Neostigmine-based reversal of intermediate acting neuromuscular blocking agents to prevent postoperative residual paralysis

BACKGROUND Neostigmine is widely used to antagonise residual paralysis. Over the last decades, the benchmark of acceptable neuromuscular recovery has increased progressively to a train-of-four (TOF) ratio of at least 0.9. Raising this benchmark may impact on the efficacy of neostigmine. OBJECTIVE(S) The systematic review evaluates the efficacy of neostigmine to antagonise neuromuscular block to attain a TOF ratio of at least 0.9. DESIGN We performed a systematic search of the literature from January 1992 to December 2015. DATA SOURCES OR SETTING PubMed, EMBASE and the Cochrane Controlled Clinical Trials database were searched for randomised controlled human studies. Search was performed without language restrictions, using the following free text terms: 'neostigmine', 'sugammadex', 'edrophonium' or 'pyridostigmine' AND 'neuromuscular block', 'reversal' or 'reverse'. ELIGIBILITY CRITERIA Studies were accepted for inclusion if they used quantitative neuromuscular monitoring and neostigmine as the reversal agent. Selected trials were checked by two of the authors for data integrity. Trials relevant for inclusion had to report the number of patients included, the type of anaesthetic maintenance, the type of neuromuscular blocking agent used, the reversal agent and dose used, the depth of neuromuscular block when neostigmine was administered and the reversal time (time from injection of neostigmine until a TOF ratio >= 0.9 was attained). RESULTS 19 trials were eligible for quantitative analysis. In patients with deep residual block [T1 (first twitch height) < 10%] 70 mu g kg(-1) neostigmine was used (five trials, 118 patients), and the mean reversal time was 17.1 min (95% confidence interval (CI) [12.4 to 21.8]). In patients with moderate residual block (T1 10% to < 25%) the mean neostigmine dose was 56 mu g kg(-1) (seven trials, 342 patients), and the mean reversal time was 11.3 min (95% CI [9.2 to 13.4]). In patients with a shallow residual block (T1 >= 25%) the mean neostigmine dose was 40 mu g kg(-1) (13 trials, 535 patients), and the mean reversal time was 8.0 min (95% CI [6.8 to 9.2]). CONCLUSION Based on the findings of this systematic review, we recommend that the administration of neostigmine be delayed until an advanced degree of prereversal recovery has occurred (i.e. a T1 > 25% of baseline), or that a recovery time longer than 15 min be accepted.