1. Department of O UTCOMES R ESEARCH Prevention of Surgical Wound Infections Presented by : Daniel Sessler, MD

2. Disclosure Slide I have no personal financial interest related to the presentation. I work with many companies that make temperature monitoring and management systems through grant and research support.

3. Infection Prevention Prophylactic Antibiotics Smoking Supplemental Oxygen Normoglycemia Normothermia Fluid Management Transfusion www.OR.org

4. 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 SCIP measure Probable “pay-for-performance” measure

5. 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

6. 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

7. Host Defense Oxidative killing by neutrophils Primary defense against surgical pathogens Oxygen is transformed to superoxide radical Killing determined by tissue oxygen Oxygen also Promotes angiogenesis Improves scar formation

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

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

10. 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

11. Postoperative Atelectasis: 30% vs. 80%

12. 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

13. Subcutaneous Oxygen Tension (n=30)

14. Oxygen & Wound Infection

15. Effect of Infections Infections prolong hospitalization by a full week

16. Oxygen Confirmation

17. PROXI Trial 30% vs. 80% perioperative oxygen Randomized, blinded 1,400 patients Primary result Wound infection rates nearly identical Why results differ from previous trials unclear Meyhoff, Lancet 2009

18. 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

19. Hypothermia & Wound Infection

20. Wound Infections: Melling, et al.

21. Surgical Care Improvement Project (SCIP) Patients included (denominator) Surgical procedure General or neuraxial anesthesia ≥60 minutes Not having documented intentional hypothermia Criteria (numerator) Active over-body intraoperative warming, or Core temp ≥36°C within 30 min before anesth end time, or Core temp ≥36°C within 15 min after anesth end time Comments A similar “pay-for-reporting” measure coming “Core temperature” sites and devices undefined

22. Transfusion can save lives Appropriate triggers unknown Associated with complications Viral infection not major risk Potential risk mechanisms Highly immunogenic Nitric oxide depletion Blood Transfusion

23. Koch, et al., 2006, Crit Care Med Older blood Younger blood N=11,963. Transfusions increase morbidities and infection

24. Marik & Corwin, 2008, Crit Care Med Transfusions double infection risk

25. Berezina, et al., 2002, J Surg Res Older blood Younger blood Stored blood degrades over time, especially after 2 weeks Younger blood Older blood

26. Older Blood Increases Infection Risk Newer blood (≤14 days) N=2,872 Older blood (>14 days) N=3,130 P Sepsis2.8%4%0.01 Pneumonia2.8%3.6%0.11 Deep sternal infection 0.87%0.80%0.76 Multi-organ failure 0.24%0.73%0.007

27. Koch, et al., NEJM 2008 Prolonged blood storage increases morbidity and mortality Older blood Younger blood

28. Smoking and Infection 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 Habitual smoking increases infection risk 23% Neumayer, et al. J Am Coll Surg, 2007 Effect of smoking perioperative cessation unclear

29. 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., NEJM 2001

30. IntraOp Glucose & Major Complications

31. Glucose Concentrations Randomized

32. Aggressive Fluid Management Volume management for colon resection 30 vs. 50 ml/kg crystalloid Tissue oxygenation in arm (n=56) 81 ± 26 vs. 67 ± 18 mmHg, P = 0.03 Arkilic, et al. Surgery 2003 Similar wound infection risk (n=255) 11.3 vs. 8.5%, P = 0.46 Kabon, et al. Anesth Analg 2005 Major limitations Small study with low power Fluid management not titrated to individual need

33. Doppler-Guided Fluid Management Speeds hospital discharge Reduces composite complications But does not reduce wound infection risk Key citations Gan, et al. Anesthesiology 2002 Noblett, et al. Br J Surg 2006 Wakeling, et al. Br J Anaesth 2005

34. Summary 1 Prophylactic antibiotics: Give one hour before incision Supplemental oxygen: Does not cause atelectasis Effect on surgical wound infection controversial Maintaining normothermia: Decreases wound infection risk 3-fold Reduces the duration of hospitalization 20%

35. Summary 2 Red cell transfusions Nearly doubles infection risk Older blood worse than younger blood Smoking: Habitual smoking slightly increases risk Effect of perioperative cessation on infection uncertain Maintaining intraoperative glucose Does not appear helpful in non-cardiac surgery Unclear if helpful in cardiac surgery Aggressive hydration does not appear to reduce infection risk Doppler guidance improves outcomes

36. Recommendations Timely antibiotic administration Consider giving 80% intraoperative oxygen Maintain Normothermia Forced-air Fluid warming Reduce red cell transfusions Smoking Not smoking lowers risk Perioperative cessation might help Euglycemia and aggressive hydration Probably prudent, but not shown to reduce infection risk

37. Department of O UTCOMES R ESEARCH