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1、1,Management of sepsis: a new bundle-ATLAS,陆一鸣 上海交通大学医学院附属瑞金医院,Definition of Sepsis,By consensus, sepsis is defined as The combination of pathologic infection and physiologic changes known collectively as the sepsis inflammatory response syndrome (SIRS) at least 2 of T 38C or 90 beats/min RR 20/min,
2、 or PaO2 12,000/mm3 or 4,000/mm3 The severity of the process is described by: Sepsis Severe sepsis Septic shock Multiple organ dysfunction syndrome (MODS) Mortality increases with the severity,Bone RC, et al. Chest 1992;101:1644-55,Sepsis 2001 Revised Definition,Suspected infection AND any two of th
3、e following: Temperature 38.3 oC or 90 / min Respiratory rate 20 / min Acutely altered mental status WBC 12,000 / mm3 or 10% Glucose 120 mg/dL in absence of diabetes,2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250-56,Martin GS N Engl J Med 2003;34
4、8:1546-1554,Epidemiology,Infection to Septic Shock,Nguyen HB et al. Ann Emerg Med 2006;48:28-54,Sepsis Causes High Mortality,Septic shock develops in about 40% of septic patients,Around 750,000 cases of sepsis per year in USA,Mortality,7%,30-40%,30-50%,45-80%,Useful Tip The average risk of death inc
5、reases by about 15-20% for each failing organ system,Ca. 31% (250K) sepsis deaths. This is more than all lung and colorectal cancer deaths combined,Infection,A pathologic process caused by invasion of normally sterile tissue or fluid or body cavity by microorganisms Pneumonia, empyema Urinary tract
6、infection Acute abdominal infection Meningitis Skin / wound / soft tissue infection Bone / joint infection Catheter infection Endocarditis Implantable device infection,Bone RC. Chest. 1992;101:1644-1655 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1
7、250-56,Severe sepsis,Sepsis complicated by organ dysfunction: Bilateral lung infiltrates with increased oxygen requirement to maintain SpO2 90% PaO2 / FiO2 2.0 mg/dL or increase 0.5 mg/dL Urine output 2 hours Total bilirubin 2 mg/dL Platelet count 1.5 or aPTT 60 secs (coagulopathy) Lactate 2 mmol/L,
8、2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250-56,Septic shock,Acute circulatory failure characterized by persistent arterial hypotension unexplained by other causes Sepsis-induced hypotension: SBP 40 mmHg from baseline Despite adequate volume re
9、suscitation (20-30 mL/kg crystalloid),2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Crit Care Med 2003;31:1250-56,Shock Definition,1895 JC Warren “momentary pause in the act of death” characterized by “cold, clammy sweat” and a “weak, thread-like” radial pulse 1899 Crile
10、Inadequate venous return manifest as hypoperfusion Modern Definition A clinical syndrome precipitated by a systemic derangement in organ perfusion resulting from the inadequate oxygen delivery to meet the metabolic demands leading to widespread cellular hypoxia and organ dysfunction,Screening for Sh
11、ock in Sepsis Infection and Lactate (LA) 4 mmol/L,Lactate 4 mmol/L 98.2% specific in predicting admission from ED 96% specific in predicting mortality in hospitalized normotensive patients,Aduen J et al. JAMA 1994;272:1678-85 Howell MD et al. Occult hypoperfusion and mortality in patients with suspe
12、cted infection. Int Care Med 2007;33:1892-9,Management : guidelines,Initial resuscitation Diagnosis Antibiotic therapy Source control Fluid therapy Vasopressors Inotropic therapy Steroids Rh APC Blood product administration,k. Mechanical ventilation l. Sedation m. Glucose control n. Renal replacemen
13、t o. Bicarbonate therapy p. Deep vein thrombosis prophylaxis q. Stress ulcer prophylaxis,Dellinger R Int Care Med 2004;30:536-555,Management of Sepsis: 3 Principles,Haemodynamic stabilisation Early Goal Directed Therapy IV fluids Litres! Vasopressors Inotropics Control the infection Early appropriat
14、e antibiotics broad spectrum initially Source control: surgical drainage, excision Modulation of the sepsis response Steroids Xigris (Recombinant activated protein C),Early Goal-directed Therapy,Central venous and arterial catheterization,CVP,No,SIRS + Infection + (SBP 4 mmol/L),Rivers E et al. Earl
15、y goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med 2001;345:1368-77,Physiologic Rationale for EGDT,Venous Oxygen Saturation (SvO2) Made Ridiculously Simple,Physiologic Effects on SvO2,EGDT in first 6 hours,Control: 3.5 Liters IVF Treatment: 5.0 Liters IVF,Rivers
16、 E et al. Early goal-directed therapy for severe sepsis and septic shock. N Engl J Med 2001;345:1368-77,Outcome Benefits of EGDT,Mortality decreased 16% (46.5 vs. 30.5%, p=0.009) Treat 6 patients to save 1 life (NNT = 6) Vasopressors by 14.5% (p=0.02) PA Catheters by 13.9% (p=0.01) Mech ventilation
17、by 15.0% (p=0.02) Hospital LOS by 3.8 days (p=0.04),Rivers E et al. Early goal-directed therapy for severe sepsis and septic shock. N Engl J Med 2001;345:1368-77,The Nuts and Bolts of Early Goal-Directed Therapy,The Nuts and Bolts of Early Goal-Directed Therapy,Target CVP 8-12 mmHg (Preload),CVP 8 m
18、mHg then continue at 150 mL/hr CVP 15 mmHg and MAP 110 mmHg Nitroglycerin 10-60 mcg/min until CVP 12 mmHg or MAP 90 mmHg,Rivers E et al. Early goal-directed therapy for severe sepsis and septic shock. N Engl J Med 2001;345:1368-77,Target MAP 65-90 mmHg (Afterload),MAP 120 bpm Vasopressin 0.01-0.04 U
19、/min Epinephrine 2-20 mcg/min MAP 110 mmHg Nitroglycerin 10-60 mcg/min until MAP 90 mmHg Hydralazine 10-40 mg IV,Rivers E et al. Early goal-directed therapy for severe sepsis and septic shock. N Engl J Med 2001;345:1368-77,Target ScvO2 70%,ScvO2 10 g/dL ScvO2 10 g/dL Dobutamine 2.5-20 mcg/kg/min tit
20、rated until ScvO2 70% Discontinue dobutamine when MAP 120 bpm Dopamine 5-10 mcg/kg/min if MAP 65 mmHg,Rivers E et al. Early goal-directed therapy for severe sepsis and septic shock. N Engl J Med 2001;345:1368-77,When to intubate and mech ventilate,Consider mech vent to decrease respiratory muscle ox
21、ygen consumption when: Significant lactic acidosis (Lactate 4 mmol/L) Respiratory distress Tachycardia SaO2 90% ScvO2 70%,Rivers E et al. Early goal-directed therapy for severe sepsis and septic shock. N Engl J Med 2001;345:1368-77,25,Asia NeTwork to ReguLAte Sepsis Care ATLAS,The ATLAS Investigator
22、s,ATLAS Investigators,ATLAS Specific Aims,To show that implementation of a sepsis bundle in multiple hospitals in Asia results in improved outcome To further validate that completion of the severe sepsis bundle results in better outcome compared to the bundle not completed,Data Collection,Bundle imp
23、lementation as standard care Weekly review of compliance De-identified patient information Multi-center database maintained at Loma Linda University LLU IRB Approved,Patient Inclusion,Adult patients in the ED having all three of: Two or more of the following: Temperature 38.3 C or 90 per min Respira
24、tion 20 per min WBC 12,000 or 10% bands Suspected or confirmed infection SBP 4 mmol/L or 2 organ dysfunction,Patient Exclusion,Trauma Emergency surgical indication Active seizure Acute pulmonary edema due to heart failure Acute stroke Acute hemorrhage Do-not-attempt-resuscitate status,The 6-Hour Sev
25、ere Sepsis Bundle,1) Initiate CVP/ScvO2 monitoring within 2 hours 2) Give broad spectrum antibiotics within 4 hours 3) Complete early goal directed therapy within 6 hours CVP 8 mmHg OR CI 65 mmHg, ScvO2 70% CVP or CI measured by any acceptable method is used as indicator for preload CVP 12 mmHg may
26、be appropriate for patient on mechanical ventilation 4) Monitor for decreasing lactate (lactate clearance),Nguyen HB et al. Implementation of a bundle of quality indicators for the early management of severe sepsis and septic shock is associated with decreased mortality. Crit Care Med 2007; 35:1105-
27、12,Data Collection,Bundle QI checklist completed at the bedside Study DCF completed by study coordinator De-identified patient information Study PI to confirm accuracy of data Copies of study DCF to submit to Loma Linda University Do not submit bundle QI checklist containing patient identifiers to L
28、oma Linda University,Outcome Measurements,Quarterly percentage compliance In-hospital mortality in patients with bundle completed vs not completed,Study Timeline,Sites maintain original copies of DCF Mail photocopies to: H. Bryant Nguyen, MD Quarterly, 15th of the month following completion of a qua
29、rtile First mailing October 15, 2008 for baseline data,Patient Characteristics,Laboratories,Baseline Hemodynamic Profile,ATLAS Bundle Outcome,CVP/ScvO2 monitoring by 2 hours Abx by 3 hours EGDT by 6 hours Lactate clearance,CVP/ScvO2 monitoring by 2 hours Abx by 3 hours EGDT by 6 hours Lactate cleara
30、nce,Data updated until November 2009: 398 patients,SSC Bundle Completion and Outcome,Lactate measured Cx prior to abx Fluid bolus Abx by 3 hours CVP 8 by 6 hours ScvO2 70 by 6 hours,Baseline compliance to the 6-hour severe sepsis bundle is low in Asia and completion of the bundle is associated with decreased mortality An organized team for severe sepsis care is likely to be associated with quality patient care In those hospitals without existing teams, quality improvement efforts are crucial to increase bundle compliance,Emergency Dept. ICU co-operation,