Is neostigmine safe and effective for neuromuscular blockade reversal in patients recovering from general anesthesia?

We read with great interest the recent published study by Ji and colleagues entitled “Efficacy and safety of neostigmine for neuromuscular blockade reversal in patients under general anesthesia: a systematic review and meta-analysis” (1). They demonstrated that neostigmine is effective and safe for neuromuscular blockade reversal in patients under general anesthesia. We appreciate Ji and colleagues for the valuable study. However, after a careful learning of the literature, we would like to pay attention to some important missing aspects in the study.

First, sensitivity analysis commonly is performed by removing one study at a time to assess the effect on the pooled results (2). In the results of sensitivity and publication bias analysis section, the authors performed the sensitivity analysis only by removing Xu et al.’s study (3), which reduced the I² statistic from 92% to 86% indicating steady results of the meta-analysis. However, we believe that the interpretation of the results is false. The authors should evaluate the effect on the overall pooled mean difference (MD) not I² after removing Xu et al.’s study.

Second, in the study by Yao et al. (4), the dosage in the neostigmine group was 20 µg/kg showed in Table 1. However, after carefully reviewing the Figure 8 in this study, we find that Yao et al.’s study was enrolled in the subgroup of dosage ≥40 µg/kg. Therefore, we believe the data should be further revised to validate the accuracy.

In short, Ji et al. revealed a significant issue with regard to the efficacy and safety of neostigmine for neuromuscular blockade reversal in patients under general anesthesia. However, the data should be further revised to validate the conclusions because of the concerns above.

Acknowledgments

Funding: None.

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References

1. Ji W, Zhang X, Liu J, et al. Efficacy and safety of neostigmine for neuromuscular blockade reversal in patients under general anesthesia: a systematic review and meta-analysis. Ann Transl Med 2021;9:1691. [Crossref] [PubMed]
2. Wu J, Wang Y, Zhao A, et al. Lung Ultrasound for the Diagnosis of Neonatal Respiratory Distress Syndrome: A Meta-analysis. Ultrasound Q 2020;36:102-10. [Crossref] [PubMed]
3. Xu K, Chen YJ, Lu ZJ, et al. Effects of neostigmine muscle relaxation antagonism on postoperative recovery of patients undergoing laparoscopy under general anesthesia. Medical Recapitulate 2020;26:3067-71.
4. Yao M, Shi H, Jiao B, et al. Effect of neostigmine antagonistic timing on residual muscle relaxation after general anesthesia -- a randomized, double-blind, parallel controlled study. Chinese Journal of Hospital Pharmacy 2021;41:191-4.