Within open Roux-en-Y gastric bypass surgery, the relative risks between the supplemental group and the 30% group were not different between the main trial and the pilot trial (P = 0.66, Breslow–Day test, Table 7). Since the number of complications was so low, we did not perform subanalysis of the data per surgical duration.
All surgical wounds become contaminated. What determines whether inevitable contamination progresses to clinical infection is largely the adequacy of host defense. The primary host defense against surgical pathogens is oxidative killing by bacteria, a process that depends on the partial pressure of oxygen over the entire range of physiologic values. Superoxide radical production is necessary for host defense and correlates directly with the inspired oxygen concentration.
Obese patients having laparoscopic surgery require more inspired oxygen to produce similar arterial oxygen partial pressures than lean individuals. They also have significantly lower subcutaneous oxygen tensions (36–41 vs 57 mm Hg).27,49 Supplemental inspired oxygen (80%) significantly increases subcutaneous oxygenation in the upper arm in morbidly obese patients: 58 vs 43 mm Hg. Tissue oxygenation progressively increases with supplemental oxygen to a maximal difference of about 40 mm Hg after 13 postoperative hours (94 vs 52 mm Hg). Supplemental oxygen also improves tissue oxygenation adjacent to abdominal wounds: 75 vs 52 mm Hg, P = 0.005.37
We were thus unsurprised that supplemental postoperative oxygen almost halved the risk of infection-related complications in our preliminary study of morbidly obese patients having open Roux-en-Y gastric bypass (n = 96).48 There was, nonetheless, no statistically significant difference in the risk of surgical site infections or associated complications in the 400 patients we randomized to supplemental (approximately 80%) or nasal cannula (approximately 30%) oxygen for 12 to 16 postoperative hours. Major complications were chosen to be serious and plausibly related to infection or wound healing, both of which were likely to be improved by supplemental oxygen. Use of a composite outcome was intuitive for this study because we expected supplemental oxygen to reduce the risk of various complications; a single outcome, such as surgical site infection, was unlikely to capture the anticipated treatment benefit so well.
The most obvious difference between the preliminary study and full trial was that a laparoscopic approach was used in 91% of the patients in the full trial, whereas all the preliminary cases were open. Although there was a nonsignificant trend toward a benefit from supplemental oxygen in open procedures in the full trial (n = 37, relative risk 0.67 [95% CI: 0.2–2.3]), there was no overall benefit when open and laparoscopic cases were combined. Since the current surgical trend is toward laparoscopic procedures even in the most morbidly obese patients, it is the results in all patients (mostly laparoscopic) that are most relevant to current practice.
The overall rate of surgical site infections and complications (13%) was lower in both groups than the 25% we expected based on previous studies25,50,51 and our preliminary data.48 However, as more Roux-en-Y gastric bypasses are done laparoscopically and surgical technique improves, the incidence of complications has decreased even in the largest patients.52,53 Neither the futility nor efficacy boundaries were crossed after recruitment of the initial quarter of the patients. However, the futility boundary was crossed at the final analysis of 400 patients (P = 0.80 > the futility boundary of 0.2757). The Executive Committee thus stopped the trial since the probability of identifying a significant difference was low even if the trial continued to completion.
When we started the trial, available evidence suggested that supplemental oxygen, continued to –6 hours postoperatively, almost halved infection risk.22 However, the extent to which supplemental oxygen might be protective for wound infection is now unclear after recent publications of the PROXI and ISO2 trials.25,54 Our current results do not directly address optimal intraoperative oxygen management since randomization was restricted to the postoperative period and all patients received supplemental oxygen in the intraoperative period. Nonetheless, our results seem inconsistent with the general theory that supplemental oxygen reduces wound infection risk.
Why supplemental oxygen does not further reduce surgical site infections and complications in the morbidly obese population remains unclear, especially given the overwhelming evidence that tissue oxygenation is a key determinant of oxidative killing and that oxidative killing is the primary defense against bacterial contamination.8,9 But it is possible that oxygen is no longer effective after the “decisive period” for infection has passed, which is determined to be within a few hours after contamination, which is the incision.
Aside from the timing and duration of supplemental oxygen administration, the major difference between previous trials of supplemental oxygen and our current results is that our patients were morbidly obese. The obese patient population was selected in this study for providing supplemental oxygen since perioperative tissue oxygenation is normally low in this population,22 and high inspired concentrations are required to return tissue partial pressures to the normal range.27 Tissue oxygenation is also impaired by frequent hypoxemic episodes during sleep by the presence of obstructive sleep apnea, which has a prevalence approaching 75% to 86% in this obese population.30–32
Consistent with their many risk factors, wound infections and infection-related complications are common in the obese. In 189 patients having colorectal procedures, for example, wound infection risk significantly correlated with the thickness of subcutaneous fat: 8% of those with <2 cm of subcutaneous fat developed a wound infection compared with 27% with >4.5-cm fat. Infected wounds had 1.2 ± 0.4 cm greater fat thickness than noninfected wounds.55 Another study of 608 patients having digestive tract surgery reported that, after multivariable analysis, obese patients (BMI >30 kg/m2) had an adjusted odds ratio for surgical site infection of 4.8 (95% CI, 2.95–7.81).56
We were unable to precisely control inspired oxygen concentration in patients assigned to supplemental oxygen. Patients randomized to supplemental postoperative oxygen thus received between 65% and 95% inspired oxygen, depending on their minute ventilation and ability to tolerate a sealed mask postoperatively. Nonetheless, in a previously published substudy, we showed that supplemental oxygen substantially increases subcutaneous oxygenation in the arm and adjacent to the surgical incision, suggesting that our administration methods were effective.49
In summary, the composite risk of wound infection and major complications related to infection or wound healing was similar in gastric bypass patients who were randomly assigned to approximately 30% or approximately 80% inspired oxygen administered from tracheal extubation through the first postoperative morning. Supplemental postoperative oxygen does not appear to be beneficial in this population.
SPOT investigators from the University of Louisville included Anupama Wadhwa, MD, Mukadder Orhan Sungur, MD, Ryu Komatsu, MD, Ozan Akça, MD, Jorge Rodriguez, MD, and Raghavendra Govinda, MD. Investigators from the Cleveland Clinic included Daniel I. Sessler, MD, Andrea Kurz, MD, Ramatia Mahboobi, MD, Ankit Maheshwari, MD, Angela Bonilla, MD, Xuegin Ding, MD, Bledar Kovachi, MD, Jing You, MS, Edward J. Mascha, PhD, Luke Reynolds, BS, James Beckman, BS, Karen Steckner, MD, FRCPC, and Sara Kazerounian. Investigators from Vienna include Edith Fleischmann, MD, Barbara Kabon, MD, Erol Erdik, MD, Gerhard Prager, MD, Eva Obwegeser, MD, and Ratzenboeck Ina, MD.
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