Supplemental Postoperative Oxygen and Wound Infection in Morbidly Obese Patients
Supplemental Postoperative Oxygen and Wound Infection in Morbidly Obese Patients
The investigators propose to test the hypothesis that the incidence of major complications
 related to infection or inadequate healing is reduced in morbidly obese patients given 80%
 inspired oxygen during, and for 12-18 hours after, surgery compared with patients given 80%
 oxygen only during surgery. The primary outcome will be a composite of major complications
 plausibly related to infection or healing.
Wound infection is a common and serious consequence of anesthesia and surgery. Infection is
 associated with major complications including intra-abdominal abscess, peritonitis without
 leakage, and sepsis. The average wound infection thus prolongs hospitalization by a week,
 doubles the need for ICU care, and doubles mortality.

 The first few hours following bacterial contamination constitute a decisive period during
 which infection is established. Techniques aimed at improving resistance to surgical wound
 infections are thus most effective when implemented during the decisive period - even though
 infections are not detected clinically until five-to-ten days after surgery.

 The primary defense against surgical pathogens is oxidative killing by neutrophils. This
 reaction critically depends on tissue oxygen tension. It is therefore unsurprising that
 subcutaneous tissue oxygen tension (PsqO2) is inversely correlated with the risk of surgical
 wound infection. As might be expected, supplemental perioperative oxygen administration
 increases tissue oxygen partial pressure (compared with an FIO2 of 30%) and decreases wound
 infection risk. While 100% oxygen is associated with atelectasis and pulmonary inflammation,
 we and others have shown that 80% oxygen is not.

 Inadequate healing is also common. Scar formation starts with transcription of pro-collagen,
 which undergoes post-translational hydroxylation of the abundant proline and lysine residues.
 This promotes the cross-linking within and between collagen strands that provides tensile
 strength which begins the healing process. The prolyl and lysyl hydroxylases that catalyze
 this reaction depend on the substrate oxygen. The Km (substrate concentration at which the
 velocity of the reaction is half-maximal) for O2 of prolyl hydroxylase has been variously
 estimated at 20, 25, and 100 mmHg. Even using the most conservative estimate, these data
 suggest that proline hydroxylation of collagen (e.g., scar formation) will be PO2 dependent
 through the range of 0 to ≈200 mmHg, with 90% of the effect occurring by 90 mmHg. In vitro
 and in vivo animal evidence supports this theory. Inadequate healing is associated with
 anastomotic leakage, wound dehiscence, and bleeding.

 In morbidly obese patients, the incidence of infection and major complications related to
 either infection or inadequate healing is 15-20% after gastric bypass based on our
 preliminary data and a review of records at Washington University. Roughly 30% of the
 American population is now obese with a body mass index (BMI) > 30 kg/m2; about 5% of the
 population is morbidly obese, with a BMI exceeding 40 kg/m2. These patients are at
 extraordinarily high risk of wound infection, and infections in these patients are especially
 severe.

 Cardiac output, circulating blood volume, and resting oxygen consumption are all increased in
 the obese; however, total blood flow is sub-normal in relation to body weight. Obesity
 augments the size of individual fat cells without increasing blood flow. Specifically, fat
 tissue is hypoperfused and poorly oxygenated. Intraoperative tissue oxygenation is abnormally
 low in obese patients and postoperative tissue oxygenation is especially low - although it
 can be improved by oxygen administration. It thus seems likely that inadequate tissue
 oxygenation contributes to the observed extraordinary high wound infection risk in obese
 patients.

 Although supplemental oxygen during surgery and for the first two-to-six hours after surgery
 halves the risk of surgical wound infection, it remains unknown whether prolonged
 supplemental postoperative oxygen significantly augments the benefits of intraoperative
 oxygen. There is some evidence suggesting that prolonged postoperative oxygen administration
 may be helpful. For example, experimental infections in guinea pigs are reduced by
 administration of supplemental oxygen for 45 h. In contrast, restricting oxygen for only 45
 minutes after contamination reduces tensile wound strength in rabbits no more than
 restricting oxygen for 5 full days. No study in humans has evaluated the effects of
 supplemental postoperative oxygen on surgical wound infection or associated complications.

 To the extent that supplemental oxygen after surgery is likely to reduce the incidence of
 major complications related to wound infection and healing, benefit is especially likely in
 morbidly obese patients because their baseline tissue oxygenation is usually sub-optimal and
 their risk is high. We thus propose to test the hypothesis that the incidence of major
 complications related to infection or inadequate healing are reduced in morbidly obese
 patients given 80% inspired oxygen during and for 12-18 hours after surgery compared with
 patients given 80% oxygen only during surgery.

 Patients will be enrolled at two OUTCOMES RESEARCH Group sites: the University of Louisville
 and the Cleveland Clinic. Patients undergoing gastric bypass will all be given 80%
 intraoperative oxygen and then randomly assigned to 30% or 80% oxygen until the first
 postoperative morning. The primary outcome will be a composite of major complications
 plausibly related to infection or healing. A maximum of 1,276 patients will provide a 90%
 power to detect a 25% reduction in the proportion of patients with at least one major
 complication. Supplemental oxygen is safe and inexpensive, costing only a few dollars per
 patient. Confirming our hypothesis would indicate that clinicians can reduce the risk of
 serious complications by making an essentially trivial modification in postoperative patient
 care.
Inclusion Criteria:

 -  Patients with a BMI > 35 kg/m2 undergoing open or laparoscopic gastric bypass

 Exclusion Criteria:

 -  Surgeon does not anticipate primary wound closure

 -  History of fever or infection within 24 hours of surgery

 -  History of susceptibility to malignant hyperthermia

 -  Current heart or lung disease