SU$G%&'( %N#)&*%+NS ,olume - Number 2 20" ary 'nn (iebert %nc. D+%1 0.0"-/sur.20.2" 0.0"-/sur.20.2"
/
Sepsis 20"1 Definitions and Guideline &3anges (ena . Napolitano
. y l n o e s u l a n o s r e p r o # . " / ! / 2 0 t a m o c . b u p t r e b e i l . e n i l n o m o r f s e i t i l a n o i t a N r o f y t i s r e v i n U i x g n a u G y b d e d a o l n w o D
'bstract
4ac5ground1 Sepsis is a global 3ealt3care issue and continues to be t3e leading cause of deat3 from infection. )arly recognition and diagnosis of sepsis is re6uired to prevent t3e transition into septic s3oc5 w3ic3 is associated wit3 a mortality rate of 708 or more. Discussion1 New definitions for sepsis and septic s3oc5 9*3ird %nternational &onsensus Definitions for Sepsis and Septic S3oc5 :Sepsis;<=> 3ave been developed. ' new screening tool for sepsis 96uic5 Se6uential +rgan #ailure 'ssessment :6S+#'=> 3as been proposed to predict t3e li5eli3ood li5eli3ood of poor outcome in out;of; intensive care unit 9%&U> patients wit3 clinical suspicion of sepsis. *3e Surviving Sepsis &aign Guidelines were recently updated and include greater evidence;based recommendations for treatment of sepsis in attempts to reduce sepsis; associated mortality. mortality. *3is review discusses t3e new Sepsis;< definitions and guidelines. ?eywords1 sepsis@ sepsis guidelines@ Sepsis;< definition@ definition@ septic s3oc5@ Surviving Sepsis &aign
epsis continues to be a maAor 3ealt3 problem world; tion> severe sepsis 9sepsis and organ dysfunction> and septic wide and is associated wit3 3ig3 mortality rates. *3e s3oc5 9sepsis and 3ypotension despite ade6uate fluid resus; %ntensive &are +ver Nations 9%&+N> study provided global citation@ #ig. >. epidemiologic data on 00!- intensive care unit 9%&U> pa; 'n international international tas5 force wit3 - participants participants was con; tients and confirmed t3at 2-< 92-.B8> of patients 3ad sepsis vened by t3e Society of &ritical &are edicine 9S&&> and on admission or during t3eir %&U stay. %n patients wit3 sep; t3e )uropean Society of %ntensive &are edicine 9)S%&> to sis %&U mortality was 2B."8 and 3ospital mortality was revise t3e current sepsis and septic s3oc5 definitions. Using :=. +ptimal evidence;based treatment association between infection and inflammation and com; of sepsis is t3erefore needed in attempts to reduce mortality pletely abandoned S%$S criteria. led over t3e last decade by t3e Surviving Sepsis &aign Sepsis is defined as life;t3reateni life;t3reatening ng organ organ dysfunction 9SS&>. *3e first step in implementation implementation of optimal sepsis caused by a dysregulated 3ost response to infection. *3e treatment is identification of patients wit3 sepsis. *3is article clinical criteria for sepsis include suspected or documented discusses t3e new *3ird %nternational %nternational &onsensus Definitions infection and an acute increase of two or more Se6uential for Sepsis and Septic S3oc5 9Sepsis;<> definitions for sepsis +rgan #ailure 'ssessment 9S+#'> points as a proxy for or; and septic s3oc5 and t3e new 20! SS& guidelines. gan dysfunction. Septic s3oc5 is defined as a subset of sepsis in w3ic3 underlying circulatory and cellular/metabolic ab; normalities are profound enoug3 to increase mortality sub; Sepsis;<1 New Definitions stantially. Septic s3oc5 is defined by t3e clinical criteria of %nitial sepsis definitions were developed at a -- con; sepsis and vasopressor t3erapy needed to elevate mean ar; sensus conference :2= wit3 a subse6uent update in t3e sepsis terial pressure C!B mm g and lactate E2 mmol/( 9" mg/d(> definitions in 200 t3at simply expanded t3e list of signs and despite ade6uate fluid resuscitation 9#ig. >. symptoms of sepsis to reflect clinical bedside experience :<=. *3e mortality rate associated wit3 t3e new septic s3oc5 *3e initial sepsis definitions included sepsis 9systemic in; definition is 3ig3 9708> compared wit3 a mortality mortality rate flammatory response syndrome :S%$S= and suspected infec; of 08 wit3 t3e new sepsis definition. ' systematic review
S
'cute &are Surgery *rauma and Surgical &ritical &are University of ic3igan ealt3 System 'nn 'rbor ic3igan.
"
N'F+(%* N'F+(%*'N+ 'N+
tality rates were examined in t3e SS& database 9*able >. *3e group re6uiring vasopressors to maintain mean arterial pressure !B mm g or greater and a lactate concentration E2 mmol/( mmol/( 9" mg/d(> after fluid resuscitation resuscitation 9group > 3ad a 3ig3er mortality 972.<8> in ris5;adAusted comparisons wit3 t3e ot3er five groups. *3is analysis led to t3e new Sepsis;< septic s3oc5 definition :!=. %t s3ould also be noted 3ow; ever t3at patients w3o met t3e Sepsis;2 criteria for septic s3oc5 9group 2> wit3 3ypotension re6uiring vasopressors but wit3out lactate elevation also 3ad a 3ig3 mortality r ate of <0.8. *3e 3ig3er mortality rate associated wit3 t3is new definition of septic s3oc5 3as important implications for trial design in septic s3oc5 and may allow decreased sample sie for future septic s3oc5 trials :=. &ontroversy remains regarding t3e inclusion of lactate in t3e Sepsis;< septic s3oc5 definition and t3e exact lactate measurement 9E 2 mmol/(> used in t3e definition. +ne study analyed a prospective co3ort of %&U patients wit3 sepsis 9n H !<2> !<2> and documented t3at patients meeting t3e Sepsis;< definition of septic s3oc5 3ad a 3ig3er mortality t3an patients meeting t3e Sepsis;2 definition 9<".-8 vs. <7.08> but only lactate values C! mmol/( were associated wit3 increased %&U mortality :"=. +t3ers report concern t3at lactate is a sensitive but not specific indicator of cellular or metabolic stress rat3er t3an IIs3oc5.JJ S%$S versus S+#' and 6S+#' in Sepsis
#%G. . *3ird %nternational &onsensus Definitions Definitions for Sepsis and Septic S3oc5 9Sepsis;<>1 9a> +riginal Sepsis;2 definitions@ 9b> New Sepsis;< definitions.
identified 77 studies reporting septic s3oc5 outcomes and t3e Delp3i process identified 3ypotension lactate concen; tration and vasopressor t3erapy as clinical criteria to iden; tify patients wit3 septic s3oc5. 4ased on t3ese parameters specific patient groups wit3 or wit3out t3ese clinical criteria were developed and t3eir prevalence and associated mor;
' retrospective retrospective analysis of t3e 'ustralian and New Keal; and %ntensive &are Society 9'NK%&S> database 92000L20<> included 0-!!< patients wit3 infection and organ failure to validate t3e severe sepsis definition :-=. %t was reported t3at ".-8 of patients 3ad two or more S%$S criteria but 2.8 did not. Using S%$S alone missed one in eig3t patients wit3 severe sepsis. *3e study confirmed t3at eac3 additional S%$S criteria increased mortality by <8 in a linear manner wit3out a transitional transitional increase w3en two S%$S criteria were met. *3ey concluded t3at t3e use of two or more S%$S criteria alone lac5ed bot3 sensitivity and specificity for diagnosing severe sepsis in %&U patients. *3e subse6uent analysis of clinical criteria for t3e new Sepsis;< definitions compared S%$S criteria t3e S+#' score t3e (ogistic +rgan Dysfunction System 9(+DS> score and t3e 6uic5 S+#' 96S+#'> score 9range 0L< points wit3 one point eac3 for systolic 3ypotension :M 00 mm g= tac3ypnea :C 22/min= or altered mentation>. *3e S+#' score 9*able 2>
-
D)#%N%*%+NS 'ND GU%D)(%N) &'NG)S
*able . Distribution and 0ortality in Septic S3oc5 &o3orts from Surviving Sepsis &aign Database
Grou Group Group Group Group Group a
a
b 2 < 7 B !
ypotension after fluids
,asopressors
(actate E2 mmol/(
es es es No Never 9pre> es
es es No No No No
es No es es es No
Frevalence Surviving Sepsis &aign Database 9n H ""70 patients> "B20 <-"B 22< <2!! 2!-! B0
97B.28> 92.28> 9.28> 9.<8> 97.<8> 90."8>
ospital mortality 72.<8 <0.8 2".8 2B.8 2-.8 ".8
eets criteria for new Sepsis;< septic s3oc5 definition. eets criteria for old Sepsis;2 septic s3oc5 definition. Data compiled from1 S3an5ar;ari F3illips GS (evey ( et al. Developing a new definition and assessing new clinical criteria for septic s3oc5. #or t3e *3ird %nternational &onsensus Definitions for Sepsis and Septic S3oc5 9Sepsis;<>. O'' 20!@<B1BL". Sepsis;< H *3ird %nternational &onsensus Definitions for Sepsis and Septic S3oc5. b
. y l n o e s u l a n o s r e p r o # . " / ! / 2 0 t a m o c . b u p t r e b e i l . e n i l n o m o r f s e i t i l a n o i t a N r o f y t i s r e v i n U i x g n a u G y b d e d a o l n w o D
20
N'F+(%* N'F+(%*'N+ 'N+
2
D)#%N%*%+NS 'ND GU%D)(%N) &'NG)S
*able 2. Se6uential 9Sepsis;$elated> +rgan #ailure 'ssessment 9Sofa> Score
a
Score System $espiration Fao2/#io 2 mm g 95Fa>
0
2
<
7
C700 9B<.<>
P 700 9B<.<>
P<00 970>
P200 92!.> wit3 respiratory support
P00 9<.<> wit3 respiratory support
PB0
P20
!.0L.- 902L207>
E2.0 9207>
&oagulation < Flatelets 0 /m( CB0 PB0 P00 (iver 4ilirubin mg/d( P.2 920> .2L.- 920L<2> 2.0LB.- 9< 9m mol/(> &ardiovascular 'F C0 mm g 'F P0 mm g Dopamine PB or dobutamine Q
b
9any dose> . y l n o e s u l a n o s r e p r o # . " / ! / 2 0 t a m o c . b u p t r e b e i l . e n i l n o m o r f s e i t i l a n o i t a N r o f y t i s r e v i n U i x g n a u G y b d e d a o l n w o D
&entral nervous system Glasgow coma c scale score
B
$enal &reatinine mg/d( 9m mol/(> Urine output m(/d
P.2 90>
0L2
.2L.- 90L0> 2.0L<.7 9L2-->
Dopamine B.LB or Dopamine EB or epinep3rine M0. or epinep3rine E0. or b b norepinep3rine M0. norepinep3rine E0.
!L-
P!
<.BL7.- 9<00L770>
EB.0 9770>
PB00
P200
#io2 H fraction of inspired oxygen@ 'F H mean arterial pressure@ Fao 2 H partial pressure of oxygen. a 'dapted from ,incent et al. :0=. b &atec3olamine &atec3olamine doses are given as mg/5g/min g/5g/min for at least 3our. c Glasgow coma scale scores range from
is widely used in critical care researc3 but is not a common clinical tool used at t3e bedside in t3e %&U :0=. *3e 6S+#' score 9#ig. 2> was developed as a simple screening tool to identify patients wit3 possible sepsis. ' 6S+#' score of two or more identifies a patient at greater ris5 of poor outcome. 'mong non;%&U encounters in patients wit3 suspected infection 6S+#' 3ad a predictive validity for in;3ospital mortality 9area under t3e receiver operating c3aracteristic curve :'U$+&= 0."> t3at was greater t3an t3e full S+#' score 9'U$+& 0.-> and S%$S 9'U$+& 0.!@ *able <>. %n contrast 3owever in t3e %&U t3e predictive
#%G. 2.
validity validity for in;3ospit in;3ospital al mortality mortality was lower lower for 6S+#' 9'U$+& 0.!!> and S%$S 9'U$+& 0.!7> compared wit3 t3e full S+#' score 9'U$+& 0.7> :B=. *3e use of t3e S+#' score in t3e Sepsis;< definition is c3allenging because S+#' is a complicated score t3at is not calculated routinely in %&Us at t3e bedside. Systemic in; flammatory response syndrome and 6S+#' are scores t3at are easily calculated at t3e bedside for use in t3e screening of patients wit3 possible sepsis. ' retrospective co3ort analysis of t3e 'NK%&S database t3at was used to assess S%$S in t3e severe sepsis definition was also used to compare t3e
Ruic5 Se6uential +rgan #ailure 'ssessment 96S+#'> 96S+#'> score for sepsis.
*able <. %n;ospital 0ortality Frediction among Fatients wit3 Fossible %nfection +utside of t3e %ntensive &are Unit *est
'U$+& curve
Sensitivity for mortality
Specificity for mortality
0.! 0.0."
!78 !"8 BB8
!B8 !8 "78
S%$S C2 S+#' C2 6S+#' C2
'U$+& H area under t3e receiver operating curve@ S%$S H sys; temic inflammato ry response respo nse syndrome@ S+#' H Se6uential +rgan #ailure 'ssessment score@ 6S+#' H 6uic5 Se6uential +rgan #ailure 'ssessment score.
. y l n o e s u l a n o s r e p r o # . " / ! / 2 0 t a m o c . b u p t r e b e i l . e n i l n o m o r f s e i t i l a n o i t a N r o f y t i s r e v i n U i x g n a u G y b d e d a o l n w o D
wit3 suspected infection and examined 6S+#' as a mortality predictor. *3e overall in;3ospital mortality was low 9"8>. *3e 6S+#' performed better t3an S%$S and S+#' in pre; diction of in;3ospital mortality 9'U$+& 0." 6S+#' vs. 0. S+#' and 0.!B S%$S>. 4ot3 6S+#' and S+#' 3ad lower sensitivity 96S+#' 08 S+#' <8 vs. S%$S -<8> and S%$S 3ad lower specificity 96S+#' -8 S+#' 08 S%$S 28> :<=. *3e use of 6S+#' versus S%$S score for a sepsis screen actually depends on w3et3er you desire increased sensitivity or specificity. *3ere is still controversy regarding t3e new Sepsis;< def; initions :7L!=. Some organiations 3ave not endorsed t3e new Sepsis;< definitions including t3e 'merican &ollege of &3est F3ysicians := t3e %nfectious Disease Society of 'merica t3e (atin 'merican Sepsis %nstitute :"= 'merican &ollege of )mergency F3ysicians none of t3e emergency medicine societies and none of t3e 3ospital medicine soci; eties. 'dditional prospective validation of t3e new Sepsis;< definitions is clearly warranted.
prognostic accuracy of t3e S+#' S+#' score S%$S criteria and 6S+#' score for in;3ospital mortality among adults wit3 sus; pected infection infection admitted admitted to t3e %&U. *3e S+#' score ased by two or more points in -0.8@ "!.8 3ad S%$S increased by score of two or more and B7.78 3ad a 6S+#' score of two or more. 'n in; crease in S+#' score of two or more 3ad greater prognost prognostic ic accuracy for in;3ospital mortality 9'U$+& 0.B<> SS& Guidelines t3an S%$S S%$S 9'U$+& 0.B"-> or t3e 6S+#' score 9'U$+& *3e SS& guidelines guidelines for t3e t3e managem management ent of severe 0.!0> :=. sepsis and septic s3oc5 were first publis3ed in 2007 :-= %nterestingly %nterestingly 6S+#' 6S+#' failed validation in a study of <0! wit3 an update in 200" :20= and 202 :2=. *3e overall goal patien patients ts wit3 suspected suspected infecti infection on from t3e emerge emergency ncy of t3e SS& SS& was to reduce mortality from severe sepsis and department epartment and ward at t3e University of &3icago. Systemic septic s3oc5. 'ctive participation in t3e SS& was was associated response syndrome 6S+#' odified )arly inflammatory response wit3 increased guideline ad3erence and reductions in sepsis; arning Score National )arly arning arning Score core 9)S> and National related mortality :22=. 'd3erence to t3e SS& guidelines was 9N)S@ *able 7> were compared. Using t3e 3ig3est non;%&U promoted via t3e use of SS& bundles w3ic3 included score of patients two or more S%$S 3ad a sensitivity of -8 elements to be com pleted in a specific timeframe after t3e and specificity of <8 for t3e composite outcome 9deat3 or diagnosis of sepsis. %&U transfer> compared wit3 B78 and !8 for 6S+#' of two or more B-8 and 08 bundl es SS& bundles for )S of five or more and !8 and !!8 for N)S of *3e SS& bundles 3ave c3anged during t3e SS& gu ide; eig3t or more respectively. *3e aut3ors concluded t3at t3e line updates 9*able B>. *3e differences between t3e 200" 6S+#' 6S+#' score s3ould not replace general early warning and 202 bundles included an increase in fluid r esus cita; scores w3en ris5;stratifying patients wit3 suspected infection tion recommended for sepsis;induced tissue 3ypoperfusion :2=. %n contrast an international prospective co3ort study from )urope included "- patients in t3e emergency department
*able 7. *3e 0odified )arly arning Score 9 )S> and National )arly arning 9N)S> Scores odified )arly arning Score 9)S> Score
< ;
$espiratory rate 9min > eart rate 9min > Systolic 4F 9mmg> Urine output 9ml/5g/3> *emperature *emperature 9 &> Neurological ;
M0 Nil
2 M" M70 L"0 P0.B M
0
2
<
7LB0 "L00
-L7 BL00 0L--
BL20 0L0
2L2L2C200
E2E2-
<".L<".B $eacting to voice
C<".! $eacting to pain
Unresponsive
2
<
2L27
C2B
National )arly arning Score 9N)S> F3ysiological parameters
<
$espiration rate +xygen saturations 'ny supplemental oxygen *emperature Systolic 4F eart rate (evel of consciousness
M" M- M
2 -2L-< es -L00
0
-L -7L-B
2L20 C-! No
<".L<-.0
C<-.
-L0
L<0
C220 C< ,.F. or U
T*3e N)S initiative flowed from t3e $oyal &ollege of F3ysiciansJ N)SD%G and was Aointly developed and funded in collaboration wit3 t3e $oyal &ollege of F3ysicians $oyal &ollege of Nursing National +utreac3 #orum and NS *raining for %nnovation.
*able B. Difference in t3e Surviving Sepsis &aign 4undles 200" 9left> vs. 202 9rig3t>
. y l n o e s u l a n o s r e p r o # . " / ! / 2 0 t a m o c . b u p t r e b e i l . e n i l n o m o r f s e i t i l a n o i t a N r o f y t i s r e v i n U i x g n a u G y b d e d a o l n w o D
Sepsis resuscitation bundle
Surviving sepsis campaign bundles
*o be accomplis3ed as soon as possible and scored over t3e first ! 3ours1 . easure serum lactate. 2. +btain blood cultures prior to antibiotic administration. <. #rom t3e time of presentation presentation administer broad; spectrum antibiotics wit3in < 3ours for )D admissions and 3our for non;)D%&U admissions. 7. %n t3e event of 3ypotension and/or lactate E Deliver an initial minimum of 20 m(/5g of crystalloid 9or colloid e6uivalent>. b> 'pply vasopressors for 3ypotension t3at does not respond to initial fluid resuscitation resuscitation to maintain mean arterial pressure 9 'F> E!B mm g. B. %n t3e event of persistent 3ypotension despite fluid resuscitation 9septic s3oc5> and/or lactate E7 mmol/( 91 a> 'c3ieve central venous pressure 9&,F> of E"L 2mmg. b> 'c3ieve central venous oxygen saturation 9Scv+2> of E08.
*o be completed wit3in < 3ours1 . easure lactate level 2. +btain blood cultures prior to administration of antibiotics <. 'dminister broad spectrum antibiotics 7. 'dminister 'dminister <0 m(/5g crystalloid for 3ypotension or lactate C7 mmol/( *o be completed wit3in ! 3ours1 B. 'pply vasopressors 9for 3ypotension t3at does not respond to initial fluid resuscitation> to maintain maintain a mean arterial pressure 9 'F> C!B mm g !. %n t3e event of persistent arterial 3ypotension despite volume resuscitation 9septic s3oc5> or initial lactate C7 mmol/( 9 ;easure central venous pressure 9&,F>T ;easure central venous oxygen saturation 9Scvo2>T . $emeasure lactate if initial lactate was elevatedT
Sepsis management bundle *o be accomplis3ed as soon as possible and scored over t3e first 27 3ours1 . 'dminister low;dose steroids for septic s3oc5 in accordance wit3 a standardied %&U policy. policy. 2. 'dminister drotrecogin alfa 9activated> in accordance wit3 a standardied %&U policy. policy. <. Glucose control maintained above lower limit of normal but PB0 mg/dl. 7. aintain inspiratory plateau pressures at P<0 cm 2 + for mec3anically ventilated patients. T*argets for 6uantitative resuscitation included in t3e guidelines are &,F of C" mm g Scvo 2 of C08 and normaliation of lactate. #rom1 www.survivingsepsis.org
920 m(/5g crystalloid in 200"@ <0 m(/5g in 202 for treat; s3oc5 in;3ospital in;3ospital mortality mortality was -.8 -.8 and delay in t3e ment of 3ypotension or elevated lactate> and discontinuation first antibiotic antibiotic administration administration was associated associated wit3 increased increased of t3e 200" sepsis management bundle 9steroids activated ris5 of deat3 :2B=. protein prot ein & glycemic glyc emic control cont rol and low plate au pressur pre ssures es in *3e maAor c3ange from t3e 202 SS& bundle is t3e mec3anically ventilated patients pati ents>. >. r emo early goal;dire goal;directed cted t3erapy recommendations recommendations emoval of early ' global prospective observational 6uality im provement ement 9resuscitation study of compliance compliance wit3 t3e t3e 202 SS& SS& bundles bundles in targets central venous pressure :&,F= C" central venous ts patien oxy; wit3 severe sepsis or septic s3oc5 included -7 patients gen saturation :Sc,+ 2= C 08 and normaliation normaliation of lactate> lactate> from t3e six;3o six;3our ur SS& bundle. bundle. *3e 20! 20! SS& bundle bundle in t3e !2 countries and documented t3at overall compliance was r ecomme volume status and tissue ecommends serial re;assessment of volume low at only -8 for t3e t3ree;3our bundle and . *3e most recent SS& bundles focus on early an; meant to be implemented wit3out interval re;evaluation. #or tibiotic treatment and fluid resuscitation resuscitation to be initiated initiated wit3in example in a patient wit3 sepsis wit3 severe 3ypoxemia and t3ree 3ours. )arly identification of patients wit3 sepsis early acute respiratory distress syndrome or 3eart failure failure fluid intravenous fluid resuscitation and early intravenous antibi; resuscitation of <0 m(/5g may not be appropriate and vaso; otic administration administration are t3e mainstay mainstay of sepsis management. pressor or cardiotonic medications may be indicated to op; &onsistent in all of t3e SS& bundles is t3e recommenda; timie tissue perfusion :2!=. e are beginning to determine tion for antibiotic administration wit3in one 3our of diagnosis ris5 factors for patients w3o are not fluid responsive in septic of sepsis. %n a study of 2"B0 patients patients wit3 severe sepsis and s3oc5 93eart failure 3ypot3ermia immunocompromised se ptic
*able !. Surviving Sepsis &aign 4undle 20! *o be completed wit3in < 3ours . easure lactate level. 2. +btain +btain blood cultures prior to administration administration of antibiotics. <. 'dminister broad spectrum antibiotics. 7. 'dminister <0 ml/5g crystalloid for 3ypotension or lactate C7 mmol/(. II*ime of presentationJJ is defined as t3e t3e time of triage in t3e emergency department or if presenting fr om anot3er care venue from t3e earliest c3art annotation consistent wit3 all elements of severe sepsis or septic s3oc5 ascertained t3roug3 c3art review. *o be completed wit3in ! 3ours B. 'pply vasopressors 9for 3ypotension t3at does not respond to initial initial fluid resuscitation> resuscitation> to maintain maintain a mean arterial pressure 9 'F> C!B mm g. !. %n t3e event of persistent 3ypotension after initial fluid administration 9 'F P!B mm g> or if initial lactate was C7 mmol/( re;assess volume status and tissue perfusion and document findings according to *able . . $e;measure lactate if initial lactate elevated. . y l n o e s u l a n o s r e p r o # . " / ! / 2 0 t a m o c . b u p t r e b e i l . e n i l n o m o r f s e i t i l a n o i t a N r o f y t i s r e v i n U i x g n a u G y b d e d a o l n w o D
Document reassessment of volume status and tissue perfusion wit3 )it3er1 $epeat focused exam 9after initial fluid resuscitation> including vital signs cardiopulmonary cardiopulmonary capillary refill pulse and s5in findings. +r two of t3e following1 easure &,F. 2 easure Scv+ . Ferform bedside cardiovascular ultrasound. Ferform dynamic ass essment of fluid responsiveness wit3 passive leg raise or fluid c3allenge. #rom1 www.survivingsepsis.org
*able . Surviving Sepsis &aign Guideline &3anges &omparing 202 and 20! $ecommendations 202
20!
Sepsis definition
Systemic manifestation of infection plus suspected (ife;t3reatening organ dysfunction caused by dysregulated response to infection. infection No severe sepsis definition Severe sepsis1 sepsis plus organ dysfunction %nitial resuscitation 't least <0 m(/5g in t3e first < 3@ crystalloid fluid 9no specific recommendation recommendation for fluid type>. 'lbumin if patients re6uire substantial fluids )arly goal;directed t3erapy protocolied care including Use dynamic resuscitation mar5ers 9passive &,F Sc,+2. leg elevation elevation **)>. *arget 'F !B mm g. Normalie lactate $e;assess 3emodynamic status to guide resuscitation. Normalie lactate ,asopressors asopr essors *arget 'F !B mm g Norepinep3rine vasopressor of c3oice@ epinep3rine if not at target 'F or vasopressin to reduce norepinep3rine re6uirement. 'void dopamine in most patients. Steroids +nly indicated in septic s3oc5 refractory to ade6uate fluids and vasopressors 'dministration of effective %, antimicrobial agents e recommend t3at administration of %, 'ntibiotic wit3in t3e first 3our of recognition of septic s3oc5 and antimicrobials be initiated initiated as soon as administration severe sepsis wit3out septic s3oc5. possible after recognition and wit3in 3 %nitial empiric anti;infective t3erapy of one or more for bot3 sepsis and septic s3oc5. drugs %nitial %, broad;spectrum antibiotic agents to t3at 3ave activity against all li5ely pat3ogens. cover all potential pat3ogens. *3e addition &ombination empirical t3erapy for neutropenic of a second gram;negative agent to t3e pati empiric regimen is recommended for tieents wit3 severe sepsis and for patients wit3 difficult critically ill patients wit3sepsis at 3ig3 ris5 cult;t ;to; treat multi;drugLresistant bacterial pat3ogens suc3 of infection wit3 multi;drugLresistant as 'cinetobacter and Fseudomonas spp. pat3ogens 9e.g. Fseudomonas 'ntimicrobial regimen s3ould be reassessed daily for 'cinetobacter etc.> to increase potential deescalation. Use of low procalcitonin t3e probability of at least one active levels agent being administered or similar biomar5ers to assist t3e clinician in t3e ay use procalcitonin to guide de;escalation discontinuation of empiric empiric antibiotics in patients patients w3o of antibiotic t3erapy. initially appeared septic but 3ave no subse6uent evidence of infection Source control 'c3ieve wit3in 2 3 if feasible 'c3ieve as soon as medically and logically feasible &,F H central venous pressure@ Sc,+2 H central venous oxygen saturation@ transt3oracic ec3ocardiograp3y@ ec3ocardiograp3y@ %, H intravenous.
'F H mean arterial pressure@ **) H
22
2<
D)#%N%*%+NS 'ND GU%D)(%N) &'NG)S
*able ". Strong $ecommendations from t3e Surviving Sepsis &aign 20! Guidelines <0 m(/5g crystalloid fluid resuscitation wit3in t3e first < 3 &rystalloids as fluid of c3oice for initial resuscitation 'gainst t3e use of 3ydroxyet3yl starc3es for intra;vascular volume replacement %nitial target mean arterial pressure of !B mm g in septic s3oc5 re6uiring vasopressors Norepinep3rine as first;line vasopressor 'dminister antibiotics wit3in 3 of recognition )mpiric broad;spectrum antimicrobial t3erapy to cover all li5ely pat3ogens $ed blood cell transfusion only w3en 3emoglobin P unless extenuating circumstances 9myocardial infarction severe 3ypoxemia acute 3emorr3age> *arget *arget tidal volume ! m(/5g for '$DS plateau pressure upper limit <0 cm 2+ &onservative fluid strategy in '$DS in patients wit3out 3ypoperfusion 'gainst t3e use of pulmonary artery cat3eter for patients wit3 sepsis;induced '$DS Frone position for sepsis;induced '$DS wit3 Fa+ 2/#i+ 2 ratio PB0 'gainst use of beta;2 agonists for patients wit3 sepsis;induced '$DS wit3out bronc3ospasm 'gainst use of #+, in adult patients wit3 sepsis;induced '$DS )levate 3ead of bed <0L7B degrees in mec3anically ventilated patients spontaneous breat3ing trials and a weaning protocol 4lood glucose control via protocol targeting blood glucose P"0 g/d( F3armacologic ,*) prop3ylaxis unfractionated or low molecular weig3t 3eparin Stress ulcer prop3ylaxis for patients wit3 ris5 factors for G% bleeding )arly enteral nutrition against parenteral nutrition in t3e first d 'gainst use of omega;< fatty acids as an immune supplement %ncorporate goals of care into treatment planning using palliative care principles w3ere appropriate '$DS H acute respiratory distress syndrome@ t3romboembolism@ G% H gastrointestinal.
#+, H 3ig3;fre6uency 3ig3;fre6ue ncy
oscillatory
ventilation@
,*) H venous
27
D)#%N%*%+NS 'ND GU%D)(%N) &'NG)S
3yperlactemia and coagulopat3 coagulopat3y> y> and may need to investi; gate alternate alternate t3erapies t3erapies in t3is population wit3 sepsis wit3 a p3enotype for refractory 3ypotension :2=. S S &
. y l n o e s u l a n o s r e p r o # . " / ! / 2 0 t a m o c . b u p t r e b e i l . e n i l n o m o r f s e i t i l a n o i t a N r o f y t i s r e v i n U i x g n a u G y b d e d a o l n w o D
e a n a r t e r i a l
G u i d e l i n e s
p r e s s u r e
2 0 !
t a r g e t
& 3 a n g e s
' number of evidence; based c3anges in tions are recommenda; evident evident in t3e 20! SS& Guideline Guideliness 9*able 9*able >. *3e most substantial c3ange in t3e new guidelines is t3at for ini; tial tial resusc resuscita itati tion on protocolied protocolied care wit3 early goal;directed t3erapy is no longer recommended. *3ere are no c3anges in recommendations regarding vasopressors 9norepinep3rine first; first; c3oice c3oice vasopresso vasopressor r add vasopre pressin or epinep3rine if not at target mean arterial pressure> and steroids 9consider for patients wit3 septic s3oc5 refractory to ade6uate fluids and vaso sop pres res; sors>. *3e new guidelines include a number of strong r e eccom; mendations wit3 moderate or 3ig3;6uality evidence 9*able ">. ' few of t3ese c3anges are 3ig3lig3ted below.
*3e new guidelines continue continue to recommend a target mean arterial pressure of !B mm g over 3ig3er targ target ets. s. ' multi; ti; center open;lab open;label el trial trial of ! patients wit3 septic s3oc5 firmed t3at con; resuscitation wit3 a 3ig3er mean arterial pressur e target of "0L"B mm g 3ad no impact impact on 2";day 2";day or -0; day mortality :2"=. 4ut t3e new guideli guidelines nes now also r ecommend1 ecommend1 II3en a better unde unders rsta tand ndiing of any any patientJs patientJs condition is obtained t3is target s3ould be individualie d to t3e per; taining circumstances.JJ circumstances.JJ *3is again reflects a move ward personali ed card of toward personali t3e patient wit3 sepsis in t3e %&U. ) a r l y
g o a l ; d i
r e c t e d
wit3 usual care in patients wit3 septic s3oc5 reported a re; duction in 3ospital mortality from 7!.B8 to <0.B8 :2-=. )arly goal; directed t3erapy was recommended in all t previous SS& guidelines 3 but 3as been removed from e t3e 20! guidelines. *3ree r multi;center randomied a controlled clinical trials p 9Frotocolied &are for y )arly Septic S3oc5 ' single;center 'ustralasian $e; suscitation randomied randomied trial trial of early in Sepsis )valuation and t3erapy y 9six; 9six; Frotocolised anage; ment goal;directe goal;directed d t3erap 3our resuscitati resuscitation on protocol protocol in Sepsis> s3owed no to ac3i ac3iev evee sp spec ecif ific ic blood benefit to early goal; pressure &,F &,F Sc,+2 directed t3erapy in t3e and 3emoglobin compared treatment of septic s3oc5. Frotocolied &are for )arly Septic S3oc5 9Fro&)SS> :<0= was conducted in t3e United States 'ustralasian $esuscitation in Sepsis )valuation 9'$%S)> :<= was conducted in 'ustralia and New Kealand and Frotocolised anagement in Sepsis 9Fro%S)> :<2= was conducted in t3e United ?ingdom. ' trial;level meta;analysis confirmed no overall benefit from early goal;directed t3erapy in septic s3oc5 :<<=. ' patient; level meta;analysis of t3e t3r e eee trials included <2< patients and -0;day mortality was similar for early goal;directed t3erapy 927.-8> and usual care 92B.78>. ' sub;group analysis of patients wit3 worse s3oc5 93ig3er lactate combined 3ypotension and 3ig3 lactate or 3ig3er predicted ris5 of deat3> also confirmed t3at early goal; directed t3erapy was not associated wit3 improved survival. )arly goal;directed t3erapy was associated wit3 increased %&U days cardiovascular support and 3ig3er costs :<7=. 4 l o o d p
D)#%N%*%+NS 'ND GU%D)(%N) &'NG)S r o d u c t
t r a n s f u s i o n
*3e 20! SS& guidelines includes a significant c3ange in t3e recommendation for red blood cell 9$4&> transfusion1 IIe recommend t3at $4& transfusion occur only w3en 3emoglobin concentration decreases to P g/d( in adults in t3e absence of extenuating circumstances suc3 as myo; cardial isc3emia severe 3ypo 3ypoxe xemi mia a or acut acutee 3emorr3 age 9strong recommendation 3ig3 6uality of evidence>.JJ *3is is different t3an t3e 202 guidelines t3at recommende recommended d early goal; directed t3erapy wit3 a target 3emoglobin of 0 g/d( in
2B
27
t3e early resuscitation of patients wit3 sepsis. *3is signifi; cant c3ange c3ange is based based on t3e results of t3e t3e *ransfus *ransfusion ion $ e; 6uirements in Septic S3oc5 9*$%SS> trial t3at compared a transfusion t3res3old of versus - g/d( in patients wit3 se ptic s3oc5 after %&U admission. No differences in -0;day mortalit isc3emic ic events events or use of life suppor supportt was rtality isc3em identified and sig; nificantly fewer $4& transfusions were administered in t3e g/ d( t3res3old group :
. y l n o e s u l a n o s r e p r o # . " / ! / 2 0 t a m o c . b u p t r e b e i l . e n i l n o m o r f s e i t i l a n o i t a N r o f y t i s r e v i n U i x g n a u G y b d e d a o l n w o D
N'F+(%* N'F+(%*'N+
2. 4one $& 4al5 $' &erra #4 et al. 'merican 'merican &ollege of &3est F3ysicians/Society of &ritical &ritical &are edicine &on; sensus &onference1 Definitions for sepsis and organ failure and guidelines for t3e use of innovative t3erapies in sepsis. &rit &are ed --2@201"!7L"7. <. (evy #in5 F F ars3all O& et al. %nternational %nternation al Sepsis Definitions &onference. 200 S&&/)S%&/'&&F/'*S/ S%S %nternational Sepsis Definitions &onference. &rit &are ed 200<@<12B0L2B!. 7. Singer Deutsc3man &S Seymour & et al. al. *3e *3ird %nternational &onsensus Definitions for Sepsis and Septic S3oc5 9Sepsis;<>. O'' 20!@<B1"0L"0. B. Seymour & (iu , %was3yna *O et al. 'ssessment of clinical clinical criteria criteria for sepsis1 #or t3e *3ird %nternational &onsensus Definitions for Sepsis and Septic S3oc5 9Sepsis; <>. O'' 20!@<B1!2L7. !. S3an5ar;ari S3an5 ar;ari F3illips GS (evy ( et al. Developing Source control a new definition and assessing new clinical criteria for septic *wo new best practice statements are included in t3e 20! s3oc51 #or t3e *3ird *3ird %nternational &onsensus Definitions for Sepsis and Septic S3oc5 9Sepsis;<>. 9Sepsis;<>. O'' 20!@<B1BL guidelines recommending prompt source control control of infection ". as 6uic5ly as possible1 as possible1 . $ussell O' (ee * Singer O et al. *3e Septic S3oc5 <.0 . e recommend t3at a specific anatomic diagnosis of Definition and *rials1 ' vasopressin and septic s3oc5 trial infection re6uiring emergent source control be experience. &rit &are ed 20@7B1-70L-7". identified or excluded as rapidly as possible in ". Driessen $G van de Foll &G ol # et al. *3e in; patients wit3 sepsis or septic s3oc5 and t3at any fluence of a c3ange in septic s3oc5 definitions on intensive re6uired re6uired source control control interve intervention ntion be im; care epidemiology and outcome1 &omparison of Sepsis; plemented as soon as medically and logistically 2 and Sepsis;< definitions. %nfect Dis 9(ond> 20@Sep 2!1L. practical after t3e diagnosis is made 94FS>. -. ?au5onen ? 4ailey Filc3er D et al. Systemic in; 2. e recommend prompt removal of intravascular ac; flammatory response syndrome criteria in defining severe cess devices t3at are a possible source of sepsis or sepsis. N )ngl O ed 20B@<21!2-L!<". septic s3oc5 after ot3er vascular access 3as been 0. ,incent O( oreno $ *a5ala *a5ala O et al. *3e S+# S+#' ' 9Sepsis; establis3ed 94FS>. $elated +rgan #ailure 'ssessment> score to describe organ dysfunction/failure. %ntensive &are ed ed --!@2210L0. Summary . $ait3 )F Udy '' 4ailey et al@ 'ustralian and New )arly recognition and diagnosis of sepsis is re6uired to pr to pr e; Kealand %ntensive &are Society 9'NK%&S> &entre for vent t3e transition into septic s3oc5 w3ic3 is associated wit3 +utcomes and $esource )valuation 9&+$)>. Frognostic a mortality rate of 708 or more. New definitions for sepsis 'ccuracy of t3e S+#' Score S%$S &riteria and 6S+#' and septic s3oc5 9Sepsis;<> 3ave been developed. *3e new score for in;3ospital mortality among adults wit3 suspected Se psis;< definition is IIlife;t3reatening IIlife;t3reatening organ dysfunction infection admitted to t3e intensive care Unit. O'' 20@ caused caused by a dysregulated 3ost response to infection.JJ *3e <12-0L<00. clinical criteria for sepsis include suspected or documented 2. &3urpe5 Snyder ' an V et al. Ruic5 Ruic5 Se psi psis;relate s;related d infection and an acute increase of two or more S+#' points +rgan #ailure 'ssessment Systemic %nflammatory $esponse Syndrome and )arly arning Scores for detecting clinical as a proxy for organ dysfunction. Septic s3oc5 is defined by deteriorat deterioration ion in infecte infected d patients patients outside outside t3e intens intensive ive t3e clinical criteria of sepsis and vasopressor t3erapy needed care unit. 'm O $espir &rit &are ed 20@-B1-0!L-. to elevate mean ar terial erial pressure C!B mm g and lactate E2 (emac3atti (emac3atti N ?rastinova ?rastinova ) et al@ al@ #renc3 Societ Society y mmol/( 9" mg/d(> despite ade6uate fluid resuscitation. ' <. #reund of )mergency )me rgency edicine &ollaborators Grou p. ognostic o gnostic Fr new screening tool for sepsis 96S+#'> 3as been proposed accuracy of Sepsis;< criteria for in;3ospital mortality among t3at includes Glasgow &oma Score of < or less respiratory patients wit3 suspected infection presenting to t3e emer; rate of 22 or more per minute and systolic blood pressure gency department. O'' 20@<1<0L<0". M00 mm g. ' 6S+#' score of two or more identifies a 7. #ar5as O. Fulm&rit* Fulm&rit*op op ten problems wit3 t3e t3e new sepsis patient at greater ris5 of poor outcome. *3e SS& guidelines definition. #ebruary 2- 20!. 3ttps1//emcrit.org/pulmcrit/ were updated recently recently and include gr eate eater evidence;based problems;sepsis;<;definition/ 9(ast accessed Oanuary B recomme recommendat ndations ions for treatmen treatmentt of sepsis sepsis in attempts to 20">. reduce sepsis;associated mor talit tality. B. &riti6ue of t3e odern Definitions for Sepsis 9Se 9Se psi psis;%%%>. www .d .d er an ge dp 3y sio lo lo gy gy .c .c om /m /m ain /r /r e6 uir ed ; 'ut3or Disclosure Statement reading/infect ious;diseases;antibiotics;and;sepsis/&3apter 820.7.0./c 820.7.0./criti 6ue;modern;definitions;sepsis;sepsis;iii No competing financial interests exist. 9last accessed Oan; uary B 20">. $eferences !. &arneiro ' FoW voa F Gomes O'. Dear Sepsis;< we are sorry to say t3at we donJt li5e you. $ev 4ras *er %ntensiva . ,incent ,incent O( ars3all O& Namendys;Silva S' et al. 's; 20@2-17L". sessment of t3e worldwide burden of critical illness1 *3e . &ortes;Fuc3 % artog &S. +pening t3e debate on t3e new intensive care over nations 9%&+N> audit. (ancet $espir sepsis definition1 definition1 &3ange is is not necessarily necessarily progress1 ed 207@21<"0L<"!. $ evi;
D)#%N%*%+NS 'ND GU%D)(%N) &'NG)S
2B
D)#%N%*%+NS 'ND GU%D)(%N) &'NG)S
. y l n o e s u l a n o s r e p r o # . " / ! / 2 0 t a m o c . b u p t r e b e i l . e n i l n o m o r f s e i t i l a n o i t a N r o f y t i s r e v i n U i x g n a u G y b d e d a o l n w o D
sion of t3e sepsis definition s3ould be based on new scien; tific insig3ts. 'm O $espir &rit &are ed 20!@-71!L". www.a ts ts Ao Ao ur na ls ls.o rg/d oi/ pdf/0.!7/rccm.20!0 7;0 7;0<7) <7)D D 9last accessed Oanuary B 20">. ". ac3ado #$ SalomaXo $ Fontes de 'evedo (& et al. on be3alf of t3e (atin 'merican Sepsis Sepsis %nstitute %nstitute.. 3y ('S% ('S% did did not endor endorse se t3e new defini definitio tions ns of sepsis publis3ed today in O''. 3ttp1//ilas.org.br/assets/ar 6uivos/upload/ statement; en.pdf en.pdf 9last 9last access accessed ed Oanuary B 20">. -. Dellinger $F $F &arlet O asur et al. Surviving Sepsis &aign guidelines for management of severe sepsis and septic s3oc5. &rit &are ed 2007@<21"B"L"<. 20. Dellinger $F $F (evy &arlet O et al. Surviving Sepsis &aign1 %nternational guidelines for management of se; se; vere sepsis and septic s3oc51 200". &rit &are ed 200"@
metri metrics cs and and outcomes in a .B;year study. %ntensive &are ed 207@701 ! 2 < L ! < < . 2<. $3odes ' F3illips G 4eale $ et al. *3e Surviving Sepsis &aign bundles and outcome1 $esults from t3e %nter; national ulticent ulticentre re Frevalenc Frevalencee Study on Sepsis 9t3e %; FreSS study>. %ntensive &are ed 20B@71!20L!2". 27. $3odes ' )vans () 'l3aani et al. Surviving Sepsis &aign1 %nternational guidelines for management of sepsis and septic s3oc51 20!. &rit &are ed 20@7B17"!L B B 2 . 2B. #errer $ artin;(oec3es % F3illips G et al. )mpiric an; tibiotic treatment reduces mort mortal alit ity y in seve severe re sepsis sepsis and and septic s3oc5 from from t3e first first 3our1 $esults from a guideline; based performance improv improveme ement nt progra program. m. &rit &are ed 2 0 7 @ 7 2 1 7 L B B . 2!. Dellinger $F $F Sc3orr &' &' (evy . ' UsersJ Guide to t3e
2! 20! Surviving Sepsis ness among initially Guidelines. &rit &are 3ypotensive patients ed 20@7B1 wit3 sepsis and septic < s3oc5. &rit &are ed " 20"@7!1"-L-". 2". 'sfar 'sfar F F ei eiani ani # # L amel O# et al. ig3 < versus low blood; " pressure target in patients B wit3 septic s3oc5. N . )ngl O ed 2. (eisman (eisman D) Doerfler Doerfler 207@<01B"
D)#%N%*%+NS 'ND GU%D)(%N) &'NG)S transf transfusi usion on in septic septic s3oc51 Subgroup analyses of t3e *$%SS trial. 'cta 'naest3esiol Scand 20@!1!!LB.
'ddre ss co rre sp on de nc
to1 Dr. (e na . Na po lit an 'c ute &a re Su rg er *ra uma and Surgic al &ritica l &are Univer sity of ic3i gan ealt3 Syste m $oom &<70 ;U Univer sity ospit al B00 )ast edical Drive SF& B0<< 'nn 'rbor % 7"0-;B0<< );mail1 lenanZumic3.edu
2
