Intraoperative Nitrous Oxide Tied to Lower Morbidity

SAN DIEGO – The risks for 30-day postoperative mortality and morbidity were lower in those whose general anesthesia contained nitrous oxide compared with matched patients who got intraoperative air, in a retrospective study of 37,609 adults undergoing major noncardiac surgery.

These findings contradict those of some previous reports, according to Dr. Ayako Shiba of the Cleveland Clinic.

She and her associates analyzed data on 37,609 procedures performed at the clinic between 2005 and 2009, and matched 12,773 patients who received nitrous oxide with 12,773 who did not get nitrous oxide by type of surgery and by a propensity score based on potential confounding variables at baseline.

They found no significant association between intraoperative administration of nitrous oxide and 30-day mortality, she reported at the annual meeting of the American Society of Anesthesiologists. In the nitrous oxide group, 0.6% died within 30 days compared with 0.8% in the air group (P = .08).

In a composite of in-hospital morbidity and mortality, the odds were significantly lower in the nitrous oxide group (8.2%) compared with the air group (9%), with an odds ratio of 0.90 in the nitrous oxide group (P = .017).

A secondary analysis looking at individual morbidities found that the risk for pulmonary/respiratory complications was significantly lower in the nitrous oxide group than in the air group (1.6% vs. 2.7%, P less than .001). Risks did not differ between groups for other individual morbidity categories, however, such as cardiac, hemorrhagic, infectious, neurologic, peripheral vascular, urinary/renal, or wound disruption, or for in-hospital mortality.

Dr. Shiba speculated that the lower rates of complications in the nitrous oxide group may have resulted from lower inspired oxygen concentrations – a direct beneficial effect of nitrous oxide – or a decrease in the use of volatile anesthetic agents.

A previous study – a randomized, controlled trial of 2,050 patients undergoing major surgery – reported that there were fewer complications in patients who did not receive perioperative nitrous oxide (Anesthesiology 2007;107:221-31).That study inspired an editorial titled, "Is It Time to Retire High-Concentration Nitrous Oxide?" (Anesthesiology 2007;107:200-1).

Although nitrous oxide has been used widely in clinical anesthesia for more than 150 years, concerns about the drug’s metabolic side effects, postoperative nausea and vomiting, and the greenhouse-gas effect have led to decreased usage in recent years, she said. An informal poll of the audience at her presentation showed that approximately three-quarters of those in attendance still use nitrous oxide as some component of anesthesia, and one-quarter have stopped using it completely.

"Considering all of the available data, we conclude that insufficient evidence supports the theory that nitrous oxide use increases the risk of either serious complications or mortality in surgical patients," she said.

The study excluded patients who needed emergency surgery or were American Society of Anesthesiology class V or VI. Pediatric cases and patients who were not under general anesthesia also were excluded.

Dr. Shiba said she has no relevant conflicts of interest.

SAN DIEGO – The risks for 30-day postoperative mortality and morbidity were lower in those whose general anesthesia contained nitrous oxide compared with matched patients who got intraoperative air, in a retrospective study of 37,609 adults undergoing major noncardiac surgery.

These findings contradict those of some previous reports, according to Dr. Ayako Shiba of the Cleveland Clinic.

She and her associates analyzed data on 37,609 procedures performed at the clinic between 2005 and 2009, and matched 12,773 patients who received nitrous oxide with 12,773 who did not get nitrous oxide by type of surgery and by a propensity score based on potential confounding variables at baseline.

They found no significant association between intraoperative administration of nitrous oxide and 30-day mortality, she reported at the annual meeting of the American Society of Anesthesiologists. In the nitrous oxide group, 0.6% died within 30 days compared with 0.8% in the air group (P = .08).

In a composite of in-hospital morbidity and mortality, the odds were significantly lower in the nitrous oxide group (8.2%) compared with the air group (9%), with an odds ratio of 0.90 in the nitrous oxide group (P = .017).

A secondary analysis looking at individual morbidities found that the risk for pulmonary/respiratory complications was significantly lower in the nitrous oxide group than in the air group (1.6% vs. 2.7%, P less than .001). Risks did not differ between groups for other individual morbidity categories, however, such as cardiac, hemorrhagic, infectious, neurologic, peripheral vascular, urinary/renal, or wound disruption, or for in-hospital mortality.

Dr. Shiba speculated that the lower rates of complications in the nitrous oxide group may have resulted from lower inspired oxygen concentrations – a direct beneficial effect of nitrous oxide – or a decrease in the use of volatile anesthetic agents.

A previous study – a randomized, controlled trial of 2,050 patients undergoing major surgery – reported that there were fewer complications in patients who did not receive perioperative nitrous oxide (Anesthesiology 2007;107:221-31).That study inspired an editorial titled, "Is It Time to Retire High-Concentration Nitrous Oxide?" (Anesthesiology 2007;107:200-1).

Although nitrous oxide has been used widely in clinical anesthesia for more than 150 years, concerns about the drug’s metabolic side effects, postoperative nausea and vomiting, and the greenhouse-gas effect have led to decreased usage in recent years, she said. An informal poll of the audience at her presentation showed that approximately three-quarters of those in attendance still use nitrous oxide as some component of anesthesia, and one-quarter have stopped using it completely.

"Considering all of the available data, we conclude that insufficient evidence supports the theory that nitrous oxide use increases the risk of either serious complications or mortality in surgical patients," she said.

The study excluded patients who needed emergency surgery or were American Society of Anesthesiology class V or VI. Pediatric cases and patients who were not under general anesthesia also were excluded.

Dr. Shiba said she has no relevant conflicts of interest.

SAN DIEGO – The risks for 30-day postoperative mortality and morbidity were lower in those whose general anesthesia contained nitrous oxide compared with matched patients who got intraoperative air, in a retrospective study of 37,609 adults undergoing major noncardiac surgery.

These findings contradict those of some previous reports, according to Dr. Ayako Shiba of the Cleveland Clinic.

She and her associates analyzed data on 37,609 procedures performed at the clinic between 2005 and 2009, and matched 12,773 patients who received nitrous oxide with 12,773 who did not get nitrous oxide by type of surgery and by a propensity score based on potential confounding variables at baseline.

They found no significant association between intraoperative administration of nitrous oxide and 30-day mortality, she reported at the annual meeting of the American Society of Anesthesiologists. In the nitrous oxide group, 0.6% died within 30 days compared with 0.8% in the air group (P = .08).

In a composite of in-hospital morbidity and mortality, the odds were significantly lower in the nitrous oxide group (8.2%) compared with the air group (9%), with an odds ratio of 0.90 in the nitrous oxide group (P = .017).

A secondary analysis looking at individual morbidities found that the risk for pulmonary/respiratory complications was significantly lower in the nitrous oxide group than in the air group (1.6% vs. 2.7%, P less than .001). Risks did not differ between groups for other individual morbidity categories, however, such as cardiac, hemorrhagic, infectious, neurologic, peripheral vascular, urinary/renal, or wound disruption, or for in-hospital mortality.

Dr. Shiba speculated that the lower rates of complications in the nitrous oxide group may have resulted from lower inspired oxygen concentrations – a direct beneficial effect of nitrous oxide – or a decrease in the use of volatile anesthetic agents.

A previous study – a randomized, controlled trial of 2,050 patients undergoing major surgery – reported that there were fewer complications in patients who did not receive perioperative nitrous oxide (Anesthesiology 2007;107:221-31).That study inspired an editorial titled, "Is It Time to Retire High-Concentration Nitrous Oxide?" (Anesthesiology 2007;107:200-1).

Although nitrous oxide has been used widely in clinical anesthesia for more than 150 years, concerns about the drug’s metabolic side effects, postoperative nausea and vomiting, and the greenhouse-gas effect have led to decreased usage in recent years, she said. An informal poll of the audience at her presentation showed that approximately three-quarters of those in attendance still use nitrous oxide as some component of anesthesia, and one-quarter have stopped using it completely.

"Considering all of the available data, we conclude that insufficient evidence supports the theory that nitrous oxide use increases the risk of either serious complications or mortality in surgical patients," she said.

The study excluded patients who needed emergency surgery or were American Society of Anesthesiology class V or VI. Pediatric cases and patients who were not under general anesthesia also were excluded.

Dr. Shiba said she has no relevant conflicts of interest.