Postoperative Pulmonary Complications in the ENIGMA II Trial: A Post Hoc Analysis.

BACKGROUND: Nitrous oxide promotes absorption atelectasis in poorly ventilated lung segments at high inspired concentrations. The Evaluation of Nitrous oxide In the Gas Mixture for Anesthesia (ENIGMA) trial found a higher incidence of postoperative pulmonary complications and wound sepsis with nitrous oxide anesthesia in major surgery compared to a fraction of inspired oxygen of 0.8 without nitrous oxide. The larger ENIGMA II trial randomized patients to nitrous oxide or air at a fraction of inspired oxygen of 0.3 but found no effect on wound infection or sepsis. However, postoperative pulmonary complications were not measured. In the current study, post hoc data were collected to determine whether atelectasis and pneumonia incidences were higher with nitrous oxide in patients who were recruited to the Australian cohort of ENIGMA II. METHODS: 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 a secondary endpoint, required a diagnostic chest radiology report with fever, leukocytosis, or positive sputum culture. Comparison of the nitrous oxide and nitrous oxide-free groups was done according to intention to treat using chi-square tests. RESULTS: Data from 2,328 randomized patients were included in the final data set. The two treatment groups were similar in surgical type and duration, risk factors, and perioperative management recorded for ENIGMA II. There was a 19.3% lower incidence of atelectasis with nitrous oxide (171 of 1,169 [14.6%] vs. 210 of 1,159 [18.1%]; odds ratio, 0.77; 95% CI, 0.62 to 0.97; P = 0.023). There was no difference in pneumonia incidence (60 of 1,169 [5.1%] vs. 52 of 1159 [4.5%]; odds ratio, 1.15; 95% CI, 0.77 to 1.72; P = 0.467) or combined pulmonary complications (odds ratio, 0.84; 95% CI, 0.69 to 1.03; P = 0.093). CONCLUSIONS: In contrast to the earlier ENIGMA trial, nitrous oxide anesthesia in the ENIGMA II trial was associated with a lower incidence of lung atelectasis, but not pneumonia, after major surgery.

External validity of four risk scores predicting 30-day mortality after surgery.

Background: Surgical risk prediction tools can facilitate shared decision-making and efficient allocation of perioperative resources. Such tools should be externally validated in target populations before implementation. Methods: Predicted risk of 30-day mortality was retrospectively derived for surgical patients at Royal Perth Hospital from 2014 to 2021 using the Surgical Outcome Risk Tool (SORT) and the related NZRISK (n=44 031, 53 395 operations). In a sub-population (n=31 153), the Physiology and Operative Severity Score for the enumeration of Mortality (POSSUM) and the Portsmouth variant of this (P-POSSUM) were matched from the Copeland Risk Adjusted Barometer (C2-Ai, Cambridge, UK). The primary outcome was risk score discrimination of 30-day mortality as evaluated by area-under-receiver operator characteristic curve (AUROC) statistics. Calibration plots and outcomes according to risk decile and time were also explored. Results: All four risk scores showed high discrimination (AUROC) for 30-day mortality (SORT=0.922, NZRISK=0.909, P-POSSUM=0.893; POSSUM=0.881) but consistently over-predicted risk. SORT exhibited the best discrimination and calibration. Thresholds to denote the highest and second-highest deciles of SORT risk (>3.92% and 1.52-3.92%) captured the majority of deaths (76% and 13%, respectively) and hospital-acquired complications. Year-on-year SORT calibration performance drifted towards over-prediction, reflecting a decrease in 30-day mortality over time despite an increase in the surgical population risk. Conclusions: SORT was the best performing risk score in predicting 30-day mortality after surgery. Categorising patients based on SORT into low, medium (80-90th percentile), and high risk (90-100th percentile) might guide future allocation of perioperative resources. No tools were sufficiently calibrated to support shared decision-making based on absolute predictions of risk.