拯救脓毒症患者行动国际严重脓毒症和脓毒性休克ppt课件

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 Car

2、e Med. 2019;41:580-637.Dellinger RP et al. Intensive Care Med. 2019;39:165-228.Copyright 2019 SCCM/ESICM; SSC 2019 GuidelinesSlide Presentations 1. Grading of Recommendations: G. Rubenfeld 2. Initial Resuscitation: D. Annane3. Infection-Related Issues: S. Opal4. Adjunctive Therapy: H. Gerlach 5. Mec

3、hanical Ventilation: J. Sevransky6. Glucose Control, Bicarbonate Therapy: C. Sprung.Slide 2Copyright 2019 SCCM/ESICM; SSC 2019 GuidelinesSlide Presentations 7. Nutrition: F. Machado, D. Angus8. Renal Replacement Therapy: S. Townsend9. Prophylaxis for Venous Thromboembolism (VTE): C. Deutschman10. St

4、ress Ulcer Prophylaxis (SUP): R. Jaeschke11. Setting Goals of Care: R. Kleinpell12. Pediatric Considerations: J. CarcilloSlide 3Copyright 2019 SCCM/ESICM; SSC 2019 Guidelines Grading of Recommendations Assessment, Development , and Evaluation (GRADE) MethodologyG. RubenfeldSlide 4Copyright 2019 SCCM

5、/ESICM;Grading of Recommendations Assessment, Development, and Evaluation (GRADE) MethodologyQuality of EvidenceSlide 5Copyright 2019 SCCM/ESICM;Downgrading and Upgrading Quality of EvidenceRCTPoor quality of planning and implementation Inconsistency of results Indirectness of evidence Imprecision o

6、f resultsHigh likelihood of reporting bias.ObservationalStudiesStart with 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 2019 SCCM/ESICM;Strength of Recom

7、mendationStrongRecommendWhen virtually all informed patients would choose the same management strategyWeak (conditional)SuggestImply that choices will differ across the range of patient values and preferencesSlide 7Copyright 2019 SCCM/ESICM;Factors That Influence Strength of RecommendationSlide 8Cop

8、yright 2019 SCCM/ESICM; SSC 2019 Guidelines Initial ResuscitationHemodynamic SupportD. Annane Initial Resuscitation Fluid Therapy Vasopressor Therapy Inotropic Therapy; Initial ResuscitationWe recommend the protocolized, quantitative resuscitation of patients with sepsis-induced tissue hypoperfusion

9、 (defined as hypotension persisting after initial fluid 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 2019 SCCM/ESICM; Initial ResuscitationDuring the first 6 hours, the goals

10、 of initial resuscitation of sepsis-induced hypoperfusion should include all of the following as a part of a treatment protocol (Grade 1C): Central venous pressure 8-12 mm HgMean arterial pressure 65 mm HgUrine output 0.5 mL/kg/hCentral venous (superior vena cava) or mixed venous oxygen saturation 7

11、0% or 65%, respectivelySlide 11Copyright 2019 SCCM/ESICM;Initial 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. 2019;345:8-7.Second multicenter

12、 randomized trial of 314 patients with severe sepsis in 8 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. 2019;6:331-334.Slide 12Copyright 2019 SC

13、CM/ESICM;Early Goal-Directed Therapy in the Treatment of Severe Sepsis 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. 2019;3

14、45: 8-7.Slide 13Copyright 2019 SCCM/ESICM; Initial ResuscitationWe suggest, 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 2019 SCCM/ESICM;Initial ResuscitationOne multicen

15、ter randomized trial demonstrated that early quantitative resuscitation based on lactate clearance (decrease by at least 10%) was non-inferior to resuscitation based on achieving ScvO2 of 70% or more.Jones A. JAMA. 2019;303:739746.A second multicenter randomized trial demonstrated that a strategy ba

16、sed on 20% decrease in lactate levels per 2 hours of the first 8 hours, in addition to achievement of an ScvO2 target, was associated with a 9.6% absolute reduction in mortality.Jansen TC. Am J Respir Crit Care Med. 2019;182:752761.Slide 15Copyright 2019 SCCM/ESICM;Lactate Clearance vs Central Venou

17、s Oxygen Saturation as Goals of Early Sepsis Therapy: MortalityJones A. JAMA. 2019;303:739746.Slide 16Copyright 2019 SCCM/ESICM;Early Lactate-Guided Therapy in Intensive Care Unit PatientsJansen TC. Am J Respir Crit Care Med. 2019;182:752761.adjusted HR= 0.61; 95% CI, 0.43-0.87; P= 0.006Slide 17Copy

18、right 2019 SCCM/ESICM; Fluid TherapyWe recommend crystalloids be used as the initial fluid of choice 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 18

19、Copyright 2019 SCCM/ESICM; Fluid Therapy - MortalityThree multicenter randomized trials showed no significant difference in mortality between crystalloids and hydroxyethyl starches.Brunkhorst F. N Engl J Med .2019;358:125-.Guidet B. Crit Care. 2019;16:R94.Myburgh JA. N Engl J Med. 2019;367:1901-1911

20、.One multicenter randomized trial demonstrated increased mortality rates with HES 130/0.42 fluid resuscitation compared to Ringer acetate (51% vs 43%. P=0.03). Perner A. N Engl J Med. 2019;367:124-134. Slide 19Copyright 2019 SCCM/ESICM;Zarychanski R. JAMA. 2019;309:678-688.Meta-analysis: HES versus

21、Other Fluids MortalityRR, 1.09; 95% CI, 1.02 to 1.17Slide 20Copyright 2019 SCCM/ESICM; Fluid Therapy - Kidney injuryThree multicenter 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.

22、2019;358:125-.Perner A. N Engl J Med. 2019;367:124-134.Myburgh JA. N Engl J Med. 2019;367:1901-1911.One multicenter randomized trial did not find an increase in the risk of acute kidney injury with hydroxyethyl starch as compared with crystalloids. Guidet B. Crit Care. 2019;16:R94.Slide 21Copyright

23、2019 SCCM/ESICM;Zarychanski R. JAMA. 2019;309:678-688.Meta-analysis: HES versus Other Fluids Renal Replacement TherapySlide 22Copyright 2019 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 c

24、rystalloids. (Grade 2C)Slide 23Copyright 2019 SCCM/ESICM;Meta-analysis: Albumin versus Other FluidsOutcomesIllustrative comparative risks (95% CI)Relative effect(95% CI)No. Of participants(studies)Quality of the evidence(GRADE)Assumed riskCorresponding riskControlOther fluids (may be crystalloid or

25、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(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 colloid

26、s)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 2019 SCCM/ESICM; Fluid TherapyWe recommend an initial fluid challenge in patients with sepsis-induced tissue hypoperfusion with suspicion of hypovolemia to achieve a mi

27、nimum 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 some patients. (Grade 1C)Slide 25Copyright 2019 SCCM/ESICM; Fluid TherapyWe recommend that a fluid challenge technique be applied wherein fluid adm

28、inistration is continued as long as there is hemodynamic improvement either based on dynamic (eg, change in pulse pressure, stroke volume variation) or static (eg, arterial pressure, heart rate) variables (Ungraded). Slide 26Copyright 2019 SCCM/ESICM;Vasopressor TherapyWe recommend that vasopressor

29、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 2019 SCCM/ESICM;Meta-analysis of Norepinephrine versus DopamineOutcomesIllustrative comparative risks* (95% CI)Relative effect(95%

30、 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 studies) moderate1,2530 per 1000482 per 1000(440 to 524)Serious adverse events - Supraventricular arrhythmiasStudy popula

31、tionRR 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 studies) moderate1,239 per 100015 per 1000(8 to 27)*The assumed risk is the median control group risk across studies. Th

32、e 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; RR: Risk ratio; 1 Strong heterogeneity in the results (I squared = 85%), however this reflects degree of e

33、ffect, 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 2019. We have lowered the quality of evidence one level for indirectness.Slide 28Copyright 2019 SCCM/ESICM; Vasopressor Therap

34、yWe suggest epinephrine (added to and potentially substituted for norepinephrine) when an additional agent is needed to maintain adequate blood pressure. (Grade 2B) Slide 29Copyright 2019 SCCM/ESICM;Meta-analysis of Norepinephrine versus EpinephrineOutcomesIllustrative comparative risks (95% CI)Rela

35、tive 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) moderate1357 per 1000343 per 1000(268 to 429)Serious adverse events - supraventricular arrhyth

36、miasStudy 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(-5 to 95)1 Grade reduced for imprecision.2 Outcome reported only in one of fo

37、ur trials.Slide 30Copyright 2019 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 vasopressin is not recommended as the single initial vasopressor for treatment of

38、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 2019 SCCM/ESICM;Meta-analysis of Norepinephrine versus VasopressinOutcomesIllustrative compar

39、ative 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) low1,2,3,4386 per 1000433 per 1000(371 to 502)Serious adverse events - s

40、upraventricular 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 per 100015 per 1000(5 to 43)Serious adverse events - stro

41、keStudy 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 events - limb ischemiaStudy populationR.R 0.54 (0

42、.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 norepinephrine versus norepinephrine.3 Unclear

43、 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 2019 SCCM/ESICM; Vasopressor TherapyWe suggest dopamine as an alternative vasopressor agent to norepinep

44、hrine 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 :norepinephrine is associated with serious arrhythmiascardiac output is known to be high and blood pressure persistently

45、low, or as salvage therapy when combined inotrope/ vasopressor drugs and low-dose vasopressin have failed to achieve MAP target . (Grade 1C) Slide 33Copyright 2019 SCCM/ESICM; Vasopressor Therapy We recommend that low-dose dopamine not be used for renal protection. (Grade 1A) We recommend that all p

46、atients requiring vasopressors have an arterial catheter placed as soon as practical if resources are available Slide 34Copyright 2019 SCCM/ESICM; Inotropic TherapyWe recommend that a trial of dobutamine infusion up to 20 g/kg/min be administered or added to vasopressor (if in use) in the presence o

47、f: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 increase cardiac index to

48、 predetermined supranormal levels. (Grade 1B) Slide 35Copyright 2019 SCCM/ESICM;SSC 2019 Guidelines Infection-Related IssuesS. OpalScreeningDiagnosis Antimicrobial therapySource controlSelective decontaminationCopyright 2019 SCCM/ESICM;Screening for Sepsis and Performance Improvement We recommend ro

49、utine 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 (Ungraded).Slide 37C

50、opyright 2019 SCCM/ESICM;Diagnosis 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 organisms, we recom

51、mend 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 same

52、time if from a different anatomic site (Grade 1C).Slide 38Copyright 2019 SCCM/ESICM;Diagnosis Cultures of other sites (preferably quantitative where appropriate), such as urine, cerebrospinal fluid, wounds, respiratory secretions, or other body fluids that may be the source of infection, should also

53、 be obtained before antimicrobial therapy if doing so does not cause significant delay in antibiotic administration (Grade 1C).We suggest the use of the 1,3 -D-glucan assay (Grade 2B), mannan and anti-mannan antibody assays (Grade 2C) when invasive candidiasis is in the differential diagnosis of inf

54、ection.Slide 39Copyright 2019 SCCM/ESICM;Diagnosis We recommend that imaging studies be performed promptly in attempts to confirm a potential source of infection. Potential sources of infection should be sampled as they are identified and in consideration of patient risk for transport and invasive p

55、rocedures (eg, careful coordination and aggressive monitoring if the decision is made to transport for a CT-guided needle aspiration). Bedside studies, such as ultrasound, may avoid patient transport (Ungraded).Slide 40Copyright 2019 SCCM/ESICM;Antimicrobial Therapy The administration of effective i

56、ntravenous antimicrobials within the first hour of recognition of septic shock (Grade 1B) and severe sepsis without septic shock (Grade 1C) should be the goal of therapy. Remark: Although the weight of the evidence supports prompt administration of antibiotics following the recognition of severe sep

57、sis and septic shock, the feasibility with which clinicians may achieve this ideal state has not been scientifically evaluated.Slide 41Copyright 2019 SCCM/ESICM;Summary: Early Antibiotics for Sepsis/Septic Shock StudiesStudy/yr Design (no.)Population/OutcomeLimitationOther Outcome Early vs. LateQual

58、ity of EvidenceKumar 2019 (1)Multicentern=2154Septic shock only; survival-HDRetrospectiveTime-response relationshipOR for death: 1.119/h delay, P.0001Moderate-high for shockBarochia 2019 (2)Meta-analysisn=654s/ss/SS; survival 28 days or HDObservationalbefore-aftern= 4 studies, homogeneous, I2=0%OR 0

59、.58 (0.33-0.85), P.0001ModerateFerrer2009 (3)Multicenter (n=2796)ss/SS; survival-HDObservationalbefore-afterTime-response relationshipOR 0.67 1 h, P.01OR 0.80 1-3 h, nsOR 0.87 3-6 h, nsModerateBarie2019 (4)Single center(n=331)Surgical ICU s/ss; survival-HDInception cohort Time-response relationshipO

60、R 1.1021 (1.003-1.038)/30 min, P.05LowLevy 2019 (5)Multicenter (n=15,022)ss/SS; survival-HDObservationalbefore-after1 h from hospital ward, or 3 h from EDOR 0.86 (0.79-0.93), P65 yr. Septic shock; survival-28 daysObservationalmatched case-control4 h from shock onset; indirect-with other intervention