Supplemental Intraoperative Oxygen and Long-term Mortality: Subanalysis of a Multiple Crossover Cluster Trial

Abstract

Background Whether supplemental oxygen worsens long-term mortality remains unclear, with contradictory trial results. The authors therefore tested the hypothesis that supplemental oxygen (80% vs. 30%) increases the hazard for long-term mortality. Methods The authors conducted a post hoc analysis of a large multiple crossover cluster trial in which more than 5,000 colorectal surgeries on 4,088 adults were allocated to receive either 30% or 80% inspired oxygen during general anesthesia. The authors assessed the effect of 80% versus 30% target-inspired oxygen on long-term mortality and calculated Kaplan–Meier survival estimates. Analysis was restricted to patients with a home address in Ohio because the authors could obtain reliable vital status information from the Ohio Department of Health (Columbus, Ohio) for them. Results A total of 3,471 qualifying colorectal surgeries performed in 2,801 patients were analyzed, including 1,753 (51%) surgeries in 1,577 patients given 80% oxygen and 1,718 surgeries in 1,551 patients given 30% oxygen. The observed incidence of death after a median of 3 yr was 13% (234 of 1,753) in the 80% oxygen group and 14% (245 of 1,718) in the 30% oxygen group. The estimated hazard ratio for mortality was 0.94 (95% CI, 0.78 to 1.13; P = 0.493). Conclusions In this post hoc analysis of a large, controlled trial, supplemental oxygen did not increase postoperative mortality. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Intraoperative Fractions of Inspiratory Oxygen Are Associated With Recurrence-Free Survival After Elective Cancer Surgery

“…In line, after a median followup of 2.3 years, a subsequent analysis of the same trial found increased long-term mortality in patients receiving 80% oxygen during cancer surgery (11). Contrarily, authors of other post-hoc analysis, combining mortality data from different RCTs, found that there was neither a difference in long-term mortality nor did they find differences in overall survival for patients randomly assigned to 30% vs. 80% FiO 2 (32,33). The median follow-up was 12.8 (3.8, 13.6) years in the trial by Greif,4.3 (3.6,4.8) years in the trial by Kurz, and 3.2 (0.5, 4.9) years in the study by Jiang (1,33,34).…”

“…Contrarily, authors of other post-hoc analysis, combining mortality data from different RCTs, found that there was neither a difference in long-term mortality nor did they find differences in overall survival for patients randomly assigned to 30% vs. 80% FiO 2 (32,33). The median follow-up was 12.8 (3.8, 13.6) years in the trial by Greif,4.3 (3.6,4.8) years in the trial by Kurz, and 3.2 (0.5, 4.9) years in the study by Jiang (1,33,34). This is in line with our finding that overall survival did not differ between high and low FiO 2 groups with a median follow-up of 3.28 (1.68, 4.97) years.…”

“…We demonstrated an independent association of FiO 2 with recurrence-free survival for CRC surgery patients but not for patients undergoing PC surgery. Interestingly, Podolyak et al and Jiang et al who did not find differences regarding cancerfree survival investigated only patients with elective colectomy in their post-hoc analysis, including RCTs (32,33). In the post-hoc analysis of the PROXI trial, about half the patients underwent colorectal surgery (12).…”

Exploring Hyperoxia Effects in Cancer—From Perioperative Clinical Data to Potential Molecular Mechanisms

“…The authors tested the effects of 80% versus 30% oxygen concentration on a composite of 30-day deep and organ-space SSIs, healing-related wound complications and mortality, and found that supplemental oxygen does not prevent major infections and healing-related complications after major intestinal surgery [ 30 ]. A recent post-hoc analysis of this study, including 3400 operations performed on 2800 patients, investigated patient long-term mortality [ 55 ]. After a median of 3 years, the incidence of death was no different in the 80% versus the 30% oxygen group (13% vs. 14%, 95% CI = 0.78–1.13; p = 0.493).…”

“…After a median of 3 years, the incidence of death was no different in the 80% versus the 30% oxygen group (13% vs. 14%, 95% CI = 0.78–1.13; p = 0.493). The analysis of 995 colorectal cancer patients also showed that 80% inspired oxygen did not influence long-term mortality [ 55 ].…”