1. O UTCOMES R ESEARCH Providing the evidence for evidence-based medicine ©

2. Infection Prevention Prophylactic Antibiotics Supplemental Oxygen Normothermia Normoglycemia Smoking www.OR.org

3. Surgical Site Infections Common >500,000 surgical site infections per year in the States 1-3% incidence overall; ≈10% after colon surgery Serious Increases hospital duration ≈1 week Doubles ICU admission and mortality Costly $1.6 billion annually in the United States 3.7 million excess hospital days yearly in the States CMS priority Probable “pay-for-performance” measure

4. Decisive Period All wounds become contaminated Infections established within 2 h of contamination Interventions most effective during “Decisive Period” Progression to infection determined by Prophylactic antibiotics Host defense

5. Prophylactic Antibiotics Effective only during the decisive period Subsequent administration useless (or harmful) Should be given within 1 hour before incision Repeat after 4-6 hours for long operations Discontinue within 24-48 hours Various guidelines for type of antibiotic In practice, surgeons choose antibiotics Our mission is to give them — on time

6. Host Defense Oxidative killing by neutrophils Primary defense against surgical pathogens Oxygen is transformed to superoxide radical –Killing determined by tissue oxygen

7. Measuring Tissue Oxygen Tissue oxygenation ≠ saturation; much lower than arterial PO 2

8. Tissue Oxygen Correlates with Infection Hopf, et al., 1996, Arch Surg

9. Supplemental Oxygen Easy to provide Inexpensive (a few cents/patient) Recent utilization Usually 30% in Europe Essentially random concentrations in the States Rationale for various concentrations unclear

10. Atelectasis: Pulmonary Function Akça, et al. 1999, Anesthesiology

11. Postoperative Atelectasis These data provide a 99% power to detect a 2% difference in the atelectasis rate, at an alpha level of 0.05

12. Hemodynamic Effects Harten, et al 2005, JCVTA 40%100% SVR18602300 CI2.82.5 MAP69

13. Greif, et al. NEJM, 2000 Hypothesis: 80% O 2 reduces wound infection risk 500 patients having elective colon resection Standardized antibiotic, anesthetic, & fluid management Intraoperative core temperature maintained at 36 o C Randomization 30% oxygen (balance nitrogen); PaO 2 ≈ 120 80% oxygen (balance nitrogen) ; PaO 2 ≈ 350 Wound infections Wounds evaluated daily by a blinded observer Pus and positive culture required for diagnosis

14. Subcutaneous Oxygen Tension (n=30)

15. Surgical Wound Infections (n=500) Oxygen is as effective as antibiotics!

16. Effect of Infections Infections prolong hospitaliation by a full week

17. Pryor, et al. JAMA, 2004 Protocol 160 patients randomized to 35% or 80% oxygen –30% at low risk of infection –Inadequate sample size; stopped early Anesthetic, fluid, and pain management uncontrolled Unblinded, retrospective evaluation of wound infection Results Five patients dropped from 80% oxygen group Patients assigned to 80% oxygen were –Twice as likely to have BMI >30 kg/m 2 –Lost more blood, received more fluid –More likely to require postoperative intubation (5 vs. 1 pt) 80% oxygen increased infection risk from 11% to 25%

18. Belda, et al. 2005, JAMA Standardized antibiotic, anesthetic, & fluid management Randomization 30% vs. 80% oxygen (balance nitrogen) Wound infections: CDC criteria by blinded observer Adjusted odds ratio 0.46 (95 CI 0.22-0.95, P = 0.04)

19. Additional Evidence

20. Temperature and Infection Hypothermia Decreases tissue oxygen Impairs numerous immune functions Hypothesis: normothermia reduces infection risk 200 patients having elective colon resection Standardized antibiotic, anesthetic, & fluid management Randomized to normothermia or ≈2°C hypothermia Wound infections Wounds evaluated daily by a blinded observer Pus and positive culture required for diagnosis

21. Kurz, et al., 1996, NEJM Beneficial effect of active warming on infection confirmed by Melling, et al. Lancet, 2001 (n = 200) Normothermia is more effective than antibiotics!

22. Forced-Air vs. Circulating-Water Kurz, et al. 1993, Anesth Analg

23. Fluid Warming Cooling by intravenous fluids 0.25°C per liter crystalloid at ambient temperature 0.25°C per unit of blood from refrigerator Cooling prevented by warming solutions Type of warmer usually unimportant Fluid warming does not prevent hypothermia! Most core cooling from redistribution 90% of heat loss is from anterior skin surface

24. Smoking Decreases Tissue Oxygen Tissue oxygen decreases: 65 ± 7 to 44 ± 3 mmHg Jensen, et al. Arch Surg, 1991 Tissue oxygen 40-50 mmHg —> infection Hopf, et al. Arch Surg, 1997 "Pack-a-day" smokers hypoxic most of the time Hypothesis: smoking Increases the risk of surgical wound infection Subjects: 200 patients having colon resection

25. Smoking and Infection (1996) Kurz et al., 1996, NEJM

26. Smoking and Infection (≥2000) Greif, et al., 2000, NEJM, n=500 No effect of smoking on infection risk Fleischmann, et al., 2005, Lancet, n=400 No effect of smoking on infection risk Belda, et al., 2005, JAMA, n=300 No effect of smoking on infection risk Conclusion No effect of smoking on infection now… Because smoking is no longer allowed in hospitals

27. Hyperglycemia and Infection Tight control of glucose improves immunity –[Gallacher et al. Diabet Med 1995] Glucose control maintains neutrophil phagocytosis –[Athos et al. Anesth Analg 1999] Mortality reduced by intensive insulin therapy in critical care patients (including cardiac surgery) –[Van Den Berghe et al., N Engl J Med 2001]

28. Summary Prophylactic antibiotics: Most effective when given within one hour before incision Supplemental oxygen: Does not cause atelectasis Halves the risk of surgical wound infection Maintaining perioperative normothermia: Reduces the risk of surgical wound infection 3-fold Reduces the duration of hospitalization 20% Smoking: No longer increases infection risk Many other harmful effects Hyperglycemia: Importance of intraoperative glucose control remains unknown

29. Recommendations Timely antibiotic administration Provide 80% oxygen when practical Maintain Normothermia Forced-air Fluid warming Euglycemia Probably prudent

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