Identifying high dose neostigmine as a risk factor for post-operative respiratory complications: a case-control study

Background: Neostigmine, an acetylcholinesterase inhibitor, is used to reverse the effects of non-depolarizing neuromuscular blocking agents. Inappropriate dosing of neostigmine can lead to post-operative respiratory complications. Post-operative respiratory complications are associated with major morbidity and mortality. The purpose of this case-control study was to determine neuromuscular blockade-related risk factors associated with post-operative respiratory complications (specifically, reintubation, respiratory insufficiency, hypoxia, and/or aspiration). Methods: We performed an Institutional Review Board-approved case-control study of all patients who underwent a general anesthetic requiring neuromuscular blockade at Tufts Medical Center between March 22, 2013 and June 1, 2019. Cases were patients who experienced post-operative complications. We identified 58 controls and 116 cases from a database of 130,178 patients during the 74-month study period. Results: After adjusting for covariates, the administration of high dose neostigmine (> 60 mg per kg ideal body weight) was associated with increased odds of post-operative respiratory complications (odds ratio = 8.2; 95% CI: 2.5-26.6, P < 0.001). Rocuronium dose and the use of train-of-four peripheral nerve stimulator were not associated with post-operative respiratory complications. Conclusions: High dose neostigmine was identified as an independent risk factor for post-operative respiratory complications. Our study suggests that inappropriate dosing of neostigmine continues to be a problem despite growing evidence of an association with respiratory complications.