High Inspired Oxygen Fraction and Surgical Site Infection

Abstract

EVIDENCE CONTINUES TO ACCUMULATE ON WHETHER the use of high inspired oxygen fraction (FIO2) is effective for preventing surgical site infections (SSIs). In 2000, a randomized trial by Greif et al demonstrated that SSIs were significantly decreased following colon surgery in patients who received 80% oxygen intraoperatively and for the first 2 hours following surgery. Subsequent clinical trials by Belda et al and by Myles et al supported the use of perioperative supplemental high inspired oxygen for reducing risk of surgical wound infection, whereas a clinical trial by Pryor et al suggested that perioperative hyperoxia was not effective in reducing SSIs (and in fact increased them). A trial by Mayzler et al reported only 5 of 38 patients as developing SSI overall and thus had inadequate power to draw conclusions. A meta-analysis of these trials, pooling the outcomes of 3001 patients, found that perioperative administration of high inspired oxygen (80% concentration) was associated with a 3% absolute reduction (crude infection rates of 12% in the control group and 9% in the group receiving 80% oxygen) and a 25% relative reduction in risk of SSI. In this issue of JAMA, Meyhoff and colleagues report the results of the PROXI trial, in which 1400 patients in 14 Danish hospitals undergoing acute or elective laparotomy were randomized to receive either 80% oxygen or 30% oxygen during and for 2 hours following their operations. The primary finding was that there were no statistically significant differences in rates of SSI with high FIO2 (131 patients [19%] in the 80% oxygen group vs 141 [20%] in the 30% oxygen group, P=.64). Likewise, there were no statistically significant differences in rates of pulmonary complications, including atelectasis, pneumonia, or respiratory failure between the groups. These findings add to the evidence base surrounding the potential role of high FIO2 for prevention of SSIs. Previous laboratory and clinical studies have shown that the partial pressure of oxygen (PO2) in wounds is important for healing. PO2 is low in surgical wounds as a result of injury, coagulation, inflammation, and, in large measure, the sympathetic nervous system stimulation and consequent vasoconstriction caused by hypothermia, hypovolemia, and pain. This wound hypoxia slows healing but can be corrected. For instance, Hartmann et al assessed wound PO2 and collagen deposition in 2 groups of patients after major abdominal operations and found that, compared with control patients given fluids per an accepted formula, those given additional fluids in response to low wound PO2 had significantly higher wound PO2 levels and significantly more collagen deposition. Moreover, oxygen also is an important factor for eradication of infection. Studies using experimental wound models have demonstrated that Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli injected into wounds could be eradicated at rates proportional to FIO2 or PO2 and that antibiotics were increasingly effective at higher FIO2. Superoxide production by leukocytes, the index of oxidative killing, has been shown to be proportional to PO2, such that production is negligible at a PO2 of 0, half maximal at 3 kPa (near the usual PO2 of a surgical wound), and maximal at about 15 kPa. In a prospective, observational study of surgical patients, vulnerability to infection was inversely proportional to wound PO2. Oxidative killing by leukocytes has been cited as a possible mechanism for this effect. Kohanski et al demonstrated another potential mechanism of action for oxygen: the main groups of bactericidal antibiotics require oxygen to exert their lethal effects in the pathogen. However, in the discussion over whether high FIO2 is good, toxic, effective, or immaterial for prevention of SSIs, the use of 80% oxygen has become the focus of the debate. Wound PO2 can be increased by supplemental oxygen, but only in the absence of vasoconstriction and under conditions conducive for supplemental oxygen to reach the periphery, including rigorous temperature control and appropriate fluid repletion. In a clinical trial by Kurz et al, patients in whom perioperative normothermia was maintained had a significant reduction in SSIs and a significant increase in collagen depo-