To the Editor:

We have read the recent article by Peyton and Wu1  with great interest, which suggested nitrous oxide–related postoperative nausea and vomiting (PONV) was correlated with the length of time exposed to nitrous oxide. Their excellent meta-analysis on this important subject deserves applause. However, we would like to add some comments to emphasize a few important issues.

First, the concentrations of inhaled nitrous oxide were ignored in the current analysis, which may have a confounding influence on the relationship between the incidence of PONV and duration of exposure to nitrous oxide besides patient sex, age, and duration of anesthesia. In fact, several studies included in this meta-analysis observed different concentrations of inhaled nitrous oxide and showed that nitrous oxide increased the incidence of PONV in a dose-dependent manner.2–4  Both duration of exposure to nitrous oxide and concentrations of inspired nitrous oxide may be significant covariates in the incidence of PONV. Therefore, it is necessary to rule out the influence of concentrations of inhaled nitrous oxide on PONV when determining whether duration of exposure to nitrous oxide was related to the incidence of PONV.

Second, the authors stratified studies based on duration of anesthesia and suggested that the effect of duration of anesthesia on nitrous oxide–induced PONV may instead simply reflect the invasiveness and magnitude of the surgery. However, the type of surgery per se may also be a confounding covariate. In this meta-analysis, more than one-third of the studies involved gynecologic surgery with or without laparoscopy, including a large sample study5  in which up to 45.1% was gynecologic surgery. Duration of anesthesia in this type of surgery was usually no more than 1 to 2 h, while nongynecologic surgeries in remaining studies were almost more than 1 to 2 h except orthopedic surgery in two studies and day case/ambulatory surgery laparoscopy in one study less than 1 h. That is to say, a big difference exists in the types of surgery among groups stratified by duration of anesthesia. Although whether the type of surgery identified as a risk factor of PONV is still somewhat controversial, increased incidence of PONV has been demonstrated in the gynecologic, laparoscopic, and middle-ear surgeries.6–8  Thus, the heterogeneity of the type of surgery may have tempered their conclusion.

Though this meta-analysis brings us closer to draw overall conclusion, it may only be regarded as an interim analysis toward reaching a final answer. Further studies are still needed to clarify the relationship between duration of exposure to nitrous oxide and the incidence of PONV.

Competing Interests

The authors declare no competing interests.

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