1. Update in Critical Care Medicine Ann Intern Med 2007;147:412-416

2. Sepsis Management: How much do we really know? Intensive Insulin Steroids rhAPC Vasopressin Dobutamine Swan-Ganz Catheters Early Dialysis ScvO2 Monitoring EGDT Nutritional Support Transfusion Targets Quantitative BAL

3. “The study was terminated early because mortality in the intensive care unit in the group assigned to intensive insulin therapy was significantly lower than that in the group assigned to conventional therapy (4.6 % vs. 8.0 %).”

4. Intensive Care = Intensive Insulin? Van den Berghe, NEJM 2006;354:449-61 1200 pts in medical ICU’s expected to stay 3 or more days Randomized to a target BG between:  80-110 (Intensive Insulin Therapy - “IIT”), vs.  180-200 Results:  Overall: NO difference in mortality MORE hypoglycemia in the IIT group  With trend towards higher mortality (67% vs 46%, p=0.1)  However, if actually did stay 3 days or more, IIT: Decreased mortality Accelerated weaning, ICU d/c, and hospital d/c

5. Intensive Care = Intensive Insulin? Van den Berghe, NEJM 2006;354:449-61 Conclusion:  IIT decreases morbidity but has no effect on mortality. Comments:  IIT seems to harm early and help late. Reasonable Goal:  <150 for the first three days then 80-100 “Demonstrates the phenomenon of exaggeration of results when trials are stopped early.”

6. Red States or Blue States ARDSnet, NEJM 2006;354:2564-75 Question:  How should fluids be managed in pts with ALI? 1000 pts randomized to:  “Conservative”I = O over 7 days  “Liberal” I > O by 7 liters over 7 days Results:  Equal 60 day mortality  Conservative: Better oxygenation More vent-free days (14.6 vs 12.1) More days not in the ICU (13.4 vs 11.2) NO increase in shock or HD

7. Red States or Blue States ARDSnet, NEJM 2006;354:2564-75 Conclusion:  In pts with ALI, a conservative fluid strategy, I=O, helps wean pts from mechanical ventilation.

8. PAC or CVC, that is the question ARDSnet, NEJM 2006;354:2213-24 Question:  Do outcomes differ for patients with ALI if PAC’s or CVC’s are used? 1000 pts randomized to PAC or CVC Results:  Equal 60 day mortality  PAC’s: No difference in lung function, kidney function, hypotension, ventilator settings, use of dialysis, or use of vasopressors BUT more total catheters (2.47 vs 1.64) and twice the number of catheter-related complication (mainly arrhythmias)

9. PAC or CVC, that is the question ARDSnet, NEJM 2006;354:2213-24 Conclusion:  PAC-guided therapy did not improve survival or organ function and was associated with more complications. Commentary:  Arrhythmia might have been due to the catheters but could also have been due to an increased use of vasopressors Bottom Line:  PAC’s should NOT be routinely used to manage ALI.

10. VAP Diagnosis Canadian Crit Care Group, NEJM 2006;355:2619-30 Question:  BAL vs Endotracheal Aspiration 740 pts randomized to:  BAL with Quantitative Culture  Endotracheal Aspiration with routine culture Results:  NO difference in mortality, ICU LOS, receipt of targeted therapy, days alive without abx, or maximum organ dysfunction score

11. Septic Shock: how soon to start Abx Kumar, Crit Care Med 2006;34:1589-96 Question:  Is delay in initiation of abx after onset of hypotension in septic shock associated with an increase in mortality. Retrospective Cohort Study  2154 pts with septic shock who started abx after onset of hypotension Findings:  Median time to effective antimicrobial therapy was 6 hrs  If given abx in first hour, 79.9% survival  Each hr delay, over the next 6 hrs, decreased survival rate by 7.6%

12. Septic Shock: how soon to start Abx Kumar, Crit Care Med 2006;34:1589-96 Supports Surviving Sepsis Campaign Rec’s

13. Bundles “A group of interventions related to a disease that when performed together result in better outcome than when individually done.” “It increases the use of evidence-based science in clinical practice and provides a mechanism to enforce teamwork.” “A bundle is not guidelines, but a method to implement the guidelines.”

14. Bundles: The Good, the Bad, and the Ugly? Ventilator Bundle Sepsis Resuscitation Bundle Sepsis Management Bundle

15. Bundles: Reasonable? Ventilator Bundle  DVT Prophylaxis  Peptic Ulcer Disease Prophylaxis  Elevation of the Head of the Bed  Sedation Vacation

16. Bundles: Lactate? ScvO2? Sepsis Resuscitation Bundle  Measure Serum Lactate  Blood Cultures before abx  Prompt Abx (3 hrs Ed; 1 hr non-ED)  If hypotensive or lactate > 4: 20 ml/kg crystalloid Vasopressors to achieve MAP > 65 mmHg  If persistent hypotension or elevated lactate: Assure CVP > 8 Achieve ScvO2 > 70% or SmvO2 > 65%

17. Bundles: rhAPC???? Sepsis Management Bundle*  Low-dose steroids  Drotrecogin alfa (activated)  Glucose control maintained > lower limit of normal, but < 150 mg/dl  Plateau pressures maintained < 30 cm H2O *Surviving Sepsis Campaign supported by Ely Lilly. rhAPC made by Ely Lilly.

19. Sepsis Management: How much do we really know? Intensive Insulin Steroids rhAPC Vasopressin Dobutamine Swan-Ganz Catheters Early Dialysis ScvO2 Monitoring EGDT Nutritional Support Transfusion Targets Quantitative BAL