High oxygen levels after surgery linked to increased long-term risk of death

Although preliminary, the study by Dr Christian S. Meyhoff of Copenhagen University Hospital and colleagues provides new evidence on possible risks -- in addition to previous data questioning the benefits -- of administering 80 percent oxygen to patients undergoing major surgery.

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The researchers evaluated long-term follow-up data from the PROXI study -- a randomized clinical trial performed to evaluate the effects of high concentrations of inhaled oxygen on infection rates after surgery. About 1,400 patients undergoing abdominal surgery were randomly assigned to receive either 80 percent or 30 percent oxygen in the perioperative period: during surgery and for two hours afterward.

In contrast to previous results, the original PROXI study found no difference in the risk of surgical wound infections. There was also a trend toward an increased short-term risk of death with 80 percent oxygen: 4.4 percent, compared to 2.9 percent in patients receiving standard treatment with 30 percent oxygen.

The increase in mortality was not statistically significant. However, it was enough to prompt a follow-up study to determine whether there was any real increase in the risk of death among patients receiving high concentrations of inhaled oxygen -- not only in the short term, but also in the subsequent months and years.

At one to three years after surgery, there were more deaths in the high-oxygen group. The long-term mortality rate was 23.2 percent for patients assigned to 80 percent oxygen, compared to 18.3 percent in the 30 percent oxygen group.

After adjustment for other factors, the difference was significant only for patients undergoing cancer surgery. In this group, the use of 80 percent oxygen was associated with a 45 percent increase in the risk of death. For patients undergoing other types of abdominal surgery, there was no difference in mortality between groups.

The long-term difference in mortality was surprising, because it appeared unrelated to any immediate harmful effects of 80 percent oxygen. (Breathing high concentrations of oxygen can cause harmful effects on the lungs in some cases.) The authors speculate on some possible mechanisms by which high oxygen concentrations could specifically affect the behavior of cancers, potentially increasing the risk of recurrence.

Dr Meyhoff and coauthors emphasize the preliminary nature of their findings -- the study was not designed to detect a difference in long-term mortality risk between 80 percent and 30 percent oxygen. They write, "Further studies are required before an association between perioperative hyperoxia and long-term mortality is established beyond reasonable doubt."

In the meantime, the findings add concerns over long-term mortality to the original PROXI results showing no reduction in infections among patients assigned to high concentrations of inhaled oxygen. The researchers conclude, "Until a clinical benefit of 80 percent perioperative oxygen is well-documented, we recommend abstaining from administering [oxygen concentrations] above what is needed to maintain sufficient arterial oxygen saturation."