sepsis: evidence based controversies
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Sepsis: Evidence Based Controversies. Rachel Hinerman, MD FCCP. Definitions. Sepsis = suspected or proven infection and some of the following: General Variables Inflammatory Variables Hemodynamic Variables Organ Dysfunction Variables Tissue Perfusion Variables. Sepsis Variables. General. - PowerPoint PPT PresentationTRANSCRIPT
Rachel Hinerman, MD FCCP
DefinitionsSepsis = suspected or proven infection and
some of the following:General VariablesInflammatory VariablesHemodynamic VariablesOrgan Dysfunction VariablesTissue Perfusion Variables
Sepsis VariablesGeneral InflammatoryFeverHypothermiaTachycardiaAltered Mental StatusEdemaHyperglycemia
LeukocytosisLeukopeniaNormal WBC with > 10
% immature formsC-reactive protein > 2
SDProcalcitonin > 2 SD
Sepsis VariablesHemodynamic Organ DysfunctionSBP <90MAP < 70SBP decrease > 40
Tissue PerfusionLactate > 1MottlingDecreased Capillary
Refill
P/F < 300UO < .5 ml/kg for 2
hours despite volume resuscitation
Cr increase > .5INR > 1.5IleusPlt < 100 KBili > 4
Severe Sepsis DefinitionSepsis induced organ dysfunction,
hypoperfusion, or hypotension Hypotension Elevated Lactic Acid Oliguria ALI with P/F < 250 without pneumonia ALI with P/F < 200 with pneumonia Cr > 2 Bili > 2 Plt < 100K INR > 1.5
Septic ShockSepsis-induced hypotension that persists despite
adequate fluid resuscitation
*All definitions cited from “Surviving Sepsis Campaign” published in Critical Care Medicine Feb 2013
Dellinger, RP. et al. Dellinger, RP. et al. Crit Care MedCrit Care Med 2004;32 2004;32
SepsisSepsisInfectioInfectionn
Severe Severe SepsisSepsis
Septic Septic ShockShock
A National Health Concern?Myocardial Infarction
Incidence 900,000Deaths 225,000Mortality 25%
Cerebrovascular AccidentIncidence 700,000Deaths 163,5000Mortality 23%
TraumaIncidence 2,900,000Deaths 42,643Mortality 1.5%
Severe SepsisIncidence 751,000Deaths 215,000Mortality 40-60%
Angus, DC. et al Crit Care Med 2000;29National Highway Traffic Safety Commission, 2003
AHA- Heart Disease and Stroke Statistics, 2005 update
Angus DC et al. Crit Care Med 2001; 29. American Cancer Society
Karon et al. Am J Public Health 2001; 91. American Heart Assoc., 2001
Deaths/Year
Source control is most vital factorAdequate resuscitation or re-established
perfusion in 6 hoursAppropriate antibiotic therapy within 1 hr of
hypotension
Determinants of Mortality
InterventionsEarly Goal Directed Therapy (EGDT)
Anti-microbialsSteroidsGlucose ControlLung Protective Ventilation
%
Bernard et al. NEJM 2001; 344. Van den Berghe et al. NEJM 2001; 345. Rivers et al. NEJM 2001; 345Annane et al. JAMA 2002; 288. ARDS-Net Investigators, NEJM; 2000
EGDT ResuscitationBegin at onset of hypotension or lactate >4Do not delay while awaiting ICU admissionInitial bolus is 30 ml/kg crystalloid
Rivers E et al. N Engl J Med 2001; 345:1368–1377
EGDTInitial Resuscitation targets
CVP 8-12 (12-15 if mechanically ventilated)Mean arterial pressure ≥65Urine output ≥ 0.5 ml/kg/hourCentral venous oxygen saturation ≥ 65%If venous oxygen target still not achieved:
trial of fluid or transfuse PRBCs to HCT ≥30% and/or start dobutamine infusion
Rivers, NEJM 2001; 345:1368
EGDT Outcomes
Rivers, E et al. N Engl J Med 2001; 345
EGDT Cost23% reduction in hospital cost
Most cost effective if patient volume > 16 cases/year
Mean reduction of 4 days per hospital admission
Cost per life saved of approximately $32,336
Reduction in hospital charges from $135,000 to $82,000
Treciak S et al. Chest 2006;129:225-232
Huang DT, et al Crit Care 2003;7:S116
Shapiro N, et al. Crit Care Med 2006;34:1025-1032
What to Use?SAFE study: 28 day outcomes
RCT n=6997, 4% albumin or normal saline Albumin group, 726 deaths - Saline group, 729
deaths New organ failure was similar in the two groups No difference: ICU or hospital LOS, mechanical
ventilation days, or days of renal-replacement therapy
Guideline: colloid or crystalloid may be usedSchierhout G et al. BMJ 1998;
316:961–964 Finfer S et al. N Engl J Med 2004;
350:2247–2256
EGDT (and we mean EARLY)Retrospective analysis of 212 patientsDiagnosis: septic shock and ALI within 72 hours Adequate initial fluid resuscitation (AIFR) group
Administration of an initial fluid bolus of ≥ 20 mL/kg prior to and achievement of a central venous pressure of ≥ 8 mm Hg within 6 h after the onset of therapy with a vasopressor
Conservative late fluid management (CLFM) Even-to-negative fluid balance measured on at
least 2 consecutive days during the first 7 days after septic shock onset
Murphy C V et al. Chest 2009;136:102-109
Mean daily fluid balance days 1 through 7
Murphy C V et al. Chest 2009;136:102-109
NONSURVIVO
RS
SURVIVOR
S
Hospital mortality for AIFR, CLFM, both, or neither
Murphy CV et al. Chest 2009; 136:102-109
18%
57%
42%
77%
EGDT & Intubation
No difference: P/F ratio at 6h; EGDT with higher P/F at 72hNo difference in intubation rates at 6 hours 7-72 hour intubation rate: EGDT 2% vs. standard 16.8%
Rivers, E et al. N Engl J Med 2001; 345
Otero R, et al. Chest 2006;130:1579-1595
VasopressorsMean arterial pressure (MAP) maintained ≥
65First choice: norepinephrine or epinephrineVasopressin 0.03 units/min may be added
VasopressinVASST Trial
Hypothesis: VP will increase survival compared to NE at 28d
779 patients in septic shock requiring vasopressors for ≥6 hours
Randomization to vasopressin or norepinephrineNo difference in 28-day survival (35.4% v 39.3%, P =.27).
When groups were stratified by severity of hypotension Low-dose NE improved survival with VP 26% v 35%, P .05 Result persisted at 90 days: mortality of 36% vs. 46 %, P =.04
Russell J et al. NEJM2008;358,9.
InotropesDobutamine infusion for suspected
myocardial dysfunction suggested by elevated cardiac filling pressures and low cardiac output
Recommend against a strategy to increase cardiac index to supranormal levels
Gattinoni L, et al. New Engl J Med 1995; 333:1025-32Hayes MA, et al. New Engl J Med 1994; 330:1717-22
InterventionsEarly Goal Directed Therapy (EGDT)
Anti-microbialsSteroidsGlucose Control
AntimicrobialsBegin therapy within the first hour of
recognizing severe sepsis or septic shockBroad spectrum: one or more agents against
likely bacterial or fungal pathogensConsider combination therapy for potentially
resistant gram negative pathogensConsider combination therapy in neutropenic
patientsNarrow coverage when culture data available
Garnacho-Montero J et al. CCM2007;25:1888-1895
AntimicrobialsStudy objective: to determine the impact of initial
antimicrobial therapy on survival in patients with septic shock
Data: 5,715 cases between 1996 and 2005 Community-acquired = 55%; nosocomial origin =
45%Appropriate empiric antimicrobial therapy = 80% Overall rate of survival to hospital discharge =
43%The survival rates:
Appropriate initial therapy 52% Inappropriate initial therapy 10%
Kumar A et al. Chest 2009;136:1237-1248
InterventionsEarly Goal Directed Therapy (EGDT)Anti-microbials
SteroidsGlucose Control
2012 Steroid GuidelinesThe ACTH stimulation test should not be
used to identify the subset of adults with septic shock who should receive hydrocortisone.
Do not use corticosteroids in the treatment of sepsis in the absence of shock.
Corticosteroid therapy may be weaned when vasopressors are no longer required.
Recommended: hydrocortisone 50 mg iv q 6 hours
Dellinger RP, et al Crit Care Med 2008;36:296-327
InterventionsEarly Goal Directed Therapy (EGDT)Anti-microbialsSteroids
Glucose Control
Glucose ControversyLeuven protocol: 80-
110Cardiac-surgical ICUReduced ICU LOSLess organ dysfunctionHypoglycemia 6.2%Decreased Mortality
3.4% ARR all patients9.4% ARR LOS >5 days
Leuven protocol: 80-110
Medical ICU Reduced ICU LOSLess ventilator daysLess acute renal injuryHypoglycemia 18%Mortality difference
Overall: no difference LOS > 3 days: ↓
mortality
Van den Berghe G, et al. NEJM 2006; 354:449-461
Van den Berghe G, et al. NEJM 2001;345:1359-1367
NICE-SUGARRCT open-label comparing intensive BS 80-110
vs.. conventional BS <180 6,104 ICU heterogeneous patientsPrimary end point: 90-day mortalitySecondary end points:
Hypoglycemia Infection Need for organ support Intensive care unit and hospital length of stay
The NICE-SUGAR Study Investigators NEJM 2008; Volume 360:1283-1297
2012 Glucose Control GuidelinesPatients with severe sepsis and
hyperglycemia in the ICU should receive intravenous insulin.
Use validated protocol for insulin dose adjustment with a target glucose <180.
All patients on intravenous insulin receive a glucose calorie source.
Dellinger RP, et al Crit Care Med 2008;36:296-327
Resuscitation “Bundles”Severe Sepsis 3 Hour Bundle
RecognitionFluid ResuscitationAntimicrobial TherapyOxygen Delivery
Severe Sepsis 6 Hour BundleLow-dose Steroids Glucose ControlLung Protective Ventilation
NYS Sepsis InitiativeHospitals shall have in place evidence-based
protocols for the early recognition and treatment of severe sepsis and septic shock.
Hospitals shall have a process for screening all adult and pediatric patients for sepsis, severe sepsis, and septic shock in the ED and hospital.
Quality measures will be collected and reported.