Nitrous oxide (N2O) promotes absorption atelectasis in poorly ventilated lung segments at high inspired concentrations. The ENIGMA Trial found a higher incidence of postoperative pulmonary complications (PPCs) and wound sepsis with N2O anesthesia in major surgery compared to FIO2 0.8 without N2O. The larger ENIGMA II trial randomised patients to N2O or air at FIO2 0.3 but found no effect on wound infection or sepsis. However, postoperative pulmonary complications were not measured. In the current study we collected post hoc data to determine if atelectasis and pneumonia incidences were higher with N2O in patients who were recruited to the Australian cohort of ENIGMA II.


Digital health records of patients who participated in the trial at 10 Australian hospitals were examined blinded to trial treatment allocation. The primary endpoint was the incidence of atelectasis, defined as lung atelectasis or collapse reported on chest radiology. Pneumonia, as secondary endpoint, required a diagnostic chest radiology report with fever, leukocytosis, or positive sputum culture. Comparison of the N2O and N2O-free groups was done according to intention-to-treat using Chi-squared tests.


Data from 2,328 randomised patients was included in the final dataset. The two treatment groups were similar in surgical type and duration and risk factors and perioperative management recorded for ENIGMA II. There was a 19.3% lower incidence of atelectasis with N2O (171/1169 (14.6%) versus 210/1159 (18.1%), odds ratio 0.77, 95% confidence interval 0.62, 0.97, p=0.023). There was no difference in pneumonia incidence (60/1169 (5.1%) versus 52/1159 (4.5%), odds ratio 1.15, 95% confidence interval 0.77, 1.72, p=0.467) or combined PPCs (odds ratio 0.84, 95% confidence interval 0.69, 1.03, p=0.093).


In contrast to the earlier ENIGMA trial, N2O anesthesia in the ENIGMA II trial was associated with a lower incidence of lung atelectasis, but not pneumonia, after major surgery.