Intraoperative Hyperoxia Does Not Reduce Postoperative Pain

Subanalysis of an Alternating Cohort Trial

Barak Cohen, MD; Sanchit Ahuja, MD; Yehoshua N. Schacham, MD; David Chelnick, BS; Guangmei Mao, PhD; Wael Ali-Sakr Esa, MD; Kamal Maheshwari, MD, MPH; Daniel I. Sessler, MD; Alparslan Turan, MD


Anesth Analg. 2019;128(6):1160-1166. 

In This Article

Abstract and Introduction


Background: Postoperative pain is common and promotes opioid use. Surgical wounds are hypoxic because normal perfusion is impaired. Local wound ischemia and acidosis promote incisional pain. Some evidence suggests that improving oxygen supply to surgical wounds might reduce pain. We therefore tested the hypothesis that supplemental (80% inspired) intraoperative oxygen reduces postoperative pain and opioid consumption.

Methods: We conducted a post hoc analysis of a large, single-center alternating cohort trial allocating surgical patients having general anesthesia for colorectal surgery to either 30% or 80% intraoperative oxygen concentration in 2-week blocks for a total of 39 months. Irrespective of allocation, patients were given sufficient oxygen to maintain saturation .95%. Patients who had regional anesthesia or nerve blocks were excluded. The primary outcome was pain and opioid consumption during the initial 2 postoperative hours, analyzed jointly. The secondary outcome was pain and opioid consumption over the subsequent 24 postoperative hours. Subgroup analyses of the primary outcome were conducted for open versus laparoscopic procedures and for patients with versus without chronic pain.

Results: A total of 4702 cases were eligible for analysis: 2415 were assigned to 80% oxygen and 2287 to 30% oxygen. The groups were well balanced on potential confounding factors. Average pain scores and opioid consumption were similar between the groups (mean difference in pain scores, -0.01 [97.5% CI, -0.16 to 0.14; P = .45], median difference in opioid consumption, 0.0 [97.5% CI, 0 to 0] mg morphine equivalents; P = .82). There were also no significant differences in the secondary outcome or subgroup analyses.

Conclusions: Supplemental intraoperative oxygen does not reduce acute postoperative pain or reduce opioid consumption.


Postoperative pain prolongs hospitalization, increases health care costs, and promotes the use of both opioid and nonopioid analgesics.[1–3] Pain is among surgical patients' leading concerns, and pain increases preoperative anxiety and postoperative sympathetic response.[4] Preventing and treating surgical pain is thus a clinical priority.

Incisional pain is multifactorial, but wound ischemia and local production and secretion of inflammatory mediators clearly contribute. Even when arterial blood is fully saturated, surgical wounds have high lactate concentrations and are therefore acidic, which, in animal models, provokes pain-related behavior.[5,6] Supplemental oxygen (eg, 80% vs 30% inspired fraction) substantially increases arterial PaO2, which in turn doubles tissue oxygenation.[7,8] Hyperoxia also promotes vasodilation. The combination of better oxygenation and perfusion reduces wound lactate concentration and possibly reduces surgical pain consequent to local acidosis.[5]

The importance of adequate wound oxygenation is perhaps most impressively demonstrated with hyperbaric oxygen, during which patients are exposed to 100% oxygen at up to 3 atmospheric pressures. The resulting markedly elevated PaO2 improves oxygenation of ischemic tissues and, in several animal models of nociception and inflammation, reduces pain.[9–12] There is also some evidence suggesting that hyperbaric oxygen reduces pain in patients with diabetic ulcers, pressure ulcers, and chronic nonhealing wounds.[13–16] However, whether supplemental oxygen at atmospheric pressure ameliorates pain remains unknown.

We therefore tested the hypothesis that intraoperative hyperoxia (inspired oxygen fraction [FIO2]; 80% vs 30%) reduces postoperative pain and opioid consumption during the initial 2 postoperative hours in adults recovering from noncardiac surgery. Secondarily, we tested the same hypothesis during the subsequent 24 postoperative hours. On an exploratory basis, we also considered subgroups of patients who had laparotomy versus laparoscopic or laparoscopic-assisted surgeries and patients who did or did not have preoperative chronic pain.