez Díaz, Madrid, Spain Heart Failure and Heart Muscle Disease Centre, Hadassah University Hospital, Jerusalem, Israel
List of Authors (Cont.) VII Stefania Lanzara Carlo Lavalle Maddalena Lettino Ana de Lorenzo Òscar Miró Christian Müller Nikolaos Nikolaou Susanna Price Massimo Santini François Schiele Richard Sutton Adam Torbicki Pascal Vranckx Christiaan Vrints Uwe Zeymer
Department of Emergency, Ospedale Madre Giuseppina Vannini, Rome, Italy Department of Cardiology, Ospedale San Filippo Neri, Rome Italy Clinical Cardiology Unit, IRCCS Istituto Clinico Humanitas, Milano, Italy Pharmacy Department, Hospital General Universitario Gregorio Marañón, Madrid, Spain Emergency Department, Hospital Clínic, University of Barcelona, Barcelona, Catalonia, Spain Department of Cardiology, University Hospital Basel, Basel,Switzerland Departement of Cardiology, Konstantopouleio General Hospital, Athens, Greece Consultant Cardiologist & Intensivist, Royal Brompton Hospital, London, United Kingdom Department of Cardiology, Ospedale San Filippo Neri, Rome, Italy Department of Cardiology, University Hospital Jean-Minjoz, Besancon, France Department of Cardiology, National Heart and Lung Institute Imperial College, London, United Kingdom Department of Pulmonary Circulation and Thromboembolic Diseases, Centre of Postgraduate Medical Education, ECZ Otwock, Poland Department of Cardiology and Critical Care Medicine, Hartcentrum Hasselt, Hasselt, Belgium Department of Cardiology, Antwerp University Hospital, Edegem, Belgium Department of Cardiology, Herzzentrum Klinikum Ludwigshafen, Ludwigshafen, Germany
1
CHAPTER 1
KEY SYMPTOMS
1.1 CHEST PAIN _________________________________________________________________ p.2
M. Lettino, F. Schiele 1.2 DYSPNEA ____________________________________________________________________ p.9
C. Müller 1.3 SYNCOPE ___________________________________________________________________ p.16
R. Sutton
1.1
Initial assessment of patients with CHEST PAIN
P.2 Low likelihood of Acute Coronary Syndrome
High likelihood of Acute Coronary Syndrome
1. Presentation
2. ECG
3. Troponin
4. Diagnosis
Noncardiac
Reference: Roffi et al. Eur Heart J 2015; eurheartj.ehv320.
UA
Other Cardiac
NSTEMI
STEMI
Factors to be considered in the evaluation after the first call for CHEST PAIN
1.1 P.3
First call for chest pain
Higher death risk / probability for ACS
Lower death risk / probability for ACS
Arguments for vital risk
• Cardiorespiratory arrest, syncope/ loss of consciousness, neurological defect • Dyspnea (see chapter 1.2 page 9) • Arrhythmias – tachycardia
• Normal consciousness • Normal breathing • Normal heart rhythm
Context, CV risk
Age >40 years, previous CV disease (MI, stroke, PE), modifiable CV risk factors (smoker, HTN, hypercholesterolemia, diabetes), chronic CV treatment
• Age <40 years, • No previous CV disease • No CV risk factors • No chronic treatment
Chest Pain
Medial/lateral thoracic pain, intense, with dyspnea
• Depends on position/palpation/ movements • Variable intensity, short duration (<1 min) • Hyperthermia
Cardiac Ischemic Pain
Retro-sternal, constriction, jaw/cervical/arm/back irradiation, spontaneous, prolonged >20 min + dyspnea, sweating, lightheadedness, nausea
• Lateral, abdominal irradiation • No neuro-vegetative symptoms
Approach after first call for out-of-hospital CHEST PAIN
1.1 P.4
VITAL RISK? (see chapter 1.1 page 3) Emergency transport with trained medical team
Yes
No
Likelihood of ACS Emergency care: Resuscitation, hemodynamic or rhythm restoration (see chapter 5)
High probability for ACS
Low probability for ACS
1.1 P.5
Emergency transport
Emergency transport with trained medical team
Hospital admission to the ED/CPU ECG, decision for reperfusion, antithrombotics, immediate transport to ED/CPU/ICCU/Cathlab (see chapter 2)
Cardiology ward
Non-cardiology ward
Discharge after prolonged observation
Factors to be considered in the evaluation during the first medical contact for CHEST PAIN
1.1 P.6
First medical contact
Higher death risk / probability for ACS
Lower death risk / probability for ACS
Hemodynamic, respiratory, neurological distress
• Cardiopulmonary arrest, hypotension, tachycardia, shock • Dyspnea, hypoxemia, lung rales (Killip class >2) • ECG: ST-segment deviation
• Normal consciousness, no motion defects • Normal HR and BP • Normal breathing and SpO2, no loss of pulse
Probability for ACS
• Context, typical symptoms consistent with myocardial ischemia • ECG changes • Hs cTn
• No CV risk, atypical symptoms, normal ECG
STEMI NSTE-ACS Uncertain diagnosis (see chapter 2.1 page 24) Type of reperfusion
Time assessment
ECG criteria for STEMI ST depression or normal ECG • Primary PCI or thrombolysis? Primary PCI if delay
<120 min (preferably <90 min) or <60 min if onset of pain <120 min Consider age, anterior wall location • Relevant times: Symptom onset, first medical contact (FMC). FMC → ECG/diagnosis; FMC → PCI; FMC → thrombolysis
• Negative hs cTn only if onset of pain >3 hours (see chapter 2.1 page 24) Normal ECG (repeat 12-lead ECG
recording if symptoms persist/recur) Other ST-segment abnormalities
• Primary PCI between 12-48 hours in patients with ongoing ischemia, symptoms or clinical/haemodynamic or electrical instability • No reperfusion if delay >12 hours and stable, asymptomatic, without ST-segment elevation
First medical contact in patients with CHEST PAIN (home-ambulance) Hemodynamic, respiratory or neurological distress? Yes Resuscitation, hemodynamic or respiratory support (see chapters 4 & 5)
No
ECG <10 min
High probability
ST-segment elevation
Low probability
No ST-segment elevation but other ECG changes or persistent pain
Type of reperfusion (primary PCI or fibrinolysis) Record times (symptom onset, FMC) Start recommended medical therapy (including antithrombotic drugs) Transfer to a centre with cath-lab Non cardiovascular disease? • Sepsis • Acute respiratory distress • GI disease, bleeding, others
ACS ?
→
Suspect ACS Uncertain diagnosis
No antithrombotic treatment Transfer to a proximity centre (with or without cath-lab)
Acute cardiovascular disease other than ACS? • Acute aortic syndrome (see chapter 7) • Pulmonary embolism (see chapter 7) • Acute pericarditis (see chapter 8) • Acute heart failure (see chapter 4)
1.1 P.7
Management of patients with CHEST PAIN (emergency room)
P.8
Hemodynamic, respiratory or neurological distress?
Yes
Other CVD or No ACS
No STEMI, NSTE-ACS with persistent pain, Hemodynamic distress
Resuscitation, hemodynamic or respiratory support (see chapters 4 & 5)
Yes Direct transfer to cath-lab
No
No direct transfer to cath-lab ED, Chest Pain Unit, cardiology ward, other wards →
STEMI (see chapter 2)
Complicated NSTEMI
• Diagnosis of NSTE-ACS (see chapter 2) • Acute aortic syndrome (see chapter 7) • Acute pulmonary embolism (see chapter 7) • Acute pericarditis (see chapter 8) • Acute heart failure (see chapter 4) • Aortic stenosis, hyperthrophic cardiomyopathy • Acute gastro-oesophageal disease • Acute pleuro-pulmonary disease • Acute psychogenic disorders
1.1
Repeat clinical and ECG examination Laboratory: cTn, renal function, Hb, D-dimers Imaging: TTE, CT scan Diagnostic coronary angiography
1.2
DYSPNEA: Diferential diagnosis
P.9 50% have ≥ 2 diagnoses, which may result in acute respiratory failure*! Basic measures
Criteria for transfer to ICU
• BP, HR, respiratory rate, SpO 2 & temperature • Start oxygen to target SpO 2 94-98% • Start i.v. line & monitor patient Investigations:
Acute heart failure Acute coronary syndrome
• ECG • BNP
Pneumonia
• Chest X-ray • Venous BG
(despite treatment for 30 minutes) • Respiratory rate >35/min • SpO2 <85%
• Blood count • D-dimers if suspicion of PE
Exacerbated COPD
or other chronic lung disease
* Defined as ≥1 criterion: • Respiratory rate ≥25/min • PaO2 ≤ 75 mmHg • SpO2 ≤ 92% in ambient air • PaCO 2 ≥ 45 mmHg with arterial pH
≤7.35
Pulmonary embolism
• SBP <90 mmHg • HR >120 bpm
• cTn
Other causes, including • Asthma • Severe sepsis • Tumor • Pneumothorax • Pleural effusion/ascites • Anxiety disorder • Anemia • Bronchitis • Metabolic acidosis • Neurologic disease
Reference: Ray P et al. Acute respiratory failure in the elderly: etiology, emergency diagnosis and prognosis. Critical Care (2006); 10 (3):R82.
DYSPNEA: Acute heart failure (see chapter 4.1)
1.2 P.10
• Immediate 12-lead ECG, cardiac monitor, BP, respiratory rate,
• Chest X-ray (lung ultrasound) pulse oximetry • Echocardiogram • Clinical findings During admission (earlier if decompensated Most commonly: lower extremity edema, jugular venous aortic stenosis or endocarditis are suspected) distension, rales, work up for underlying cardiac disease and triggers • Coronary angiography • Laboratory findings Emergent in patients with ACS; delayed in Complete blood count, chemistries, cardiac enzymes, BNP, patients with suspected coronary artery disease TSH, ABG as needed • Positioning • Oxygen • Nitroglycerin
Keep head of bed elevated above level of legs Up to 12 l/min via rebreather mask, titrate oxygen saturation to 94% 1-2 SL tablets or 2-3 patches 10 mg (1st choice). In pulmonary edema with severe shortness of breath: NTG drip 0.05% (100 mg in 200 ml) - Start with 25 µg/min = 3 ml/h, check BP after 5 and 10 min - Increase dose by 25 µg/min at a time as long as SBP >90 mmHg - Additional BP check 5 and 10 min after each increase in dosing - Check BP every 20 min once a steady drip rate is reached • Furosemide 40-120 mg i.v. (adjust based on kidney function and clinical findings; monitor creatinine) • Morphine 2 mg i.v. (preceeded by 10 mg i.v. metoclopramide PRN) if patient is in severe dyspnoea • Consider digoxin 0.5 (-1.0) mg i.v. in patients with atrial fibrillation • Anticoagulation Therapeutic dosing in ACS and atrial fibrillation: Enoxaparin 1 mg/kg body weight as 1st dose
1.2 P.11 Unstable after 30 minutes
Stable after 30 minutes
CCU/ICU transfer
Ward transfer
Reference: Ware L B and Matthay M A. Acute Pulmonary Edema. New Engl J Med (2005); 353:2788-2796.
1.2
DYSPNEA: Acute pulmonary embolism (see chapter 7.2)
P.12 Priorities: 1. Vital signs 2. Diagnostic screening dependent upon clinical stratification
ABG, ECG, chest X-ray plus clinical assessment of PE probability (risk factors) plus monitoring
Hemodynamically unstable
Initiate transfer to ICU
Immediate TTE (if available)
Hemodynamically stable
Wells criteria for PE: • Clinical signs and symptoms of • • •
Result inconclusive CT-angio →
Right ventricular dysfunction
• • •
deep vein thrombosis (DVT) No alternative diagnosis (or alternative diagnosis less likely than PE) Heart rate >100/min Immobilization or operation within the last 4 weeks Previous DVT or PE Hemoptysis Malignant tumor with treatment within the last 6 months or palliative care
Score
+ 3.0 + 3.0 + 1.5 + 1.5 + 1.5 + 1.0 + 1.0
1.2 P.13 PE confirmed: Treatment
(see chapter 7.2)
Outpatient management possible? Risk stratification →
Low probability Total score <2
Intermediate probability Total score 2-6
High probability Total score >6
Copyright: Stein PD, Woodard PK, Weg JG, et al. Diagnostic pathways in acute pulmonary embolism: recommendations of the PIOPED II investigators. Am J Med (2006); 119:1048–55. - Goldhaber SZ. Pulmonary embolism. Lancet (2004); 363 (9417) 1295-1305. - Agnelli G and Becattini C. Acute Pulmonary Embolism. New Engl J Med (2010); 363:266-274.
1.2
DYSPNEA: COPD exacerbation
P.14 • Verify diagnosis (DD: PE, acute heart failure, pneumothorax) • Oxygen administration SpO2 target 88-92% (Beware of carbonarcosis: ABC after 1 h) →
Definition: Known COPD and/or • Progressive dyspnea and/or • Change in quantitiy and color of sputum and/or • Heavy coughing
• COPD classification (GOLD) • Etiology
• History, clinical examination (blood pressure, pulse, oxygen saturation, vigilance)
• Laboratory findings: Blood count, coagulation, ProCT, perhaps BNP, D-Dimers • Chest X-ray; ECG (exclusion of differential diagnoses) • Sputum cultures (always in case of hospitalisation or previous outpatient antibiotic treatment)
• Oxygen therapy 2-(4) l; target saturation 90% • Salbutamol/ipratropium inhalations ≥4-6 x/d, if needed long-term inhalation • Systemic steroids prednisone 0.5 mg/kg of body weight for 5 days • Antibiotic treatment should be considered; always indicated in stage Gold IV • Physiotherapy Copyright: Leuppi JD et al. JAMA. 2013 Jun 5; 309(21):2223-31.
• Hospitalisation indicated? • Evaluate ICU criteria • NIV indicated?
• Follow-up
DYSPNEA: Community-acquired pneumonia
1.2 P.15
Objective: diagnostics, risk stratification & empirical immediate treatment <2(-4) hours Definition • Chest X-ray • Laboratory workup • Sputum • Blood cultures (2x2) • Legionella antigen (urine) • Pneumococcus antigen (urine)
if dyspnea & cough clinical chemistry; BGA; procalcitonin if patient admitted if patient admitted if Legionellosis suspected if no other pathogen isolated
Risk stratification manageable on an outpatient basis? - Pneumonia Severity Index - CURB-65 →
• Treatment; procalcitonin guided treatment • Consider outpatient treatment where PSI I-III or CURB65 0 or 1 • Minimum 5-day course of treatment and afebrile for 48-72h, 7-10 days, 14 days where intracellular organisms (e.g. Legionella) are present Complications Copyrights: Mandell LA et al. Infectious Diseases Society of America/American Thoracic Society consensus guideli nes on the management of community-acquired pneumonia in adults. Clin Infect Dis. (2007); 44 Suppl 2:S27-72. - Halm EA and Teirstein AS. Management of Community-Acquired Pneumonia New Engl J Med (2002); 347:2039-2045. - Woodhead M et al. Guidelines for the management of adult lower respirato ry tract infections ERJ December 1, (2005); 26 (6) 1138-1180.
SYNCOPE: Assessment of patients with transient loss of conscioussness (TLOC)
1.3 P.16
Syncope is a transient loss of consciousness due to global cerebral hypoperfusion (usually, itself due to period of low blood pressure) characterised by rapid onset, short duration, spontaneous and complete recovery. The differentiation between syncope and non-syncopal conditions with real or apparent LOC can be achieved in most cases with a detailed clinical history but sometimes can be extremely difficult. The following questions should be answered: • Was LOC complete? • Was LOC transient with rapid onset and short duration? • Did the patient recover spontaneously, completely and without sequelae? • Did the patient lose postural tone? If the answers to these questions are positive, the episode has a high likelihood of being syncope. If the answer to one or more of these questions is negative, exclude other forms of LOC before proceeding with syncope evaluation. Loss of Consciousness?
No
• Accidental • Fall • Other abnormal mental state
No
• Coma • Intoxication
Yes Transient, rapid onset, short time, self-terminating Trauma
Yes
• Metabolic disturbance • Aborted sudden death
Not Trauma
TLOC
Syncope Reference: Sutton R. Clinical classification of syncope. - Prog Cardiovasc Dis. (2013); 55(4):339-44.
Epilepsy
Psychogenic
SYNCOPE: Diagnostic criteria (1) Diagnostic criteria with initial evaluation
1.3 P.17
Vasovagal syncope is diagnosed if syncope is precipitated by emotional distress or orthostatic stress and is associated with typical prodrome. Situational syncope is diagnosed if syncope occurs during or immediately after specific triggers. Orthostatic syncope is diagnosed when it occurs after standing up and there is documentation of orthostatic hypotension. Arrhythmia related syncope is diagnosed by ECG when there is: • Persistent sinus bradycardia <40 bpm in awake or repetitive sinoatrial block or sinus pauses >3 s • Mobitz II 2nd or 3rd degree AV block • Alternating left and right BBB • VT or rapid paroxysmal SVT • Non-sustained episodes of polymorphic VT and long or short QT interval • Pacemaker or ICD malfunction with cardiac pauses Cardiac ischemia related syncope is diagnosed when syncope presents with ECG evidence of acute ischemia with or without myocardial infarction. Cardiovascular syncope is diagnosed when syncope presents in patients with prolapsing atrial myxoma, severe aortic stenosis, pulmonary hypertension, pulmonary embolus or acute aortic dissection. Reference: Moya A et al. Eur Heart J(2009) 30, 2631–2671 (1).
SYNCOPE: Evaluation and risk stratification of patients with suspected syncope
1.3
Once syncope is considered to be the likely diagnosis, risk stratification is required to determine further management. P.18 Patients with suspected syncope presenting to ED or clinic
“Uncertain” or unexplained syncope
Certain diagnosis of syncope
Risk stratification
Initiate therapy Inpatient SMU, outpatient SMU or personal physician as appropriate
High risk
Hospital admission Inpatient SMU
Intermediate risk
Low risk
Observation Unit Home if stable, Admit to hospital if evidence of high risk
Home Outpatient SMU referral
Outpatient SMU for diagnosis, treatment and follow-up as appropriate
Copyright: Sutton R, Brignole M, Benditt DG. Key challenges in the current management of syncope. Nat Rev Cardiol. (2012 ); (10):590-8.
SYNCOPE: Diagnostic criteria (2) Diagnostic criteria with provocation maneuvers
1.3 1. 3 P.19
Carotid sinus massage
Orthostatic Hypotension
Indications
Recommendations: Recommendations: Active standing Indications
• CSM is indicated in patients >40 years with syncope of unknown aetiology after initial evaluation; • CSM should be avoided in patients with previous previous MI, TIA or stroke within the past 3 months and in patients with carotid bruits (except if carotid Doppler studies excluded significant stenosis)
• Manual intermittent intermittent determination with sphygmomanometer sphygmomanometer of BP supine and, when OH is suspected, during active standing for 3 min is indicated as initial evaluation; • Continuous beat-to-beat non-invasive pressure measurement may be helpful in cases of doubt
Diagnostic criteria
Diagnostic criteria
• CSM is diagnostic if syncope is reproduced in presence of asystole longer than 3 s and/or a fall in systolic BP >50 mmHg
• The test is diagnostic when there is a symptomatic fall in systolic BP from baseline value ≥20 mmHg or diastolic BP ≥10 mmHg or a decrease in systolic BP to <90 mmHg; • The test should be considered considered diagnostic when there is an asymptomatic fall in systolic BP from baseline value ≥20 mmHg or diastolic BP >10 mmHg or a decrease in systolic BP to <90 mmHg
Reference: Moya A et al. Eur Heart J(2009) 30; 2631–2671 (2).
Treatment according to type of SYNCOPE (1)
1.3 1. 3 P.20
Treatment of reflex syncope
• Explanation Explanati on of the diagnosis, provision of reassurance and explanation of risk of recurrence are in all patients • Isometric PCM are indicat indicated ed in patients with prodrome • Cardiac pacing should should be considered in patients with dominant dominant cardioinhibitory CSS • Cardiac pacing should be considered considered in patients with frequent recurrent recurrent reflex syncope, age >40 years and documented spontaneous cardioinhibitory response during monitoring • Midodrine may be indicated in patients with VVS refractory to lifestyle lifestyle measures • Tilt training may be useful for education education of patients but long-term benefit depends on compliance • Cardiac pacing may be indicated in patients with tilt-induced cardioinhibitory cardioinhibitory response with recurrent frequent unpredictable unpredictable syncope and age >40 after alternative therapy has failed • Triggers or situations situatio ns inducing syncope must be avoided as much as possible • Hypotensive Hypotensive drugs must be modified or discontinued • Cardiac pacing is not indicated in the absence of a documented cardioinhibitory cardioinhibitory reflex • Beta-adrenergic Beta-adrenergic blocking drugs drugs are not indicated • Fluid consumption consumption and salt in the diet should be increased increased Copyright: Moya A et al . Eur Heart J(2009) 30; 2631–2671 (3).
Treatment of orthostatic hypotension
• Adequate hydration hydration and salt intake must be maintained • Midodrine should be administered administered as adjunctive therapy if needed • Fludrocortisone Fludrocortisone should be administered as adjunctive therapy if needed • PCM may be be indicated • Abdominal binders and/or and/or support stockings to reduce venous pooling may be indicated • Head-up tilt sleeping sleeping (>10°) to increase fluid volume may be indicated • Triggers or situations inducing inducing syncope syncope must be avoided as much as possible • Hypotensive Hypotensive drugs administered administered for concomitant conditions must be discontinued or reduced
Treatment according to type of SYNCOPE (2)
1.3 1. 3 P.21
Treatment of arrhythmic syncope Cardiac Pacing
Catheter ablation
• Pacing is indicated in patients with sinus node disease in whom syncope is demonstrated to be due to sinus arrest (symptom-ECG (symptom-ECG correlation) without a correctable cause • Pacing is indicated in sinus node disease patients with syncope and abnormal CSNRT • Pacing is indicated in sinus node disease patients with syncope and asymptomatic pauses >3 sec. (with possible exceptions of young trained persons, during sleep and in medicated patients) • Pacing is indicated in patients with syncope syncope and 2 nd degree Mobitz II, advanced or complete AV AV block • Pacing is indicated in patients patients with syncope, BBB and positive EPS • Pacing should be considered in patients patients with unexplained syncope and BBB • Pacing may be indicated indicated in patients with unexplained syncope and sinus node disease with persistent sinus bradycardia bradycardia itself itsel f asymptomatic • Pacing is not indicated in patients with unexplained unexplained syncope without evidence of any conduction disturbance
• Catheter ablation is indicated in patients patients with symptom/ arrhythmia ECG ECG correlation in both SVT and VT in the absence of structural heart disease (with exception of atrial fibrillation) • Catheter ablation may be indicated indicated in patients with syncope due to the onset of rapid atrial fibrillation
Copyright: Moya A et al. Eur Heart J(2009) 30; 2631–2671 (4).
Antiarrhythmic drug therapy
• Antiarrhythmic drug therapy, therapy, including rate control ddrugs, rugs, is indicated in patients with syncope due to onset of rapid atrial fibrillation • Drug therapy should be considered in patients patients with symptom/ arrhythmia ECG correlation in both SVT and VT when catheter ablation cannot be undertaken or has failed Implantable Cardioverter Defibrillator (ICD)
• ICD is indicated in patients with documented VT and structural heart disease • ICD is indicated when sustained monomorphic VT is induced at EPS in patients with previous myocardial infarction • ICD should be considered considered in patients with documented VT and inherited cardiomyopathies or channelopathies
2
CHAPTER 2
ACUTE CORONARY SYNDROMES
2.1 GENERAL CONCEPTS ______________________________________________________ p.24
H. Bueno 2.2 NON ST�SEGM ENT ELE VATION ACS _______________________________________ p.29
H. Bueno 2.3 ST�SEGME NT ELE VATION MI �STEM I� ______________________________________ p.35
P. Vranckx, B. Ibañez
ACUTE CORONARY SYNDROMES: Diagnosis (1)
2.1
CHEST PAIN
P.24
or symptoms sugestive of myocardial ischemia ECG
ST elevation
Repolarization not interpretable
(persistent)
(i.e. LBBB, pacemaker...) Pain resolves with nitroglycerin No
ST/T abnormalities
Yes
1st hsTn
hs-cTn>ULN
hs-cTn
Potential noncardiac causes for abnormal Tn
Consider STEMI hs-cTn >x5 ULN or clinical diagnosis clear
Normal ECG
Pain onset <6 h
Pain onset >6 h
Re-test hs-cTn (3h later) See next page for 1 h rule-in & rule-out algorithm hs-cTn (1 value >ULN) ∆
hs-cTn no change
STEMI References: Roffi M. Eur Heart J 2016; 37:267-315. Ibañez B. Eur Heart J 2018; 39:119-177.
NSTEMI
Unstable Angina
Work-up differential diagnoses
ACUTE CORONARY SYNDROMES: Diagnosis (2) 0-1 H Rule-in & rule out test for NSTEMI
P.25
Suspected NSTEMI
0h
Other
Rule-out
Observe
0h≥D ng/l or 0-1h≥ E ng/l
Rule-in
A
B
C
D
E
hs-cTnT (Elecsys)*
5
12
3
52
5
hs-cTnl (Architect)*
2
5
2
52
6
0,5
5
2
107
19
hs-cTnl (Dimension Vista)* Vista)* *Cut-off levels are assay-specific.
2.1 2. 1
• NSTEMI can be ruled-out at presentation, if hs-cTn concentration is very low • NSTEMI can be ruled out by the combination of low baseline levels and the lack of a relevant increase within 1 h • NSTEMI is highly likely if initial hs-cTn concentration is at least moderately elevated or hs-cTn concentrations show a clear rise within the first hour Reference: Roffi M. Eur Heart J 2016; 37:267-315. 37:267-315.
ACUTE CORONARY SYNDROMES: Differential diagnosis (1)
2.1 2. 1 P.26
Causes of chest pain Not related to ACS Primary cardiovascular
• Acute pericarditis, pericarditis, pericardial effusion • Acute myocarditis • Severe hypertensive hypertensive crisis • Stress cardiomyopathy (Tako-Tsubo syndrome) • Hypertrophic cardiomyopathy, aortic stenosis • Severe acute acute heart failure • Acute aortic syndrome (dissection, hematoma) • Pulmonary embolism, pulmonary pulmonary infarction infarction • Cardiac contusion Primary non-cardiovascular non-cardiovascular
• Oesophageal spasm, oesophagitis, Gastro Esophageal Reflux (GER) • Peptic ulcer disease, cholecystitis, pancreatitis • Pneumonia, bronchitis, asthma attack • Pleuritis, pleural effusion, pneumothorax • Pulmonary embolism, sev severe ere pulmonary hypertension • Thoracic trauma • Costochondritis, rib fracture • Cervical / thoracic vertebral or discal damage • Herpes Zoster
Causes of troponin elevation Not related to ACS Primary cardiovascular
• Acute myo(peri)carditis • Severe Severe hypertensive crisis • Pulmonary edema or severe severe congestive heart failure failure • Stress cardiomyopat cardi omyopathy hy (Tako-T (Tako-Tsubo subo syndrome) • Post- tachy- or bradyarrhythmias • Cardiac contusion or cardiac procedures (ablation, cardioversion, or endomyocardial biopsy) • Aortic dissection, aortic aorti c valve disease or hypertrophic cardiomyopathy cardiomyopathy • Pulmonary embolism, severe severe pulmonary hypertension Primary non-cardiovascular
• • • • • •
Renal dysfunction (acute or chronic) Critical illness (sepsis, repiratory failure…) Acute neurological damage (i.e. stroke, subarachnoid hemorrhage) Severe burns (affecting >30% >30% of body surface area) Rhabdomyolysis Drug toxicity (chemotherapy with adriamycin, 5-fluorouracil 5-fluorouracil,, herceptin, snake venoms…) • Inflammatory Inflammatory or degenerative muscle diseases • Hypothyroidism • Infiltrative diseases (amyloidosis, hemochromatosis, sarcoidosis) • Scleroderma
ACUTE CORONARY SYNDROMES: Differential diagnosis (2) Causes of repolarisation abnormalities in the ECG not related to ACS
2.1 2. 1 P.27
ST-segment elevation Fixed
• LV aneurysm aneurys m • LBBB, WPW, WPW, hypertrophic hypertroph ic cardiomyopathy, LVH LVH • Pacemaker stimulation • Early repolarisation (elevated (elevated J-point) J-point) Dynamic
• Acute (myo)pericarditis (myo)pericarditis • Pulmonary embolism • Electrolyte disturbances disturbances (hyperkalemia) (hyperkalemia) • Acute brain damage (stroke, (stroke, subarachnoid hae haemorrhage) • Tako Tsubo Tsubo syndrome ST-segment depression Fixed
• Abnormal QRS (LBBB, WPW, WPW, pacemaker stimulation…) stimulation…) • LVH, hypertrophic cardiomyopathy cardiomyopathy • Chronic ischemic heart disease Dynamic
• • • • •
Acute (myo)pericarditis (myo)pericarditis Acute pulmonary hypertension Electrolyte disturbances disturbances (hyperkalemia) (hyperkalemia) Intermitent LBBB, WPW, WPW, pacing Post-tachycardia Post-tachycardia / cardioversion cardioversion
• Severe hypertensive crisis • Drug effects (digoxin) • Shock, pancreatitis • Hyperventilation • Tako Tsubo syndrome
Negative T waves
• Normal variants, i.e. women (right precordial leads), children, teenagers • Evolutive changes post myocardial infarction • Chronic ischemic heart disease • Acute (myo)pericarditis, (myo)pericarditis, cardiomyopathies • BBB, LVH, LVH, WPW • Post-tachycardia Post-tachycardia or pacemaker stimulation • Metabolic or ionic disturbances Prominent T waves
• Normal variants, variants, i.e. i.e. early repolarisation • Metabolic or ionic disturbances (i.e. hyperkalemia) • Acute neurological damage (stroke, (stroke, subarachnoid hae haemorrhage)
GENERAL APPROACH A PPROACH to the patient with chest pain/suspected ACS 1 Clinical Evaluation
2 ECG
3 Diagnosis / Risk assessment
(<10 min)
4 Medical Treatment
STEMI (see chapter 2.3)
2.1 2. 1 5 Invasive Strategy
P.28
Primary PCI Thrombolysis for STEMI if primary PCI not timely available
• Clinical presentation (BP, HR)
Quality of chest pain Clinical context Probability of CAD
Emergent <2 hours
• ECG presentation • Past history
ECG
NSTE ACS (see chapter 2.2)
Physical examination
• Ischemic risk (i.e. GRACE, TIMI scores) • Bleeding risk (i.e. CRUSADE score)
Anti-ischemic therapy Antiplatelet therapy Anticoagulation
Urgent 2-24 hours Early 24-72 hours
• Additional information (labs, imaging...) optional
ACS unclear (Rule out ACS)
Chest Pain Unit (see chapter 1.1)
No ACS
Rule out noncardiac causes
No / Elective
2.2
NON ST�SEGMENT ELEVATION ACS: Risk stratification (1)
P.29 Ischemic risk GRACE risk score
TIMI risk score
Predictive Factors
• Age • HR* • SBP* • Creatinine (mg/dl)* • Killip class* • Cardiac arrest* • ST-segment deviation • Elevated cardiac markers Outcomes
In-hospital, 6-month, 1-year and 3-year mortality 1-year death/MI
Predictive Factors
• Age 65 years • At least 3 risk factors for CAD • Significant (>50%) coronary stenosis • ST deviation • Severe anginal symptoms (>2 events in last 24h) • Use of aspirin in last 7 days • Elevated serum cardiac markers
Probability of all-cause mortality from hopital discharge to 6 months (%) 50 40 30
Outcome
20 10 0
70
90
1 10
130
150
170
190
GRACE Risk Score
210
All-cause mortality/new or recurrent MI/severe recurrent ischemia requiring urgent revascularisation at 14 days
50
Risk of 14 days events (%)
40 30 20 10 0 0-1
2
3
4
5
TIMI Risk Score
Risk calculation http://www.gracescore.org/WebSite/WebVersion.aspx
Risk calculation http://www.timi.org/index.php?page=calculators * At admission.
>=6
NON ST�SEGMENT ELEVATION ACS: Risk stratification (2)
2.2 P.30
Bleeding risk CRUSADE risk score Risk calculation www.crusadebleedingscore.org
Predictive Factors
• Sex • HR* • SBP* • Creatinine (mg/dl)* • Baseline hematocrit* • GFR: Cockcroft-Gault* • Diabetes • Prior vascular disease • Signs of congestive heart failure*
50
Probability of in-hospital major bleeding(%)
40 30 20 10
Outcome
0 0
In-hospital major bleeding
20
40
60
80
100
CRUSADE Bleeding Score * At admission.
Copyrights: Eagle KA et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month post-discharge death in an international registry. JAMA. (2004); 291(22):2727-33. - Antman EM, et al. The TIMI risk score for unstable angina/non-ST elevation MI: A method for prognostication and therapeutic decision making. JAMA. (2000); 284(7):835-42. - Subherwal S, et al Baseline risk of major bleeding in non-ST-segmentelevation myocardial infarction: the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes wi th Early implementation of the ACC/AHA Guidelines) Bleeding Score. Circulation (2009); 119(14):1873-82.
NON ST�SEGMENT ELEVATION ACS: Treatment (1) General overview
2.2 P.31
Initial treatment*
• Nitrates • Morphine • Oxygen (if SpO2 <90%)
Pharmacological treatment*
Antithrombotic therapy
Anticoagulation
Myocardial revascularisation
Anti ischemic treatment
Other preventive therapies
• Nitrates • Beta-blockers • Calcium antagonists
• Statins • ACE inh. (or ARB) • Aldosterone inhibitors
PCI CABG
Antiplatelets
One of the following: • Fondaparinux • Enoxaparin • UFH • Bivalirudin
Aspirin + one of: • Ticagrelor • Prasugrel • Clopidogrel
Optionally: • GP IIb/IIIa inhibitors • Cangrelor
For more information on individual drug doses and indications,
*
SEE CHAPTER 3 SECONDARY PREVENTION AFTER ACS & CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
NON ST-SEGMENT ELEVATION ACS: Treatment (2) Risk criteria mandating invasive strategy in NSTE-ACS
2.2 P.32
Very-high-risk criteria
• Haemodynamic instability or cardiogenic shock • Recurrent or ongoing chest pain refractory to medical treatment • Life-threatening arrhythmias or cardiac arrest • Mechanical complications of MI • Acute heart failure • Recurrent dynamic ST-T wave changes, particularly with intermittent ST-elevation
High-risk criteria
• Rise or fall in cardiac troponin compatible with MI • Dynamic ST- or T-wave changes (symptomatic or silent) • GRACE score >140
Intermediate-risk criteria
• Diabetes mellitus • Renal insufficienty (eGFR <60 ml/min/1.73 m2) • LVEF <40% or congestive heart failure • Early post-infarction angina • Prior PCI • Prior CABG • GRACE risk score >109 and <140
Low-risk criteria
• Any characteristics not mentioned above
Reference: Roffi M. Eur Heart J 2016; 37:267-315.
NON ST-SEGMENT ELEVATION ACS: Treatment (3) Timing and strategy for invasive management
2.2 P.33
Symptoms Onset
First medical contact
NSTE-ACS diagnosis
PCI centre
EMS or Non–PCI centre Immediate transfer to PCI centre
Very high n o i t a c i f i t a r t s k s i
Same-day transfer
High
High
Transfer
Intermediate
Intermediate
Transfer optional
R
c i t y u g e e p t a a r r e t h s T
Very high
Low
Immediate Invasive (<2 hr)
Early invasive (<24 hr)
Reference: Roffi M. Eur Heart J 2016; 37:267-315.
Invasive (<72 hr)
Low
Non-invasive testing if appropriate
STEMI Treatment (1): Reperfusion strategy
2.3 P.34
Time to PCI? ECG STEMI diagnosis
0
Alert & transfer to PCI centre
≤120min
120min
>
Primary PCI strategy
Fibrinolysis strategya Bolus of fibrinolyticb
10 min
90 min
k c o l c y g e t a r t S
6
0 - 9 0 m i n
Transfer to PCI centre Wire crossing (reperfusion) Rescue PCI
No
Meet reperfusion criteria?
Yes
≥
1 2 0 m i n
2 hours Routine PCI strategy 24 hours a b
If fibrinolysis is contra-indicated, direct for primary PCI strategy regardless of time to PCI. 10 min is the maximum target delay time from STEMI diagnosis to fibrinolytic bolus administration, however, it should be given as soon as possible after STEMI diagnosis (after ruling out contra-indications).
Reference: Ibañez B. Eur Heart J 2018; 39:119-177.
STEMI Treatment (2): Medical management of patients treated with primary PCI
2.3 P.35
Oxygen when SpO2 <90% STEMI diagnosis
Aspirin Loading
Prasugrel or ticagrelor loading (clopidogrel as alternative)
i.v. Beta-blocker i.v. Opioids/tranquilizer
Wire crossing (reperfusion)
DURING PCI: radial access, UFH (enoxaparin/bivalirudin as alternatives)
High dose statin (e.g. atorvastatin 80 mg or rosuvastatin 40 mg)
Hospital Admission
Oral β-blocker ACE inhibitor
Hospital Discharge
Aspirin maintenance
Prasugrel or ticagrelor maintenance (clopidogrel as alternative)
Reference: Ibañez B. Eur Heart J 2018; 39:119-177.
Mineralocorticoid receptor antagonist (if LVEF <40% and heart failure)
STEMI Treatment (3): Medical management of patients treated with fibrinolysis
2.3 P.36
Oxygen when SpO2 <90% Fibrinolysis bolus
STEMI diagnosis
10min
Hospital Admission
Enoxaparin i.v. Opioids/tranquilizer
Aspirin loading
Clopidogrel loading
Coronary angiography ± PCI (2-24h)
High dose statin (e.g. atorvastatin 80 mg or rosuvastatin 40 mg) Oral β-blocker ACE inhibitor
Hospital Discharge
Aspirin Clopidogrel maintenance maintenance
Reference: Ibañez B. Eur Heart J 2018; 39:119-177.
Mineralocorticoid receptor antagonist (if LVEF <40% and heart failure)
3
CHAPTER 3
SECONDARY PREVENTION AFTER ACS 3.1 GENERAL SECONDARY PREVENTION STRATEGIES AND LIPID LOWERING _____________________________________________________
p.38
H. Bueno, S. Halvorsen 3.2 ANTITHROMBOTIC TREATMENT ___________________________________________ p.41
F. Costa, S. Halvorsen
3.1
SECONDARY PREVENTION STRATEGIES after ACS
P.38 Acute Coronary Syndrome
Hospitalization
1- Acute care • Drug therapy • Coronary revascularisation 2- Cardiovascular risk assessment (e.g. concealed and uncontrolled risk factors) 3- Initiate secondary prevention and set treatment goals
Plan and schedule Cardiac Rehabilitation
Cardiac Rehabilitation programme
Education and counselling
• Risk factor control (e.g. weight control, smoking cessation, blood pressure and lipid control) • Diet/nutritional counseling • Physical activity counseling/ excercise training • Psychosocial management, sex advice • Vocational advice
Cardioprotective drugs in secondary prevention
Antithrombotic therapy
Lipid lowering
BP/LVD/ HF control
Glucose control
Aspirin + P2Y12 inhibitor (12 months)
High intensity statin therapy
ACEI / ARB*, Beta-blockers*, MRA*
Metformin Insulin*
3.1 P.39
Re-evaluate lifestyle, control of risk factors, psychosocial factors and adherance to therapy Adjustment of secondary prevention therapies. Consider polypill, if needed
Reinforce education Psychosocial support After Discharge
After 12 months consider*: Ticagrelor 60 mg bid
Consider adding Consider Consider Ezetimibe* dose adjustment SGLT2 inhibitor* PCSK9 inhibitor* Consider ARNI* GLP-1 agonists*
Anticoagulation?**
* When individually indicated and without specific contraindications. - ** Rivaroxaban 2.5 mg bid pending approval for indication in chronic CAD.
Reference modified from Cortés-Beringola A. Eur J Prev Cardiol 2017; 24(3 suppl): 22-28.
After ACS: POTENTIAL STRATEGIES TO OPTIMIZE SECONDARY PREVENTION THERAPY
3.1 P.40
Potential strategies to optimize secondary prevention therapy after ACS
• Participation in a comprehensive, multi-disciplinary cardiac rehabilitation programme after hospital discharge • Coordination with primary care provider (and other specilaists) in therapeutic plan and objectives • Re-check and reinforce advise on all lifestyle changes (diet, physical activity, smoking cessation…) during follow-up visits • Check and optimise doses of all indicated secondary prevention drugs • Use of specialist support, nicotine replacement therapies, varenicline, and/or bupropion individually or in combination for patients who do not quit or restart smoking • Use of ezetimibe and/or a PCSK9 inhibitor in patients who remain at high risk with LDL-cholesterol >70 mg/dl despite apropriate diet and maximally tolerated doses of statins • Use of a polypill or combination therapy in patients with suboptimal adherence to drug therapy
ANTITHROMBOTIC TREATMENT: Dual antiplatelet therapy duration in patients with ACS (1)
3.2 P.41
PCI
Treatment indication
Stable CAD
Device used
DES/BMS or DCB
ACS BRS
DES/BMS or DCB
High Bleeding Risk No
Time A C
1mo
Yes A C
No A P
Class I A 1
A T
A P
or
1mo DAPT Class IIb C 6mo DAPT
3mo
High Bleeding Risk
A C
3mo DAPT Class IIa B
A C
A T
A T
or 2
A C
3
6mo DAPT Class IIa B
12mo DAPT
12mo DAPT
≥
6mo
Yes
Class IIa C
Class I A
A C
12mo
DAPT >6mo Class IIb A
30mo
A T
or A P A C >12mo DAPT
4
Class IIb B
Reference: Valgimigli M, et al. Eur Heart J. 2018; 39:213-260.
A = Aspirin C = Clopidogrel P = Prasugrel T = Tricagrelor
ANTITHROMBOTIC TREATMENT: Dual antiplatelet therapy duration in patients with ACS (2) CABG
Treatment indication
Stable CAD
Device used
No indication for DAPT unless concomitant or prior indication overrides
3.2 P.42
Medical Treatment Alone
ACS
Stable CAD
High Bleeding Risk No
Yes
ACS
No indication for DAPT unless concomitant or prior indication overrides
High Bleeding Risk No
Yes
Time A P
1mo
A T
A C
A T
A T
3
3mo
A C
6mo DAPT
>
Class IIa C
Class IIa C
12mo DAPT
12mo DAPT
Class I C
Class I C
6mo
3
or
or A C
A C
1mo DAPT
12mo A T or
30mo
A P A C
12mo DAPT
>
Class IIb C
Reference: Valgimigli M, et al. Eur Heart J. 2018; 39:213-260.
A T or A C
12mo DAPT
>
Class IIb C
A = Aspirin C = Clopidogrel P = Prasugrel T = Tricagrelor
ANTITHROMBOTIC TREATMENT: Switching between P2Y12 inhibitors for DAPT after ACS (1)
3.2 P.43
CLOPIDOGREL l
) r e m g i d o g 0 p ( 6 c l o g D r n l L p r i o d o s i ) e r f d g m g d o s e o u n 0 e l a s c e a r 6 0 g P r e c t i i n g ( u m D i p s t L l r a e s r e s t p i r r g i d o e r l a p o C l a f t h 2 4
PRASUGREL
ACCUTE SETTING ALWAYS RELOAD
i r r T e s i p e c a r c t g e l i o c t i e m o r L C i n g f 2 4 l p r D ( p i h o a 8 i o r 1 n a f d 0 d o t e g c m d l o o r l r e g s i p ) a s l L i n g d o g t t D ( r e i c a g 6 0 l 0 r e m l o r g ) d o s e
Ticagrelor LD (180 mg) 24h after last prasugrel dose Prasugrel LD (60 mg) 24h after last ticagrelor dose
Reference: Valgimigli M, et al. Eur Heart J. 2018;39:213-260.
TICAGRELOR
ANTITHROMBOTIC TREATMENT: Switching between P2Y12 inhibitors for DAPT after ACS (2)
3.2 P.44
CLOPIDOGREL
) . d . o s e q g e l d m g r ) 1 0 i d o ( d . . s e D q p o M l o m g e l d e l s t c r r 7 5 u g u g r l a ( s s a e M D p r a P r a f t l e h r l a s t g 2 4 o i d t e r p f o C l h a 2 4
PRASUGREL
CHRONIC SETTING
Ticagrelor LD (90 mg b.i.d.) 24h after last prasugrel dose Prasugrel LD (60 mg) 24h after last ticagrelor dose
Reference: Valgimigli M, et al. Eur Heart J. 2018;39:213-260.
T 2 4 r i c h a r a f g e o t e r l r l a s M t c D ( 2 4 C l o l p 0 h i o p 9 a f d m i o g d t o g g b e r r e r e . i l a s l L . d. l d t t D ) o ( s e i c a 6 0 g r 0 e l m o r g ) d o s e
TICAGRELOR
ANTITHROMBOTIC TREATMENT: Risk scores validated for DAPT duration decision-making
3.2 P.45
PRECISE-DAPT score
DAPT score
At the time of coronary stenting
After 12 months of uneventful DAPT
Short DAPT (3-6 months) vs. Standard/long DAPT (12-24 monts)
Standard DAPT (12 months) vs. Long DAPT (30 months)
Time of use DAPT duration strategies assessed Score calculation
Age
HB
≥75 65 to <75 <65 Cigarette smoking Diabetes mellitus MI at presentation Prior PCI or prior MI Paclitaxel-eluting stent Stent diameter <3 mm CHF or LVEF <30% Vein graft stent
WBC Age CrCl Prior Bleeding Score Points Score range Decision making cut-off Electronic calculator
0 to 100 points
— 2 to 10 points
Score ≥25 → Short DAPT Score <25 → Standard/long DAPT
Score ≥2 → Long DAPT Score <2 → Standard DAPT
www.precisedaptscore.com
www.daptstudy.org
— 2 pt — 1 pt 0 pt + 1 pt + 1 pt + 1 pt + 1 pt + 1 pt + 1 pt + 2 pt + 2 pt
ANTITHROMBOTIC TREATMENT in patients with concomitant indication for DAPT and chronic oral anticoagulation (1)
3.2 P.46
• HIGH RISK OF BLEEDING? k t High HAS-BLED: Hypertension, abnormal liver/renal function, prior stroke, bleeding diathesis, labile INR if on VKA, age >65, drugs s n : 1 i r e (e.g. NSAIDs or antiplatelets), alcohol abuse, ABC score: Age, Biomarkers (GDF-15, hs cTnT, Hb) and Clinical history of prior bleeding m t P s E n e s T i e • HIGH RISK OF RECURRENT CORONARY ISCHEMIC EVENTS? S t a s s ACS at presentation, prior ST, stenting of last remaining vessel, CrCL <60 ml/min, ≥3 stents implanted or lesions treated, P a bifurcation with 2 stents, overall stentlengh >60 mm, treatment of CTO
e p : y t 2 t n P E e T m S t a e r T
DUAL THERAPY
(preferable)* or
• Aspirin 75-100 mg q.d.
(If High BR Low IR)
TRIPLE THERAPY
DAPT: • Clopidogrel 75 mg q.d.
(If High BR High IR) or (If Low BR High IR) n o i t a : r 3 u d P t E n T e S m t a e r T
OAC: • NOAC* (preferable) - Apixaban 5 mg b.i.d. (reduce to 2.5 mg b.i.d. (1) - Dabigatran 110 mg b.i.d. (preferable while on DAPT) or 150 mg b.i.d. - Edoxaban 60 mg q.d. (reduce to 30 mg q.d. (2) - Rivaroxaban 20 mg q.d. (reduce to 15 mg q.d. (3) or 15 mg (may be considered DAPT/SAPT) or • VKA dose ajusted: consider maintaining INR in the lower part of the recommended target range (e.g. 2.0-2.5 for AF and MV in aortic position, 2.5-3.0 for MV in mitral position)
SAPT: • Clopidogrel 75 mg q.d.
and
• Aspirin 75-100 mg q.d.
DUAL (12 mo.)
DUAL THERAPY strategy: BR>IR
TRIPLE (for
1 mo.)
BR
TRIPLE (up
to 6 mo.)
TRIPLE THERAPY strategy:
OAC alone
DUAL (up
to 12 mo.)
OAC alone
DUAL
Reference adapted from Valgimigli M et al. Eur Heart J. 2018;39:213-260.
(up to 12 mo.)
OAC alone
In case of selecting dual therapy immediately after stent implantation clopidogrel should be selected as single antiplatelet agent. Aspirin should however be administered at the time of the intervention. *
Age ≥80 years, body weight ≤60 kg or serum creatinine level ≥1.5 mg/dL. (2) CrCl of 30–50 ml/min, body weight ≤60 kg, concomitant use of verapamil, quinidine or dronedarone. (3) CrCl 30-49 ml/min. (1)
ANTITHROMBOTIC TREATMENT: Management of DAPT after ACS in patients with indication for surgery
PRASUGREL
3.2 P.47
PRASUGREL(2)
STOP
CLOPIDOGREL
CLOPIDOGREL
SURGERY
STOP
TICAGRELOR
TICAGRELOR(2)
STOP
ASPIRIN(1) //
••••••
9
••••••
8
••••••
7
••••••
6
••••••
Minimal delay for P2Y12 interruption
(1)
5
••••••
4
••••••
3
••••••
2
••••••
1
••••••
0
••••••••••••••••••
1-4
Days after surgery
= Expected average platelet function recovery Decision to stop aspirin throughout surgery should be made on a single case basis taking into account the surgical bleeding risk (2) In patients not requiring OAC
Reference: Valgimigli et al. Eur Heart J.2018; 39:213-260.
ANTITHROMBOTIC TREATMENT: Management of acute bleeding after ACS
3.2 P.48
ANTITHROMBOTIC TREATMENT MANAGEMENT DURING BLEEDING Active bleeding and unstable hemodynamic putting patient’s life immediately at risk?
Yes
No
LIFE-THREATENING BLEEDING
e.g. massive overt genitourinary, respiratory or upper/lower gastrointestinal bleeding, active intracranial, spinal or intraocular haemorrhage, or any bleeding SEVERE BLEEDING
Hospitalization required?
Yes
Hb loss >5 g/dl Hb loss <5 g/dl
No
MODERATE BLEEDING
e.g. genitourinary, respiratory or upper/lower gastrointestinal bleeding with significant blood loss or requiring transfusion
Significant blood loss (>3 g/dl) ? Yes
No
MILD BLEEDING
Requires medical intervention or further evaluation? No
e.g. severe genitourinary, respiratory or upper/lower gastrointestinal bleeding
Yes
e.g. not self resolving epistaxis, moderate conjunctival bleeding, genitourinary or upper/lower gastrointestinalbleeding without significant blood loss, mild haemoptysis
TRIVIAL BLEEDING e.g. skin bruising or ecchimosis,
self-resolving epistaxis, minimal conjunctival bleeding
STOP ALL ANTITHROMBOTIC MEDICATIONS
and reverse OAC. Once bleeding has ceased, re-evaluate the need for DAPT or SAPT, preferably with the P2Y12 inhibitor especially in case of upper GI bleeding CONSIDER STOPPING DAPT
and continue with SAPT, preferably with the P2Y12 inhibitor especially in case of upper GI bleeding. Once bleeding has ceased, re-evaluate the need for DAPT or SAPTa CONSIDER STOPPING OAC
or even reversal until bleeding is controlled, unless prohibitive thrombotic risk (i.e. mechanical heart valve in mitral position, cardiac assist device )b-c-d Reinitiate treatment within one week if clinically indicated. If Bleeding persist despite treatment, or treatment is not possible CONSIDER STOPPING ALL ANTITHROMBOTIC MEDICATIONS CONSIDER STOPPING DAPT
and continue with SAPT, preferably with the P2Y12 inhibitorespecially in case of upper GI bleeding Reinitiate DAPT as soon as deemed safea CONSIDER STOPPING OAC
or even reversal until bleeding is controlled, unless very high thrombotic risk (i.e. mechanical heart valves, cardiac assist device, CHA2DS2-VASc ≥4 ).b-c-d Reinitiate treatment within one week if clinically indicated. CONTINUE DAPT a , CONTINUE OAC c CONTINUE DAPT, CONTINUE OAC Consider skipping one single next pill
Consider shortening DAPT duration or switching to less potent P2Y12 inhibitor (i.e. from ticagrelor/prasugrel to clopidogrel), especially if recurrent bleeding occurs Reinitiate treatment within one week if clinically indicated. For Vitamin-K antagonist consider a target INR of 2.0-2.5 unless overriding indication (i.e. mechanical heart valves or cardiac assist device) for NOAC consider the lowest effective dose. - cIn case of triple therapy consider downgrading to dual therapy, preferably with clopidogrel and OAC. - d If patients on dual therapy, consider stopping antiplatelet therapy if deemed safe. a
b
Reference: Valgimigli et al. Eur Heart J.2018; 39:213-260.
ANTITHROMBOTIC TREATMENT: Management of antiplatelet therapy after acute GI bleeding
3.2 P.49
Acute upper GI haemorrhage in patient using antiplatelet agent(s) (APT) Upper GI endoscopy demonstrates a nonvariceal source of bleeding (e.g. peptic ucler bleed)
High risk endoscopic stigmata identified
Low risk endoscopic stigmata identified
(Forrest classification* Ia, Ib, IIa, IIb)
(Forrest classification* IIc, III)
APT used for secondary prophylaxis (known cardiovascular disease)
APT used for secondary prophylaxis (known cardiovascular disease)
Patients on low dose ASA alone
Patients on low dose ASA alone
• Resume low-lose ASA by day 3 following in dex endoscopy • Second-look endoscopy at the discretion of the endoscopist may be considered
• Continue low-dose ASA without interruption
Paptients on dual antiplatelet therapy (DAPT)
• Continue low dose ASA without interruption • Early cardiology consultation for recommendation of second resumption/ continuation of second APT • Second-look endoscopy at the discretion of the endoscopoist may be considered
Paptients on dual antiplatelet therapy (DAPT)
• Continue DAPT without interruption *The Forrest classification in defined as follows: Ia spuring hemorrhage, Ib oozing hemorrhage, IIa nonbleeding visible vessel, IIb an adherent clot, IIc flat pigme nted spot, and III clean base ucler. Reference: Halvorsen et al. Eur Heart J 2017; 38: 1455-62.
4
CHAPTER 4
ACUTE HEART FAILURE
4.1 WET�AND�WARM HEA RT FAILURE PATIE NT
______________________________ p.52
V.P. Harjola, O. Miró 4.2 CARDIOGENIC SHOCK �WET�AND�COLD�
P. Vranckx, U. Zeymer
___________________________________ p.61
Clinical profiles of patients with acute heart failure
4.1
Clinical profiles of patients with acute heart failure based on the presence/absence of congestion and/or hypoperfusion
P.52
CONGESTION (-)
HYPOPERFUSION (-)
HYPOPERFUSION (+) Cold sweaty extremities, Oliguria, Mental confusion, Dizziness, Narrow pulse pressure
WARM-DRY
COLD-DRY
CONGESTION (+) Pulmonary congestion, orthopnoea/paroxismal, nocturnal dyspnoea, peripheral (bilateral) oedema, jugular venous dilatation, congested hepatomegaly, gut congestion, ascites, hepatojugular reflux
WARM-WET
COLD-WET
Hypoperfusion is not synonymous with hypotension, but often hypoperfusion is accompanied by hypotension.
Reference: Ponikowski P et al. Eur J Heart Fail. 2016; 18(8):891-975. DOI: 10.1002/ejhf.592.
ACUTE HEART FAILURE: Diagnosis and causes (2)
4.1 P.53
1 Symptoms: Dyspnea (on effort or at rest)/
breathlessness, fatigue, orthopnea, cough, weight gain/ankle swelling. 2 Signs: Tachypnea, tachycardia, low or normal blood pressure, raised jugular venous pressure, 3rd/4th heart sound, rales, oedema, intolerance of the supine position. 3 Cardiovascular risk profile: Older age, HTN, diabetes, smoking, dyslipidemia, family history, history of CVD. 4 Precipitants/causes that need urgent management (CHAMP): Acute coronary syndrome. Hypertensive
emergency. Rapid arrhythmias or severe bradyarrhythmia/conduction disturbance. Mechanical causes. Pulmonary embolism. 5 Differential diagnosis: Exacerbated pulmonary disease, pneumonia, pulmonary embolism, pneumothorax, acute respiratory distress syndrome, (severe) anaemia, hyperventilation (metabolic acidosis), sepsis/septic shock, redistributive/hypovolemic shock. Reference: McMurray JJ et al. Eur Heart J (2012); 33:1787-847. Ponikowski P et al. Eur J Heart Fail. 2016; 18:891-975.
FACTORS TRIGGERING ACUTE HEART FAILURE
• Acute coronary syndrome • Tachyarrhythmia (e.g. atrial fibrillation, ventricular tachycardia) • Excessive rise in blood pressure • Infection (e.g. pneumonia, infective endocarditis, sepsis). • Non-adherence with salt/fluid intake or medications • Toxic substances (alcohol, recreational drugs) • Drugs (e.g. NSAIDs, corticosteroids, negative inotropic substances, cardiotoxic chemotherapeutics) • Exacerbation of chronic obstructive pulmonary disease • Pulmonary embolism • Surgery and perioperative complications • Increased sympathetic drive, stress-related cardiomyopathy • Metabolic/hormonal derangements (e.g. thyroid dysfunction, diabetic ketosis, adrenal dysfunction, pregnancy and peripartum related abnormalities) • Cerebrovascular insult • Acute mechanical cause : myocardial rupture complicating ACS (free wall rupture, ventricular septal defect, acute mitral regurgitation), chest trauma or cardiac intervention, acute native or prosthetic valve incompetence secondary to endocarditis, aortic dissection or thrombosis
Initial management of a patient with ACUTE HEART FAILURE
P.54
Patient with suspected AHF
Urgent phase after first medical contact
1. Cardiogenic shock ?
Yes
No
2. Respiratory failure ?
Yes
No
Immediate phase (initial 60-120 minutes)
Circulatory support • pharmacological • mechanical Ventilatory support • oxygen • non-invasive positive pressure ventilation (CPAP, BiPAP) • mechanical ventilation
Immediate stabilization and transfer to ICU/CCU Indentification of acute aeticology : C = Acute Coronary syndrome H = Hypertension emergency A = Arrhythmia M = Acute Mechanical cause P = Pulmonary embolism No
Yes
Diagnostic work-up to confirm AHF Clinical evaluation to select optimal management Reference: Ponikowski P et al. Eur J Heart Fail. 2016; 18(8): 891-975. DOI: 10.1002/ejhf.592.
4.1
Immediate initiation of specific treatement
ACUTE HEART FAILURE: Airway (A) and breathing (B) Oxygen therapy and ventilatory support in acute heart failure
P.55
Upright position
Pre-hospital or emergency room
No
RESPIRATORY DISTRESS?
SpO2 <90%, RR>25, Work of breathing, orthopnea
Conventional oxygen therapy
Yes
CPAP
Intubation
In hospital
No
"PERSISTENT" RESPIRATORY DISTRESS?
Yes Venous/Arterial blood gases SIGNIFICANT HYPERCAPNIA AND ACIDOSIS
Conventional oxygen therapy
Intolerance
PS-PEEP
NORMAL pH AND pCO2
CPAP
Intubation
After 60-90 min
Weaning SUCCESS
Room air Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17:544-58.
4.1
FAILURE
4.1 4. 1
ACUTE HEART FAILURE: Initial diagnosis (CDE)
P.56 C - CIRCULATION*
HR (bradycardia [<60/min], [<60/min], normal [60-100/min], [60-10 0/min], tachycardia [>100/min]), rhythm (regular, irregular), SBP (very low [<90 mmHg], low, normal [110-140 mmHg], high [>140 mmHg]), and elevated jugular pressure should be checked. INSTRUMENTATION & INVESTIGATIONS:
Intravenous line (peripheral/central) (peripheral/central) and BP monitoring (arterial line in shock and severe ventilatory/gas-exchange disturbances) Laboratory measures
• Cardiac markers (troponin, BNP/NT BNP/NT-proBNP/MR-proANP) -proBNP/MR-proANP) • Complete blood count, electrolytes, creatinine, urea, glucose, inflammation, TSH • Consider arterial or venous venous blood gases, gases, lactate, lactate, D-dimer (suspicion of acute pulmonary embolism)
Standard 12-lead ECG
• Rhythm, rate, rate, conduction times t imes?? • Signs of ischemia/myocardial infarction? Hypertrophy?
Echocardiography
a) Immediately Immediately in in haemodynamically haemodynamically unstable patients b) Within 48 48 hours when cardiac cardiac structure structure and function are either not known known or may have changed since previous studies
Ventricular function (systolic and diastolic)? Estimated left-and right-side filling pressures? Lung ultrasound? Presence of valve dysfunction (severe stenosis/ insufficiency)? Pericardial tamponade?
ACTIONS:
Rule in/out acute heart failure as cause of symptoms and signs Determine clinical profile Start as soon as possible treatment of both heart failure and the factors identified as triggers Establish cause
4.1 4. 1 P.57 D – DISABILITY DUE TO NEUROLOGICAL DETERIORATION
• Normal consiousness/altered mental status? Measurement of mental state with AVPU (alert, visual, pain or unresponsive) or Glasgow • Coma Scale: EMV score <8 Consider endotracheal intubation intubatio n and mechanical ventilation • Anxiety, severe dyspnea? Consider cautious administration administratio n of morphine 2 mg i.v i.v. bolus, preceded by antiemetic as needed
E – EXPOSURE & EXAMINATION
• Temperature/fever: central and peripheral • Weight • Skin/extremities: circulation (e.g. capilary refill), color • Urinary output (<0.5 ml/kg/hr) ml/kg/hr) Consider inserting indwelling indwelling catheter; the benefits should outweigh the risks of infection infection and long-term complications complications
References: Mebazaa A et al. Intensive Care Med. (2016); 42(2):147-63; 42(2):147-63; Mueller C et al. Eur Heart Hear t J Acute Cardiovasc Care. (2017); 6(1):81-6.
ACUTE HEART FAILURE: FAILUR E: Management of patients with with acute heart failure based on clinical profile during an early phase
4.1 4. 1 P.58
Patient with AHF
Bedside assessment to identify haemodynamic profiles
PRESENCE OF CONGESTION a? Yes (95% of all AHF patients)
No (5% of all AHF patients)
"WET" patient
"DRY" patient
ADEQUATE PERIPHERAL PERFUSION? Yes
"WET" and "WARM" patient (typically elevated or normal systolic blood pressure)
Yes
No
"DRY" and "WARM" Adequately perfused Compensated
No "DRY" and "COLD" Hypoperfused, hypovolemic
≈
Adjust oral therapy
Consider fluid challenge Consider inotropic agent if still hypoperfused
4.1 4. 1 P.59 "WET" and "COLD" patient Systolic blood pressure <90 mmHg Vascular type-fluid redistribution Hypertension predominates
• Vasodilator • Diuretic
a
Cardiac type-fluid accumulation Congestion predominates
• Diuretic • Vasodilator • Ultrafiltration (consider if diuretic diuretic resistance)
Yes
• Inotropic agent • Consider vasopressor in refractory cases • Diuretic (when perfusion corrected) • Consider machanical circulatory support if no response to drugs
No
• Vasodilators • Diuretics • Consider inotropic agent In refractory cases
Symptoms/signs Symptoms/signs of congestion: orthopnoea, paroxysmal nocturnal dyspnoea, breathlessness, bi-basilar rales, abnormal blood pressure response to the Valsalva maneuver (left-sided); symptoms of gut congestion, jugular venous distension, hepatojugular reflux, hepatomegaly, ascites, and peripheral oedema (right-sided).
For more information on individual drug doses and indications,
SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE Reference: Ponikowski P et al. Eur J Heart Fail. 2016; 18(8):891-975. DOI: 10.1002/ejhf.592.
ACUTE HEART FAILURE: Management of acute heart failure
4.1 P.60
n i m 0 2 1 O T P U N O I T A V R E S B O
DIAGNOSTIC TESTS
No acute heart failure
Confirmed acute heart failure
MONITORING
TREATMENT OBJECTIVES to prevent organ dysfunction:
Dyspnea (VAS, RR), BP, SpO 2, HR and rhythm, urine output, peripheral perfusion
Improve symptoms, maintain SBP >90 mmHg and peripheral perfusion, mantain SpO 2 >90% (see table in pages 63-64)
REASSESSMENT Clinical, biological and psychosocial parameters by trained nurses
E G R A H C S I D / N O I S S I M D A
Observation unit (<24h) Risk stratification: ensure patient
Ward (cardiology, internal
ICU/CCU
medicine, geriatrics)
is at low risk before direct discharge
Discharge home Visit to cardiologist <1-2 weeks
Rehabilitation program
Palliative care hospitals
Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17: 544-58 and Miró Ò et al. Ann Intern Med (2017); 167:698-705.
ACUTE HEART FAILURE: Treatment (C) and preventive measures
4.0 4.1
Management of oral therapy in AHF in the first 48 hours
P.61
Normotension/ Hypertension
Hypotension <100 >90 mmHg
<90 mmHg
Low heart rate <60 50 bpm
<50 bpm
≥
Potassium ≤3.5 mmol/L
>5.5 mmol/L
Renal impairment Cr <2.5, eGFR >30
Cr >2.5, eGFR <30
ACE-I/ARB
Review/ increase
Reduce/ stop
Stop
No change
No change
Review/ increase
Stop
Review
Stop
Beta-blocker
No change
Reduce/ stop
Stop
Reduce
Stop
No change
No change
No change
No change
MRA
No change
No change
Stop
No change
No change
Review/ increase
Stop
Reduce
Stop
Diuretics
Increase
Reduce
Stop
No change
No change
Review/ No change
Review/ increase
No change
Review
Sacubitril/ Valsartan
Review/ increase
Stop
Stop
No change
No change
Review/ increase
Stop
Review
Stop
Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17(6):544-58.
ACUTE HEART FAILURE: Treatment (C) and preventive measures (Cont.)
P.62
Management of oral therapy in AHF in the first 48 hours
Normotension/ Hypertension Other vasodilators
(amiodarone, non-dihydropyridine CCB, ivabradine)
<100 >90 mmHg
<90 mmHg
Low heart rate <60 50 bpm
<50 bpm
≥
Potassium ≤3.5 mmol/L
>5.5 mmol/L
Renal impairment Cr <2.5, eGFR >30
Cr >2.5, eGFR <30
Increase
Reduce/ stop
Stop
No change
No change
No change
No change
No change
No change
Review
Reduce/ stop
Stop
Reduce/ stop
Stop
Review/ stop(*)
No change
No change
No change
(nitrates) Other heart rate slowing drugs
Hypotension
4.1
Thrombosis prophylaxis should be started in patients not anticoagulated. (*) Amiodarone.
Reference adapted from Mebazaa A et al. Eur J Heart Fail. (2015); 17(6):544-58.
CARDIOGENIC SHOCK: Definition
4.2 P.63
Clinical condition defined as the inability of the heart to deliver an adequate amount of blood to the tissues to meet resting metabolic demands as a result of impairment of its pumping function. Cardiogenic shock is equal to wet-cold phenotype. The clinical signs of hypoperfusion are listed in page 65. In addition, blood lactate is typically elevated above 2 mmol/L.
Hemodynamic criteria to define cardiogenic shock • Systolic blood pressure <80 to 90 mmHg or mean arterial pressure 30 mmHg lower than baseline • Severe reduction in cardiac index: <1.8 l/min/m2 without support or <2.0 to 2.2 l/min/m2 with support • Adequate or elevated filling pressure: Left ventricular end-diastolic pressure >18 mmHg or Right atrial pressure >10 to 15 mmHg
CARDIOGENIC SHOCK: Causes LV pump failure is the primary insult in most forms of CS, but other parts of the circulatory system contribute to shock with inadequate compensation or additional defects
4.2 P.64
CARDIOGENIC SHOCK: Initial triage and management This protocol should be initiated as soon as cardiogenic shock/end organ hypoperfusion is recognised and should not be delayed pending intensive care admission. T N E M T R A P E D Y C N E G R E M E
• Age: 65–74, ≥75 • Heart rate >100 beats per minute • Systolic blood pressure <100 mmHg • Proportional pulse pressure ≤25 % (CI <2.2 l/min/m2) • Orthopnea (PCWP >22 mmHg) • Tachypnea (>20/min), >30/min (!) • Killip class IV • Clinical symptoms of tissue hypoperfusion/hypoxia: - cool extremities - decreased urine output (urine output <40 ml/h) - decreased capillary refill or mottling - alteration in mental status
INITIAL RESUSCITATION
• CORRECT: hypoglycemia & hypocalcemia, • TREAT: sustaned arrhythmias: brady- or tachycardia • Isotonic saline-fluid challenge - 200-300 ml over 30 min period to achieve a central venous pressure of 8 to 12 mmHg or until perfusion improves (with a maximum of 500 ml) • CONSIDER NIMV for comfort (fatigue, distress) or as needed: - To correct acidosis - To correct hypoxemia • INOTROPIC SUPPORT (dobutamine, levosimendan and/or vasopressor support)
5 min
• Arterial and a central venous catheterization with a catheter T capable of measuring central venous 15 min I N oxygen saturation U E • Standard transthoracic R echocardiogram to assess left (and A C right) ventricular function and for E V the detection of potential mechanical I complications following MI 60 min S N • Early coronary angiography in E T specialized myocardial intervention N I centre when signs and/or symptoms C of ongoing myocardial ischemia A I D (e.g. ST-segment elevation myocardial R A infarction). C
P.65
EARLY TRIAGE & MONITORING
Start high flow O 2 Establish i.v. access
0 min
4.2
TREATMENT GOALS
• a mean arterial pressure of 60 mmHg or above, • a mean pulmonary artery wedge pressure of 18 mmHg or below, • a central venous pressure of 8 to 12 mmHg, • a urinary output of 0,5 ml or more per hour per kilogram of body weight • an arterial pH of 7.3 to 7.5 • a central venous saturation (ScvO 2) ≥70% (provided SpO 2 ≥93% and Hb level ≥9 g/dl) In persistent drug-resistant cardiogenic shock, consider mechanical circulatory support
CARDIOGENIC SHOCK: Treatment and ventilator procedures
4.2 P.66
For more informations on individual drug doses and indications:
Ventilator mode Tidal Volume goal Plateau Pressure goal Anticipated PEEP levels Ventilator rate and pH goal Inspiration: Expiration time Oxygenation goal: • PaO2 • SpO2
Pressure assist/control Reduce tidal volume to 6-8 ml/kg lean body weight ≤30 cm H2O 5-10 cm H2O 12-20, adjusted to achieve a pH ≥7.30 if possible 1:1 to 1:2 50-80 mmHg >90%
Predicted body weight calculation: • Male: 50 + 0.91 (height in cm - 152.4) • Female: 45.5 + 0.91 (height in cm - 152.4) Some patients with CS will require increased PEEP to attain functional residual capacity and maintain oxygenation, and peak pressures above 30 cm H2O to attain effective tidal volumes of 6-8 ml/kg with adequate CO2 removal.
For more information on individual drug doses and indications,
SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
CARDIOGENIC SHOCK: management following STEMI
4.2 P.67
Assess volume status Treat sustained arrhythmias: brady - or tachy Consider mechanical ventilation for comfort (during PCI) and/or as needed: • to correct acidosis • to correct hypoxemia Inotropic support (dobutamine and/or vasopressor support) Signs (ST-segment elevation or new LBBB) and/or clinical symptoms of ongoing myocardial ischemia Yes
l a c i t r n o a p h p c u e s m y r o m r t e a l t - u t c r r o i h c S
Early coronary angiography Pulmonary artery catheter ± IABP in selected patients in a specialised Myocardial Intervention Centre
±
No NSTEACS, Delayed CS
Pump failure RV, LV, both
Emergency echocardiography ± Tissue doppler imaging ± Color flow imaging
• Acute severe mitral valve regurgitation • Ventricular septum rupture • Severe aortic/mitral valve stenosis
Operating theater ± coronary angiography
PCI ± stenting of the culprit lesion
CABG + correct mechanical complications
Aortic dissection Pericardial tamponade
CARDIOGENIC SHOCK: Mechanical circulatory support, basic characteristics
4.2 P.68
1-month
...
2-weeks 72-hrs IABP
Impella 2.5 Impella 5.0 Tandemheart
Levitronix
Left ventricular support Partial support
ECMO
BiVentricular support Full support Pulmonary support
Level of support
Implantable
4.2 P.69 Type Intra-aortic balloon pump Impella Recover LP 2.5 CP LP 5.0
Support
Balloon Pulsatile flow counterpulsation Axial flow
Continuous flow
Tandemheart Cardiohelp
Centrifugal flow
Access
<0.5 L Arterial: 7.5 French
<2.5 L <4.0 L <5.0 L
Arterial: 12 French Arterial: 14 French Arterial: 21 French
<5.0 L
Venous: 21 French Arterial: 15-17 French
<5.0 L
Venous: 15-29 French Arterial: 15-29 French
Continuous flow
Different systems for mechanical circulatory support are available to the medical community. The available devices differ in terms of the insertion procedure, mechanical properties, and mode of action. A minimal flow rate of 70 ml/kg/min, representing a cardiac index of at least 2.5 L/m2, is generally required to provide adequate organ perfusion. This flow is the sum of the mechanical circulatory support output and the remaining function of the heart. The SAVE-score may be a tool to predict survival for patients receiving ECMO for refractory cardiogenic shock (www.save-score.com).
5 P.71
CHAPTER 5
CARDIAC ARREST AND CARDIOPULMONARY RESUSCITATION N. Nikolaou, L. Bossaert
THE CHAIN OF SURVIVAL
Monsieurs KG, et al. European Resuscitation Council Guidelines for Resuscitation 2015. Section 1 Executive Summary. Resuscitation 2015; 95C:1-80, DOI:10.1016/j.resuscitation.2015.07.038
OUT OF HOSPITAL CARDIAC ARREST: Assessment of a collapsed victim and initial treatment
P.72
VICTIM COLLAPSES Approach safely Check response Victim responds Victim unresponsive Leave victim as found Find out what is wrong Reassess victim regularly
Shout for help Open airway Assess breathing Breathing normally
Put victim in recovery position and call for an ambulance
Not breathing normally Call for an ambulance Start CPR 30:2 Send or go for an AED
AED not available 30 chest compressions: 2 rescue breaths
5
As soon as AED arrives Start AED, listen to and follow voice prompts AED Assesses rhythm
5
P.73 Shock advised
No shock advised
1 shock
Immediately resume CPR 30:2 for 2 min
Immediately resume CPR 30:2 for 2 min
Continue until victim starts to wake up: to move, open eyes, and breathe normally
IN�HOSPITAL CARDIAC ARREST: Assessment of a collapsed victim and initial treatment
5
P.74 Collapsed/sick patient
Shout for HELP & assess patient
No
Signs of life?
Yes
Call resuscitation team Assess ABCDE Recognise & treat oxygen; monitoring, i.v. access
CPR 30:2 with oxygen and airway adjuncts
5
Apply pads/monitor Attempt defibrillation if appropriate
Call resuscitation team if appropriate
Advanced Life Support when resuscitation team arrives
Handover to resuscitation team
P.75
IN�HOSPITAL CARDIAC ARREST: Advanced life support
5
P.76 Unresponsive and not breathing normally ? Call resuscitation team CPR 30:2 Attach defibrillator/monitor Minimise interruptions
Assess rhythm
Shockable (VF/Pulseless VT)
Non-shockable (PEA/Asystole)
5
1 Shock
Return of spontaneous circulation IMMEDIATE POST
Immediately resume: CPR for 2 min Minimise interruptions DURING CPR • Ensure high-quality chest compressions • Minimise interruptions to compressions • Give Oxygen • Use waveform capnography • Continuous chest compressions when advanced airway in place • Vascular access (intravenous, intraosseous) • Give adrenaline every 3-5 min • Give amiodarone after 3 shocks • Correct reversible causes
CARDIAC ARREST TREATMENT
• Use ABCDE approach • Aim for SaO2 94-98% • Aim for normal PaCO2 • 12-lead ECG • Treat precipitating cause • Temperature control / Therapeutic hypothermia CONSIDER • Ultrasound imaging • Mechanical chest compressions to facilitate transfer/treatment • Coronary angiography and PCI • Extracorporeal CPR
P.77 Immediately resume: CPR for 2 min Minimise interruptions
REVERSIBLE CAUSES • Hypoxia • Hypovolaemia • Hypo-/hyperkalaemia/metabolic • Hypothermia
• Thrombosis • Tamponade - cardiac • Toxins • Tension pneumothorax
IN�HOSPITAL CARDIAC ARREST: Drug therapy during advanced life support
5
P.78 Cardiac Arrest
Shockable rhythm (VF, pulseless VT)
Non-shockable rhythm
Give adrenaline and amiodarone after 3rd shock
Adrenaline: 1mg i.v. (10 ml 1:10,000 or 1 ml 1:1000) given as soon as circulatory access is obtained Repeat every 3-5 min (alternate loops) Give without interrupting chest compressions
Adrenaline: 1 mg i.v. (10 ml 1:10,000 or 1 ml 1:1000) repeated every 3-5 min (alternate loops) given without interrupting chest compressions
Amiodarone 300 mg bolus i.v. Second bolus dose of 150 mg i.v. if VF/VT persists followed by infusion of 900 mg over 24 h
6
CHAPTER 6
RHYTHM DISTURBANCES
6.1 SUPRAVENTRICULAR TACHYCARDIAS AND ATRIAL FIBRILLATION ____ p.80
J. Brugada 6.2 VENTRICU LAR TACHYCARDIAS __________________________________________ p.84
M. Santini, C. Lavalle, S. Lanzara 6.3 BRADYARRHYTHMIAS ____________________________________________________
B. Gorenek
p.87
6.1
TACHYARRHYTHMIAS: Diagnostic criteria
P.80
Tachycardia >100 beats/min
Regular
Irregular
QRS morphology similar to QRS morphology in sinus rhythm?
QRS morphology similar to QRS morphology in sinus rhythm?
YES
NO
QRS complex QRS complex <120 msec >120 msec
QRS complex <120 msec
QRS complex >120 msec
Supraventr. Tachycardia
Fascicular Tachycardia or SVT with aberrant conduction
Ventricular Tachycardia or SVT with aberrant conduction
Supraventr. Tachycardia + BBB
YES
NO
QRS complex QRS complex <120 msec >120 msec
Variable QRS morphology
AF conducting over AVN
AF + BBB or AF + WPW
AF + WPW
Irregular Ventricular Tachycardia
6.1
TACHYARRHYTHMIAS: Diagnostic maneuvers
P.81
Regular tachycardia
Vagal maneuvers or i.v. adenosine Tachycardia terminates
AV relation changes
More As than Vs
No change
More Vs than As
Wide QRS complex
• Concordant precordial pattern (all leads + or all leads –) • No RS pattern in precordial leads • RS pattern with beginning of R wave to nadir of S wave >100 msec Consider SVT using the AV node (AVNRT, AVNT)
Atrial flutter or atrial tachycardia
Ventricular Tachycardia
Ventricular Tachycardia
Narrow QRS complex
Typical morphology in V1 & V6
Ventricular Tachycardia
Consider Sinus tachycardia or non proper administration of adenosine (too slow, insufficient dose, etc)
TACHYARRHYTHMIAS: Therapeutic algorithms (1)
6.1 P.82
Regular Supraventricular Tachycardias with or without bundle branch block
Hemodynamically non-stable
Hemodynamically stable
Immediate electrical cardioversion
Vagal maneuvers and/or i.v. Adenosine
No termination
Termination
Irregular and narrow QRS complex Tachycardia
Less than 48 hours since initiation AND hemodynamically stable
Hemodynamically non-stable
Cardioversion
If no cardioversion is considered: rate control using betablockers or calcium antagonists, together with proper anticoagulation , if required
Electrical or pharmacological using oral or i.v. flecainide (only in normal heart) or i.v. vernakalant
Immediate electrical Cardioversion
Anticoagulation is initiated using i.v. heparine Narrow QRS complex tachycardia
Wide QRS complex tachycardia
Reconsider diagnosis: sinus tachycardia, atrial tachycardia
Reconsider the diagnosis of Ventricular Tachycardia even if hemodynamically stable
If no evidence: Intravenous verapamil
Do not administer verapimil
More than 48 hours OR unknown time of initiation, AND Patient chronically anticoagulated OR a TEE showing no thrombus
Electrical or pharmacological Cardioversion
TACHYARRHYTHMIAS: Therapeutic algorithms (2)
6.1 P.83
Irregular and wide QRS complex Tachycardia
Hemodynamically non-stable Immediate electrical Cardioversion If no cardioversion is considered: rate control using betablockers or calcium antagonists (only if VT and AF+WPW is excluded), together with proper anticoagulation if required
More than 48 hours or unknown initiation, AND patient chronically anticoagulated or a TEE showing no thrombus Electrical or pharmacological Cardioversion
Less than 48 hours since initiation AND hemodynamically stable Cardioversion electrical or pharmacological using oral or i.v. flecainide (only in normal heart) or i.v. amiodarone Anticoagulation is initiated using i.v. heparin
VENTRICULAR TACHYSCARDIAS: Diferential diagnosis of wide QRS tachyscardias
6.2 P.84
EKG signs of atrio-ventricular dissociation st
1 Step
Random P waves unrelated to QRS complexes Capture beats / fusion beats / second degree V-A block
Yes
No 2nd Step
Concordant pattern in precordial leads
Yes
No RS morphology in any of the precordial leads
VT
No 3rd Step
An interval >100 ms from the beginning of the QRS complex to the nadir of S in a precordial lead
Yes
No
Morphology in precordial leads
Morphology in aVR lead
6.2 P.85 RBBB morphology
Yes
LBBB morphology
Initial R wave No
V1: qR, R, R’ V6: rS,QS
V1: rsR’, RSR’ V6: qRs
V6: R
V1: rS; R >30 ms, S nadir >60 ms, notching of the S wave
V6: qR, QS
Yes
Initial R wave or q >40 msec No
Yes
Notch in the descending Q wave limb No
VT
Aberrant conduction
VT
Yes
Vi/Vt
1
≤
No
Aberrant conduction
6.2
Management of wide QRS TACHYSCARDIAS
P.86
Hemodynamic Tolerance Non-stable Pulseless ACLS Resuscitation algorithm
• Immediate high- energy defibrillation (200 J biphasic or 360 monophasic) • Resume CPR and continue according to the ACLS algorithm Drugs used in the ACLS algorithm • Epinephrine 1 mg i.v./i.o.
(repeat every 3-5 min) • Vasopressin 40 i.v./i.o. • Amiodarone 300 mg i.v./i.o. once then consider an additional 150 mg i.v./i.o. dose • Lidocaine 1-1.5 mg/kg first dose then 0.5-0-75 mg/kg i.v./i.o. for max 3 doses or 3 mg/kg • Magnesium loading dose 1-2 gr i.v./i.o. for torsade des pointes
Stable With pulse • Sedation or analgesia • Synchronised cardioversion
100 to 200 J (monophasic) or 50-100 J (biphasic)
Irregular rhythm
Regular rhythm
Differential Diagnosis
Vagal maneuver and/or i.v. adenosine (push)
No
Yes
AF with aberrant ventricular conduction
• β-blockers • i.v. • Verapamil or diltazem Pre excited AF
• Class 1 AADs Polymorphic VT
• Amiodarone
Interruption or slow down HR No
Yes
Differential Diagnosis (see chapter 6.1 page 81)
SVT
Amiodarone 150 mg i.v.
(can be repeated up to a maximum dose of 2.2 g in 24 h) Synchronised cardioversion
BRADYARRHYTHMIAS: Definitions and diagnosis
6.3 P.87
Sinus node dysfunction
• Sinus bradycardia: It is a rhythm that originates
Atrioventricular (AV) blocks
• First degree AV block: Atrioventricular impulse
from the sinus node and has a rate of under 60 beats per minute
transmission is delayed, resulting in a PR interval longer than 200 msec
• Sinoatrial exit block: The depolarisations that occur in
• Second degree AV block: Mobitz type I (Wenckebach
the sinus node cannot leave the node towards the atria
block): Progressive PR interval prolongation, which precedes a nonconducted P wave
• Sinus arrest: Sinus pause or arrest is defined as the
transient absence of sinus P waves on the ECG
• Second degree AV block: Mobitz type II: PR interval
remains unchanged prior to a P wave that suddenly fails to conduct to the ventricles • Third degree (complete) AV block:
No atrial impulses reach the ventricle
BRADYARRHYTHMIAS: Treatment (1)
6.3 P.88
• Rule out and treat any underlying causes of bradyarrhythmia • Treat symptomatic patients only For more information on individual drug doses and indications,
SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE Temporary transvenous pacing
Be Careful! • Complications are common! • Shall not be used routinely • Use only as a last resource when chronotropic drugs are insufficient • Every effort should be made to implant a permanent pacemaker as soon as possible, if the indications are established.
Indications limited to: • High-degree AV block without escape rhythm • Life threatening bradyarrhythmias, such as those that occur during interventional procedures, in acute settings such as acute myocardial infarction, drug toxicity.
BRADYARRHYTHMIAS: Treatment (2) Pacemaker therapies in sinus node dysfunction
6.3 P.89
Permanent pacemaker is indicated in the following settings:
• Documented symptomatic bradycardia, including frequent sinus pauses that produce symptoms • Symptomatic chronotropic incompetence • Symptomatic sinus bradycardia that results from required drug therapy for medical conditions Permanent pacemaker is not recommended in the following settings:
• Asymptomatic patients • Patients for whom the symptoms suggestive of bradycardia have been clearly documented to occur in the absence of bradycardia • Symptomatic bradycardia due to nonessential drug therapy
BRADYARRHYTHMIAS: Treatment (3) Pacemaker therapies in atrioventricular blocks
6.3 P.90
Permanent pacemaker therapy is indicated in the following settings regardless of associated symptoms:
• Third-degree AV block • Advanced second-degree AV block • Symptomatic Mobitz I or Mobitz II second-degree AV block • Mobitz II second-degree AV block with a wide QRS or chronic bifascicular block • Exercise-induced second- or third-degree AV block • Neuromuscular diseases with third- or second-degree AV block • Third- or second-degree (Mobitz I or II) AV block after catheter ablation or valve surgery when block is not expected to resolve Permanent pacemaker is not recommended in the following settings:
• Asymptomatic patients • Patients for whom the symptoms suggestive of bradycardia have been clearly documented to occur in the absence of bradycardia • Symptomatic bradycardia due to nonessential drug therapy
7
CHAPTER 7
ACUTE VASCULAR SYNDROMES
7.1 ACUT E AORTIC SYNDROM ES ______________________________________________
p.92
A. Evangelista 7.2 ACUT E PULMONA RY EMBO LISM __________________________________________ p.102
A. Torbicki
ACUTE AORTIC SYNDROMES: Concept and classification (1) Types of presentation
7.1 P.92
Classic aortic dissection
Separation of the aorta media with presence of extraluminal blood within the layers of the aortic wall. The intimal flap divides the aorta into two lumina, the true and the false
Intramural hematoma (IMH)
Aortic wall hematoma with no entry tear and no two-lumen flow
Penetrating aortic ulcer (PAU)
Atherosclerotic lesion penetrates the internal elastic lamina of the aorta wall
Aortic aneurysm rupture
(contained or not contained)
ACUTE AORTIC SYNDROMES: Concept and classification (2) Anatomic classification and time course
7.1 P.93
DeBakey’s Classification
• Type I and Type II dissections both originate in the ascending aorta In type I, the dissection extends distally to the descending aorta In type II, it is confined to the ascending aorta • Type III dissections originate in the descending aorta Stanford Classification
• Type A includes all dissections involving the ascending aorta regardless of entry site location • Type B dissections include all those distal to the brachiocephalic trunk, sparing the ascending aorta
De Bakey
Type I
Type II
Type III
Stanford
Type A
Type A
Type B
Time course
• Acute: <14 days • Subacute: 15-90 days • Chronic: >90 days Adapted with permission from Nienaber CA, Eagle KA, Circulation 2003;108(6):772-778. All rights reserved.
Copyright: Nienaber CA, Eagle KA. Aortic dissection: new frontiers in diagnosis and management: Part II: therapeutic management and follow-up. Circulation (2003); 108(6),772-778.
ACUTE AORTIC SYNDROME: Clinical suspicion and differential diagnosis
7.1 P.94
SYMPTOMS AND SIGNS SUGGESTIVE OF AAS • Abrupt and severe chest/back pain with maximum intensity at onset • Pulse/pressure deficit - Peripheral or visceral ischemia - Neurological deficit • Widened mediastinum on chest X -ray • Risk factors for dissection • Other - Acute aortic regurgitation - Pericardial effusion - Hemomediastinum/hemothorax
DIFFERENTIAL DIAGNOSIS • Acute coronary syndrome (with/without ST-segment elevation) • Aortic regurgitation without dissection • Aortic aneurysms without dissection • Musculoskeletal pain • Pericarditis • Pleuritis • Mediastinal tumours • Pulmonary embolism • Cholecystitis • Atherosclerosis or cholesterol embolism
General approach to the patient with suspected ACUTE AORTIC SYNDROME
7.1 P.95
Consider acute aortic dissection in all patients presenting with:
• Chest, back or abdominal pain • Syncope • Symptoms consistent with perfusion deficit (central nervous system, visceral myocardial or limb ischemia)
Pre-test risk assessment for acute aortic dissection High-risk conditions • Marfan’s syndrome • Connective tissue disease • Family history of aortic disease • Aortic valve disease • Thoracic aortic aneurysm
High-risk pain features Chest, back or abdominal pain described as:
Abrupt at onset, severe in intensity, and ripping/sharp or stabbing quality
High-risk exam features • Perfusion deficit:
- Pulse deficit - SBP differential - Focal neurological deficit • Aortic regurgitation murmur • Hypotension or shock
Copyright: Hiratzka et al. 2010 Guidelines on Thoracic Aortic Disease. Circulation. (2010) ; 121: page-310 (fig 25 step 2).
Laboratory tests required for patients with ACUTE AORTIC dissection
7.1 P.96
Laboratory tests
To detect signs of:
Red blood cell count
Blood loss, bleeding, anaemia
White blood cell count
Infection, inflammation (SIRS)
C-reactive protein
Inflammatory response
ProCalcitonin
Differential diagnosis between SIRS and sepsis
Creatine kinase
Reperfusion injury, rhabdomyolysis
TroponinIorT
Myocardial ischaemia, myocardial infarction
D-dimer
Aortic dissection, pulmonary embolism, thrombosis
Creatinine
Renal failure (existing or developing)
Aspartate transaminase / alanine aminotransferase
Liver ischaemia, liver disease
Lactate
Bowel ischaemia, metabolic disorder
Glucose
Diabetes mellitus
Blood gases
Metabolic disorder, oxygenation
Reference: Eur Heart J 2014; eurheartj.ehu281.
7.1
ACUTE CHEST PAIN
P.97 Medical history + clinical examination + ECG
UNSTABLE
HAEMODYNAMIC STATE
TTE + TOE/CT°
AAS confirmed
AAS excluded Consider alternate diagnosis
High probability (score 2-3) or typical chest pain
D-dimers d,e + TTE + Chest X-ray
TTE
Signs of AD
STEMI can be associated with AAS in rare cases.
a
Pending local availability, patient characteristics, and physician experience.
Proof of type-A AD by the presence of flap, aortic regurgitation, and/or pericardial effusion.
c
STABLE
Low probability (score 0-1)
No argument for AD b
Consider alternate diagnosis CT (MRI or TOE) b
Preferably point-of-care, otherwise classical. Also troponin to detect non–ST-segment elevation myocardial infarction.
AAS confirmed
Definite Type A -ADc
Inconclusive
Refer on emergency to surgical team and pre-operative TOE
CT (or TOE)
Widened mediastinum
d e
STEMIa : see ESC guidelines 169
AAS confirmed
Consider alternate diagnosis
Flowchart for decision-making based on pre-test sensitivity of acute aortic syndrome. Reference: Eur Heart J 2014; eurheartj.ehu281.
Consider alternate diagnosis repeat CT if necessary
7.1
Details required from imaging in ACUTE AORTIC dissection
P.98 Aortic dissection
• Visualization of intimal flap • Extent of the disease according to the aortic anatomic segmentation • Identification of the false and true lumens (if present) • Localization of entry and re-entry tears (if present) • Identification of antegrade and/or retrograde aortic dissection • Identification grading, and mechanism of aortic valve regurgitation • Involvement of side branches • Detection of malperfusion (low flow or no flow) • Detection of organ ischaemia (brain, myocardium, bowels, kidneys, etc.) • Detection of pericardial effusion and its severity • Detection and extent of pleural effusion • Detection of peri-aortic bleeding • Signs of mediastinal bleeding
Intramural haematoma
• Localization and extent of aortic wall thickening • Co-existence of atheromatous disease (calcium shift) • Presence of small intimal tears
Penetrating aortic ulcer
• • • •
In all cases
• Co-existence of other aortic lesions: aneurysms, plaques, signs of inflammatory disease, etc.
Localization of the lesion (length and depth) Co-existence of intramural haematoma Involvement of the peri-aortic tissue and bleeding Thickness of the residual wall
ACUTE AORTIC SYNDROMES MANAGEMENT: General approach
7.1 P.99
ACUTE AORTIC DISSECTION
Type A
Type B
(Ascending aorta involvement)
(No ascending aorta involvement)
Uncomplicated
Open Surgery with/without Endovascular Therapy
Medical treatment
Complicated (malperfusion, rupture)
Endovascular Therapy or Open Surgery (TEVAR)
ACUTE AORTIC SYNDROMES: Initial management
7.1 P.100
1 • Detailed medical history and complete physical examination (when possible) 2 • Standard 12-lead ECG: Rule-out ACS, documentation of myocardial ischemia 3 • Intravenous line, blood sample (CK, cTn, myoglobin, white blood count, D-dimer, hematocrit, LDH) 4 • Monitoring: HR and BP 5 • Pain relief (morphine sulphate) (see chapter 4) 6 • Noninvasive imaging (see previous page) 7 • Transfer to ICU
For more information on individual drug doses and indications,
SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
7.1
ACUTE AORTIC SYNDROMES: Surgical management
P.101 TYPE A ACUTE AORTIC DISSECTION
TYPE B ACUTE AORTIC DISSECTION
URGENT SURGERY (<24h) Graft replacement of ascending aorta +/- arch with/without aortic valve or aortic root replacement/repair (depending on aortic regurgitation and aortic root involvement)
Definitive diagnosis by clinical presentation and imaging Yes COMPLICATED defined as:
Emergency Surgery • Haemodynamic instability (hypotension/shock) • Tamponade • Severe acute aortic regurgitation • Impending rupture • Flap in aortic root • Malperfusion syndrome
Elective/individualised Surgery • Non-complicated intramural hematoma • Comorbidities • Age >80 years
• Impending rupture • Malperfusion • Refractory HTN • SBP (<90 mmHg) • Shock
MEDICAL MANAGEMENT and TEVAR
MEDICAL MANAGEMENT and OPEN SURGERY REPAIR if TEVAR contraindicated
No UNCOMPLICATED defined as: No features of complicated dissection
MEDICAL MANAGEMENT and imaging surveillance protocol • On admission • At 7 days • At discharge • Every 6 months thereafter
Risk-adjusted management strategies in ACUTE PULMONARY EMBOLISM
7.2 P.102
Clinical suspicion Yes
No
Shock / hypotension?
Diagnostic algorithm as for suspected high-risk PE
Diagnostic algorithm as for suspected not high-risk PE PE confirmed Assess clinical risk (PESI or SPESI)
PE confirmed
PESI Class III-IV or sPESI ≥ I
PESI Class I-II or sPESI = 0
Intermediate risk Consider further risk stratificaiton RV function (echo or CT) a Laboratory testing b Both positive
One positive or both negative
7.2 High-risk
Intermediate-high risk
Intermediate-low risk
Primary reperfusion
A/C; monitoring consider rescue reperfusiond
Hospitalization A/C e
Low riskc
P.103
Consider early discharge and home treatment if feasible f
If echocardiography has already been performed during diagnostic work-up for PE and detected RV dysfunction, or if the CT already performed for diagnostic work–up has shown RV enlargement (RV/LV (left ventricular) ratio ≥0.9, a cardiac troponin test should be performed except for cases in which primary reperfusion is not a therapeutic option (e.g. due to severe comorbidity or limited life expectancy of the patient).
a
Markers of myocardial injur y (e.g. elevated cardiac troponin I or T concentrations in plasma), or of heart failure as a result of (right) ventricular dysfunction (elevated natriuretic peptide concentrations in plasma). If a laboratory test for a cardiac biomarker has already been performed during initial diagnostic work-up (e.g. in the chest pain unit) and was positive, then an echocardiogram should be considered to assess RV function, or RV size should be (re)assessed on CT.
b
Patients in the PESI Class I-II, or with sPESI of 0, and elevated cardiac biomarkers or signs of RV dysfunction on im aging tests, are also to be classified into the intermediate-low risk category. This might apply to situations in which imaging or biomarker results become available before calculation of the clinical severity index. These patients are probably no candidates for home treatment.
c
Thrombolysis, if (and as soon as) clinical signs of haemodynamic decompensation appear; surgical pulmonary embolectomy or percutaneous catheter-directed treatment may be considered as alternative options to systemic thrombolysis, particularly if the bleeding risk is high.
d
Monitoring should be considered for patients with confirmed PE and a positive troponin test, even if there is no evidence of RV dysfunction on echocardiography or CT.
e
The simplified version of the PESI has not been validated in prospective home treatment trials; inclusion criteria other than the PESI were used in two single-armed (non-randomized) management studies.
f
Reference: Eur Heart J 2014; 35:3033-3073.
7.2
ACUTE PULMONARY EMBOLISM: Diagnosis CARDIOVASCULAR Symptoms/Signs
RESPIRATORY Symptoms/Signs
Dyspnea
including but not limited to:
including but not limited to:
Suspect acute PE
• Chest pain (angina) • Syncope • Tachycardia • ECG changes • NT-proBNP ↑ • Troponin ↑
YES
• Chest pain (pleural) • Pleural effusion • Tachypnea • Hemoptysis • Hypoxemia • Atelectasis
Shock? or SBP <90 mmHg? or SBP fall by >40 mmHg?
NO
persisting >15 min, otherwise unexplained
Management algorithm for UNSTABLE patients Reference: IACC Textbook (2015) chapter 66 Pulmonary embolism - page 638 - figure 66.1.
Management algorithm for initially STABLE patients
P.104
Management algorithm for unstable patients with suspected ACUTE PULMONARY EMBOLISM
P.105
CT angiography immediately available and patient stabilised
No Echocardiography (bedside)
Yes
Yes CT* Angio
patient stabilised
RV pressure overload CUS TEE
Right heart, pulmonary artery or venous thrombi?
No
Yes
Search for other causes
positive
No further diagnostic tests feasible
Primary PA reperfusion Primary PA reperfusion not justified negative * Consider also pulmonary angiography if unstable patient in hemodynamic lab. Reference: IACC Textbook (2015) chapter 66 Pulmonary embolism - page 639 - figure 66.2.
7.2
ACUTE PE: Management strategy for initially unstable patients with confirmed high risk pulmonary embolism
7.2 P.106
Shock or hypotension Contraindications for thrombolysis
YES
No
Relative
Absolute
Primary PA reperfusion strategy
Thrombolysis
Low-dose transcatheter thrombolysis / clot fragmetation
Surgical or Percutaneous catheter embolectomy (availability/experience)
Supportive treatment
i.v. UFH, STABILISE SYSTEMIC BLOOD PRESSURE, CORRECT HYPOXEMIA
Management algorithm for initially stable patients with suspected ACUTE PULMONARY EMBOLISM
7.2 P.107
Asses clinical (pre-test) probalility
Low or intermediate “PE unlikely“ negative
High or “PE likely“
D-dimer
positive
CUS
CT angiography
negative
Anticoagulation not justified
CT angiography
positive
Anticoagulation required
negative
Confirm by CUS V/Q scan or angiography
Anticoagulation not justified
Reference: IACC Textbook (2015) chapter 66 Pulmonary embolism - page 640 - figure 66.3.
CUS positive
positive
Anticoagulation required
Suggested management strategy for initially stable patients with (non-high risk) confirmed PE
7.2 P.108
Markers for myocardial injury
Positive
Positive
Negative
Markers for RV overload
Positive
Positive
Negative
Clinical risk assessment score (PESI)
Positive (class III-V)
Positive (class III-V)
Negative (class I-II)
Suggested initial anticoagulation
UFH i.v./LMWH s.c.
LMWH/Fonda/apixaban/ rivaroxaban
apixaban/rivaroxaban
Monitoring (ICU)* rescue thrombolysis
Hospitalisation** (telemonitoring)
Early discharge***
STRATEGY
* When all markers are positive. - ** When at least one marker is positive. - *** When all markers are negative.
For more information on individual drug doses and indications,
SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
PULMONARY EMBOLISM: Pharmacological treatment Key drugs for initial treatment of patients with confirmed PE
e l b a t s n U
e l b a t S
Alteplase (rtPA) (intravenous)
100 mp/2h or 0.6 mp/kg/15 min (max 50 mp)
Urokinase (intravenous)
3 million IU over 2h
Streptokinase (intravenous)
1.5 million IU over 2h
Unfractionated heparin (intravenous)
80 IU/kg bolus + 18 IU/kg/h
Enoxaparine (subcutaneous)
1 mp/kg BID or 1.5 mp/kg QD
Tinzaparin (subcutaneous)
175 U/kg QD
Fondaparinux (subcutaneous)
7.5 mp (50-100 kg of body weight) 5 mp for patients <50 kg, 10 mp for patients >100 kg
Rivaroxaban (oral)
15 mp BID (for 3 weeks, then 20 mp QD)
Apixaban (oral)
10 mg bid (for 7 days, than 5 mg bid) For more information on individual drug doses and indications,
SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE
7.2 P.109
8
CHAPTER 8
ACUTE MYOCARDIAL/ PERICARDIAL SYNDROMES 8.1 ACUTE MYOCARDITIS _____________________________________________________
p.112
A. Keren, A. Caforio 8.2 ACUTE PERICARDITIS AND CARDIAC TAMPONADE ______________________ p.117
C. Vrints, S. Price
8.1
ACUTE MYOCARDITIS: Definition and causes
P.112 MYOCARDITIS (WHO /ISFC): Inflammatory disease of the myocardium diagnosed by established histological, immunological and immunohistochemical criteria.
CAUSES OF MYOCARDITIS
INFECTIOUS
• Viral • Bacterial • Spirochaetal • Fungal • Protozoal • Parasitic • Rickettsial
IMMUNE-MEDIATED
• Allergens:
Tetanus toxoid, vaccines, serum sickness, Drugs • Alloantigens: Heart transplant rejection • Autoantigens: Infection-negative lymphocytic, infection-negative giant cell, associated with autoimmune or immune oriented disorders
TOXIC
• Drugs • Heavy Metals • Hormones, e.g. catecholamines (Pheochromocytoma) • Physical agents
ACUTE MYOCARDITIS: Diagnostic criteria (1) Diagnostic criteria for clinically suspected myocarditis
8.1 P.113
Clinical presentations with or without ancillary findings
• Acute chest pain (pericarditic or pseudo-ischemic) • New-onset (days up to 3 months) or worsening dyspnea or fatigue, with or without left/right heart failure signs • Palpitation, unexplained arrhythmia symptoms, syncope, aborted sudden cardiac death • Unexplained cardiogenic shock and/or pulmonary oedema Ancillary findings which support the clinical suspicion of myocarditis
• Fever ≥38.1°C within the preceding 30 days • A respiratory or gastrointestinal infection • Previous clinically suspected or biopsy proven myocarditis • Peri-partum period • Personal and/or family history of allergic asthma • Other types of allergy • Extra-cardiac autoimmune disease • Toxic agents • Family history of dilated cardiomyopathy, myocarditis Reference: Caforio ALP et al. Eur Heart J. (2013) Jul 3 (15).
Diagnostic criteria I. ECG/Holter/stress test features: Newly abnormal ECG and/or Holter
and/or stress testing, any of the following: • I to III degree atrioventricular block, or bundle branch block, ST/T wave changes (ST elevation or non ST elevation, T wave inversion), • Sinus arrest, ventricular tachycardia or fibrillation and asystole, atrial fibrillation, frequent premature beats, supraventricular tachycardia • Reduced R wave height, intraventricular conduction delay (widened QRS complex), abnormal Q waves, low voltage II. Myocardiocytolysis markers: Elevated cTnT/cTnI III. Functional/structural abnormalities on echocardiography
• New, otherwise unexplained LV and/or RV structure and function abnormality (including incidental finding in apparently asymptomatic subjects): regional wall motion or global systolic or diastolic function abnormality, with or without ventricular dilatation, with or without increased wall thickness, with or without pericardial effusion, with or without endocavitary thrombi IV. Tissue characterisation by CMR:
Edema and/or LGE of classical myocarditic pattern
ACUTE MYOCARDITIS: Diagnostic criteria (2) Acute myocarditis should be clinically suspected in the presence of:
8.1 P.114
One or more of the clinical presentations shown in the Diagnostic Criteria * with or without Ancillary Features* AND
One or more Diagnostic Criteria from different categories (I to IV) * OR
when the patient is asymptomatic, two or more diagnostic criteria from different categories (I to IV) * in the absence of: 1) angiographically detectable coronary artery disease
2) known pre-existing cardiovascular disease or extra-cardiac causes that could explain the syndrome
(e.g. valve disease, congenital heart disease, hyperthyroidism, etc.) Suspicion is higher with higher number of fulfilled criteria *
Endomyocardial biopsy is necessary to:
1) confirm the diagnosis of clinically suspected myocarditis, 2) identify the type and aetiology of inflammation, and 3) provide the basis for safe immunosuppression
(in virus negative cases).
*SEE CHAPTER 9 DRUGS USED IN ACUTE CARDIOVASCULAR CARE Reference: Caforio ALP et al. Eur Heart J. (2013) Jul 3 (16).
ACUTE MYOCARDITIS: Diagnostic and management protocol
8.1
History, Physycal examination; ECG; Echocardiogram; Laboratory tests (Troponin, CRP, ESR, blood cell count, BNP); CMR; If available, serum cardiac autoantibodies
P.115
Clinically suspected myocarditis Consider coronary angiography and EMB No coronary artery disease Hemodynamically stable Preserved LV function No eosinophilia No significant rhythm or conduction disturbances Not associated with systemic immune disease *
Hemodynamically unstable, decreased LV function, cardiogenic shock Pharmacological and, if needed, mechanical circulatory support (ECMO, LVAD/Bi-VAD, bridge to heart transplant or to recovery) Lymphocytic
General supportive therapy General supportive therapy Immunosuppression if unresponsive and virus negative EMB
Giant cell, eosinophilic, sarcoidosis (acute decompensation)
Immunosuppression if infection-negative EMB
*If myocarditis is associated with systemic immune disease exacerbation, therapy overlaps with treatment of the background disease (usually immunosuppression).
Management of patients with life-threatening ACUTE MYOCARDITIS
8.1 P.116
• Patients with a life-threatening presentation should be sent to specialised units with capability for hemodynamic monitoring, cardiac catheterisation and expertise in endomyocardial biopsy. • In patients with hemodynamic instability a mechanical cardio-pulmonary assist device may be needed as a bridge to recovery or to heart transplantation. • Heart transplant should be deferred in the acute phase, because recovery may occur, but can be considered for hemodynamically unstable myocarditis patients, including those with giant cell myocarditis, if optimal pharmacological support and mechanical assistance cannot stabilise the patient • ICD implantation for complex arrhythmias should be deferred until resolution of the acute episode, with possible use of a lifevest during the recovery period.
Reference: Caforio ALP et al. Eur Heart J. 2013 Jul 3 (18).
8.2
ACUTE PERICARDITIS: Diagnosis
P.117 DIAGNOSIS (≥ 2 of the following):
• Chest pain (pleuritic) varying with position • Pericardial friction rub • Typical ECG changes (PR depression and/or diffuse concave ST-segment elevation) • Echocardiography: new pericardial effusion
Yes
Equivocal or no
Consider cardiac MRI
Myopericarditis if: ↑ Troponin
Echocardiography: ↓ LV-function
Acute pericarditis
Delayed enhancement pericardium
Consider alternative diagnoses
8.2
ACUTE PERICARDITIS: Management
P.118
Acute pericarditis
Other causes • Post cardiac injury syndrome • Post cardiac surgery • Post MI: Dressler syndrome • Uremic • Neoplastic • Collagen vascular diseases (e.g. SLE) • Bacterial • Tuberculous
High-risk features? • Fever >38°C • Subacute onset • Anticoagulated • Trauma • Immunocompromised • Hypotension • Jugular venous distension • Large effusion
Yes
Stable
Ibuprofen + colchicine Further testing for underlying etiology
Most frequent cause: Viral pericarditis
No
Outpatient treatment
Aspirin 800 mg or Ibuprofen 600 mg BID - 2 weeks
Hospital admission
Tamponade? Pericardiocentesis
If persisting or recurrent chest pain : Add colchicine 0.5 mg once (<70 kg) or 0.5 mg BID (≥70 kg) for 3 months Avoid corticosteroids!
CARDIAC TAMPONADE: Diagnosis and management Physical examination • Distended neck veins • Shock • Pulsus paradoxus • Muffled heart sounds ECG • Sinus tachycardia • Microvoltage QRS • Electrical alternans
Tamponade ? Echocardiography with respirometer
• Presence of a moderate to large pericardial effusion • Diastolic collapses of right atrium and right ventricle • Ventricular interdependence • Increased tricuspid and pulmonary flow velocities (>50%) with decreased mitral and aortic flow velocities (>25%) during inspiration (predictive value >90%)
Percutaneous pericardiocentesis & drainage Consider surgical drainage Avoid PEEP ventilation
Tamponade
Not performed in routine Cardiac catheterization Early • Right atrial pressure ↑ • Loss of X-descent Late • Aortic pressure ↓ • Pulsus paradoxus • Intracardiac diastolic pressure equilibration
8.2 P.119
9
CHAPTER 9
DRUGS IN ACUTE CARDIOVASCULAR CARE Ana de Lorenzo
9
Oral antiplatelets
P.122 Drug n i r i p s A
r o l e r g a c i T l e r g u s a r P
Indications
Dose
Primary (not universally approved) and secondary cardiovascular disease prevention
LD (if ACS): 150-300 mg oral MD: 75-100 mg oral QD
ACS (all patients at moderate-to-high risk of ischaemic events, e.g. elevated cardiac troponins)
LD: 180 mg oral MD: 90 mg oral BID
Secondary prevention 1-3 years post-MI
MD: 60 mg oral BID
ACS with planned PCI
LD: 60 mg oral MD: 10 mg oral QD
Dose adjustments -
-
Comments Major contraindications: GI bleeding-active peptic ulcer
Major contraindications: previous intracerebral hemorrhage, severe hepatic impairment, strong CYP3A4 inhibitors
MD: 5 mg QD weight <60kg
Contraindication: previous stroke/TIA Prasugrel is generally not recommended in elderly, and if positive benefit/risk 5 mg is recommended
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Oral antiplatelets (Cont.)
P.123 Drug
l e r g o d i p o l C
Indications
Dose
Dose adjustments
ACS + PCI or medical management (patients who cannot receive ticagrelor or prasugrel) and in ACS patients at high bleeding risk (e.g. patients who require oral anticoagulation)
LD: 300-600 mg oral MD: 75 mg oral QD
STEMI + fibrinolysis <75 years
LD: 300 mg oral MD: 75 mg oral QD
-
STEMI + fibrinolysis ≥75 years
LD: 75 mg oral MD: 75 mg oral QD
-
Secondary prevention >12 months post coronary stenting
MD: 75 mg oral QD
Comments Prasugrel and ticagrelor have not been studied as adjuncts to fibrinolysis and oral anticoagulants
-
Prasugrel and ticagrelor have not been studied as adjuncts to fibrinolysis and oral anticoagulants
-
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Intravenous antiplatelets
P.124 Drug
b a m i x i c b A
Indications Adjunct to PCI for bailout situations or thrombotic complications
Dose adjustments
LD: 0.25 mg/Kg i.v. MD: 0.125 μg/Kg/ min i.v. (max: 10 μg/ min) for 12h -
ACS treated medically or with PCI e d i t a b i f i t p E
Dose
LD: 180 μg/Kg i.v. (at a 10 min interval) If STEMI and PCI: add a second 180 mcg/kg i.v. bolus at 10 min MD: 2 μg/Kg/min i.v. infusion
Reduce infusion dose to 1 μg/kg/ min if CrCl 30-50 ml/min
Comments Contraindications: Active internal bleeding - History of CVA within 2 years - Bleeding diathesis - Preexisting thrombocytopenia - Recent (within 2 months) intracranial or intraspinal surgery or trauma - Recent (within 2 months) major surgery - Intracranial neoplasm, arteriovenous malformation, or aneurysm - Severe uncontrolled hypertension - Presumed or documented history of vasculitis - Severe hepatic failure or severe renal failure requiring haemodialysis - Hypertensive retinopathy Contraindications: Bleeding diathesis or bleeding within the previous 30 days - Severe uncontrolled hypertension - Major surgery within the preceding 6 weeks - Stroke within 30 days or any history of hemorrhagic stroke Coadministration of another parenteral GP II b/III a inhibitor - Severe renal impairment or dependency on renal dialysis - History of intracranial disease - Clinically significant hepatic impairment - Thrombocytopenia Prothrombine time >1.2 times control or INR ≥2
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Intravenous antiplatelets (Cont.)
P.125 Drug
n a b i f o r i T
r o l e r g n a C
Indications ACS treated medically or with PCI
All patients undergoing PCI (elective + ACS) immediate onset + rapid offset (platelet recovery in 60min)
Dose LD: 25 μg/Kg i.v. over 5 min MD: 0.15 μg/Kg/ min i.v. Infusion to 18 hours IV Bolus of 30 μg/Kg + IV infusion of 4 μg/kg/min for at least 2 hours from start of PCI
Dose adjustments CrCl <30 ml/min: decrease 50% bolus and infusion dose
Comments Contraindications: A history of thrombocytopenia following prior exposure Active internal bleeding or a history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month Major contraindications:
-
Significant active bleeding or stroke Transition to oral P2Y12 inhibitors variable according to type of agent
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Oral anticoagulants and antagonists
P.126 Drug
Indications
l Treatment and o r prophylaxis a n i of thrombosis r m u a f r o a c o W n e c A
n a b a x i p A
Dose
Dose adjustments
INR goal of 2-3 (INR: 2.5-3.5 for mechanical mitral valve prostheses or double valve replacement)
Assessing individual risks for thromboembolism and bleeding
Prevention of stroke and systemic embolism in NVAF
5 mg oral BID
2.5 mg oral BID 1) when at least 2 of the following characteristics: age ≥80, Cr >1.5 mg/dl or weight <60Kg 2) when CrCl 15-29 ml/min
Treatment of DVT and PE
10 mg oral BID for the first 7 days followed by 5 mg oral BID
Prevention of recurrent DVT and PE
Comments
-
-
Contraindicated if CrCl <15 ml/min or severe hepatic impairment
2.5 mg oral BID -
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Oral anticoagulants and antagonists (Cont.)
P.127 Drug
Indications Prevention of stroke and systemic embolism in NVAF
n a r t a g i b a D
n a b a x o d E
Dose
Dose adjustments
Comments
150 mg oral BID
110 mg BID (if age ≥80, increased bleeding risk or concomitant use of verapamil)
Contraindicated if CrCl <30 ml/min or severe hepatic impairment Active clinically significant bleeding Concomitant treatment with systemic ketoconazole, cyclosporine, itraconazole and dronedarone
Prevention of stroke and systemic embolism in NVAF
60 mg oral QD
Treatment of DVT and PE and prevention of recurrent DVT and PE
60 mg oral QD
30 mg oral QD 1) when CrCl 15-50 ml/min 2) weight <60Kg 3) concomitant use of the following P-glycoprotein inhibitors: ciclosporin, dronedarone, erythromycin, or ketoconazole.
Edoxaban can be initiated in patients who may require cardioversion. Treatment should be started at least 2 hours before cardioversion
Treatment of DVT and PE in patients who have been treated with a parenteral anticoagulant for 5-10 days and prevention of recurrent DVT and PE in patients who have been previously treated
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Oral anticoagulants and antagonists (Cont.)
P.128 Drug
n a b a x o r a v i R
Indications
Dose
Dose adjustments
Prevention of stroke and systemic embolism in NVAF
20 mg oral QD
CrCl <50 ml/min: 15 mg QD
Treatment of DVT and PE and prevention of recurrent DVT and PE
15 mg oral BID for the first 3 weeks followed by 20 mg QD
Reduce the maintenance dose to 15 mg QD if bleeding risk outweighs the risk for recurrent DVT and PE (not formally approved)
Prevention of atherothrombotic events
2.5 mg oral BID
-
Comments Contraindicated if CrCl <15 ml/min or hepatic disease associated with coagulopathy and clinically relevant bleeding risk Rivaroxaban can be initiated in patients who may require cardioversion Treatment should be started at least 4 hours before cardioversion
Anticoagulant antagonists b a m u z i c u r a d I
Specific reversal agent for dabigatran
5g i.v. over 5 to 10 min Another 5g dose if prolonged clotting times and: - recurrence of clinically relevant bleeding - if potential re-bleeding would be life-threatening - second emergency surgery/urgent procedure
-
Dabigatran treatment can be reinitiated 24h after administration of idarucizumab, other antithrombotic therapy at any time Relevant coagulation parameters are aPTT, dTT or ECT
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Oral anticoagulants and antagonists (Cont.)
P.129 Drug
Indications
Dose
Dose adjustments
Comments
Anticoagulant antagonists Patients with asymptomatic high INR with or without mild haemorrhage Anticoagulant ) K n i m a t i V ( e n o i d a n e m o t y h P
INR
Reversal for vitamin K antagonists
i.v. Vitamin K
5-9
1-2.5 mg or 2-5 mg for a rapid reversal (additional dose of 1-2 mg if INR remains high after 24h)
0.5-1 mg
>9
2.5-5 mg (up to 10 mg)
1 mg
5-8
1-2 mg
1-2 mg
>8
3-5 mg
1-2 mg
Warfarin
Acenocoumarol
Oral Vitamin K
Severe or life-threatening haemorrhage Anticoagulant Warfarin
Acenocoumarol
Situation
i.v. Vitamin K
Concomitant treatment
Severe haemorrhage
5-10 mg
CCP or FFP
Life-threatening
10 mg
CCP, FFP or rFVIIa
Severe haemorrhage
5 mg
CCP, FFP or rFVIIa
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Parenteral anticoagulants
P.130 Drug
Indications
Dose
Dose adjustments
NSTE-ACS
LD: 4,000 IU i.v. MD: 1,000 IU/h i.v.
STEMI
Primary PCI: 70-100 IU/Kg i.v. when no Target aPTT: 50-70s or 1.5 to GP-IIb/IIIa inhibitor is planned. 50-60 IU/Kg i.v. 2.0 times that of control to be bolus with GP-IIb/IIIa inhibitors - Fibrinolysis/ monitored at 3, 6, 12 and 24h No reperfusion: 60 IU/kg i.v. bolus (max: 4,000 IU) followed by an i.v. infusion of 12 IU/kg (max: 1,000 IU/h) for 24-48h
Treatment of DVT and PE
80 IU/Kg i.v. bolus followed by 18 IU/Kg/h
According to aPTT, thromboembolic and bleeding risk
NSTE-ACS
2.5 mg QD s.c. up to 8 days or hospital discharge
Acute bacterial endocarditis Severe hepatic impairment: caution advised Contraindicated if CrCl <20 ml/min If >100Kg and CrCl 30-50 ml/min: Contraindicated for DVT/PE 10 mg followed by 7.5 mg/24h s.c. treatment if CrCl <30 ml/min CrCl 20-50 ml/min: 1.5 mg QD s.c.
H F U
x STEMI u n i r a p a d Treatment of n o F DVT and PE
Prevention of VTE
Fibrinolysis/No reperfusion: 2.5 mg i.v. bolus followed by 2.5 mg QD s.c. up to 8 days or hospital discharge 5 mg QD s.c. (<50kg); 7.5 mg QD s.c. (50-100kg); 10 mg QD s.c. (>100kg) 2.5 mg QD s.c.
Target aPTT: 50-70s or 1.5 to 2.0 times that of control to be monitored at 3, 6, 12 and 24h
Comments Monitoring for heparin-induced thrombocytopenia (HIT) Dose-independent reaction
-
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Parenteral anticoagulants (Cont.)
P.131 Drug
Indications
Dose
PCI for NSTE-ACS 0.75 mg/kg i.v. bolus followed immediatelly by 1.75 mg/kg/h infusion which may be continued for up to 4h post PCI as clinically warranted and further continued at a reduced infusion dose of 0.25 mg/kg/h for 4-12h as clinically necessary n i d u r i l a v i B
PCI for STEMI
0.75 mg/kg i.v. bolus followed immediatelly by 1.75 mg/kg/h infusion which should be continued for up to 4h after the procedure After cessation of the 1.75 mg/kg/h infusion, a reduced infusion dose of 0.25 mg/kg/h may be continued for 4-12h
PCI for elective cases
0.75 mg/kg i.v. bolus followed immediatelly by 1.75 mg/kg/h infusion which may be continued for up to 4h post PCI as clinically waranted
Dose adjustments Patients undergoing PCI with CrCl 30-50 ml/min should receive a lower infusion rate of 1.4 mg/kg/h No change for the bolus dose
Comments Contraindicated if CrCl <30 ml/min Active bleeding or increased risk of bleeding, severe uncontrolled hypertension, subacute bacterial endocarditis
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Parenteral anticoagulants (Cont.)
P.132 Drug
Indications
Dose
Dose adjustments
Comments
If >75 years: no LD and MD 0.75 mg/Kg BID s.c. CrCl <30 ml/min: no LD and MD 1 mg/Kg QD s.c. If >75 years and CrCl <30 ml/min: no LD and 0.75 mg/Kg QD s.c.
Monitoring for HIT Anti Xa monitoring during treatment with LMWH might be helpful in pregnancy, extreme body weights and renal impairment
NSTE-ACS
30 mg i.v. + 1 mg/kg s.c. BID
STE-ACS
Primary PCI: 0.5 mg/Kg i.v. bolus In patients with CrCl <30 ml/min: Fibrinolysis/No reperfusion: regardless of age, the s.c. doses a) Age <75 years: 30 mg i.v. bolus followed by are given once daily 1 mg/Kg BID s.c. until hospital discharge for a max of 8 days The first two doses should not exceed 100 mg b) Age >75 years: no bolus; 0.75 mg/Kg BID s.c. - The first two doses should not exceed 75 mg
Treatment of DVT and PE
1 mg/Kg s.c. BID or 1.5 mg/Kg s.c. QD
n i r a p a x o n E
Prevention of VTE 40 mg s.c. QD
CrCl <30 ml/min: 1 mg/Kg/24h s.c. CrCl <30 ml/min: 20 mg s.c. QD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Parenteral anticoagulants (Cont.)
P.133 Drug
Indications
n Prevention of VTE i r a p a z Treatment of DVT n i T and PE
Dose 3,500 IU s.c. QD (moderate risk) 4,500 IU s.c. QD (high risk) 175 IU/Kg s.c. QD
Prevention of VTE 2,500 IU s.c. QD (moderate risk) 5,000 IU s.c. QD (high risk)
Dose adjustments -
n Treatment of DVT i r and PE a p e t l a D
200 IU/Kg QD or 100 IU/Kg BID s.c.
Anti Xa monitoring if renal impairment
n Anticoagulant in a b patients with HIT o r t a g r A
Initial i.v. infusion dose: 2 μg/kg/min (not to exceed 10 μg/kg/min) Patients undergoing PCI: 350 μg/kg i.v. followed by 25 μg/kg/min i.v.
Renal and hepatic impairment: caution advised
Comments Monitoring for HIT Anti Xa monitoring during treatment with LMWH might be helpful in pregnancy, extreme body weights and renal impairment Dalteparin: In cancer patients, dose of 200 IU/kg (max: 18,000 IU)/24h for 1 month, followed by 150 IU/ kg/24h for 5 months After this period, vitamin K antag or a LMWH should be continued indefinitely or until the cancer is considered cured Monitored using aPTT goal: 1.5 to 3.0 times the initial baseline value PCI: ACT goal: 300-450s
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Fibrinolytics
P.134 Drug ) K S ( e s a n i k o t p e r t S
Indications STEMI <12 hours
Treatment of PE
STEMI <12 hours ) A P t ( e s a l p e t l A
Treatment of PE
Dose 1.5 million units over 30-60 min i.v. 250,000 IU as a LD over 30min, followed by 100,000 IU/h over 12-24h
15 mg i.v. bolus: 0.75 mg/kg over 30 min (up to 50 mg) then 0.5 mg/kg over 60 min i.v. (up to 35 mg) Total dose of 100 mg: 10 mg i.v. bolus followed by 90 mg i.v. for 2h
Dose adjustments -
-
-
If weight <65 Kg: max dose <1.5 mg/kg
Comments Absolute contraindications to fibrinolytics:
Previous intracranial haemorrhage or stroke of unknown origin at any time Ischaemic stroke in the preceding 6 months Central nervous system damage or neoplasms or atrioventricular malformation Recent major trauma/surgery/head injury (within the preceding 3 weeks) Gastrointestinal bleeding within the past month Known bleeding disorder (excluding menses) Aortic dissection Non-compressible punctures in the past 24h (e.g. liver biopsy, lumbar puncture)
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Fibrinolytics (Cont.)
P.135 Drug
Indications STEMI <12 hours
e s ) a A l p P e t t r e ( R
STEMI <12 hours
e ) s a A l p P e t t c K e N n T e ( T
Dose 10 units + 10 units i.v. bolus given 30 min apart
Dose adjustments Renal and hepatic impairment: caution advised
Single i.v. bolus over 10 seconds: 30 mg if <60kg 35 mg if 60 to <70kg 40 mg if 70 to <80kg 45 mg if 80 to <90kg 50 mg if ≥90kg
-
Comments Absolute contraindications to fibrinolytics:
Previous intracranial haemorrhage or stroke of unknown origin at any time Ischaemic stroke in the preceding 6 months Central nervous system damage or neoplasms or atrioventricular malformation Recent major trauma/surgery/head injury (within the preceding 3 weeks) Gastrointestinal bleeding within the past month Known bleeding disorder (excluding menses) Aortic dissection Non-compressible punctures in the past 24h (e.g. liver biopsy, lumbar puncture)
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Antiischemic drugs
P.136 Drug
Indications
Dose
Dose adjustments
Comments
Beta-blockers: Preferred over calcium channel blockers - Contraindicated if coronary spasm, severe bradycardia, AV block, severe bronchospasm
NSTE-ACS
LD: 25-100 mg oral MD: 25-100 mg QD
STEMI
l o l i d e v r a C l o l o r p o s i B
l o l o n e t A
Only if normal LVEF
25-100 mg QD, titrate as tolerated up to 100 mg QD only if no LVSD or CHF
Elderly: start at a lower dose CrCl 15-35 ml/min: max dose 50 mg/day; CrCl <15 ml/min: max dose 25 mg/day
NSTE-ACS
LD: 3.125-25 mg oral MD: 3.125-25 mg BID
Caution in elderly and hepatic impairment
Preferred if LVSD/HF
STEMI
3.125-6.25 mg BID, titrated as tolerated up to 50 mg BID
NSTE-ACS
LD: 1.25-10 mg oral MD: 1.25-10 mg QD
Caution in renal or hepatic impairment
Preferred if LVSD/HF
STEMI
1.25-5 mg QD, titrate as tolerated up to 10 mg QD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Antiischemic drugs (Cont.)
P.137 Drug
Indications
Dose
Dose adjustments
Comments
Beta-blockers: Preferred over calcium channel blockers - Contraindicated if coronary spasm, severe bradycardia, AV block, severe bronchospasm l o l o r p o t e M
NSTE-ACS
LD: 25-100 mg oral MD: 25-100 mg BID
STEMI
5-25 mg BID, titrate as tolerated up to 200 mg QD
Caution in hepatic impairment
Preferred if LVSD/HF
Calcium antagonists: Consider if beta-blockers are contraindicated. First option in vasospastic angina l i m a p a r e V
ACS
LD: 80-120 mg oral MD: 80-240 mg TID-QD
Caution in elderly, renal or hepatic impairment
Contraindicated if bradycardia, HF, LVSD
m e z a i t l i D
ACS
LD: 60-120 mg oral MD: 60-300 mg TID-QD
Caution in elderly and hepatic impairment
Contraindicated if bradycardia, HF, LVSD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Antiischemic drugs (Cont.)
P.138 Drug
Indications
Dose
Dose adjustments
Comments
Calcium antagonists: Consider if beta-blockers are contraindicated. First option in vasospastic angina e n i p i d o l m A
ACS
LD: 5-10 mg oral, MD: 5-10 mg QD
ACS
If intolerant or unresponsive to nitroglycerin s.l. 5 μg/min - Increase by 5 mcg/min q 3-5 min up to 20 μg/min If 20 mcg/min is inadequate, increase by 10 to 20 μg/min every 3 to 5 min Max dose: 400 μg/min 1-2 puff s.l. every 5 min as needed, up to 3 puffs in 15 min
Caution in hepatic impairment
Contraindicated if hypotension
Nitrates
. v . i n i r e c y l g o r t i N
y a r p s
Angina
l a t Angina u e g l n b i l a b t u s
0.3 to 0.6 mg s.l. or in the buccal pouch every 5 min as needed, up to 3 doses in 15 min
-
-
-
Contraindicated if severe hypotension and coadministration with phosphodiesterase inhibitors The most common adverse effects are headache and dizziness i.v. nitroglycerin requires NON-PVC containers
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Antiischemic drugs (Cont.)
P.139 Drug
Indications
e t a r t i n o n o m e d i b r o s o s I
Angina
e e d i t a b r r t o i s i n o d s I
Angina
l n i r a e m c r h c y e t l d g s a o n p r t i a r t N
Angina
Dose
Dose adjustments
Comments
5-10 mg BID with the two doses given 7h apart (8am and 3pm) to decrease tolerance development - then titrate to 10 mg BID in first 2-3 days Extended release tablet: Initial: 3060 mg given in the morning as a single dose Titrate upward as needed, giving at least 3 days between increases Max daily single dose: 240 mg
-
Contraindicated if severe hypotension and coadministration with phosphodiesterase inhibitors The most common adverse effects are headache and dizziness
Initial dose: 5 to 20 mg orally 2 or 3 times/day MD: 10 to 40 mg orally 2 or 3 times a day Extended release: 40 to 160 mg/day orally
-
0.2 to 0.4 mg/h patch applied topically once a day for 12 to 14h per day; titrate as needed and tolerated up to 0.8 mg/h
-
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Antiischemic drugs (Cont.)
P.140 Drug
Indications
Dose
Dose adjustments
Comments
Other antiishemic drugs e n i d a r b a v I
Stable angina
5-7.5 mg oral BID
Stable angina
Initial dose: 375 mg oral BID Use with caution in renal and hepatic After 2-4 weeks, the dose should be impairment, CHF, elderly, low weight titrated to 500 mg BID and, according to the patient’s response, further titrated to a recommended max dose of 750 mg BID
Contraindicated if CrCl <30 ml/ min, concomitant administration of potent CYP3A4 inhibitors, moderate or severe hepatic impairment
Stable angina
Modified-release: 35 mg oral BID
Contraindicated in parkinson disease, parkinsonian symptoms, tremors, restlessleg syndrome, movement disorders, severe renal impairment
e n i z a l o n a R
e n i d i z a t e m i r T
Caution in elderly and CrCl <15 ml/min
Caution in elderly and 30
Contraindicated if severe hepatic impairment
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Lipid lowering drugs
P.141 Drug
Indications
Dose
Dose adjustments
Comments
Statins: Primary or secondary prevention of cardiovascular disease For secondary prevention, start with high doses initiated early after admission and downtitrate if side effects. Target LDL-C levels <70 mg/dl
-
Atorvastatin LDL-C reduction
Rosuvastatin Pitavastatin Simvastatin Fluvastatin Pravastatin Lovastatin
<30%
30-40%
40-50%
>50%
Simva 10 mg
Simva 20-40 mg
Simva/ezet 20/10 mg
Simva/ezet 40/10 mg
Lova 20 mg
Ator 10 mg
Ator 20-40 mg
Ator 40-80 mg
Prava 10-40 mg
Rosu 5 mg
Rosu 10 mg
Rosu 20-40 mg
Pita 1 mg
Pita 2 mg
Pita 4 mg
Fluva 20-40 mg
Fluva 80 mg
CrCl <30 ml/min: start 5 mg QD, max: 10 mg QD CrCl 30-59 ml/min: start 1 mg QD, max 2 mg/day; CrCl 10-29 ml/min: not defined Severe renal impairment: start 5 mg QPM Caution in severe renal impairment
Contraindicated in patients with active liver disease or with unexplained elevation of liver function enzyme levels
Significant renal impairment: start 10 mg QD CrCl <30 ml/min: caution if dose >20 mg QD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Lipid lowering drugs (Cont.)
P.142 Drug
Indications
Dose
Dose adjustments
Comments
Others Ezetimibe
Hypercholesterolaemia
10 mg oral QD
Avoid use if moderate-severe hepatic impairment
Hyperlipidemia
48-160 mg oral QD May adjust dose q 4-8 weeks
CrCl 50-90 ml/min: start 48-54 mg QD
Hyperlipidemia
900-1,200 mg/day oral
Fenofibrate
Gemfibrozil
-
Contraindicated if CrCl <50 ml/min or hepatic impairment
Contraindicated if severe renal impairment or hepatic dysfunction Statins may increase muscle toxicity: avoid concomitant use
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Lipid lowering drugs (Cont.)
P.143 Drug
Indications
Dose
Dose adjustments
Comments
PCSK9 Inhibitors Hypercholesterolaemia and mixed dyslipidaemia
Evolocumab
Homozygous familial hypercholesterolaemia
Hypercholesterolaemia and mixed dyslipidaemia
Alirocumab
140 mg s.c. every 2 weeks or 420 mg every month Homozygous familial hypercholesterolaemia: 420 mg s.c every month Up-titrate to 420 mg every 2 weeks if a response is not achieved Start dose: 75 mg s.c. every 2 weeks
-
If a larger LDL-C reduction (>60%) is required, the start dose could be 150 mg every 2 weeks, or 300 mg every 4 weeks The dose can be individualised based on LDL-C level, goal of therapy, and response. Max dose: 150 mg once every 2 weeks
Most common side effects: Nasopharingitis, upper respiratory tract infection, headache and back pain
Most common side effects: Upper respiratory tract signs and symptoms, pruritus and injection site reactions
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Heart failure & hypertension
P.144 Drug
Indications
Dose
Dose adjustments
Comments
ACEI l i r p o t p a C
l i r p a l a n E l i r p o n i s i L
HF
Start: 6.25 mg oral TID Target dose: 50 mg TID
HTN
Start: 12.5 mg oral BID Target dose: 25-50 mg TID Max 450 mg/day
CrCl >50 ml/min: 75-100% of the normal dose CrCl 10-50 ml/min: 25-50% CrCl <10 ml/min: 12.5%
HF, HTN
Start: 2.5 mg oral BID Target dose: 10-20 mg BID
CrCl 30-80 ml/min: start 5 mg/day CrCl 10-30 ml/min: start 2.5 mg/day
HF
Start: 2.5-5.0 mg oral QD Target dose: 20-35 mg QD
CrCl 31-80 ml/min: start 5-10 mg/day CrCl 10-30 ml/min: start 2.5-5 mg/day CrCl <10 ml/min: start 2.5 mg/day
HTN
10-20 mg oral QD Max: 80 mg QD
Check renal function, electrolytes, drug interactions Major contraindications: History of angioedema, known bilateral renal artery stenosis, pregnancy (risk)
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Heart failure & hypertension (Cont.)
P.145 Drug
Indications
Dose
Dose adjustments
l i r p o d n i r e P
HF
Start: 2 mg oral QD Target dose: 8 mg QD
HTN
Start: 4 mg QD Max dose: 8 mg QD
l i r p i m a R
HF, HTN
Start: 2.5 mg oral QD Target dose: 5 mg BID
CrCl <40 ml/min: start 1.25 mg QD, max 5 mg/day Caution in elderly and hepatic impairment
HF
Start: 0.5 mg oral QD Target dose: 4 mg QD
CrCl <30 ml/min or severe hepatic impairment: start 0.5 mg
HTN
2-4 mg oral QD
CrCl <30 ml/min or severe hepatic impairment: start 0.5 mg
l i r p a l o d n a r T
CrCl >60 ml/min: start 4 mg/day CrCl 31-60 ml/min: start 2 mg/day CrCl 15-30 ml/min: start 2 mg every other day CrCl <15ml/min: 2 mg on the day of dialysis
Comments Check renal function, electrolytes, drug interactions Major contraindications: History of angioedema, known bilateral renal artery stenosis, pregnancy (risk)
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Heart failure & hypertension (Cont.)
P.146 Drug
Indications
Dose
Dose adjustments
Comments
ARB n a t r a s e d n a C
n a t r a s o L
n a t r a s l a V
HF, HTN
Start: 4-8 mg oral QD Target dose: 32 mg QD
If renal or hepatic impairment: start 4 mg/day
HF
Start: 50 mg oral QD Target dose: 150 mg QD
CrCl <20 ml/min: 25 mg QD Caution if hepatic impairment
HTN
50-100 mg oral QD
CrCl <20 ml/min: 25 mg QD Caution if hepatic impairment
HF
Start: 40 mg oral BID Target dose: 160 mg BID
If mild-moderate hepatic impairment: max dose 80 mg/day
HTN
80-160 mg QD
If mild-moderate hepatic impairment: max dose 80 mg/day
If ACEI is not tolerated Check renal function, electrolytes, drug interactions Major contraindications: History of angioedema, known bilateral renal artery stenosis, pregnancy (risk)
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Heart failure & hypertension (Cont.)
P.147 Drug
Indications
Dose
Dose adjustments
Comments
Neprilysin inhibitor/ARB
n a t r a s l a V / l i r t i b u c a S
Symptomatic chronic HF with reduced ejection fraction
Start: 49 mg/51 mg oral BID Target dose: 97 mg/103 mg BID
Do not initiate if K >5.4 mmol/l or SBP <100 mmHg Start dose of 24 mg/26 mg BID if SBP 100-110 mmHg or CrCl 30-60 ml/min
Do not co-administer with an ACEI or ARB. It must not be started for at least 36 hours after discontinuing an ACEI Contraindicated if history of angioedema related to ACEI or ARB Hereditary or idiopathic angioedema Concomitant use with aliskiren if diabetes mellitus or renal impairment Severe hepatic impairment, biliary cirrhosis and cholestasis
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Heart failure & hypertension (Cont.)
P.148 Drug
Indications
Dose
Dose adjustments
Comments
Beta-blockers: Check 12 - lead ECG l o l o n e t A
) 1 ( e v i t c e l e s o i d r a C
l o l o r p o s i B
l o l o r p o t e M
HTN
Start: 25 mg oral QD Usual dose: 50-100 mg QD
CrCl 10-50 ml/min: decrease dose 50% CrCl <10 ml/min: decrease dose 75%
HF
Start: 1.25 mg oral QD Target dose: 10 mg QD
HTN
Start: 2.5-5 mg oral QD Usual dose: 5-10 mg QD Max dose: 20 mg QD
CrCl <20 ml/min: max dose 10 mg QD Hepatic impairment: avoid use
HF
Start: 12.5-25 mg oral QD Target dose: 200 mg QD
HTN
100-400 mg QD Max dose: 400 mg QD
Major contraindications: asthma, 2nd or 3rd degree AV block
Hepatic impairment: start with low doses and titrate gradually
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Heart failure & hypertension (Cont.)
P.149 Drug
Indications
Dose
Dose adjustments
Comments
Beta-blockers: Check 12- lead ECG ) 2 ( e v i t c e l e s o i d r a C
e v i t c e l e s o i d r a c n o N
l o l o v i b e N
l o l i d e v r a C
HF
Start: 1.25 mg oral QD Target dose: 10 mg QD
HTN
Start: 2.5 mg oral QD Usual dose: 5 mg QD
HF
Start: 3.125 mg oral BID Target dose: 25-50 mg BID
HTN
Start: 12.5 mg oral QD Usual dose: 25 mg QD and max dose: 25 mg BID or 50 mg QD
Renal impairment or elderly: start dose 2.5 mg QD, titrate to 5 mg QD Hepatic impairment: contraindicated
Major contraindications: asthma, 2nd or 3rd degree AV block
Caution in elderly Contraindicated if hepatic impairment
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Heart failure & hypertension (Cont.)
P.150 Drug
Indications
Dose
Dose adjustments
Comments
Other vasodilators
HTN
Start: 5 mg oral QD, increase after 1-2 weeks Max: 10 mg/day
Elderly or secondary agent: start 2.5 mg QD Hepatic impairment: start 2.5 mg QD
e n i p i d e f i N
HTN
Extended-release form:
Renal and hepatic impairment: caution advised
l i m a p a r e V
HTN
e n i p i d o l m A
Start 20 mg oral BID or TID Max: 60 mg BID
Immediate-release form:
Dose: 80-120 mg oral TID; Start: 80 mg TID; Max: 480 mg/day
Start 40 mg oral TID in elderly or small stature patients
Contraindicated if cardiogenic shock, 2nd or 3rd degree AV block, severe hypotension
Contraindicated if bradycardia, HF, LVSD
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Heart failure & hypertension (Cont.)
P.151 Drug
Indications
Dose
Dose adjustments
Comments
Loop diuretics e d i m e s o r u F e d i m e s r o T
HF
20-40 mg i.v. bolus, continuous 100 mg/6h (adjust based on kidney function and clinical findings; monitor creatinine)
HTN
10-40 mg oral BID
HF
10-20 mg oral or i.v. QD
HTN
5 mg oral or i.v. QD Max 10 mg QD
Anuria: contraindicated Cirrhosis/ascites: caution advised -
Hepatic impairment: initial dose should be reduced by 50% and dosage adjustments made cautiously
-
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Heart failure & hypertension (Cont.)
P.152 Drug
Indications
Dose
Dose adjustments
Comments
Thiazides e n o d i l a h t r o l h C e d i z a i h t o r o l h c o r d y H e d i m a p a d n I
HF
50-100 mg oral QD MD: 25-50 mg QD
Elderly: max dose 25 mg/day CrCl <25 ml/min: avoid use
-
HTN
Start 12.5-25 mg oral QD; Max: 50 mg/day
Elderly: max dose 25 mg/day CrCl <25 ml/min: avoid use
-
HF
25-200 mg oral/day
CrCl <25 ml/min: avoid use Hepatic impairment: caution advised
-
HTN
HTN
Start 12.5-25 mg oral QD MD: may increase to 50 mg oral as a single or 2 divided doses
CrCl <25 ml/min: avoid use Hepatic impairment: caution advised
Start 1.25 mg PO QAM x4weeks, then increase dose if no response Max: 5 mg/day
CrCl <25 ml/min: avoid use Hepatic impairment: caution advised
-
-
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Heart failure & hypertension (Cont.)
P.153 Drug
Indications
Dose
Dose adjustments
Comments
Aldosterone-antagonists e n o t c a l o n o r i p S
HF
Start 25 mg oral QD Target dose: 25-50 mg QD
HTN
e n o n e r e l p E
50-100 mg/day oral
CrCl <10 ml/min, anuria or acute renal impairment: contraindicated Severe hepatic impairment and elderly: caution advised
Check renal function, electrolytes, drug interactions Produces gynecomastia
HF
Start 25 mg oral QD Target dose: 50 mg QD
Elderly: caution advised CrCl <50 ml/min: contraindicated
HTN
50 mg oral QD-BID Max: 100 mg/day
Check renal function, electrolytes, drug interactions Major contraindications: strong CYP3A4 inhibitors
HF
5-7.5 mg oral BID
Caution in elderly and CrCl <15ml/min
Contraindicated if severe hepatic impairment
Others e n i d a r b a v I
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Inotropics & vasopressors
P.154 Drug n a d n e m i s o v e L
t c e f f e
e n o n i r l i M
Indications
Dose
Dose adjustments
Comments
HF/cardiogenic shock
LD: 6 to 12 μg/kg i.v. over 10 min (given only if immediate effect is needed) followed by 0.05 to 0.2 μg/kg/min as a continuous infusion for 24h
Avoid use if CrCl <30 ml/min or severe hepatic impairment
Calcium sensitizer and ATP-dependent potassium channel opener
HF/cardiogenic shock
50 μg/kg i.v. in 10-20 min, continuous 0.3750.75 μg/kg/min
Renal: Same bolus. Adjust infusion: CrCl 50 ml/min: start 0.43 μg/kg/min CrCl 40 ml/min: start 0.38 μg/kg/min CrCl 30 ml/min: start 0.33 μg/kg/min CrCl 20 ml/min: start 0.28 μg/kg/min CrCl 10 ml/min: start 0.23 μg/kg/min CrCl 5 ml/min: start 0.20 μg/kg/min
Phosphodiesterase inhibitor Caution if atrial flutter Hypotensive drug
Cardiogenic
0.5-5 μg/min (0.25-2.5ml of a 1:250,000 dilution) i.v. infusion
ß
/ l shock e o n n i l e a r e n t e r o r Bradyarrhythmias p p o o s I s I
Bolus: 20-40 μg i.v. Infusion: 0.5 μg/min of 2 mg/100 ml normal saline
-
ß1, ß2 agonist Contraindicated in patients with tachyarrhythmia, tachycardia or heart block caused by digitalis intoxication, ventricular arrhythmias which require inotropic therapy, angina pectoris, recent ACS, hyperthyroidism
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Inotropics & vasopressors (Cont.)
P.155 Drug e n i m a t u b o D e n i m a p o D
t c e f f e
e n i l a n e r d a r o N
Indications Cardiogenic shock
Cardiogenic shock
Cardiogenic shock
Dose
Dose adjustments
2-20 μg/kg/min i.v.
Dopaminergic effect: 2-5 μg/Kg/min i.v. ß effect : 5-15 μg/Kg/min i.v. a effect : 15-40 μg/Kg/min i.v.
Comments
-
ß1, a1/ß2 agonist Increases contractility with little effect on heart rate and blood pressure. Reduces pulmonary and systemic VR, PCP
-
ß, a, dopaminergic agonist Increases BP, PAP, heart rate, cardiac output and pulmonary and systemic VR More arrhythmogenic than dobutamine and noradrenaline
0.05-0.2 μg/kg/min i.v. titrate to effect
1, ß1 agonist Increases BP and PAP Little arrhythmogenic a
-
a
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Antiarrhythmics
P.156 Drug
Indications
Dose
Dose adjustments
Comments
AF
15-18 mg/kg i.v. over 60min, followed by infusion of 1-4 mg/min
Reduce LD to 12 mg/kg in severe renal impairment Reduce MD by one-third in moderate renal impairment and by two-thirds in severe renal impairment Caution in elderly and asthma
Hypotension (negative inotropic agent) Lupus-like syndrome Contraindicated if myasthenia gravis, AV block, severe renal impairment
Pulseless VT/VF
1-1.5 mg/kg i.v./i.o. bolus (can give additional 0.5-0.75 mg/kg i.v./i.o. push every 5-10 min if persistent VT/VF, max cumulative dose = 3 mg/kg), followed by infusion of 1-4 mg/min
1-2 mg/min infusion if liver disease or HF
Contraindicated if advanced AV block, bradycardia, hypersensitivity to local anesthetics Caution in HF, renal impairment and elderly May cause seizures, psychosis Stop if QRS widens >50%
Group I e d (termination); i m a . stable VT v n i . (with a pulse) i a c o r P
e n i . a v c i . o Stable VT d i L (with a pulse)
1-1.5 mg/kg i.v. bolus (can give additional 0.5-0.75 mg/kg i.v. push every 5-10 min if persistent VT, max cumulative dose = 3 mg/kg), followed by infusion of 1-4 mg/min
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Antiarrhythmics (Cont.)
P.157 Drug
Indications
Dose
Dose adjustments
Comments
Group I
e d i n . i v . a i c e l F
e n o n . e v f . a i p o r P
SVT, ventricular arrhythmias
2 mg/kg (max 150 mg) i.v. over 30 min This may be followed by an infusion at a rate of 1.5 mg/kg/h for 1 h, reduced to 0.1-0.25 mg/kg/h for up to 24h, max cumulative dose = 600 mg
Severe renal impairment: caution advised
Contraindicated if cardiogenic shock, recent MI, 2nd or 3rd degree AV block
PSVT, ventricular arrhythmias
LD: 0.5-2 mg/kg i.v. direct over aminimum of 3-5min MD: 0.5-2.5 mg/kg i.v. direct q8h (max 560 mg/day) or continuous infusion up to 23 mg/h
May need to reduce dose in renal or hepatic failure
Contraindicated if unstable HF, cardiogenic shock, AV block, bradycardia, myasthenia gravis severe hypotension, bronchospastic disorders, Brugada syndrome
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Antiarrhythmics (Cont.)
P.158 Drug
Indications
Dose
Dose adjustments
Comments
Group II Arrhythmias l o l . o v n i . e t A
2.5 mg i.v. over 2.5 min every 5 min (max 10 mg)
Caution in elderly and/or severe renal impairment
Contraindicated if cardiogenic shock, bradycardia and greater than first-degree block, unstable HF
Arrhythmias l o l o r . p v . o i t e M
2.5-5 mg i.v. over 5min, may repeat every 5 min (max 15 mg)
Caution if severe hepatic impairment
Contraindicated if cardiogenic shock, bradycardia and greater than first-degree block, unstable HF
Arrhythmias l o l o n . a v . r i p o r P
Initially given as slow i.v. boluses of 1 mg, repeated at 2 min intervals (max: 10 mg in conscious patients and 5 mg if under anesthesia)
-
Contraindicated if cardiogenic shock, bradycardia and greater than first-degree block, asthma, unstable HF
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Antiarrhythmics (Cont.)
P.159 Drug
Indications
Dose
Dose adjustments
Comments
Group III AF (termination) e n Stable VT o r . a v (with a pulse) . d i o i m A Pulseless VT/VF
e n o r a d e n o r D
Paroxysmal or persistent AF prevention
5 mg/Kg i.v. over 30min, followed by infusion of 1 mg/min for 6h, then 0.5 mg/min
-
150 mg i.v. over 10 min followed by infusion of 1 mg/min for 6h, then 0.5 mg/min
-
300 mg bolus i.v. (can give additional 150 mg i.v. bolus if VF/VT persists) followed by infusion of 900 mg over 24h
-
Reduce infusion rate if bradycardia, AV block, hypotension Bolus should be avoided if hypotension or severe LV dysfunction Highly vesicant agent
400 mg oral BID -
Contraindicated if severe renal or liver dysfunction, LVSD, symptomatic HF, permanent AF, bradycardia… (multiple contraindications)
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Antiarrhythmics (Cont.)
P.160 Drug
Indications
Dose
Dose adjustments
Comments
Group IV PSVT; AF (rate control) m e . z v a i . i t l i D
0.25 mg/kg i.v. over 2 min (may repeat with 0.35 mg/kg i.v. over 2 min), followed by infusion of 5-15 mg/h
PSVT; AF (rate control)
2.5-5 mg i.v. over 2 min (may repeat up to max cumulative dose of 20 mg); can follow with infusion of 2.5-10 mg/h
l i m a . v p i . a r e V
e n i s . o v . n i e d A
Rapid conversion to a normal sinus rhythm of PSVT including those associated with accessory bypass tracts (WPW syndrome)
Hepatic impairment: caution advised
-
-
Contraindicated if AF+WPW, tachycardias QRS (except RVOT-VT), fascicular VT, bronchospasm, age >70 years Antidote: - LVD: Calcium gluconate, dobutamine - Bradycardia/AV block: Atropine, Isoproterenol
-
Contraindicated if sick sinus syndrome, second or third degree Atrio-Ventricular (AV) block (except in patients with a functioning artificial pacemaker), chronic obstructive lung disease with evidence of bronchospasm (e.g. asthma bronchiale), long QT syndrome, severe hypotension; decompensated states of heart failure - Adenosine can cause AF
Rapid i.v. boluses separated by 2 min: 6 mg → 6 mg → 12 mg
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Antiarrhythmics (Cont.)
P.161 Drug
Indications
Dose
Dose adjustments
Comments
Others m u e i s t a e f n l g u a s M
t n a l a k a n r e V
VT-Torsades de Pointes
Bolus: 1-2g i.v./i.o. over 5 min Perfusion: 5-20 mg/min i.v.
Conversion of recent onset AF
3 mg/kg i.v. over 10 min If AF persists, a second 10mininfusion of 2 mg/kg, 15 min later may be administered
Caution if severe renal failure
-
Contraindicated if myasthenia gravis
Contraindicated if ACS within the last 30 days, severe aortic stenosis, SBP <100 mmHg, HF class NYHA III/IV, severe bradycardia, sinus node dysfunction or 2nd or 3rd degree heart block, prolonged QT at baseline, use of i.v. antiarrhythmics (class I and class III) within 4h prior to, as well as in the first 4h after, vernakalant administration
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs
P.162 Drug
Indications
Dose
Dose adjustments
Comments
Benzodiazepines: Use of benzodiazepines may lead to the development of physical and psychic dependence upon these products. The risk of dependence increases with dose and duration of treatment. Benzodiazepines may induce anterograde amnesia. Discontinuation: dosage should be reduced slowly Short-acting benzodiazepines Moderate or m severe anxiety a or anxiety l o z associated with a r p depression l
250-500mcg oral TID as short as possible, increasing if required to a total of 3 mg daily
Elderly or debilitating disease: 250mcg BID or TID and gradually increased if needed and tolerated Renal impairment or mild-moderate hepatic impairment: caution
Contraindicated if myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome, severe hepatic insufficiency
1 mg oral at bedtime. This may be increased to 1.5 mg or 2 mg if necessary
Frail, debilitated or elderly: start with half a tablet. Max dose: 1 mg Chronic pulmonary, insufficiency, cerebrovascular disease and chronic renal or hepatic impairment: caution
Contraindicated if acute pulmonary insufficiency, severe respiratory insufficiency, myasthenia gravis, phobic or obsessional states and sleep apnoea syndrome, monotherapy in depression or anxiety associated with depression and chronic psychosis and alcohol intake
A
Insomnia m a l o z a r p o L
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs
P.163 Drug
Indications
Dose
Dose adjustments
Comments
Short-acting benzodiazepines l a r o m a p e z a r o L
n o i t c e j n i m a p e z a r o L
Severe anxiety Premedication before surgery
Anxiety: 1-4 mg oral in divided doses Insomnia: 1-2 mg oral before retiring Premedication before surgery: 2-3 mg oral the night before operation 2-4 mg oral 1-2h before the procedure
Pre-operative medication, acute anxiety states, acute excitement or acute mania, status epilepticus
Premedication: 0.05 mg/Kg By the i.v. route the injection should be given 30-45 min before surgery By the i.m. route the injection should be given 1-1.5h before surgery Acute anxiety: 0.025-0.03 mg/kg i.v./i.m. Repeat 6 hourly Status epilepticus: 4 mg i.v.
Elderly: may respond to lower doses Renal or hepatic impairment: lower doses may be sufficient
Contraindicated if acute pulmonary insufficiency, respiratory depression, sleep apnoea, obsessional states, severe hepatic insufficiency, myasthenia gravis
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.164 Drug
Indications
Dose
Dose adjustments
Comments
Short-acting benzodiazepines l a r o m a p e z a t e m r o L
Short-term treatment of insomnia
Insomnia l a r o m a l o z a d i M
0.5-1.5 mg oral before retiring. The initial dosage may be increased to 2 mg in individual cases if this proves necessary
Elderly: may respond to lower doses Chronic respiratory insufficiency: a lower dose is recommended Severe renal impairment: caution
Contraindicated if myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome, acute intoxication with alcohol, hypnotics, analgesics or psychotropic drugs, severe liver insufficiency
DOSE / DOSE ADJUSTMENTS: 7.5-15 mg oral at bedtime COMMENTS: Caution in adults >60years, chronically ill or debilitated patients, patients with chronic
respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired cardiac function - Contraindicated if conscious sedation in patients with severe respiratory failure or acute respiratory depression - Severe cardiorespiratory adverse events have been reported (respiratory depression, apnoea, respiratory arrest and/or cardiac arrest). Such life-threatening incidents are more likely to occur when the injection is given too rapidly or when a high dosage is administered
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.165 Drug
Indications
Dose
Dose adjustments
Comments
Short-acting benzodiazepines Short-acting sleep-inducing drug ) 1 ( n o i t c e j n i m a l o z a d i M
DOSE / DOSE ADJUSTMENTS: Indications
Adults <60 y
Conscious sedation
i.v. Initial dose: Titration doses: Total dose:
Anaesthesia premedication
i.v. 1-2 mg repeated i.m. 0.07-0.1 mg/kg
Adults ≥60 y/debilitated or chronically ill
2-2.5 mg i.v Initial dose: 1 mg Titration doses: 3.5-7.5 mg Total dose:
0.5-1 mg 0.5-1 mg <3.5 mg
i.v. Initial dose: 0.5 mg Slow uptitration as needed i.m. 0.025-0.05 mg/kg
COMMENTS: Caution in adults >60years, chronically ill or debilitated patients, patients with chronic
respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired cardiac function - Contraindicated if conscious sedation in patients with severe respiratory failure or acute respiratory depression - Severe cardiorespiratory adverse events have been reported (respiratory depression, apnoea, respiratory arrest and/or cardiac arrest). Such life-threatening incidents are more likely to occur when the injection is given too rapidly or when a high dosage is administered
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.166 Drug
Indications Short-acting sleep-inducing drug
) 2 ( n o i t c e j n i m a l o z a d i M
Dose
Dose adjustments
Comments
DOSE / DOSE ADJUSTMENTS: Indications
Adults <60 y
Adults ≥60 y/debilitated or chronically ill
Anaesthesia induction
i.v. 0.15-0.2 mg/kg (0.3-0.35 without premedication)
i.v. 0.05-0.15 mg/kg (0.15-0.3 without premedication)
Sedative component in combined anaesthesia
i.v. Intermittent doses of 0.03-0.1 mg/kg or continuous infusion of 0.03-0.1 mg/kg/h
i.v. Lower doses than recommended for adults <60 years
Sedation in ICU
i.v. LD: 0.03-0.3 mg/kg in increments of 1-2.5 mg MD: 0.03-0.2 mg/kg/h
COMMENTS: Caution in adults >60years, chronically ill or debilitated patients, patients with chronic
respiratory insufficiency, patients with chronic renal failure, impaired hepatic function or with impaired cardiac function - Contraindicated if conscious sedation in patients with severe respiratory failure or acute respiratory depression - Severe cardiorespiratory adverse events have been reported (respiratory depression, apnoea, respiratory arrest and/or cardiac arrest). Such life-threatening incidents are more likely to occur when the injection is given too rapidly or when a high dosage is administered
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.167 Drug
Indications
Dose
Dose adjustments
Comments
Long-acting benzodiazepines m a p e z a m o r B
Insomnia, short-term treatment of anxiety or panic attacks
Anxiety, adjunctive therapy in m epilepsy
a z a b o l C
1.5-3 mg oral up to TID If a severe condition: 6-12 mg oral BID or TID
Elderly or hepatic impairment: lower doses are recommended
Contraindicated if myasthenia gravis, severe hepatic impairment, severe respiratory insufficiency, sleep apnoea syndrome
Anxiety: 20-30 mg oral daily in divided doses or as a single dose given at night. Doses up to 60 mg daily have been used in severe anxiety Epilepsy: starting dose of 20-30 mg oral per day, increasing up to a max of 60 mg daily
Elderly: lower doses may be used Chronic or acute severe respiratory insufficiency, renal or hepatic impairment: lower doses are recommended
Contraindicated if history of drug or alcohol dependence, myasthenia gravis, severe respiratory insufficiency, sleep apnoea syndrome, severe hepatic impairment
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.168 Drug
Indications
Dose
Dose adjustments
Comments
Long-acting benzodiazepines Epileptic disease and m seizures a
p e z a n o l C
l a r o e t a p e z a r o l C
Anxiety, insomnia
Oral: Initial dose not to exceed 1 mg/day; MD: 4-8 mg i.v.: 1 mg by slow injection or slow infusion. Repeat dose if needed (1-4 mg are usually sufficient)
Elderly: initial dose should not exceed 0.5 mg/day Chronic pulmonary insufficiency, renal or mild-moderate hepatic impairment: may require lower doses
Contraindicated if acute pulmonary insufficiency, severe respiratory insufficiency, sleep apnoea syndrome, myasthenia gravis, severe hepatic insufficiency, coma or in patients known to be abusing pharmaceuticals, drugs or alcohol
5-30 mg oral at bedtime or in divided doses
Elderly, renal and hepatic impairment: lower doses may be required
Contraindicated if myasthenia gravis, severe decompensated respiratory insufficiency, sleep apnoea syndrome, severe hepatic impairment Caution if alcohol deprivation, give thiamine before administering glucose containing i.v. fluids
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.169 Drug
Indications
Dose
Dose adjustments
Comments
Long-acting benzodiazepines e t a n o p i e t z c a e r j n o i l C
e d i x o p e z a i d r o l h C
Agitation, confusion, aggressiveness, premedication, tetanus, alcoholism
Agitation, confusion, aggressiveness: 20-200 mg/day, i.m./i.v. followed by oral therapy Premedication: 20-50 mg/day i.m./i.v. Alcoholism: 50-100 mg every 3-4h Benign tetanus (without tracheostomy) 120-500 mg/day i.v. Malignant tetanus (with tracheostomy and assisted ventilation): 500-2,000 mg/day i.v.
Elderly, renal and hepatic impairment: lower doses may be required
Contraindicated if myasthenia gravis, severe decompensated respiratory insufficiency, sleep apnoea syndrome, severe hepatic impairment Caution if alcohol deprivation, give thiamine before administering glucose containing i.v. fluids
Anxiety, muscle spasm, symptomatic relief of acute alcohol withdrawal
Anxiety: starting dose 5 mg/day oral: usual dose up to 30 mg in divided doses increasing to a max of 100 mg/day, in divided doses, adjusted on an individual basis Insomnia associated with anxiety: 10-30 mg oral at bedtime Muscle spasm: 10-30 mg/day oral in divided doses Alcohol withdrawal: 25-100 mg, repeated if necessary, in 2-4h
Elderly and/or debilitated patients, renal or hepatic impairment: dosage should not exceed half the adult dose
Contraindicated if acute pulmonary insufficiency, sleep apnoea, respiratory depression, phobic and obsessional states, chronic psychosis, severe hepatic impairment, myasthenia gravis
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.170 Drug
Indications
Dose
Dose adjustments
Comments
Long-acting benzodiazepines Anxiety
) 1 ( m a p e Insomnia associated z a with anxiety i D
5-30 mg oral daily in divided doses or 10 mg i.v. or i.m. and repeated after an interval of not less than 4h
Elderly and debilitated patients: half of the recommended dose
0.5 mg/kg rectal Dose can be repeated every 4-12h. Max 30 mg
Hepatic impairment and severe renal impairment: a lower dose is recommended
5-15 mg oral before retiring
Cerebral palsy
5-60 mg oral daily in divided doses
Upper motor neuronic spasticity
5-60 mg oral daily in divided doses
Contraindicated if phobic or obsessional states; chronic psychosis, hyperkinesis, acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency, myasthenia gravis, sleep apnoea, severe hepatic impairment, acute porphyria
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.171 Drug
Indications
Dose
Dose adjustments
Comments
Long-acting benzodiazepines Muscle spasm ) 2 ( m a p e Tetanus z a i D
5-15 mg oral daily in divided doses or 10 mg i.v. or i.m. and repeated after after an interval of not less than 4h 0.5 mg/Kg rectal. Dose can be repeated every 4-12h. Max 30 mg 0.1-0.3 mg/Kg i.v. and repeated every 1-4h; alternatively, a continuous infusion of 3-10 mg/ kg/24h may be used. 0.5 mg/kg rectal. Dose can be repeated every 4-12h. Max 30 mg
Elderly and debilitated patients: half of the recommended dose Hepatic impairment and severe renal impairment: a lower dose is recommended
Contraindicated if phobic or obsessional states; chronic psychosis, hyperkinesis, acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency, myasthenia gravis, sleep apnoea, severe hepatic impairment, acute porphyria
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.172 Drug
Indications
Dose
Dose adjustments
Comments
Long-acting benzodiazepines Epilepsy
) 3 ( m a p e z a Alcohol withdrawal i D
Premedication before surgery
2-60 mg oral daily in divided doses or 10-20 mg i.v.or i.m. The dose can be repeated if necessary after 30-60min. If indicated, this may be followed by slow i.v. infusion (max total dose 3 mg/kg over 24h) or 0.5 mg/kg rectal Dose can be repeated every 4-12h. Max 30 mg 5-20 mg oral, repeated if necessary in 2-4h 0.5 mg/kg rectal Dose can be repeated every 4-12h. Max 30 mg Delirium tremens: 10-20 mg i.v. or i.m.
Elderly and debilitated patients: half of the recommended dose Hepatic impairment and severe renal impairment: a lower dose is recommended
Contraindicated if phobic or obsessional states; chronic psychosis, hyperkinesis, acute pulmonary insufficiency; respiratory depression, acute or chronic severe respiratory insufficiency, myasthenia gravis, sleep apnoea, severe hepatic impairment, acute porphyria
5-20 mg oral
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.173 Drug
Indications
Dose
Dose adjustments
Comments
15 mg oral at bedtime.
Elderly, chronic pulmonary insufficiency, renal or hepatic impairment: lower dose is recommended
Contraindicated if myasthenia gravis, severe pulmonary insufficiency, respiratory depression, phobic or obsessional states, chronic psychosis, sleep apnoea, severe hepatic insufficiency
Elderly, renal impairment, gross liver damage, decreased liver function, sleep apnoea and chronic pulmonary insufficiency: caution
Contraindicated if acute pulmonary insufficiency
Long-acting benzodiazepines Insomnia m a p e z a r u l F
If severe insomnia: 30 mg oral but residual effects on awakening are more frequent at this dose
Other sedatives ) 1 ( e l o z a i h t e m o l C
Management of restlessness and agitation in the elderly
192 mg (1 capsule) oral TID
Severe insomnia in the elderly
192-384 mg oral (1-2 capsules) at bedtime
Alcohol combined with clomethiazole particularly in alcoholics with cirrhosis can lead to fatal respiratory depression even with short term use
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.174 Drug
Indications
Dose
Dose adjustments
Comments
Other sedatives ) 2 ( e l o z a i h t e m o l C
INDICATIONS: Alcohol withdrawal INITIAL DOSE: 2-4 capsules oral, if necessary repeated after some hours
Day 1: first 24h: 9-12 capsules, divided into 3 or 4 doses Day 2: 6-8 capsules, divided into 3 or 4 doses Day 3: 4-6 capsules, divided into 3 or 4 doses
e Sedation of adult ICU n patients i d i m o t e d e m x e D
Days 4-6: A gradual reduction in dosage until the final dose
Elderly, renal impairment, gross liver damage, decreased liver function, sleep apnoea and chronic pulmonary insufficiency: caution
Contraindicated if acute pulmonary insufficiency Alcohol combined with clomethiazole particularly in alcoholics with cirrhosis can lead to fatal respiratory depression even with short term use
Caution if hepatic impairment, impaired peripheral autonomic activity, pre-existing bradycardia Frail patients: a lower starting infusion rate should be considered
The drug provides analgesia and does not cause respiratory depression. Associated with a lower prevalence of ICU delirium compared to benzodiazepines. Primary adverse effects are dose-related bradycardia and hypotension. Dexmedetomidine should not be administered by loading or bolus dose
Administration for more than 9 days is not recommended
Switch to dexmedetomidine: initial i.v. infusion rate of 0.7 mcg/kg/h Titrate upwards to achieve desired level of sedation, range 0.2-1.4 mcg/kg/h Max dose: 1.4 mcg/kg/h Max duration: 14 days
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.175 Drug
Indications
Dose
Dose adjustments
Comments
Other sedatives e n i m a l y x o D
Insomnia
n Insomnia in patients i n ≥55 years o t a l e M l o f o p o r P
Sedation during intensive care
12.5-25 mg oral at bedtime Max duration: 7 days
Renal and hepatic impairment: caution
2 mg oral at bedtime Max duration: 13 weeks
Renal impairment: caution Hepatic impairment: not recommended
Initiate at 5 mcg/Kg/min i.v. (0.3 mcg/Kg/h) and titrate to achieve sedation goals by 5 mcg/Kg/min every 5 min Maintenace rates of 5-50 mcg/Kg/ min may be required Avoid prolonged infusions >50 mcg/Kg/min
Elderly: rate of infusion should be reduced. Rapid bolus administration is not indicated in this group of patients
Contraindicated if hypersensitive to other antihistamines Caution if: asthma, narrow angle glaucoma, prostatic hypertrophy, stenosing peptic ulcer, pyloric/ duodenal obstruction, bladder neck obstruction, concurrent use with MAOIs Do not use in patients with autoimmune diseases Do not crush or chew tablets Rapid onset (1-2 min) and short duration (3-5 min or longer if prolonged infusion) Avoid loading doses because of the risk of hypotension Monitor blood lipid levels, blood pressure Propofol has no analgesic properties
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.176 Drug
Indications
Dose
Dose adjustments
Comments
Other sedatives m e d i p l o Z e n o l c i p o Z
Insomnia
10 mg oral at bedtime Max duration: 4 weeks
Elderly, debilitated patients, hepatic impairment: initial dose 5 mg
Contraindicated if obstructive sleep apnoea, myasthenia gravis, severe hepatic insufficiency, acute and/or severe respiratory depression
Insomnia
7.5 mg oral at bedtime Max duration: 4 weeks
Elderly, hepatic or renal impairment: initial dose 3.75 mg
Contraindicated if myasthenia gravis, severe sleep apnoea syndrome, severe respiratory or severe hepatic insufficiency
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.177 Drug
Indications
Dose
Dose adjustments
Comments
Neuroleptics: Extrapyramidal symptoms and neuroleptic malignant syndrome may occur with all neuroleptics. Elderly people with dementia who are treated with antipsychotics are at a small increased risk of death compared with those who are not treated Typical neuroleptics Schizophrenia and other psychoses e n i z a m Intractable hiccup o r p r o l h C Nausea and
vomiting in terminal illness
Oral: Initially 25 mg TID or 75 mg at bedtime increasing by daily amounts of 25 mg to an effective MD (75-300 mg daily, some patients may require up to 1g) I.M.: 25-50 mg every 6-8h Oral: 25-50 mg TID or QD I.M.: 25-50 mg and if this fails 25-50 mg by slow i.v. infusion
Elderly (schizophrenia, nausea and vomiting): start with ⅓ - ½ usual adult dose
Contraindicated if liver or renal dysfunction, epilepsy, Parkinson, hypothyroidism, cardiac failure, phaeochromocytoma, agranulocytosis myasthenia gravis, prostate hypertrophy, history of narrow angle glaucoma Caution in patients with risk factor for stroke, seizures, cardiovascular disease or a family history of QT prolongation
Oral: 10-25 mg every 4-6h I.M.: 25 mg initially then 25-50 mg every 3-4h until vomiting stops, then change to orally
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.178 Drug
Indications
Dose
Dose adjustments
Comments
Typical neuroleptics e n i z a n e h p u l F
Schizophrenia and other psychoses
Patients without previous exposure of fluphenazine: start 12.5 mg i.m Next dose depends on patient’s response (12.5-100 mg) When administered as maintenance therapy, a single injection may be effective for up to 4weeks or longer
Elderly (over 60): a lower dose is recommended Liver and renal disease: caution
Contraindicated if comatose states, marked cerebral atherosclerosis, liver failure, renal failure, phaeochromocytoma, severe cardiac insufficiency, severely depressed states, existing blood dyscrasias Caution if arrythmias, Parkinson, narrow angle glaucoma, thyrotoxicosis, hypothyroidism, epilepsy, myasthenia gravis, prostatic hypertrophy, severe respiratory disease
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.179 Drug
Indications
Dose
Dose adjustments
Acute phase: 2-20 mg/day oral as a single dose or in divided doses Chronic phase: 1-3 mg oral TID, may be increased up to 20 mg/day in divided doses, depending on the response Max daily dose: 20 mg
DOSE ADJUSTMENTS:
Comments
Typical neuroleptics Schizophrenia, psychoses and mania
) 1 ( l a r o l o d i r e p o l a H
Psychomotor anti-agitation
Acute phase: Moderate symptomatology 1.5-3.0 mg oral BID or TID Severe symptomatology/resistant patients 3-5 mg oral BID or TID Chronic phase: 0.5-1 mg oral TID, may be increased to 2-3 mg TID, if required, MD: gradually reduced to the lowest effective MD Max daily dose: 20 mg
Elderly: start with half the dosage stated for adults and adjusted according to the results if necessary Contraindicated if comatose states, CNS depression, Parkinson, lesions of the basal ganglia, clinical significant cardiac disorders, QT interval prolongation, history of ventricular arrhythmia or Torsades de pointes, clinically significant bradycardia, 2nd or 3rd degree heart block, uncorrected hypokalaemia and use of other QT prolonging drugs Caution if renal failure, liver disease, epilepsy, hyperthyroidism, phaeochromocytoma Bioavailability from the oral route is about 60% of that from the i.m. route and readjustment of dose may be required COMMENTS:
i.v. haloperidol can be associated with QT prolongation and torsades de pointes
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.180 Drug
Indications
Dose
Dose adjustments
Comments
Typical neuroleptics Gilles de la Tourette l o ) syndrome, severe tics, d i intractable hiccup r 2 e ( p l o a r l a o H n o i t c e j n i l o d i r e p o l a H
Rapid control of the symptoms of hostility, aggression, hyperactivity, disruptive and violent behaviour, confusion, emotional withdrawal, hallucinations and delusions associated with acute and chronic schizophrenia, mania, and hypomania, and organic brain syndrome Nausea and vomiting
Starting dose 1.5 mg oral TID adjusted according to response A daily MD of 10 mg may be required in Gilles de la Tourette syndrome Max daily dose: 20 mg Initial doses of 2-10 mg i.m. Depending on the response of the patients, subsequent doses may be given every 4-8h up to a max of 18 mg/day
DOSE ADJUSTMENTS:
Elderly: start with half the dosage stated for adults and adjusted according to the results if necessary Contraindicated if comatose states, CNS depression, Parkinson, lesions of the basal ganglia, clinical significant cardiac disorders, QT interval prolongation, history of ventricular arrhythmia or Torsades de pointes, clinically significant bradycardia, 2nd or 3rd degree heart block, uncorrected hypokalaemia and use of other QT prolonging drugs Caution if renal failure, liver disease, epilepsy, hyperthyroidism, phaeochromocytoma Bioavailability from the oral route is about 60% of that from the i.m. route and readjustment of dose may be required COMMENTS:
i.v. haloperidol can be associated with QT prolongation and torsades de pointes
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.181 Drug
Indications
Dose
Dose adjustments
Comments
Typical neuroleptics Management of pain, restlessness or distress in terminally ill patient
e n i z a m o r p e m o Psychiatric v conditions e L
e n i z a y c i r e P
Anxiety, psichiatric conditions
12.5-25 mg i.m. or i.v. injection. In cases of severe agitation, up to 50 mg may be used, repeated every 6-8h or 25-200 mg/day by continuos s.c. infusion or 12.5-50 mg oral every 4-8h
Elderly: caution
Caution if liver dysfunction or cardiac disease, bradycardia or 2nd or 3rd degree heart block, risk of QT interval prolongation
Elderly Severe conditions: Initially 15-30 mg/day in divided doses Mild or moderate conditions: start 5-10 mg/day. Half or quarter the normal adult dose may be sufficient as MD
Caution if liver or renal dysfunction, epilepsy, Parkinson, hypothyroidism, cardiac failure, phaeochromocytoma, myasthenia gravis, prostrate hypertrophy, history of narrow angle glaucoma, agranulocytosis, risk of QT interval prolongation Discontinue if unexplained fever
Bed patients: initially the total daily dose 100-200 mg oral, usually divided into 3 doses, gradually increased to 1g daily if necessary Severe conditions: Initially 75 mg/ day oral in divided doses. Titrate according to patient response at weekly intervals; MD: max dose 300 mg/day Mild or moderate conditions: Initially 15-30 mg/day oral divided in two doses, with a larger dose being given in the evening
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.182 Drug
Indications
Dose
Dose adjustments
Comments
Typical neuroleptics e n i z a n e h p r e P
Anxiety, psichiatric conditions, nausea and vomiting, intractable hiccup
DOSE ADJUSTMENTS:
patient response. Max daily dose: 24 mg
Elderly: one quarter or one half of the recommended adult dosage
COMMENTS: Contraindicated if leucopenia, or in association with drugs liable to cause bone marrow
depression, or to patients in comatose states - Caution if liver disease, severe respiratory disease, renal failure, epilepsy, Parkinson, history of narrow angle glaucoma, hypothyroidism, myasthenia gravis, phaeochromocytoma, prostatic hypertrophy, risk of QT interval prolongation Schizophrenia, other psychoses
e d i z o m i P
DOSE: 4 mg oral TID. Titrate according to
DOSE:
DOSE ADJUSTMENTS:
Chronic schizophrenia: 2-20 mg oral daily, with 2 mg as a starting dose This may be increased according to response and tolerance
Elderly: half the normal starting dose Caution if hepatic, renal impairment or phaeochromocytoma
Other psychoses: an initial dose of 4 mg oral daily which may then be gradually increased, if necessary, according to response, max 16 mg daily
COMMENTS: Contraindicated if risk of QT interval prolongation,
known uncorrected hypokalaemia, hypomagnesaemia, clinically significant cardiac disorders, clinically significant bradycardia, severe central nervous system depression, depression, Parkinson, concomitant use with CYP3A4 or CYP2D6 inhibiting drugs, serotonin uptake inhibitors
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.183 Drug
Indications
Dose
Dose adjustments
Comments
Typical neuroleptics e n i z a r e p o u l f i r T
Anxiety, depressive symptoms, agitation, nausea and vomiting
Acute psychoses l o x i h t n e p o l c u Z
Low dosage: 2-4 mg/day oral, given in divided doses, according to the severity of the patient’s condition High dosage: 5 mg oral BID, after a week this may be increased to 15 mg/ day. If necessary, further increases of 5 mg may be made at three-day intervals
DOSE ADJUSTMENTS:
50-150 mg i.m., repeated if necessary after 2-3 days Some patients may need an additional injection between 1-2 days after the first injection Max accumulated dosage: 400 mg
DOSE ADJUSTMENTS:
Elderly: starting dose should be reduced by at least half COMMENTS: Contraindicated if comatose patients, existing
blood dyscrasias or known liver damage, uncontrolled cardiac decompensation Caution if CV disease , Parkinson, risk of QT interval prolongation Elderly, renal or hepatic impairment: caution, a lower dose may be necessary COMMENTS: Contraindicated if circulatory collapse, depressed
level of consciousness Caution if Parkinson, epilepsy, risk of QT interval prolongation, cardiac disease, or arrhythmias, narrow angle glaucoma, myasthenia gravis, prostatic hypertrophy, hypothyroidism, hyperthyroidism, phaeochromocytoma
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.184 Drug
Indications
Dose
Dose adjustments
Comments
Atypical neuroleptics: 3 differences with typical neuroleptics: the risk of extrapyramidal symptoms is lower, tardive dyskinesia is reduced and the ability to block serotonin-2 receptors is present. Atypical neuroleptics have been associated with new-onset diabetes and metabolic syndrome e d i r p l u s i m A e n i p a n e s A
Schizophrenia
For acute psychotic episodes: 400-800 mg/day oral In individual cases, the daily dose may be increased up to 1,200 mg/day Doses should be adjusted individually Administered QD at oral doses up to 300 mg, higher doses BID
Elderly: caution CrCl 30-60 ml/min: reduce to a half CrCl 10-30 ml/min: reduce to a third
Contraindicated if concomitant prolactin-dependent tumours, phaeochromocytoma, combination with levodopa Caution if epilepsy, risk of QT interval prolongation
Severe manic episodes associated with bipolar type I disorder
5 mg s.l. BID The dose can be increased to 10 mg BID based on individual clinical response and tolerability
Elderly, moderate hepatic impairment: caution
Caution if Parkinson, risk of QT interval prolongation, seizures Do not use in severe hepatic impairment or CrCl <15ml/min Do not chew or swallow tablets
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.185 Drug
Indications
Dose
Dose adjustments
Comments
Atypical neuroleptics e l o z a r p i p i r A
e n i p a z n a l O
Schizophrenia, manic episodes in bipolar type I disorder
Oral: 10-15 mg QD with a MD of 10-30 mg QD i.m.: Recommended initial dose: 9.75 mg Dose range: 5.25-15 mg A second injection may be administered 2h after the first injection, on the basis of individual clinical status and no more than three injections should be given in any 24h period Max daily dose: 30 mg/day mg/day
Caution if elderly, el derly, severe severe hepatic impairment
Orodispersible tablet should be placed in the mouth, it will rapidly disperse in saliva Caution if known CV disease, history of QT prolongation, epilepsy, epilepsy, concomitant administration of potent CYP3A4 or CYP2D6 inhibitors
Psichiatric conditions
Schizophrenia: recommended starting dose 10 mg/da m g/dayy orally
Elderly, renal or hepatic impairment: consider a lower starting dose (5 mg/day)
Contraindicated if risk of narrow-angle glaucoma Caution if Parkinson, low leukocyte and/ or neutrophil counts for any reason, risk of QT interval prolongation Orodispersible tablet should be placed in the mouth, it will rapidly disperse in saliva
Manic episode: Starting dose 15 mg QD oral in monotherapy or 10 mg QD in combination therapy. therapy. Then, adjust dose according to response: 5-20 mg/day
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.186 Drug
Indications
Dose
Dose adjustments
Comments
Atypical neuroleptics Schizophrenia, schizoaffective disorder e n o d i r e p i l a P
6 mg oral QD, administered in the morning. Some patients may benefit from lower or higher doses within the recommended range of 3-12 mg QD (6-12 mg for schizoaffective disorder)
Caution if elderly patients with dementia with risk factors for stroke Mild renal impairment: initial dose 3 mg QD (max 6 mg) Moderate-severe Moderate-severe renal impairment: initial dose 1.5 mg QD (max 3 mg) CrCl <10 ml/min: not recommended
Caution if severe hepatic impairment, seizures, Parkinson, Parkinson, risk of QT interval prolongation, low leukocyte and/ or neutrophil counts for any reason, known CV disease, cerebrovascular disease or conditions that predispose the patient to hypotension Do not chew, divide, or crush Take it the same way with regard to meals
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.187 Drug
Indications
Dose
Dose adjustments
Comments
Atypical neuroleptics Schizo Schizophr phrenia enia
e n i p a i t e u Q
IRF: IRF: Tota Totall daily daily dose dose for for the first first 4 days days is: is: 50 mg (Day (Day 1), 1), 100 100 mg mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4), then th en 150-750 150-750 mg/day Administered in 2 divided doses PRF: Starting dose 300 mg oral on Day 1 and 600 mg on Day 2 MD: 400-800 mg/da m g/dayy Moderate-severe IRF: Total Total daily dose for the th e first 4 days is: 100 mg (Day 1), 200 mg manic episodes (Day 2), 300 mg (Day 3) and 400 mg (Day 4) in bipolar Further dosage adjustments up to 800 mg/day mg/day disorder Administered in 2 divided doses PRF: Starting dose 300 mg oral on Day 1 and 600 mg on Day 2 MD: 400-800 mg/da m g/dayy Depression IRF: Total Total daily dose for the th e first 4days is: 50 mg (Day 1), 100 mg in bipolar (Day 2), 200 mg (Day 3) and 300 mg (Day 4) disorders The recommended daily dose is 300 mg Administered at bedtime PRF: Total Total daily dose for the t he first 4 days is: 50 mg oral (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4) Recommended daily dose: 300 mg Major depressive PRF: 50 mg on Day 1 and 2, and 150 mg on Day 3 and 4 at bedtime episodes Max dose 300 mg/day
DOSE ADJUSTMENTS:
Elderly, hepatic impairment: caution, a lower dose may be necessary COMMENTS: Contraindicated
if concomitant administration of cytochrome P450 3A4 inhibitors, such as HIV-protease HIV-protease inhibitors, azoleantifungal agents, erythromycin, clarithromycin and nefazodone Caution if low leukocyte and/or neutrophil counts for any reason, history of seizures, cerebrovascular disease, cardiovascular disease, disease, risk of QT interval prolongation It could be used if Parkinson disease PRF: tablets should not be split, chewed or crushed
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.188 Drug
Indications
Dose
Dose adjustments
Comments
Atypical neuroleptics
) 1 ( e n o d i r e p s i R
Schizophrenia
Start 2 mg/day oral (QD or in 2 divided doses) The dosage may be increased on the 2nd day to 4 mg MD: 4-6 mg
Elderly: 0.5 mg BID Caution if renal or hepatic impairment
Manic episodes in bipolar disorder
Start with 2 mg oral QD Dosage adjustments, if needed, should occur at intervals of not less than 24h and in dosage increments of 1 mg/day. mg/day. Max daily dose 6 mg
Elderly: start with 0.5 mg BID This dosage can be individually adjusted with 0.5 mg BID increments to 1-2 mg BID Caution if renal or hepatic impairment
Persistent aggression in patients with moderate to severe Alzheimer’s dementia
Start with 0.25 mg oral BID This dosage can be individually adjusted by increments of 0.25 mg BID, not more frequently than every other day, if needed. Optimum dose is 0.5 mg BID for most patients
Caution if renal or hepatic impairment
Caution if known cardiovascular cardiovascular disease, low leukocyte and/ and /or neutrophil counts for any reason, Parkinson, risk of QT interval prolongation Orodispersable tablet: place the tablet on the tongue
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.189 Drug
Indications
Dose
Dose adjustments
Comments
Atypical neuroleptics ) 2 ( e n o d i r e p s i R
Conduct disorder
Acute and chronic schizophrenia e d i r i p l u S
50kg: starting dose 0.5 mg oral QD This dosage can be individually adjusted by increments of 0.5 mg QD not more frequently than every other day, if needed. Optimum dose is 1 mg QD for most patients <50kg: starting dose 0.25 mg oral QD This dosage can be individually adjusted by increments of 0.25 mg QD not more frequently than every other day, if needed. Optimum dose is 0.5 mg QD
Caution if renal or hepatic impairment
Caution if known cardiovascular disease, low leukocyte and/or neutrophil counts for any reason, Parkinson, risk of QT interval prolongation Orodispersable tablet: place the tablet on the tongue
Starting dose: 400-800 mg oral daily, given as one or two tablets twice daily (morning and early evening) Predominantly positive symptons: starting dose of at least 400 mg oral BID, increasing if necessary up to a max of 1,200 mg BID Predominantly negative symptoms respond to doses below 800 mg oral daily, a starting dose of 400 mg BID is recommended Patients with mixed positive and negative symptoms: 400-600 mg oral BID
Renal impairment: caution
Contraindicated if phaeochromocytoma and acute porphyria, concomitant prolactindependent tumours, association with levodopa or antiparkinsonian drugs Caution if Parkinson, epilepsy, low leukocyte and/or neutrophil counts for any reason, risk of QT interval prolongation
≥
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
9
Sedatives and neuropsychiatric drugs (Cont.)
P.190 Drug
Indications
Dose
Dose adjustments
Comments
Atypical neuroleptics Behavioral disorders in dementia patients e d i r p a i T
e n o d i s a r p i Z
Starting dose 50 mg oral/i.m./i.v. BID, increasing if necessary to 100 mg TID Max dose 400 mg/day
Elderly: caution
Schizophrenia Bipolar type I disorder
Initial dose 40 mg oral BID with food Then, dose may be increased to 60-80 mg BID Max dose 80 mg BID
Elderly, renal or hepatic impairment: caution, a lower dose may be necessary
Acute treatment of agitation in schizophrenia
10-20 mg i.m. administered as required up to a max dose of 40 mg/day Doses of 10 mg may be administered every 2h
Huntington’s disease
CrCl 30-60 ml/min: 75% of the normal dose 1,200 mg/day oral/i.m./i.v. divided CrCl 10-30 ml/min: 50% of the normal dose in 3 doses CrCl <10 ml/min: Progressive reduction to a MD 25% of the normal dose
Contraindicated if phaeochromocytoma, concomitant prolactin-dependent tumours, association with levodopa or antiparkinsonian drugs Caution if epilepsy, Parkinson, low leukocyte and/or neutrophil counts for any reason, risk of QT interval prolongation Contraindicated if known history of QT prolongation, decompensated heart failure, recent MI It could the parenteral drug of choice for patients with Parkinson disease
DISCLAIMER: The guidance suggested in this document does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses.
Abbreviations APTT = Activated partial thromboplastin time AB = Airway and breathing ABG = Arterial blood gas AADs = Antiarrhythmic drugs AAS = Acute aortic syndrome ACEI = Angiotensin converting enzyme inhibitor ACLS = Advanced cardiovascular life support ACS = Acute coronary syndrome ACT = Activated clotting time AD = Aortic Dissection AED = Automated external defibrillator AF = Atrial fibrillation Ao = Aortic aPTT = Activated partial thromboplastin time ARB = Angiotensin receptor blockers AS = Aortic stenosis AV = Atrioventricular AVN = Atrioventricular node AVNRT = Atrioventricular nodal re-entrant tachycardia AVNT = Atrioventricular nodal tachycardia BID = Twice a day BBB = Bundle branch block
P.191 BLS = Basic life support BNP = Brain natriuretic peptide BP = Blood pressure CABG = Coronary artery bypass grafting CAD = Coronary artery disease Cath Lab = Catheterisation laboratory CCB = Calcium channel blockers CCU = Coronary care unit CHF = Congestive heart failure CMR = Cardiovascular magnetic resonance COPD = Chronic obstructive pulmonary disease CPAP = Continuous positive airway pressure CPR = Cardiopulmonary resuscitation Cr = Creatinine blood level (mg/dL) CrCl = Creatinine clearance CS = Cardiogenic shock CSM = Carotid sinus massage CSNRT = Corrected sinus node recovery time CSS = Carotid sinus syndrome CT = Computed tomography CT-angio = Computed tomography angiography cTn = Cardiac troponin CUS = Compression venous ultrasound
Abbreviations (Cont.) CV = Cardiovascular CVA = Cerebrovascular accident CXR = Chest X-ray DAPT = Dual antiplatelet therapy DD = Dyastolic dysfunction DM = Diabetes mellitus dTT = Diluted thrombin time DVT = Deep vein thrombosis ECG = Electrocardiogram ECT = Ecarin clotting time ED = Emergency department EG = Electrograms eGFR = Estimated glomerular filtration rate (ml/min/1.73 m2) EMB = Endomyocardial biopsy EMS = Emergency medical services EPS = Electrophysiological study ERC = European Resuscitation Council ESR = Erythrocyte sedimentation rate ETT = Exercice treadmill testing FFP = Fresh frozen plasma FMC = First medical contact
P.192 GER = Gastroesophageal reflux GFR = Glomerular flow rate GI = Gastrointestinal GP = Glycoprotein Hb = haemoglobin HF = Heart failure HIT = Heparin-induced thrombocytopenia HOCM = Hypertrophic obstructive cardiomyopathy HTN = Hypertension HR = Heart rate hsTn = High-sensitive troponin IABP = Intra-aortic balloon pump ICC = Intensive cardiac care ICCU = Intensive cardiac care unit ICD = Implantable cardioverter defibrillator IHD = Ischemic heart disease IMH = Intramural hematoma IRF = Immediate-release formulation ISFC = International Society and Federation of Cardiology i.o. = Intraosseous IV = Invasive ventilation
Abbreviations (Cont.) i.v. = Intravenous KD = Kidney disease LBBB = Left bundle branch block LD = Loading dose LGE = Late gadolinium enhancement LMWH = Low-molecular weight heparin LOC = Loss of consciousness LV = Left ventricular LVD = Left ventricular dysfunction LVEF = Left ventricular ejection fraction LVH = Left ventricular hypertrophy LVSD = Left ventricular systolic dysfunction MCS = Mechanical circulatory support MD = Maintenance dose MDCT = Computed tomography with >4 elements MI = Myocardial infarction MRA = Mineralocorticoid receptor antagonist MRI = Magnetic resonance imaging Mvo = Microvascular obstruction NIV = Non-invasive ventilation NOAC = New oral anticoagulants NSAID = Non-steroidal anti-inflammatory drugs
P.193 NSTE-ACS = Non ST-segment elevation acute coronary syndrome NSTEMI = Non ST-segment elevation myocardial infarction NTG = Nitroglycerin NT-proBNP = N-terminal pro brain natriuretic peptide NVAF = Non-valvular atrial fibrillation NYHA = New York Heart Association OH = Orthostatic hypotension PAP = Pulmonary arterial pressure PAU = Penetrating aortic ulcer PCI = Percutaneous coronary intervention PCM = Physical counter-measures PCP = Pulmonary capillary pressure PE = Pulmonary embolism PEA = Pulmonary endarterectomy PEEP = Positive end expiratory pressure PPC = Prothrombin complex concentrate PR = Pulmonary regurgitation PRECISE-DAPT = PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Anti Platelet Therapy
Abbreviations (Cont.) PRF = Prolonged-release formulation ProCT = Procalcitonin PRN = Pro re nata PS-PEEP = Pressure support-positive endexpiratory pressure PSVT = Paroxysmal supraventricular tachycardia QD = Once a day QPM = Every evening rFVIIa = Recombinant factor VIIa rtPA = Recombinant tissue plasminogen activator RV = Right ventricular RVOT-VT = Right ventricular outflow tract ventricular tachycardia SBP = Systemic blood pressure s.c = Subcutaneous SIRS = systemic inflammatory response syndrome SLE = Systemic lupus erythematosus SMU = Syncope management units STE-ACS = ST-segment elevation acute coronary syndrome STEMI = ST-segment elevation myocardial infarction
SVT = Supraventricular tachycardia Spo2 = Oxygen saturation TEE = Transesophageal echocardiography TEVAR = Thoracic endovascular aortic repair TIA = Transient ischemic attack TID = Three times a day TLOC = Transient loss of consciousness TOE = Transoesopageal echocardiography TSH = Thyroid-stimulating hormone TTE = Transthoracic echocardiography UA = Unstable angina UFH = Unfractionated heparin ULN = Upper limit of normal VF = Ventricular fibrillation VR = Vascular resistance VT = Ventricular tachycardia VTE = Venous thromboembolism VVS = Vasovagal syncope WBC = white blood cell count WHO = World Health Organization WPW = Wolff-Parkinson-White
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References and copyright acknowledgments (Cont.) Reproduced With permission of Oxford University Press (UK) © European Society of Cardiology Habib G, et al. 2015 ESC Guidelines for the management of infective endocarditis. European Heart Journal Aug 2015, DOI: 10.1093/eurheartj/ehv319. Priori, SG, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death. European Heart Journal Aug 2015, DOI: 10.1093/eurheartj/ehv316 . Adler Y, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases. European Heart Journal Aug 2015, DOI: 10.1093/eurheartj/ehv318 . Roffi M, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. European Heart Journal Aug 2015, DOI: 10.1093/eurheartj/ehv320 . Erbel R, et al. 2014 ESC Guidelines on the diagnosis and treatment of aortic diseases. European Heart Journal Aug 2014, DOI: 10.1093/eurheartj/ehu281 . Konstantinides SV, et al. 2014 ESC Guidelines on the diagnosis and management of acute pulmonary embolism. European Heart Journal Nov 2014, 35 (43) 3033-3073; DOI: 10.1093/eurheartj/ehu283. Lip GYH, et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). European Heart Journal Dec 2014, 35 (45) 3155-3179; DOI: 10.1093/eurheartj/ehu298.
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References and copyright acknowledgments (Cont.) Windecker S, et al. 2014 ESC/EACTS Guidelines on myocardial revascularization. European Heart Journal Oct 2014, 35 (37) 2541-2619; DOI: 10.1093/eurheartj/ehu278. Caforio ALP, Pankuweit S, Arbustini E, Basso C, Gimeno-Blanes J, Felix SB, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. European Heart Journal (2013); July 3. DOI: 10.1093/eurheartj/eht210. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Böhm M, Dickstein K et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. European Heart Journal (2012) DOI: 10.1093/eurheartj/ehs104. Steg G, James SK Atar D, Badano LP, Blömstrom-Lundqvist C, Borger MA, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European Heart Journal (2012); DOI: 10.1093/eurheartj/ehs215. Steg PG, et al. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European Heart Journal Oct 2012, 33 (20) 2569-2619; DOI: 10.1093/eurheartj/ehs215. Moya A, Sutton R, Ammirati F, Blanc JJ, Brignole M, Dahm JB, et al. ESC Guidelines for the diagnosis and management of syncope. European Heart Journal (2009); DOI:10.1093/eurheartj/ehp298. Ibañez B, et al. 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC), European Heart Journal (2017) 00, 1–66 doi:10.1093/eurheartj/ehx393.
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References and copyright acknowledgments (Cont.) M Valgimigli et al. 2017 ESC focused update on dual antiplatelet therapy in coronary artery disease developed in collaboration with EACTS: The Task Force for dual antiplatelet therapy in coronary artery disease of the European Society of Cardiology (ESC) and of the European Association for Cardio-Thoracic Surgery (EACTS). European Heart Journal (2018) 39, 3, 213–260. DOI:10.1093/eurheartj/ehx419. Halvorsen et Al. Management of antithrombotic therapy after bleeding in patients with coronary artery disease and/or atrial fibrillation: expert consensus paper of the European Society of Cardiology Working Group on Thrombosis. Eur Heart J. 2017 May 14; 38(19):1455-1462. doi: 10.1093/eurheartj/ehw454. Reproduced with permission of Sage Publications (UK) © European Society of Cardiology Alejandro Cortés-Beringola et Al. - Planning secondary prevention: Room for improvement. European Journal of Preventive Cardiology. DOI:10.1177/2047487317704954. Reproduced with permission from John Wiley & Sons © European Society of Cardiology Mebazaa A et al. Eur J Heart Fail. (2015); Recommendations on pre-hospital and early hospital management of acute heart failure. DOI:10.1093/eurheartj/ehv066.
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Disclaimer and Copyrights This is a publication of the Acute Cardiovascular Care Association (ACCA), a branch of the European Society of Cardiology. Its content reflects the opinion of the authors based on the evidence available at the time it was written and does not necessarily imply an endorsement by ACCA or the ESC. The guidance suggested in the Clinical Decision Making Toolkit does not override the individual responsibility of the healthcare professional to make appropriate decisions according to each patient’s circumstances and profile, as well as local regulations and licenses. Some content, illustrations/tables/figures were inspired and/or adapted from ESC Guidelines and other existing sources, with permission granted by the original publishers.
Acknowledgements We are indebted to all the authors for their commitment and for the strong effort to synthesise their wide scientific knowledge and clinical experience into simple algorithms and schemes using the aim to help clinicians in everyday clinical practice in the easiest possible manner as the main driver of their work. The support of this initiative by the ACCA board members was essential to launch this initiative as was the hard work of the ESC staff to make this project move forward. January 2018
