1. Sepsis: Evidence Based Controversies
Rachel Hinerman, MD FCCP

2. Definitions
Sepsis = suspected or proven infection and some of the following:
General Variables
Inflammatory Variables
Hemodynamic Variables
Organ Dysfunction Variables
Tissue Perfusion Variables
SIRS- A clinical response arising from a nonspecific insult, including 2 of the following:

3. Sepsis Variables General Inflammatory Fever Hypothermia Tachycardia
Altered Mental Status
Edema
Hyperglycemia
Leukocytosis
Leukopenia
Normal WBC with > 10 % immature forms
C-reactive protein > 2 SD
Procalcitonin > 2 SD

4. Sepsis Variables Hemodynamic Organ Dysfunction Tissue Perfusion
SBP <90
MAP < 70
SBP decrease > 40
Tissue Perfusion
Lactate > 1
Mottling
Decreased Capillary Refill
P/F < 300
UO < .5 ml/kg for 2 hours despite volume resuscitation
Cr increase > .5
INR > 1.5
Ileus
Plt < 100 K
Bili > 4

5. Severe Sepsis Definition
Sepsis 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

6. Septic Shock
Sepsis-induced hypotension that persists despite adequate fluid resuscitation
*All definitions cited from “Surviving Sepsis Campaign” published in Critical Care Medicine Feb 2013

7. Dellinger, RP. et al. Crit Care Med 2004;32
Spectrum Of Severity
Infection
Sepsis
Severe Sepsis
Septic Shock
Sepsis associated with any of the single organ dysfunctions is defined as severe sepsis, Although not shown here, severe sepsis with two or more organs out is MODS. Severe sepsis with hypotension refractory to resuscitation is septic shock.
Dellinger, RP. et al. Crit Care Med 2004;32

8. Scope of The Problem

9. A National Health Concern?
Myocardial Infarction
Incidence 900,000
Deaths 225,000
Mortality 25%
Cerebrovascular Accident
Incidence 700,000
Deaths 163,5000
Mortality 23%
Trauma
Incidence 2,900,000
Deaths 42,643
Mortality 1.5%
Severe Sepsis
Incidence 751,000
Deaths 215,000
Mortality 40-60%
Angus, DC. et al Crit Care Med 2000;29
National Highway Traffic Safety Commission, 2003
AHA- Heart Disease and Stroke Statistics, 2005 update

10. Relative Mortality
Deaths/Year
More people die in one year in North America from severe sepsis than from breast cancer, lung cancer, and colon cancer combined
More than 751,000 cases of severe sepsis in US annually. Increasing 1.5 % per annum, 1 mil/yr 2020 projection
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

11. Determinants of Mortality
Source control is most vital factor
Adequate resuscitation or re-established perfusion in 6 hours
Appropriate antibiotic therapy within 1 hr of hypotension

12. Improving Outcomes

13. Interventions Early Goal Directed Therapy (EGDT) Anti-microbials
Steroids
Glucose Control
Lung Protective Ventilation

14. Absolute Risk Reduction%
EGDT- ARR 15.1%; NNT 7
Bernard et al. NEJM 2001; 344. Van den Berghe et al. NEJM 2001; 345. Rivers et al. NEJM 2001; 345
Annane et al. JAMA 2002; 288. ARDS-Net Investigators, NEJM; 2000

15. Rivers E et al. N Engl J Med 2001; 345:1368–1377
EGDT Resuscitation
Begin at onset of hypotension or lactate >4
Do not delay while awaiting ICU admission
Initial bolus is 30 ml/kg crystalloid
Or mixed venous greater than or equ to 65%; Dobut infusion to max 20microgr/kg/minute. Early goal-directed resuscitation has been shown to The consensus panel judged use of central venous and mixed venous oxygen saturation targets to be equivalent. Either intermittent or continuous measurements of oxygen saturation were judged to be acceptable. Studies of patients with shock indicate that mixed venous oxygen saturation runs 5–7% lower than central venous oxygen saturation (Scvo2) Reinhart K, Kuhn HJ, Hartog C, et al: Continuous central venous and pulmonary artery oxygen saturation monitoring in the critically ill. Intensive Care Med 2004; 30:1572–1578
Rivers E et al. N Engl J Med 2001; 345:1368–1377

16. EGDT Initial Resuscitation targets
CVP (12-15 if mechanically ventilated)
Mean arterial pressure ≥65
Urine output ≥ 0.5 ml/kg/hour
Central 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

17. Rivers, NEJM 2001; 345:1368

18. Rivers, E et al. N Engl J Med 2001; 345
EGDT Outcomes
Rivers, E et al. N Engl J Med 2001; 345

19. EGDT Cost 23% 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
Cost-Effectiveness of EGDT- SHLD DEMONSTARTE FISCAL JUSTIFICATION. The potential benefits that can be realized through a program such as EGDT should demonstrate fiscal justification. An examination118 of EGDT included factors such as additional training, personnel, possible physical plant changes, and equipment necessary to screen patients, and concluded that EGDT is a cost-effective intervention. Huang et al118 in a formal cost-effectiveness analysis found that EGDT can provide up to a 23.4% reduction in hospital costs related to the treatment of patients with severe sepsis and septic shock. EGDT was found to be most cost-effective if the volume of patients exceed 16 patients per year. The cost-effectiveness was demonstrated in all models of care including whether the care was provided primarily by the ED, rapid response team, or the ICU. For HFH in particular, there was a mean reduction of 4 days per hospital admission (a 32.6% reduction in hospital length of stay) for survivors and a 13.9% reduction in PAC use (both p < 0.03). Similar findings have been noted by other investigators. Shapiro et al83 have reported a cost per life saved of $32,336, and Trzeciak et al82 found a reduction in median hospital facility charges from $135,199 to $82,233 (reduction, 39.2%; p = 0.14) and in PAC use from 43.8 to 9.1% (p = 0.01).
Trzeciak, S, Dellinger, RP, Abate, NL, et al Translating research to clinical practice: a 1-year experience with implementing early goal-directed therapy for septic shock in the emergency department. Chest 2006;129, [CrossRef][Medline]
Shapiro, NI, Howell, MD, Talmor, D, et al Implementation and outcomes of the Multiple Urgent Sepsis Therapies (MUST) protocol. Crit Care Med 2006;34,
Huang, DT, Angus, DC, Dremsizov, TT, et al Cost-effectiveness of early goal-directed therapy in the treatment of severe sepsis and septic shock [abstract]. Crit Care 2003;7(suppl),S116
Treciak S et al. Chest 2006;129:
Huang DT, et al Crit Care 2003;7:S116
Shapiro N, et al. Crit Care Med 2006;34:

20. 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 used
Background It remains uncertain whether the choice of resuscitation fluid for patients in intensive care units (ICUs) affects survival. We conducted a multicenter, randomized, double-blind trial to compare the effect of fluid resuscitation with albumin or saline on mortality in a heterogeneous population of patients in the ICU. Methods We randomly assigned patients who had been admitted to the ICU to receive either 4 percent albumin or normal saline for intravascular-fluid resuscitation during the next 28 days. The primary outcome measure was death from any cause during the 28-day period after randomization. Results Of the 6997 patients who underwent randomization, 3497 were assigned to receive albumin and 3500 to receive saline; the two groups had similar baseline characteristics. There were 726 deaths in the albumin group, as compared with 729 deaths in the saline group (relative risk of death, 0.99; 95 percent confidence interval, 0.91 to 1.09; P=0.87). The proportion of patients with new single-organ and multiple-organ failure was similar in the two groups (P=0.85). There were no significant differences between the groups in the mean (±SD) numbers of days spent in the ICU (6.5±6.6 in the albumin group and 6.2±6.2 in the saline group, P=0.44), days spent in the hospital (15.3±9.6 and 15.6±9.6, respectively; P=0.30), days of mechanical ventilation (4.5±6.1 and 4.3±5.7, respectively; P=0.74), or days of renal-replacement therapy (0.5±2.3 and 0.4±2.0, respectively; P=0.41).
Conclusions In patients in the ICU, use of either 4 percent albumin or normal saline for fluid resuscitation results in similar outcomes at 28 days.
65. Finfer S, Bellomo R, Boyce N, et al: A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med 2004; 350:2247–2256
68. Schierhout G, Roberts I: Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: A systematic review of randomized trials. BMJ 1998; 316:961–964
Although administration of hydroxyethyl starch may increase the risk of acute renal failure in patients with sepsis, variable findings preclude definitive recommendations 69. Schortgen F, Lacherade JC, Bruneel F, et al: Effects of hydroxyethyl starch and gelatin on renal function in severe sepsis: A multicentre randomized study. Lancet 2001; 357:911–916
Schierhout G et al. BMJ 1998; 316:961–964
Finfer S et al. N Engl J Med 2004; 350:2247–2256

21. EGDT (and we mean EARLY)
Retrospective analysis of 212 patients
Diagnosis: 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:
Adequate initial fluid resuscitation (AIFR) group was defined as the. Conservative late fluid management (CLFM) was defined as even-to-negative fluid balance measured on at least 2 consecutive days during the first 7 days after septic shock onset.
The study cohort was made up of 212 patients with ALI complicating septic shock. Hospital mortality was statistically lowest for those achieving both AIFR and CLFM and higher for those achieving only CLFM, those achieving only AIFR, and those achieving neither (17 of 93 patients [18.3%] vs. 13 of 31 patients [41.9%] vs. 30 of 53 patients [56.6%] vs. 27 of 35 [77.1%], respectively; p < 0.001).
Murphy C V et al. Chest 2009;136:

22. Mean daily fluid balance days 1 through 7
NONSURVIVORS
SURVIVORS
Mean (± SE) cumulative daily fluid balance for days 1 through 7 following the onset of septic shock. Nonsurvivors are depicted by squares, and survivors by circles. * = p < 0.05.
Murphy C V et al. Chest 2009;136:

23. Hospital mortality for AIFR, CLFM, both, or neither
77%
57%
42%
18%
Hospital mortality according to whether or not patients achieved AIFR, CLFM, both, or neither. Results: The study cohort was made up of 212 patients with ALI complicating septic shock. Hospital mortality was statistically lowest for those achieving both AIFR and CLFM and higher for those achieving only CLFM, those achieving only AIFR, and those achieving neither (17 of 93 patients [18.3%] vs. 13 of 31 patients [41.9%] vs. 30 of 53 patients [56.6%] vs. 27 of 35 [77.1%], respectively; p < 0.001).
Hospital mortality:
AIFR and CLFM- 18%
Only CLFM- 42%
AIFR only- 57%
Achieving neither- 77%
Murphy CV et al. Chest 2009; 136:

24. Rivers, E et al. N Engl J Med 2001; 345
EGDT & Intubation
Comparing the PaO2/fraction of inspired oxygen (FIO2) ratios between the EGDT and standard-care groups. Despite more volume resuscitation in the EGDT group during initial 6 h, there was no net difference in PaO2/FIO2 ratio (p = 0.34)
No difference: P/F ratio at 6h; EGDT with higher P/F at 72h
No difference in intubation rates at 6 hours
7-72 hour intubation rate: EGDT 2% vs. standard %
Rivers, E et al. N Engl J Med 2001; 345
Otero R, et al. Chest 2006;130:

25. Vasopressors Mean arterial pressure (MAP) maintained ≥ 65
First choice: norepinephrine or epinephrine
Vasopressin 0.03 units/min may be added
Rationale
-there is no high qual evidence to rec one catechol over another.
-norepi is more potent than da and may be more effect at revers hypotens in pts c sept shk
-Da more tachy and arrythmogenic
-86. Regnier B, Rapin M, Gory G, et al: Hemodynamic effects of dopamine in septic shock. Intensive Care Med 1977; 3:47–53
-place art catheter ASAP grade 1D- using a cuff is inaccurate and AC allows cont analysis and immed response

26. Vasopressin VASST 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 norepinephrine
No 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
The VASST study’s primary hypothesis is that low dose Vasopressin infusion compared to Norepinephrine infusion will increase 28-day survival in human septic shock. Patients are eligible to participate in the study if they have septic shock, at least one other sepsis related organ failure and are on vasopressor infusion(s) for ≥ 6 hours (≥5mcg/kg/min) or for ≥3 hours if in severe septic shock (≥15mcg/kg/min of vasopressor requirements). Patients who participate are randomized to receive either Norepinephrine or Vasopressin. Norepinephrine is started at 1.3ug/min and is titrated up to 15ug/min in 40 min. Vasopressin is started at units/min and is titrated up to 0.03 units/min in 40min.The Vasopressin in Septic Shock Trial ---When we set the sample size for VASST, we estimated that the mortality from septic shock would be 60%. However, the mortality in the control group in VASST was 39.3%, so the power was less than originally planned.
(VASST) was recently completed.[10] VASST analyzed 779 patients in septic shock requiring vasopressors for at least 6 hours and having at least 1 additional dysfunctional organ system present for less than 24 hours, who were randomized to receive AVP or norepinephrine (NE). Overall there was no difference in 28-day survival between groups (35.4% vs. 39.3%, P =.27). However, the groups were stratified according to severity of hypotension (requiring > 15 mcg/min or < 15 mcg/min of NE at enrollment), and the patients taking lower-dose NE had improved survival with AVP (26.5% vs. 35.7%, P =.05). This result persisted at 90 days, when mortality was 35.8% vs. 46.1%, P =.04). There were no differences in MAP, although the addition of AVP to NE predictably resulted in a reduction in NE dose. Digital ischemia was somewhat more common in the AVP group (P =.06), while cardiac arrest was slightly more common in the NE group (P =.11).
Russell J et al. NEJM2008;358,9.

27. Inotropes
Dobutamine 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
-Dobut first chce for pts c low measured or suspected cardiac output c adequate filling pressure and adequ MAP.
-2 lg prospect trials failed to benefit in opts c sever sepsis- inc ox deliv to supranormal targets
Gattinoni L, et al. New Engl J Med 1995; 333:
Hayes MA, et al. New Engl J Med 1994; 330:

28. Interventions Anti-microbials Early Goal Directed Therapy (EGDT)
Steroids
Glucose Control

29. Garnacho-Montero J et al. CCM2007;25:1888-1895
Antimicrobials
Begin therapy within the first hour of recognizing severe sepsis or septic shock
Broad spectrum: one or more agents against likely bacterial or fungal pathogens
Consider combination therapy for potentially resistant gram negative pathogens
Consider combination therapy in neutropenic patients
Narrow coverage when culture data available
In the presence of septic shock, each hour delay in achieving administration of effective antibiotics is associated with a measurable increase in mortality Kumar A, Roberts D, Wood KE, et al: Duration of hypotension prior to initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34:1589– Because patients with severe sepsis or septic shock have little margin for error in the choice of therapy, the initial selection of antimicrobial therapy should be broad enough to cover all likely pathogens. There is ample evidence that failure to initiate appropriate therapy (i.e., therapy with activity against the pathogen that is subsequently identified as the causative agent) correlates with increased morbidity and mortality (45–48). McCabe WR, Jackson GG: Gram negative bacteremia. Arch Intern Med 1962; 110:92–100 [Context Link]
-Although no study or meta-analysis has convincingly demonstrated that combination therapy produces a superior clinical outcome for individual pathogens in a particular patient group, combination therapies do produce in vitro synergy against pathogens in some models (although such synergy is difficult to define and predict). In some clinical scenarios, such as the two preceding, combination therapies are biologically plausible and are likely clinically useful even if evidence has not demonstrated improved clinical outcome (53–56). Combination therapy for suspected known Pseudomonas pending sensitivities increases the likelihood that at least one drug is effective against that strain and positively affects outcome (57). Garnacho-Montero J, Sa-Borges M, Sole-Violan J, et al: Optimal management therapy for Pseudomonas aeruginosa ventilator-associated pneumonia: An observational, multicenter study comparing monotherapy with combination antibiotic therapy. Crit Care Med 2007; 25:1888–1895
Garnacho-Montero J et al. CCM2007;25:

30. Antimicrobials
Study 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%
Objective: Our goal was to determine the impact of the initiation of inappropriate antimicrobial therapy on survival to hospital discharge of patients with septic shock. Conclusions: Inappropriate initial antimicrobial therapy for septic shock occurs in about 20% of patients and is associated with a fivefold reduction in survival. Efforts to increase the frequency of the appropriateness of initial antimicrobial therapy must be central to efforts to reduce the mortality of patients with septic shock.
The decrease in survival with inappropriate initial therapy ranged from 2.3-fold for pneumococcal infection to 17.6-fold with primary bacteremia.
Kumar A et al. Chest 2009;136:

31. Diagnosis Obtain cultures before starting antimicrobial therapy
Obtain two or more blood cultures (BC)
One or more BC should be percutaneous
One BC from each vascular access devise in for > 48 hrs
Urine and sputum cultures
Other cultures as dictated by initial exam and imaging
Prompt imaging studies in search of source
-BC negative in > 50% of cases- so base antibiot changes on clinical judgement
-Obt cxs prior to antibiotics provided this does not delay antimicr administration
Imaging studies prompt if safe to do so…
Rapid steriliz of blood cxs can occur within a few hrs of antibiotic administration
Vasc access device- BC through EACH LUMEN- if the same org is recovered from both the VAD and peripheral- the likelihood of the right dx is enhanced In addition, if the vasc access devise cx is positive much earlier than the periph cx (und 2 hours) the data support that the VAD is the source of infection Blot F, Schmidt E, Nitenberg G, et al: Earlier positivity of central venous versus peripheral blood cultures is highly predictive of catheter-related sepsis. J Clin Microbiol 1998; 36:105–109
-Diagnostic studies may identify a source of infection that requires removal of a foreign body or drainage to maximize the likelihood of a satisfactory response to therapy. However, even in the most organized and well-staffed healthcare facilities, transport of patients can be dangerous, as can placing patients in outside-unit imaging devices that are difficult to access and monitor. Balancing risk and benefit is therefore mandatory in those settings.
-recomm quantit cxs of blood, respiratory secretions (or semiquant)

32. Interventions Steroids Early Goal Directed Therapy (EGDT)
Anti-microbials
Steroids
Glucose Control

33. Dellinger RP, et al Crit Care Med 2008;36:296-327
2012 Steroid Guidelines
The 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
No ACTH- bc of CORTICUS trial. Also most cortisol assays measure total and free cortisol, while free is likely the pertinent measurement. The corticol assays may over or underestimate the the actual cortisol level since the relationship between free and total cortisol depends on serum protein concentration.
Dex can lead to profound and prolonged supression of the adrenal axis and along with no ACTH test, no need for dex.
Dellinger RP, et al Crit Care Med 2008;36:

34. Interventions Glucose Control Early Goal Directed Therapy (EGDT)
Anti-microbials
Steroids
Glucose Control

35. Glucose Controversy Leuven protocol: 80-110 Cardiac-surgical ICU
Reduced ICU LOS
Less organ dysfunction
Hypoglycemia 6.2%
Decreased Mortality
3.4% ARR all patients
9.4% ARR LOS >5 days
Leuven protocol:
Medical ICU
Reduced ICU LOS
Less ventilator days
Less acute renal injury
Hypoglycemia 18%
Mortality difference
Overall: no difference
LOS > 3 days: ↓ mortality
Study 1- We would say "No, not quite." The original study recruited only surgery patients from a single center where all subjects received intravenous glucose and parenteral nutrition, starting immediately postoperatively, a practice that is not the norm. Study2- dec icu and hospital los. Los > 3 days, hospit mortality 52% v 43% c tight control. 36% with los < 3 days, and there was no way to predict los., 3 fold higher rate of hypoglycemia.
Van den Berghe G, et al. NEJM 2006; 354:
Van den Berghe G, et al. NEJM 2001;345:

36. The NICE-SUGAR Study Investigators NEJM 2008; Volume 360:1283-1297
RCT open-label comparing intensive BS vs.. conventional BS <180
6,104 ICU heterogeneous patients
Primary end point: 90-day mortality
Secondary end points:
Hypoglycemia
Infection
Need for organ support
Intensive care unit and hospital length of stay
Methods Within 24 hours after admission to an intensive care unit (ICU), adults who were expected to require treatment in the ICU on 3 or more consecutive days were randomly assigned to undergo either intensive glucose control, with a target blood glucose range of 81 to 108 mg per decilite, or conventional glucose control with a target of 180 mg or less per deciliter. We defined the primary end point as death from any cause within 90 days after randomization.
Results Of the 6104 patients who underwent randomization, 3054 were assigned to undergo intensive control and 3050 to undergo conventional control; data with regard to the primary outcome at day 90 were available for 3010 and 3012 patients, respectively. The two groups had similar characteristics at baseline. A total of 829 patients (27.5%) in the intensive-control group and 751 (24.9%) in the conventional-control group died (odds ratio for intensive control, 1.14; 95% confidence interval, 1.02 to 1.28; P=0.02). The treatment effect did not differ significantly between operative (surgical) patients and nonoperative (medical) patients (odds ratio for death in the intensive-control group, 1.31 and 1.07, respectively; P=0.10). Severe hypoglycemia (blood glucose level, 40 mg per deciliter [2.2 mmol per liter]) was reported in 206 of 3016 patients (6.8%) in the intensive-control group and 15 of 3014 (0.5%) in the conventional-control group (P<0.001). There was no significant difference between the two treatment groups in the median number of days in the ICU (P=0.84) or hospital (P=0.86) or the median number of days of mechanical ventilation (P=0.56) or renal-replacement therapy (P=0.39).
Conclusions In this large, international, randomized trial, we found that intensive glucose control increased mortality among adults in the ICU: a blood glucose target of 180 mg or less per deciliter resulted in lower mortality than did a target of 81 to 108 mg per deciliter.
The NICE-SUGAR Study Investigators NEJM 2008; Volume 360:

37. 2012 Glucose Control Guidelines
Patients 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:

38. Resuscitation “Bundles”
Severe Sepsis 3 Hour Bundle
Recognition
Fluid Resuscitation
Antimicrobial Therapy
Oxygen Delivery
Severe Sepsis 6 Hour Bundle
Low-dose Steroids
Glucose Control
Lung Protective Ventilation

39. Gao F, et al. Critical Care 2006; 9:R764-770
Outcomes
Prospective observational study: 101 patients
Rate of compliance with 6 and 24 hour bundles
Impact of compliance on hospital mortality
52% Compliance with the 6 hour bundle
Mortality 23% compliant vs. 49% non-compliant
30% compliance with the 24 hour bundle
Mortality 21% compliant vs. 50% non-compliant
Gao F, et al. Critical Care 2006; 9:R

40. NYS Sepsis Initiative
Hospitals 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.