Using high inspired concentrations of oxygen in the perioperative period may reduce the risk of surgical site infections for patients undergoing colo-rectal surgery. It does not appear to confer benefit for other patient groups.

We live side by side with an element that both feeds us and damages us simultaneously: oxygen. Reactive oxygen species cause lipid peroxidation of cell membranes and disrupt DNA. They interfere with gene expression and cause altered cell growth and necrosis. This happens all the time, and we have developed anti-oxidant scavenging systems for clearing up the debris. So oxygen is toxic. Conversely, oxygen kills bacteria – facilitating the activity of neutrophils, thus enhancing immune function, it is anti-inflammatory,¹ it is a vasoconstrictor (may reverse vasoplegia) and it redistributes blood flow to the kidneys and splanchnic circulation.^2-4 Oxygen is potentially therapeutic in sepsis.⁵

Surgical site infections (SSI) result in significant morbidity, delayed hospital discharge and increased healthcare costs. There is a known association between SSI and hypoperfusion, contaminated wounds, perioperative hyperglycaemia and hypothermia⁶ and obesity. It has long been proposed that the use of perioperative hyperoxia to high risk patients may result in a reduction in the risk of SSIs. The converse argument is that hyperoxia is toxic to the lungs^7;8 and results in increased atelectasis and, potentially, an increase in postoperative pulmonary complications.⁹

The scientific rationale for preoperative hyperoxia is that oxidative killing by neutrophils, the primary defence against surgical pathogens, depends critically on tissue oxygenation.¹⁰ Hopf and colleagues¹¹ performed a non interventional, prospective study of subcutaneous wound oxygen tension(PsqO₂) and its relationship to the development of woundinfection in surgical patients. One hundred and thirty general surgical patients were enrolled and PsqO₂ was measured perioperatively. There was an inverse relationship between wound oxygen tension and the risk of developing surgical site infections (SSI). They hypothesized that manipulating FiO₂ may increase PsqO₂ and reduce SSIs.

Grief et al¹² randomly assigned 500 patients undergoing colorectal resection to receive 30 percent or 80 percent inspired oxygen during the operation and for two hours afterward. This was a very well constructed study. Anaesthetic treatment was standardized, and all patients received prophylactic antibiotic therapy, standardized fluid regimens and kept euthermic perioperatively. Wounds were evaluated daily until the patient was discharged and then at a clinic visit two weeks after surgery. The arterial and subcutaneous partial pressure of oxygen was significantly higher in the patients given 80 percent oxygen than in those given 30 percent oxygen. The duration of hospitalization was similar in the two groups. Among the 250 patients who received 80 percent oxygen, 13 (5.2 percent; 95 percent confidence interval, 2.4 to 8.0 percent) had surgical-wound infections, as compared with 28 of the 250 patients given 30 percent oxygen (11.2 percent; 95 percent confidence interval, 7.3 to 15.1 percent; P=0.01). The absolute difference between groups was 6.0 percent (95 percent confidence interval, 1.2 to 10.8 percent) NNT 15.

These data were confirmed by a smaller study from Spain. Belda et al¹³ undertook a double-blind, randomizedcontrolled trial of 300 patients aged 18 to 80 years who underwentelective colorectal surgery. Patients were randomly assigned to either30% or 80% fraction of inspired oxygen (FIO₂), intraoperatively,and for 6 hours after surgery. Anaesthetic treatment and antibioticadministration were standardized.A total of 143 patients received 30% perioperativeoxygen and 148 received 80% perioperative oxygen. Surgical siteinfection occurred in 35 patients (24.4%) administered 30% FIO₂and in 22 patients (14.9%) administered 80% FIO₂ (P=.04). Therisk of SSI was 39% lower in the 80% FIO₂ group (relative risk[RR], 0.61; 95% confidence interval [CI], 0.38-0.98) vs the30% FIO₂ group. After adjustment for important covariates, theRR of infection in patients administered supplemental oxygenwas 0.46 (95% CI, 0.22-0.95; P = .04). Similar results were reported by Bickel and colleagues, in a 210 patients with acute appendicitis (5.6% versus 13.6%, p = 0.4, ARR 7 NNT – 13).¹⁴

Pryor et al claimed opposite results.¹⁵ This study included 165 patients that were undergoing general surgery, and were randomized to 30% or 80% oxygen. The overall incidence of SSI was18.1%. In an intention-to-treat analysis, the incidence of infectionwas significantly higher in the group receiving FIO₂ of 0.80than in the group with FIO₂ of 0.35 (25.0% vs 11.3%; P = .02).FIO₂ remained a significant predictor of SSI (P = .03) in multivariateregression analysis. Patients who developed SSI had a significantlylonger length of hospitalization after surgery (mean [SD], 13.3[9.9] vs 6.0 [4.2] days; P<.001).

This study was criticized for a number of reasons. It is unclear whether or not the group assignment was truly blind. Tissue oxygenation was not blind. Wound infection was identified by retrospective chart review, a highly unreliable technique. There was no standardization of fluid therapy, temperature or antibiotic prophylaxis. Patients receiving80% oxygen were more likely to be obese, had longer operations,and lost more blood. All these factors may be associated withincreased risk of SSI. Significantly more patients in the high FiO₂ group went back to the PACU intubated post op. Finally, the incidence of wound infections, at 25%, was high in the hyperoxic group compared with the study by Grief, ¹² but similar to the control group in the study by Belda.¹³

Maragakis et al¹⁶ undertook a case-control retrospective review of SSIs in patients undergoing spinal surgery. Two hundred and eight charts were reviewed. The authors claimed that the use of an FiO2 of <50% significantly increased the risk of SSI (OR, 12; 94% CI, 4.5-33; P < 0.001). This study has the same flaws as that by Prior and colleagues,(50) albeit with opposite results.

Myles et al ¹⁷ enrolled a 2,050 patients into a study that randomized them to either FiO₂ of 80% or 30%, plus 70% nitrous oxide. Patients that were given a high FiO2 had significantly lower rates of major complications (odds ratio, 0.71; 95% confidence interval, 0.56-0.89; P = 0.003) and severe nausea and vomiting (odds ratio, 0.40; 95% confidence interval, 0.31-0.51; P < 0.001). Among patients admitted to the intensive care unit postoperatively, those in the nitrous oxide-free group were more likely to be discharged from the unit on any given day than those in the nitrous oxide group (hazard ratio, 1.35; 95% confidence interval, 1.05-1.73; P = 0.02). It is unclear whether these data represent a beneficial effect of oxygen or a detrimental effect of nitrous oxide.

The Proxi trial ¹⁸ included 685 patients in 14 Danish hospitals. Patients were randomized to 80% versus 30% oxygen. Temperature, fluid therapy and type of surgery were not controlled. Similar to the Pryor trial, the incidence of SSIs were in excess of 20% (20.1%) in the control group, not significantly different from the study group (19.1%). There was no difference in pulmonary complications between the groups. Clearly the extraordinarily high number of SSIs in both groups made a statistically significant difference in outcomes unlikely. A large number of patients had undergone emergency surgery and had contaminated wounds. Hence, a direct comparison with previous studies cannot be made.

However, comparisons have been made and here have been several meta-analyses (MA) of hyperoxia and surgical site infections. These differ in outcomes depending on whether or not one includes the Myles¹⁷ data. Where Myles’s study is included, the MA supports hyperoxia.¹⁹ Where it is excluded – MAs routinely exclude papers for reasons that are not always obvious – hyperoxia is shown not to be beneficial.²⁰ My own conclusion is that there is tremendous heterogenicity between these studies: well controlled studies of colonic surgery where anaesthesia and perioperative care was standardised resulted in better outcomes. Poorly controlled studies (Pryor / Meyhoff), without standardisation resulted in very high levels of SSI in both groups. The excess adverse outcomes in the Pryor study suggests that there were substantial differences between the groups in terms of type and length of surgery, severity of illness etc. and that this study was fatally flawed.

My conclusion: if you are providing anaesthesia for bowel surgery, and will not be using nitrous oxide, 80% oxygen is unlikely to be harmful, and is potentially beneficial. Whether or not to extend this hyperoxia into the postoperative period is very controversial.

References

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This review copyright Patrick Neligan 2012. All rights reserved. Do not reproduce without permission.