Neuromuscular blocking agents (NMBAs) are drugs that induce skeletal muscle paralysis/relaxation via inhibition of the neurotransmitter acetylcholine at the neuromuscular junction. Normally, acetylcholine produces electrical depolarization at the motor end-plate, which subsequently induces skeletal muscle contraction, allowing movement. NMBAs can be further classified as depolarizing (e.g. succinylcholine) or nondepolarizing (e.g. vecuronium, rocuronium) (1). The use of NMBAs in the perioperative setting facilitates tracheal intubation, protects patients from vocal cord injury, and improves surgical conditions by suppressing voluntary or reflex skeletal muscle movements (2). They are used in combination with general anesthetics. At the end of surgery, the blockade is reversed. Major side effects or complications are rare, but some patients may experience muscle weakness even after neuromuscular blockade reversal.

Typically, after surgery, neuromuscular blockade is easily reversed after the administration of acetylcholinesterase inhibitors. However, several studies have reported that patients often suffer from postoperative muscle weakness, even after neuromuscular blockade reversal. This phenomenon, also known as residual neuromuscular block, is defined as the presence of signs or symptoms of muscle weakness in the postoperative period after the intraoperative administration of NMBAs followed by blockade reversal. Quantitatively, residual neuromuscular blockade can be defined as a train of four ratios (TOF) less than 0.9, as measured by a nerve stimulation test, in the post-anesthesia care unit (PACU) secondary to non-depolarizing muscle relaxants administration (2). One of the most dangerous manifestations of residual neuromuscular blockade is respiratory muscle paralysis. Examples of this include difficulty swallowing, slurred speech, and inability to breathe. Respiratory muscle paralysis can greatly increase the risk of aspiration, pneumonitis, pneumonia, and severe hypoxia. Even small degrees of residual paralysis with a train of four ratios greater than 0.6 may lead to clinically relevant consequences, like marked impairment of upper airway integrity and swallowing (2).

As previously mentioned, neuromuscular blockade is typically reversed with the administration of acetylcholinesterase inhibitors. Neostigmine is a commonly used acetylcholinesterase inhibitor, which competitively antagonizes residual neuromuscular blockade by preventing metabolism of acetylcholine. Unfortunately, because the competitive mechanism is limited, neostigmine only reliably reverses mild-to-moderate neuromuscular blocks. Sugammadex, in contrast, reverses neuromuscular blocks by encapsulating and binding molecules of the NMBAs rocuronium and vecuronium (3). Incidentally, it has been found that sugammadex is more effective at delivering full neuromuscular blockade reversal without residual weakness compared to neostigmine. For instance, in a prospective study, Brueckmann et al. found that 0 of 74 patients given sugammadex had TOFR <0.9 on admission to the recovery room. In contrast, 33 out of 76 (43%) patients given neostigmine did. Cammu et al. reported similar findings in 2012. In a study of 624 patients, 15% of those who received no reversal agent developed residual block (TOFR <0.9) as did 15% of those who received neostigmine. However, only 1 of the 44 patients who received sugammadex had residual block. Additionally, Ledowski et al. demonstrated that the incidence of postoperative nausea and vomiting was lower after the administration of sugammadex compared to neostigmine. Notably, this effect was only significant in elderly patients.

Ultimately, further randomized controlled studies designed to control for confounding factors (e.g. comorbidities, type of surgery, ventilation strategy) are needed to establish the advantage of sugammadex over neostigmine in reducing postoperative muscle weakness after neuromuscular blockade reversal. As always, a careful choice of neuromuscular blocking agent, proper quantitative monitoring of neuromuscular function, and adequate titration of reversal drug dosage are highly recommended to reduce the incidence of residual neuromuscular blockade and associated adverse outcomes, including respiratory muscle dysfunction (3).

References

1. Hristovska AM, Duch P, Allingstrup M, Afshari A. Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults. Cochrane Database Syst Rev. 2017;8(8):CD012763. Published 2017 Aug 14. doi:10.1002/14651858.CD012763
2. Firde M, Yetneberk T, Adem S, Fitiwi G, Belayneh T. Preventive strategies of residual neuromuscular blockade in resource-limited settings: Systematic review and guideline. International Journal of Surgery Open. 2020;26:73-80. doi:https://doi.org/10.1016/j.ijso.2020.08.010
3. Ruetzler K, Li K, Chhabada S, et al. Sugammadex Versus Neostigmine for Reversal of Residual Neuromuscular Blocks After Surgery: A Retrospective Cohort Analysis of Postoperative Side Effects. Anesth Analg. 2022;134(5):1043-1053. doi:10.1213/ANE.0000000000005842
4. Hunter JM. Reversal of residual neuromuscular block: complications associated with perioperative management of muscle relaxation. Br J Anaesth. 2017;119(suppl_1):i53-i62. doi:10.1093/bja/aex318