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Postoperative Pulmonary Complications after Administration of Sugammadex vs. Neostigmine for Reversal of Neuromuscular Blockade

Neuromuscular blockades are agents commonly used during surgical operations where muscular contraction may compromise the efficacy of the procedure. The molecular configuration of neuromuscular blockades mimics acetylcholine. Through post-synaptic binding of the acetylcholine receptor, selective agents inhibit muscular contraction and induce local paralysis.[1] However, residual paralysis post-surgery poses a serious health risk and can affect up to 40 percent of patients who are not given a neuromuscular blockade reversal agent;[2] therefore, the mitigation and attenuation of neuromuscular blockade is a critical, active process. Common agents used for postoperative neuromuscular blockade reversal include sugammadex and neostigmine.

Sugammadex and neostigmine have been viewed as near equivalents until recently; both agents are commonly used in hospitals around the U.S. for reversal of the neuromuscular blockade. Sugammadex is a γ-cyclodextrin with slight modifications. More specifically, at each sixth-carbon position, it has eight carboxyl thioether groups. It has no cholinergic effects and instead forms a complex with neuromuscular blockade agents in the synapse via a negatively-charged attack on their quaternary nitrogen. Though pioneered by a Scottish company many years earlier, the drug was only recently approved by the FDA for use within the U.S. in 2015.[3]

Neostigmine, on the other hand, works by inhibiting acetylcholinesterase and therefore requires co-administration of a muscarinic receptor antagonist, which has the effect of reducing the activity of the parasympathetic nervous system. Common muscarinic receptor antagonists include glucopyrronium bromide or atropine. As is generally the rule in medicine, the administration of additional drugs alongside the primary active agent increases the risk of off-target effects. Neostigmine has a number of other therapeutic uses outside of reversal of neuromuscular blockade, such as the treatment of myasthenia gravis and Ogilvie syndrome, and was patented in 1933.[4] It is a simple analog of physostigmine and is significantly cheaper than equivalent doses of sugammadex.[5]

Around five percent of patients undergoing non-cardiac surgery experience pulmonary complications following operation.[6] Inadequate reversal of neuromuscular blockade is a known contributing risk factor. A study published in 2020 by Kheterpal et al. sought to determine whether use of sugammadex versus neostigmine for reversal of neuromuscular blockade could reduce risk of postoperative pulmonary complications. Approximately 45,000 patients were investigated. The authors concluded that sugammadex resulted in a 30 percent decrease in risk for postoperative pulmonary complications as compared to neostigmine. Patients who received sugammadex also experienced a 47 percent decreased risk of pneumonia and 55 percent reduced risk of respiratory failure.3 Therefore, this study would suggest that anesthesia providers should consider the use of sugammadex over neostigmine when considering risk factors for post-operative pulmonary complications, particularly in patients with existing respiratory vulnerabilities.

[1] Appiah-Ankam, J., & Hunter, J. (2004). Pharmacology of neuromuscular blocking drugs. Continuing Education In Anaesthesia Critical Care & Pain, 4(1), 2-7. 

[2] Srivastava, A., & Hunter, J. (2009). Reversal of neuromuscular block. British Journal Of Anaesthesia, 103(1), 115-129.

[3] U.S. Food and Drug Administration (FDA) (2016). “Bridion (sugammadex) Injection.”

[4] Aeschliman, John A., U.S. Patent 1,905,990 (1933).

[5] Aaron F. Kopman (2010). Neostigmine versus Sugammadex: Which, When, and How Much? Anesthesiology. 113:1010–1011

[6] Kheterpal, Vaughn, & Dubovoy. (2020). Sugammadex Versus Neostigmine for Reversal of Neuromuscular Blockade and Postoperative Pulmonary Complications: A Multicenter Matched Cohort Analysis. Anesthesiology.