Is appropriately conducted neostigmine reversal inferior to sugammadex?

We have some comments and questions about the paper by Paech et al. which evaluated the recovery characteristics of patients receiving either sugammadex 2 mg.kg−1 or neostigmine 40 mcg.kg−1 and glycopyrrolate 400 mcg for reversal of neuromuscular block 1. The authors state that “neuromuscular function was monitored quantitatively using train of four (TOF) peripheral nerve stimulation”. Can they please clarify which device was used? There are differences in performance and efficacy of devices incorporating acceleromyography or electromyography 2. Was quantitative monitoring used to guide reversal dosing and ensure recovery to TOF ratio > 0.9 at recovery? If used and recorded, how long did it take to reach TOF ratio 0.9 in both groups, given that median time from reversal to extubation was only 7 min in both sugammadex and neostigmine groups? Reversal of NMB was performed at a median TOF count of 2, however, the range of TOF responses at time of reversal varied widely, from 0 to 4 twitches in both patient groups, with no statistical difference between groups. Can the authors comment on the breakdown of cases reversed at TOF counts 2 and 3 (moderate block) and TOF count 4 with measurable TOF ratios (recovery phase)? Sugammadex at 2 mg.kg−1 would be expected to reliably reverse all these levels of block. However, neostigmine reversal is more effective at a dose of 50–70 mcg.kg−1, once a TOF count of 4 is re-established 3, 4. The study dose of 40 mcg.kg−1 might not reliably reverse all patients to TOF ratio 0.9 within the mean (IQR) study times of 7 min (4–10 min) for neostigmine. Is it possible that the tracheas of some patients in the neostigmine group were extubated with residual muscle weakness, with potential impact on study outcomes, for example, of blurred vision? We would suggest that the higher early recovery incidence of blurred vision in the neostigmine group is only of clinical significance if the patient groups had comparable TOF ratios at extubation. However, despite these questions, there was little or no difference in measured outcomes, patient length of stay and patient satisfaction with their experience. In this relatively large study of around 300 patients, use of neostigmine was not associated with a greater incidence of postoperative nausea and vomiting (PONV) than with sugammadex. It is telling that the study was conducted over 5 years and was eventually terminated early due to recruitment issues from changes in practice, in particular, the use of total intravenous anaesthesia (TIVA) and multi-drug anti-emetic prophylaxis. Women undergoing gynaecological laparoscopic surgery are at high risk of PONV. Unsurprisingly, PONV rates of 49% and 51% for sugammadex and neostigmine, respectively, achieved with single anti-emetic prophylaxis and volatile anaesthesia, were eventually deemed unacceptable. Arguably this decision might have occurred earlier? Sugammadex may well be a superior drug to neostigmine/glycopyrrolate, but its high cost ensures that it is variably available and used. This study reassuringly demonstrates that neostigmine can be used for effective NMB reversal with minimal postoperative sequelae. The key lies in planning, monitoring and where possible, minimising NMB use. Adequate neostigmine reversal dosage (50–70 mcg.kg−1 for moderate block levels) should be administered, ideally after recovery to TOF count = 4, with adequate time allowed before awakening, and objective quantitative NMB measurement used throughout, especially to ensure awakening and recovery, without muscle weakness and residual NMB.