Chapter 20. Prevention of Surgical Site Infections (continued)

Subchapter 20.3. Supplemental Perioperative Oxygen

Background

Low oxygen content in devitalized tissues predisposes them to bacterial colonization, which is thought to be a key pathophysiologic step in the initiation of surgical site infections.¹ Administration of high concentrations of oxygen increases wound oxygen tension, allowing for more effective neutrophil function and the potential for reduced infection rates.²

Practice Description

The practice of perioperative oxygen supplementation involves administration of 80% oxygen and 20% nitrogen by endotracheal tube intraoperatively and by sealed mask and manifold system or conventional non-rebreather mask for the first two hours of recovery. Oxygen is increased to 100% immediately before extubation, with the concentration returned to 80% as soon as deemed safe by the anesthesiologist.³

Prevalence and Severity of the Target Safety Problem

See Subchapter 20.1.

Opportunities for Impact

Administration of oxygen is a routine part of perioperative care. However the frequency with which high oxygen concentrations (as described above) are administered is not known.

Study Designs and Outcomes

We identified one randomized controlled trial evaluating the effect of high concentration oxygen supplementation on surgical site infections (Table 20.3.1).³ The primary outcome was incidence of wound infection within 15 days after surgery (Level 1). Wounds were considered infected when bacteria were cultured from pus expressed from the incision or aspirated from a loculated collection within the wound.³

Evidence for Effectiveness of the Practice

The clinical characteristics of the intervention and control groups were similar at baseline, including risk of infection as assessed by a modified Study on the Efficacy of Nosocomial Infection Control (SENIC) score (p=0.8) and National Nosocomial Infection Surveillance System (NNISS) score (p=0.86). The incidence of wound infection was significantly less in the intervention group (13/250, 5%) than in the control group (28/250, 11%, p=0.014). The results remain statistically significant when the study definition of "infection" is broadened to include wounds with pus but no bacterial growth on culture (7% vs. 14%, p=0.012). Perioperative administration of high levels of oxygen was associated with a 54% relative risk reduction (95% CI: 12%-75%) of wound infection within 15 days of surgery. ASEPSIS (Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissues, Isolation of bacteria, and duration of inpatient Stay⁴) scores were also significantly better with high levels of oxygen (3 vs. 5, p=0.01). Although longer follow-up might have identified additional wound infections, the authors argue that it was unlikely that these events would take place preferentially in one group as the proposed therapeutic effect of oxygen appears limited to the immediate perioperative period.³ Admission to the intensive care unit and death were less frequent in the intervention group, but the difference failed to achieve statistical significance.

Two additional randomized controlled trials of perioperative supplemental oxygen were identified.^5,6 Both found a significant reduction in postoperative nausea and vomiting, but neither study evaluated the effect on wound infections.

Potential for Harm

The study by Greif et al reported no adverse affects related to the intervention. Several potential risks of high oxygen concentrations should be noted. High oxygen concentrations may present a fire hazard when heated surgical instruments (e.g., lasers) are introduced into the airway.^7-11 Such concentrations can also induce lung injury in certain vulnerable patients¹² or precipitate atelectasis in patients at risk.^3,13,14 Hyperoxic mixtures may increase oxidative myocardial injury in patients undergoing cardiopulmonary bypass.¹⁵ Finally, patients who undergo resuscitation with 100% oxygen may have worsened neurologic outcomes, possibly also as a result of increased oxygen free-radical generation.^16,17

Costs and Implementation

The incremental direct costs associated with administering high oxygen concentrations are minimal, as oxygen delivery systems are elements of routine perioperative care and employ equipment readily available in operating rooms.

Comment

Administration of perioperative oxygen in high concentrations seems a promising adjunctive therapy: the practice is simple, the equipment needed is readily available, and a multicenter randomized trial has demonstrated its efficacy.

However, there are significant questions about the generalizability of the approach to expanded populations of surgical patients. All patients in the Grief et al study had core temperature maintained at 36ºC, were aggressively hydrated, and had postoperative pain treated with opioids in order to maximize wound perfusion. To what degree the effectiveness of the practice is affected by changes in these "co-interventions" has not been assessed. There is reason for concern regarding use of high concentrations of oxygen in patients undergoing procedures associated with low blood flow (e.g., cardiopulmonary bypass), or in whom local production of oxygen free radicals may cause further organ injury (e.g., patients with head trauma).

Additionally, questions remain regarding whether modifications to the protocol used would impart similar or greater benefit. For example, would oxygen administration by nasal cannula at 10 LPM be as effective as oxygen delivered by a sealed mask? Would longer duration of therapy impart additional benefit? These questions should be answered in future trials.

Table 20.3.1. Randomized controlled trial of supplemental perioperative oxygen*

Study	Study Population	Intervention	Resultsa
Greif, 20003	500 patients undergoing colorectal resection; multicenter study, 1996-98	80% oxygen, 20% nitrogen during surgery and the first 2 hours of recovery	Wound infection: ARR 0.06 (95% CI, 0.018-0.102) RR 0.46 (95% CI, 0.25-0.88) ASEPSISc score: 3 vs. 5 (p=0.01) ICU admission: 2.0% vs. 4.8% (p=0.14) Mortality: 0.4% vs. 2.4% (p=0.13)

* ARR indicates absolute risk reduction; CI, confidence interval; ICU, intensive care unit; and RR, relative risk. The ASEPSIS scoring system incorporates Additional treatment, Serous discharge, Erythema, Purulent exudate, Separation of deep tissues, Isolation of bacteria, and duration of inpatient Stay⁴.

^a Outcomes within 15 days of surgery, expressed as rates in intervention vs. control groups.

References

1. Hopf HW, Hunt TK, West JM, et al. Wound tissue oxygen tension predicts the risk of wound infection in surgical patients. Arch Surg 1997;132:997-1004.

2. Hopf H, Sessler DI. Routine postoperative oxygen supplementation. Anesth Analg 1994;79:615-616.

3. Greif R, Akca O, Horn EP, Kurz A, Sessler DI. Supplemental perioperative oxygen to reduce the incidence of surgical-wound infection. Outcomes Research Group. N Engl J Med 2000;342:161-167.

4. Wilson AP, Treasure T, Sturridge MF, Gruneberg RN. A scoring method (ASEPSIS) for postoperative wound infections for use in clinical trials of antibiotic prophylaxis. Lancet 1986;1:311-313.

5. Greif R, Laciny S, Rapf B, Hickle RS, Sessler DI. Supplemental oxygen reduces the incidence of postoperative nausea and vomiting. Anesthesiology 1999;91:1246-1252.

6. Goll V, Akca O, Greif R, et al. Ondansetron is no more effective than supplemental intraoperative oxygen for prevention of postoperative nausea and vomiting. Anesth Analg 2001;92:112-117.

7. Healy GB. Complications of laser surgery. Otolaryngol Clin North Am 1983;16:815-820.

8. Hunsaker DH. Anesthesia for microlaryngeal surgery: the case for subglottic jet ventilation. Laryngoscope 1994;104:1-30.

9. Aly A, McIlwain M, Duncavage JA. Electrosurgery-induced endotracheal tube ignition during tracheotomy. Ann Otol Rhinol Laryngol 1991;100:31-33.

10. Barnes AM, Frantz RA. Do oxygen-enriched atmospheres exist beneath surgical drapes and contribute to fire hazard potential in the operating room? Aana J 2000;68:153-161.

11. de Richemond AL, Bruley ME. Use of supplemental oxygen during surgery is not risk free. Anesthesiology 2000;93:583-584.

12. Donat SM, Levy DA. Bleomycin associated pulmonary toxicity: is perioperative oxygen restriction necessary? J Urol 1998;160:1347-1352.

13. Akca O, Podolsky A, Eisenhuber E, et al. Comparable postoperative pulmonary atelectasis in patients given 30% or 80% oxygen during and 2 hours after colon resection. Anesthesiology 1999;91:991-998.

14. Lentschener C. Prevention of atelectasis during general anaesthesia. Lancet 1995;346:514-515.

15. Ihnken K, Winkler A, Schlensak C, et al. Normoxic cardiopulmonary bypass reduces oxidative myocardial damage and nitric oxide during cardiac operations in the adult. J Thorac Cardiovasc Surg 1998;116:327-334.

16. Zwemer CF, Whitesall SE, D'Alecy LG. Cardiopulmonary-cerebral resuscitation with 100% oxygen exacerbates neurological dysfunction following nine minutes of normothermic cardiac arrest in dogs. Resuscitation 1994;27:159-170.

17. Rubertsson S, Karlsson T, Wiklund L. Systemic oxygen uptake during experimental closed-chest cardiopulmonary resuscitation using air or pure oxygen ventilation. Acta Anaesthesiol Scand 1998;42:32-38.

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Subchapter 20.4. Perioperative Glucose Control

Background

Diabetes is a well-known risk factor for perioperative medical complications. Poor glucose control is an independent risk factor for surgical site infections^1-5 in a range of surgical procedures. Increased risk for infection is thought to result from a combination of clinically apparent effects of longstanding hyperglycemia (e.g., macro- and microvascular occlusive disease) and subtle immunologic defects, most notably neutrophil dysfunction.^6-12 Hyperglycemia may also impair the function of complement and antibodies, reducing the opsonic potential of these factors and impairing phagocytosis, further reducing barriers to infection.^13,14 Although many of the clinically apparent manifestations of diabetes are not easily reversed in the perioperative period, there is a small literature that suggests that improving glucose control can improve immunologic function and reduce the incidence of surgical site infections (SSI).^6-8,12

Perioperative management of glucose for diabetic patients commonly includes withholding or administering a reduced dose of the patients' usual hypoglycemic agent(s) and commencing a low-rate intravenous glucose infusion while patients are NPO prior to surgery. The infusion is continued postoperatively until the patient is able to eat and resume outpatient diabetes therapy. Often a sliding scale insulin regimen, a schedule of subcutaneous regular insulin dosage contingent on capillary blood glucose measurements, is also continued through the perioperative period. However, use of a sliding scale may result in wide variations in serum glucose,¹⁵ opening the rationale of this method to question.^16-18

Practice description

Aggressive glucose control in the perioperative period can be achieved using a continuous intravenous insulin infusion (CII). Nursing staff monitor fingerstick (or arterial line drop-of-blood sample) glucose measurements and adjust the infusion rate based on a protocol intended to maintain serum glucose within a certain range. For example, the target range for the original Portland Protocol was between 151 and 200 mg/dL.^16,19,20 In the most recent version, the range is between 125 and 175 mg/dL.²¹

Prevalence and Severity of the Target Safety Problem

Little evidence exists to describe the practice of CII in prevention of surgical site infections in broad surgical practice. The small amount of evidence available describes its use in patients undergoing cardiac surgery, primarily coronary artery bypass grafting (CABG). Diabetes is a well-described risk factor for sternal wound infections, a catastrophic complication of median sternotomy.^19,22-25 Sternal wound infections occur in 0.8% to 2% of unselected patients undergoing median sternotomy and CABG.^20,22,23 Diabetic patients, who comprise between 17 and 20% of all patients undergoing CABG, have been reported to have an incidence of sternal wound infections as high as 5.6%.²⁶ Such infections are associated with marked increases in morbidity and costs. Furnary et al reported that patients with sternal wound infections had an average increased length of stay of 16 days and a higher mortality rate (19% vs. 3.8% in patients without sternal wound infections).²⁰ (See also Subchapter 20.1).

Opportunities for Impact

More than 700,000 Americans underwent open-heart surgery in 1998 alone.²⁷ Up to 20% of these patients may be candidates for continuous insulin infusion. Although CII is included in the recent ACC/AHA Guidelines for CABG Surgery,²⁸ there are no data on the extent to which the measure is currently used during cardiac or other surgical procedures.

Study Designs and Outcomes

We identified one prospective before-after study that compared rates of deep sternal wound infections (DSWI) in diabetic patients undergoing CABG before and after implementation of an aggressive CII protocol.²⁰ DSWI included infections involving the sternum or mediastinal tissues, including mediastinitis. An older study from the same authors was not reviewed as it reported findings at an earlier point in the same trial.¹⁹ Additional studies examined the use of CII in perioperative patients but did not report Level 1 clinical outcomes relevant to patient safety (e.g., mortality, wound infection) and were also not reviewed.²⁹

Evidence for Effectiveness of the Practice

Furnary et al found that aggressive glucose control with CII was associated with a reduction in deep sternal wound infections.²⁰ The effect of the intervention remained statistically significant in a logistic regression model adjusting for multiple potential confounding variables. Furthermore, the demographic characteristics were generally biased against the CII group, which had a significantly higher percentage of patients with hypertension, renal insufficiency, and obesity but fewer patients with congestive heart failure. However, the authors did not adjust for long-term markers of glucose control such as glycosylated hemoglobin, nor did they describe other changes in patient care systems that resulted from changing patients to insulin infusions. Continuous insulin infusions require closer attention by nursing staff both for monitoring of infusion equipment and for frequent measurements of blood glucose. It is possible that the improved outcomes were due to closer overall attention to the patient. Although 74% of DSWI occurred after initial discharge (raising the concern that the shorter length of stay in the sliding scale insulin group may have resulted in some infection not being detected), the authors reported that they directly followed-up all diabetic patients for one year from the time of surgery.³⁰ The personnel, equipment, surgical techniques, and use of prophylactic antibiotics were similar throughout the study period.³¹ Nonetheless, it is likely that secular trends in the care of patients undergoing cardiac surgery account for some of the impact attributed to CII.

Potential for Harm

Hypoglycemic episodes are the most concerning adverse event associated with intensive glucose management with intravenous insulin. These episodes result in a range of medical complications, from delirium to myocardial infarction resulting from increased sympathetic activity. Furnary noted that, using the standardized protocol in their study, no cases of symptomatic hypoglycemia occurred in either group of patients.³⁰ However, CII protocols intended to maintain normoglycemia in surgical patients have been associated with high rates (40%) of postoperative hypoglycemia requiring treatment (<60 mg/dL glucose).³²

Costs and Implementation

The equipment and personnel required to administer intravenous insulin are readily available. Although a formal cost-effectiveness analysis of the practice has not yet been performed, limited data are available. Furnary et al estimate the additional expense of CII at $125-150 per patient.³³ While this likely includes direct costs of CII such as infusion equipment and additional nursing care for more frequent monitoring of glucose and adjustment of insulin infusion rates, it may underestimate the true costs of the practice at other sites, particularly during early phases of implementation. Furnary reported that the practice required a significant period of time for staff to gain familiarity and expertise with CII, and that by the end of the study they had in place a system that required no significant changes in care patterns for CII to be administered.³⁴ In early phases of implementation there may be additional costs related to excess time spent by patients in ICU or high-level care areas (i.e., stepdown units) rather than regular wards. The start-up costs in terms of training and system changes, and whether the approach is easily adaptable to sites that lack the capability to administer CII in numerous inpatient settings, have yet to be determined.

It seems likely that savings from averted infections may substantially compensate for the incremental direct costs of CII. Based on Furnary's findings and cost assumptions, the average DSWI was associated with $26,000 in additional charges (not costs). Of 1499 patients in the intervention group, the number of DSWIs prevented was 10 (95% CI: 4-21) and the average cost to prevent one DSWI was approximately $21,000 (95% CI: $10,000-$52,500). Of course, these figures do not incorporate the potential effects of the intervention on other sites of infection, mortality, adverse events, and patients' preferences (utilities) for these possible health states.

Comment

An increasing body of evidence demonstrates that tight control of blood glucose improves overall outcomes of patients with diabetes.^35-37 Emerging data, coupled with an increasing appreciation of the deleterious effects of hyperglycemia on immune function, strongly support the supposition that aggressive control of perioperative glucose reduces the incidence of surgical site infections. Although the practice has been implemented at a number of institutions and is also being used in diabetic patients undergoing non-cardiac surgeries,³⁴ studies of its effectiveness in these settings have not yet been published. Until additional evidence is available, preferably from blinded randomized controlled trials, the intervention can be considered promising but not yet proven to be causally associated with improved outcomes.

Table 20.4.1. Prospective, before-after study of aggressive perioperative glucose control*

Study	Study Population	Comparison Groups	Resultsa
Furnary, 199920	2467 diabetic patients undergoing cardiac surgery at a community hospital	968 patients treated with sliding scale SQ insulin (1987-91) 1499 patients treated with CII to target glucose of 150-200 mg/dL until POD 3 (1991-97)	Deep surgical wound infections Unadjusted: 1.9% vs. 0.8% (p=0.011) Adjusted RR 0.34 (95% CI: 0.14-0.74) Mortality: 6.1% vs. 3.0% (p=0.03) Length of Stay: 10.7d vs. 8.5d (p<0.01)

* CI indicates confidence interval; CII, continuous intravenous insulin; POD, postoperative day; and RR, relative risk.

^a Results reported as pre-intervention (sliding scale SQ insulin) vs. post-intervention (CII).

References

1. Medina-Cuadros M, Sillero-Arenas M, Martinez-Gallego G, Delgado-Rodriguez M. Surgical wound infections diagnosed after discharge from hospital: epidemiologic differences with in-hospital infections. Am J Infect Control 1996;24:421-428.

2. Kanat A. Risk factors for neurosurgical site infections after craniotomy: a prospective multicenter study of 2944 patients. Neurosurgery 1998;43:189-190.

3. Moro ML, Carrieri MP, Tozzi AE, Lana S, Greco D. Risk factors for surgical wound infections in clean surgery: a multicenter study. Italian PRINOS Study Group. Ann Ital Chir 1996;67:13-19.

4. Barry B, Lucet JC, Kosmann MJ, Gehanno P. Risk factors for surgical wound infections in patients undergoing head and neck oncologic surgery. Acta Otorhinolaryngol Belg 1999;53:241-244.

5. Richet HM, Chidiac C, Prat A, Pol A, David M, Maccario M, et al. Analysis of risk factors for surgical wound infections following vascular surgery. Am J Med 1991;91:170S-72S.

6. Marhoffer W, Stein M, Schleinkofer L, Federlin K. Monitoring of polymorphonuclear leukocyte functions in diabetes mellitus—a comparative study of conventional radiometric function tests and low-light imaging systems. J Biolumin Chemilumin 1994;9:165-170.

7. Terranova A. The effects of diabetes mellitus on wound healing. Plast Surg Nurs 1991;11:20-25.

8. Allen DB, Maguire JJ, Mahdavian M, Wicke C, Marcocci L, Scheuenstuhl H, et al. Wound hypoxia and acidosis limit neutrophil bacterial killing mechanisms. Arch Surg 1997;132:991-996.

9. Nolan CM, Beaty HN, Bagdade JD. Further characterization of the impaired bactericidal function of granulocytes in patients with poorly controlled diabetes. Diabetes 1978;27:889-894.

10. Bagdade JD, Walters E. Impaired granulocyte adherence in mildly diabetic patients: effects of tolazamide treatment. Diabetes 1980;29:309-311.

11. Mowat A, Baum J. Chemotaxis of polymorphonuclear leukocytes from patients with diabetes mellitus. N Engl J Med 1971;284:621-627.

12. MacRury SM, Gemmell CG, Paterson KR, MacCuish AC. Changes in phagocytic function with glycaemic control in diabetic patients. J Clin Pathol 1989;42:1143-1147.

13. Hennessey PJ, Black CT, Andrassy RJ. Nonenzymatic glycosylation of immunoglobulin G impairs complement fixation. JPEN J Parenter Enteral Nutr 1991;15:60-64.

14. Black CT, Hennessey PJ, Andrassy RJ. Short-term hyperglycemia depresses immunity through nonenzymatic glycosylation of circulating immunoglobulin. J Trauma 1990;30:830-832.

15. Queale WS, Seidler AJ, Brancati FL. Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus. Arch Intern Med 1997;157:545-552.

16. Zinman B. Insulin regimens and strategies for IDDM. Diabetes Care 1993;16(Suppl 3):24-28.

17. Kletter GG. Sliding scale fallacy. Arch Intern Med 1998;158:1472.

18. Shagan B. Does anyone here know how to make insulin work backwards? Why sliding scale insulin coverage doesn't work. Pract Diabetol 1990;9:1-4.

19. Zerr KJ, Furnary AP, Grunkemeier GL, Bookin S, Kanhere V, Starr A. Glucose control lowers the risk of wound infection in diabetics after open heart operations. Ann Thorac Surg 1997;63:356-361.

20. Furnary AP, Zerr KJ, Grunkemeier GL, Starr A. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures. Ann Thorac Surg 1999;67:352-360.

21. Starr Wood Cardiac Group. Starr Wood Research - Continuous Intravenous Insulin Infusion. Available at: http://www.starrwood.com/research/insulin.html. Accessed June 11, 2001.

22. Borger MA, Rao V, Weisel RD, Ivanov J, Cohen G, Scully HE, et al. Deep sternal wound infection: risk factors and outcomes. Ann Thorac Surg 1998;65:1050-1056.

23. Trick WE, Scheckler WE, Tokars JI, Jones KC, Reppen ML, Smith EM, et al. Modifiable risk factors associated with deep sternal site infection after coronary artery bypass grafting. J Thorac Cardiovasc Surg 2000;119:108-114.

24. Zacharias A, Habib RH. Factors predisposing to median sternotomy complications. Deep vs superficial infection. Chest 1996;110:1173-1178.

25. Whang W, Bigger JT. Diabetes and outcomes of coronary artery bypass graft surgery in patients with severe left ventricular dysfunction: results from The CABG Patch Trial database. The CABG Patch Trial Investigators and Coordinators. J Am Coll Cardiol 2000;36:1166-1172.

26. Golden SH, Peart-Vigilance C, Kao WH, Brancati FL. Perioperative glycemic control and the risk of infectious complications in a cohort of adults with diabetes. Diabetes Care 1999;22:1408-1414.

27. American Heart Association. 2001 Heart and Stroke Statistical Update. Available at: http://www.americanheart.org/statistics/medical.html. Accessed June 11, 2001.

28. Eagle KA, Guyton RA, Davidoff R, Ewy GA, Fonger J, Gardner TJ, et al. ACC/AHA Guidelines for Coronary Artery Bypass Graft Surgery: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery). American College of Cardiology/American Heart Association. J Am Coll Cardiol 1999;34:1262-1347.

29. Lazar HL, Chipkin S, Philippides G, Bao Y, Apstein C. Glucose-insulin-potassium solutions improve outcomes in diabetics who have coronary artery operations. Ann Thorac Surg 2000;70:145-150.

30. Furnary AP. Continuous intravenous insulin infusion reduces the incidence of deep sternal wound infection in diabetic patients after cardiac surgical procedures [discussion]. Ann Thorac Surg 1999;67:360-62.

31. CTSNet, the Cardiothoracic Surgery Network. Use of historical controls may weaken conclusions. Available at: Available at: http:www.ctsnet.org/forum/78/0/2240. Accessed June 18, 2001.

32. Chaney MA, Nikolov MP, Blakeman BP, Bakhos M. Attempting to maintain normoglycemia during cardiopulmonary bypass with insulin may initiate postoperative hypoglycemia. Anesth Analg 1999;89:1091-1095.

33. Star Wood Cardiac Group. The Portland Insulin Protocol - Frequently Asked Questions Page 1. Available at: http://www.starrwood.com/research/Insulin_FAQ1.html. Accessed June 11, 2001.

34. Starr Wood Cardiac Group. The Portland Insulin Protocol - Frequently Asked Questions Page 2. Available at: http://www.starrwood.com/research/Insulin_FAQ2.html. Accessed June 11, 2001.

35. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993;329:977-986.

36. The effect of intensive diabetes therapy on the development and progression of neuropathy. The Diabetes Control and Complications Trial Research Group. Ann Intern Med 1995;122:561-568.

37. Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy. The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med 2000;342:381-389.

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