Response to "A novel use of neostigmine reversal for intraoperative neural monitoring during thyroid surgery"

We read the letter article which you sent us. We sincerely appreciated the authors' interest in our paper.1 Neostigmine does not directly degrade or chelate the effect of neuromuscular blocking agents (NMBAs), but indirectly reverses their effect by inhibiting acetylcholinesterase and increasing acetylcholine at the neuromuscular junction. Increased acetylcholine can overcome the competitive inhibition of NMBAs. The role of neostigmine is reversal of residual neuromuscular blockade for patient safety at emergence. To recover spontaneous breathing movement at the end of surgery, neostigmine should be administered when the train-of-four count is at least 3.2 However, to achieve timely intraoperative neuromonitoring (IONM), neostigmine should be administered at the point of modest neuromuscular blockade, which occurs around the initiation of surgery. Additionally, the time from neostigmine administration to the initial vagus nerve check point (V1) determines its dose; the shorter is the time between administration and V1, the higher the neostigmine dose. That time was approximately at the 26 min mark in our study. We believe that 2 mg of neostigmine is appropriate for IONM during open thyroid surgery. In our previous study, we reported that 1 mg/kg of sugammadex was sufficient for IONM and had fewer intraoperative bucking events than 2 mg/kg of sugammadex.3 Likewise, titration of neostigmine to 1 mg may be an option. However, this has not yet been proven. Additionally, it should be noted that neostigmine cannot incapacitate the effect of NMBA as promptly as sugammadex. A previous Cochrane review showed that sugammadex resulted in fewer adverse events compared to neostigmine, and that bradycardic events were especially reduced.4 Bradycardia is the most common cardiovascular adverse event associated with neostigmine which has a cardiac muscarinic effect. Other more severe AEs include complete heart block and even asystole. Additionally, neostigmine can induce other life-threatening complications, like bronchoconstriction. Therefore, it has long been standard practice to co-administer neostigmine and an anticholinergic agent (like glycopyrrolate), even though the occurrence of neostigmine-induced bradycardia may be dose-dependent. Therefore, the use of neostigmine alone must be thoroughly investigated to ascertain its safety, even at low doses. Lastly, our study included patients who were indicated for use of rocuronium, thus those with renal insufficiency were automatically excluded. Although we investigated the efficacy of neostigmine in our study,1 we usually use sugammadex after rocuronium administration to apply IONM for patients with renal disease during thyroid surgery in the clinical setting. A recent systematic review article with a meta-analysis showed that sugammadex may effectively and safely reverse rocuronium-induced neuromuscular blockade in patients with end-stage renal disease.5 We read the comments by the authors on our study with interest and we agree that further investigation is necessary. All authors declare no conflict of interest.