1、Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic ShockSlide PresentationsSprung CL,Angus DC,Annane D,Carcillo JA,Deutschman CS,Gerlach H,Jaeschke R,Kleinpell RM,Machado FR,Opal S,Rubenfeld G,Sevransky J,Townsend SR,Dellinger RP.Dellinger RP et al.Crit Care Med.2013;41:
2、580-637.Dellinger RP et al.Intensive Care Med.2013;39:165-228.Copyright 2014 SCCM/ESICM SSC 2012 GuidelinesSlide Presentations 1.Grading of Recommendations:G.Rubenfeld 2.Initial Resuscitation:D.Annane3.Infection-Related Issues:S.Opal4.Adjunctive Therapy:H.Gerlach 5.Mechanical Ventilation:J.Sevransky
3、6.Glucose Control,Bicarbonate Therapy:C.Sprung.Slide 2Copyright 2014 SCCM/ESICM SSC 2012 GuidelinesSlide Presentations 7.Nutrition:F.Machado,D.Angus8.Renal Replacement Therapy:S.Townsend9.Prophylaxis for Venous Thromboembolism(VTE):C.Deutschman10.Stress Ulcer Prophylaxis(SUP):R.Jaeschke11.Setting Go
4、als of Care:R.Kleinpell12.Pediatric Considerations:J.CarcilloSlide 3Copyright 2014 SCCM/ESICM SSC 2012 Guidelines Grading of Recommendations Assessment,Development,and Evaluation(GRADE)MethodologyG.RubenfeldSlide 4Copyright 2014 SCCM/ESICMGrading of Recommendations Assessment,Development,and Evaluat
5、ion(GRADE)MethodologyQuality of EvidenceSlide 5Copyright 2014 SCCM/ESICMDowngrading and Upgrading Quality of EvidenceRCTPoor quality of planning and implementation Inconsistency of results Indirectness of evidence Imprecision of resultsHigh likelihood of reporting bias.ObservationalStudiesStart with
6、 a“low quality”ratingMagnitude of the effect is very large or large Dose-response relationship All plausible biases would decrease the magnitude of an apparent treatment effectSlide 6Copyright 2014 SCCM/ESICMStrength of RecommendationStrong Recommend When virtually all informed patients would choose
7、 the same management strategyWeak(conditional)Suggest Imply that choices will differ across the range of patient values and preferencesSlide 7Copyright 2014 SCCM/ESICMFactors That Influence Strength of RecommendationSlide 8Copyright 2014 SCCM/ESICM SSC 2012 Guidelines Initial ResuscitationHemodynami
8、c SupportD.Annane Initial Resuscitation Fluid Therapy Vasopressor Therapy Inotropic TherapyCopyright 2014 SCCM/ESICM Initial ResuscitationWe recommend the protocolized,quantitative resuscitation of patients with sepsis-induced tissue hypoperfusion(defined as hypotension persisting after initial flui
9、d challenge or lactate 4 mmol/L).This protocol should be initiated as soon as hypoperfusion is recognized and should not be delayed pending ICU admission.Slide 10Copyright 2014 SCCM/ESICM Initial ResuscitationDuring the first 6 hours,the goals of initial resuscitation of sepsis-induced hypoperfusion
10、 should include all of the following as a part of a treatment protocol(Grade 1C):Central venous pressure 8-12 mm Hg Mean arterial pressure 65 mm Hg Urine output 0.5 mL/kg/h Central venous(superior vena cava)or mixed venous oxygen saturation 70%or 65%,respectivelySlide 11Copyright 2014 SCCM/ESICMInit
11、ial ResuscitationOne randomized single-center trial demonstrated reduced mortality with early quantitative resuscitation for emergency department patients presenting with septic shock.Rivers E.N Engl J Med.2001;345:1368-1377.Second multicenter randomized trial of 314 patients with severe sepsis in 8
12、 Chinese centers reported a 17.7%absolute reduction in 28-day mortality(survival rates,75.2%vs.57.5%,P=0.001).EGDT Collaborative Group of Zhejiang Province.Zhongguo Wei Zhong Bing Ji Jiu Yi Xue.2010;6:331-334.Slide 12Copyright 2014 SCCM/ESICMEarly Goal-Directed Therapy in the Treatment of Severe Sep
13、sis and Septic ShockControlEGDTRelative Risk(95%Confidence Interval)P In-Hospital46.530.50.58(0.38-0.87)0.00928-day Mortality 49.233.30.58(0.39 0.87)0.0160-day Mortality 56.944.30.67(0.46-0.96)0.03Rivers E.N Engl J Med.2001;345:1368-1377.Slide 13Copyright 2014 SCCM/ESICM Initial ResuscitationWe sugg
14、est,in patients with elevated lactate levels as a marker of tissue hypoperfusion,targeting resuscitation to normalize lactate as rapidly as possible.(Grade 2C)Slide 14Copyright 2014 SCCM/ESICMInitial ResuscitationOne multicenter randomized trial demonstrated that early quantitative resuscitation bas
15、ed on lactate clearance(decrease by at least 10%)was non-inferior to resuscitation based on achieving ScvO2 of 70%or more.Jones A.JAMA.2010;303:739746.A second multicenter randomized trial demonstrated that a strategy based on 20%decrease in lactate levels per 2 hours of the first 8 hours,in additio
16、n to achievement of an ScvO2 target,was associated with a 9.6%absolute reduction in mortality.Jansen TC.Am J Respir Crit Care Med.2010;182:752761.Slide 15Copyright 2014 SCCM/ESICMLactate Clearance vs Central Venous Oxygen Saturation as Goals of Early Sepsis Therapy:MortalityJones A.JAMA.2010;303:739
17、746.Slide 16Copyright 2014 SCCM/ESICMEarly Lactate-Guided Therapy in Intensive Care Unit PatientsJansen TC.Am J Respir Crit Care Med.2010;182:752761.adjusted HR=0.61;95%CI,0.43-0.87;P=0.006Slide 17Copyright 2014 SCCM/ESICM Fluid TherapyWe recommend crystalloids be used as the initial fluid of choice
18、 in the resuscitation of severe sepsis and septic shock.(Grade 1B)We recommend against the use of hydroxy-ethyl starches for fluid resuscitation of severe sepsis and septic shock.(Grade 1B)Slide 18Copyright 2014 SCCM/ESICM Fluid Therapy-MortalityThree multicenter randomized trials showed no signific
19、ant difference in mortality between crystalloids and hydroxyethyl starches.Brunkhorst F.N Engl J Med.2008;358:125-139.Guidet B.Crit Care.2012;16:R94.Myburgh JA.N Engl J Med.2012;367:1901-1911.One multicenter randomized trial demonstrated increased mortality rates with HES 130/0.42 fluid resuscitatio
20、n compared to Ringer acetate(51%vs 43%.P=0.03).Perner A.N Engl J Med.2012;367:124-134.Slide 19Copyright 2014 SCCM/ESICMZarychanski R.JAMA.2013;309:678-688.Meta-analysis:HES versus Other Fluids MortalityRR,1.09;95%CI,1.02 to 1.17Slide 20Copyright 2014 SCCM/ESICM Fluid Therapy-Kidney injuryThree multi
21、center randomized trials showed a significant increase in the risk of acute kidney injury with hydroxyethyl starch as compared with crystalloids.Brunkhorst F.N Engl J Med.2008;358:125-139.Perner A.N Engl J Med.2012;367:124-134.Myburgh JA.N Engl J Med.2012;367:1901-1911.One multicenter randomized tri
22、al did not find an increase in the risk of acute kidney injury with hydroxyethyl starch as compared with crystalloids.Guidet B.Crit Care.2012;16:R94.Slide 21Copyright 2014 SCCM/ESICMZarychanski R.JAMA.2013;309:678-688.Meta-analysis:HES versus Other Fluids Renal Replacement TherapySlide 22Copyright 2
23、014 SCCM/ESICM Fluid TherapyWe suggest the use of albumin in the fluid resuscitation of severe sepsis and septic shock when patients require repeated boluses of crystalloids.(Grade 2C)Slide 23Copyright 2014 SCCM/ESICMMeta-analysis:Albumin versus Other FluidsOutcomesIllustrative comparative risks(95%
24、CI)Relative effect(95%CI)No.Of participants(studies)Quality of the evidence(GRADE)Assumed riskCorresponding riskControlOther fluids (may be crystalloid or colloid)Short-term mortalityStudy populationRR 0.84(0.73 to 0.97)1683(11 studies)moderate342 per 1000287 per 1000(249 to 332)Short-term mortality
25、(albumin vs crystalloids)444 per 1000377 per 1000(324 to 440)RR 0.85(0.73 to 0.98)1402(4 studies)moderate1Short-term mortality(albumin vs other colloids)342 per 1000195 per 1000(249 to 396)RR 0.81(0.57 to 1.16)281(7 studies)moderate11Grade reduced for imprecision.Slide 24Copyright 2014 SCCM/ESICM Fl
26、uid TherapyWe recommend an initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a minimum of 30 mL/kg of crystalloids(a portion of this may be albumin equivalent).More rapid administration and greater amounts of fluid may be needed in
27、some patients.(Grade 1C)Slide 25Copyright 2014 SCCM/ESICM Fluid TherapyWe recommend that a fluid challenge technique be applied wherein fluid administration is continued as long as there is hemodynamic improvement either based on dynamic(eg,change in pulse pressure,stroke volume variation)or static(
28、eg,arterial pressure,heart rate)variables(Ungraded).Slide 26Copyright 2014 SCCM/ESICMVasopressor TherapyWe recommend that vasopressor therapy initially target a mean arterial pressure(MAP)of 65 mm Hg.(Grade 1C)We recommend norepinephrine as the first-choice vasopressor.(Grade 1B)Slide 27Copyright 20
29、14 SCCM/ESICMMeta-analysis of Norepinephrine versus DopamineOutcomesIllustrative comparative risks*(95%CI)Relative effect(95%CI)No.of participants(studies)Quality of the evidence(GRADE)Assumed riskCorresponding riskDopamineNorepinephrineShort-term mortalityStudy populationRR 0.91(0.83 to 0.99)2043(6
30、 studies)moderate1,2530 per 1000482 per 1000(440 to 524)Serious adverse events-Supraventricular arrhythmiasStudy populationRR 0.47(0.38 to 0.58)1931(2 studies)moderate1,2229 per 100082 per 1000(34 to 195)Serious adverse events-Ventricular arrhythmiasStudy populationRR 0.35(0.19 to 0.66)1931(2 studie
31、s)moderate1,239 per 100015 per 1000(8 to 27)*The assumed risk is the median control group risk across studies.The corresponding risk(and its 95%confidence interval)is based on the assumed risk in the comparison group and the relative effect of the intervention(and its 95%CI).CI:Confidence interval;R
32、R:Risk ratio;1 Strong heterogeneity in the results(I squared=85%),however this reflects degree of effect,not direction of effect.We have decided not to lower the evidence quality.2 Effect results in part from hypovolemic and cardiogenic shock patients in De Backer,NEJM 2010.We have lowered the quali
33、ty of evidence one level for indirectness.Slide 28Copyright 2014 SCCM/ESICM Vasopressor TherapyWe suggest epinephrine(added to and potentially substituted for norepinephrine)when an additional agent is needed to maintain adequate blood pressure.(Grade 2B)Slide 29Copyright 2014 SCCM/ESICMMeta-analysi
34、s of Norepinephrine versus EpinephrineOutcomesIllustrative comparative risks(95%CI)Relative effect(95%CI)No.of participants(studies)Quality of the evidence(GRADE)Assumed riskCorresponding riskEpinephrineNorepinephrine Short-term mortalityStudy populationRR 0.96(0.77 to 1.21)540(4 studies)moderate135
35、7 per 1000343 per 1000(268 to 429)Serious adverse events-supraventricular arrhythmiasStudy populationRR 1.10(0.62 to 1.96)330(1 study)low1,2118 per 1000130 per 1000(58 to 198)Serious adverse events-ventricular arrhythmiasStudy populationRR 0.64(0.27 to 1.51)330(1 study)low1,275 per 100048 per 1000(-
36、5 to 95)1 Grade reduced for imprecision.2 Outcome reported only in one of four trials.Slide 30Copyright 2014 SCCM/ESICM Vasopressor TherapyVasopressin up to 0.03 units/minute can be added to norepinephrine with the intent of raising MAP to target or decreasing norepinephrine dosage.Low-dose vasopres
37、sin is not recommended as the single initial vasopressor for treatment of sepsis-induced hypotension,and vasopressin doses higher than 0.03-0.04 units/minute should be reserved for salvage therapy(failure to achieve adequate MAP with other vasopressor agents).Slide 31Copyright 2014 SCCM/ESICMMeta-an
38、alysis of Norepinephrine versus VasopressinOutcomesIllustrative comparative risks(95%CI)Relative effect(95%CI)No.of participants(studies)Quality of the evidence(GRADE)Assumed riskCorresponding riskVasopressinNorepinephrineShort-term mortalityStudy populationRR 1.12(0.96 to1.30)963(7 studies)low1,2,3
39、,4386 per 1000433 per 1000(371 to 502)Serious adverse events-supraventricular arrhythmiasStudy populationR.R 7.25(2.30 to 22.90)116(3 studies)low1,2,3,545 per 1000325 per 1000(103 to 1000)Serious adverse events-ventricular arrhythmiasStudy populationR.R 0.78(0.27 to 2.22)801(2 studies)low1,2,3,420 p
40、er 100015 per 1000(5 to 43)Serious adverse events-strokeStudy populationRR 1.04(0.07 to 16.51)778(1 study)low1,2,3,43 per 10003 per 1000(0 to 42)Serious adverse events-acute coronary eventsStudy populationR.R 1.05(0.44 to 2.50)849(3 studies)low1,2,3,423 per 100024 per 1000(10 to 58)Serious adverse e
41、vents-limb ischemiaStudy populationR.R 0.54(0.25 to 1.19)826(2 studies)low1,2,3,436 per 100019 per 1000(-4 to 36)1 Variations in type of molecule(vasopressin vs terlipressin)and in dose.2 Some studies have compared vasopressin with norepinephrine,and some studies have compared vasopressin plus norep
42、inephrine versus norepinephrine.3 Unclear risk of bias in some studies(methods for allocation concealment,blinding).4 Imprecision with wide confidence intervals spanning harm and benefit.5 Imprecision.Only 21 events.Slide 32Copyright 2014 SCCM/ESICM Vasopressor TherapyWe suggest dopamine as an alter
43、native vasopressor agent to norepinephrine only in highly selected patients(eg,patients with low risk of arrhythmias and/or low heart rate).(Grade 2C)Phenylephrine is not recommended except in circumstances where:a)norepinephrine is associated with serious arrhythmiasb)cardiac output is known to be
44、high and blood pressure persistently low,or c)as salvage therapy when combined inotrope/vasopressor drugs and low-dose vasopressin have failed to achieve MAP target.(Grade 1C)Slide 33Copyright 2014 SCCM/ESICM Vasopressor TherapyWe recommend that low-dose dopamine not be used for renal protection.(Gr
45、ade 1A)We recommend that all patients requiring vasopressors have an arterial catheter placed as soon as practical if resources are available Slide 34Copyright 2014 SCCM/ESICM Inotropic TherapyWe recommend that a trial of dobutamine infusion up to 20 g/kg/min be administered or added to vasopressor(
46、if in use)in the presence of:myocardial dysfunction as suggested by elevated cardiac filling pressures and low cardiac output,orongoing signs of hypoperfusion,despite achieving adequate intravascular volume and adequate mean arterial pressure.(Grade 1C)We recommend against the use of a strategy to i
47、ncrease cardiac index to predetermined supranormal levels.(Grade 1B)Slide 35Copyright 2014 SCCM/ESICMSSC 2012 Guidelines Infection-Related IssuesS.OpalScreeningDiagnosis Antimicrobial therapySource controlSelective decontaminationCopyright 2014 SCCM/ESICMScreening for Sepsis and Performance Improvem
48、ent We recommend routine screening of potentially infected seriously ill patients for severe sepsis to increase the early identification of sepsis and allow implementation of early sepsis therapy(Grade 1C).Performance improvement efforts in severe sepsis should be used to improve patient outcomes(Un
49、graded).Slide 37Copyright 2014 SCCM/ESICMDiagnosis We recommend obtaining appropriate cultures before antimicrobial therapy is initiated if such cultures do not cause significant delay(45 minutes)in the start of antimicrobial(s)administration(Grade 1C).To optimize identification of causative organis
50、ms,we recommend obtaining at least two sets of blood cultures(both aerobic and anaerobic bottles)before antimicrobial therapy,with at least one drawn percutaneously and one drawn through each vascular access device,unless the device was recently(48 hours)inserted.Blood cultures can be drawn at the s
