Comparative efficacy of sugammadex and neostigmine in postoperative nausea and vomiting management: a meta‑analysis of randomized controlled trials

The Takeaway

In this meta-analysis, reversal with sugammadex decreased PONV metrics, especially when given at after the return of the second twitch.

Study Design

• 20 trials, 2014 or later
• In total, 3,058 adult cases and 190 pediatric cases, with 780 undergoing laparoscopic surgery and 803 receiving non-laparoscopic surgery.

Physiology Refresh

Neostigmine was once the primary agent used to reverse non-depolarizing neuromuscular blockade at the end of surgery. It works by inhibiting acetylcholinesterase, which increases acetylcholine at the neuromuscular junction. However, this increase also affects muscarinic receptors throughout the body, especially in the gastrointestinal tract.

Excess acetylcholine can lead to increased GI motility and secretions, contributing to nausea and vomiting. Mechanoreceptors in the GI tract can send afferent signals to the vomiting center of the brain and initiate the vomiting reflex. Glycopyrrolate is administered concurrently to counteract these muscarinic side effects. It is an anticholinergic that does not cross the blood-brain barrier and helps mitigate bradycardia, excessive salivation, and GI hyperactivity.

However, glycopyrrolate does not fully block all muscarinic activity. Some parasympathetic stimulation remains, which may still trigger postoperative nausea and vomiting (PONV). Additionally, if neostigmine is given too early—before full return of spontaneous neuromuscular function—it can result in partial reversal. This may leave patients with residual weakness, impaired upper airway muscle tone, or difficulty clearing secretions, all of which can increase the risk of PONV.

Abstract

Postoperative nausea and vomiting (PONV) are frequent complications that can occur after surgical procedures. Sugammadex, known for its effectiveness as a muscle relaxant antagonist, offers several advantages over neostigmine, however, there is still insufficient evidence to demonstrate its superiority in reducing PONV. This meta-analysis sought to assess the efficacy of sugammadex versus neostigmine in the management of PONV. Two independent investigators conducted a comprehensive review of randomized controlled trials (RCTs) across PubMed, Embase, and the Cochrane Library. The meta-analysis was performed using Review Manager software. Our meta-analysis scrutinized twenty studies that included 3248 participants. The results showed that sugammadex was effective in reducing postoperative nausea (RR = 0.65, 95% CI 0.48 to 0.88) versus neostigmine. Sugammadex reduced the dosage of opioids (SMD = 0.55, 95% CI -0.18 to 1.27) compared with neostigmine when the time of administration is T₂ (RR = 0.54, 95% CI 0.31 to 0.93). The use of sugammadex markedly lowered the occurrence of nausea during non-laparoscopic surgical procedures (RR = 0.42, 95% CI 0.27 to 0.65). This study demonstrated that sugammadex outperformed neostigmine in reducing PONV. Various factors, including the type of surgical procedure, timing of drug administration and dosage, might influence the efficacy of sugammadex.

Excerpts

five distinct risk factors independently predicting PONV include a history of smoking, age and gender, motion sickness, and a prior history of PONV, each of which increases the risk by approximately 20%

the likelihood of PONV may also be associated with the anesthesia techniques employed, the administration of anesthesia, and post-surgical pain management.

The incidence of PONV approaches 30% among general hospital patients, with rates ranging from 70 to 80% in high-risk populations

PONV is influenced by three distinct categories of risk factors: unique to each patient, the anesthesia technique employed, and the characteristics of the surgical procedure

Key results indicated: (1) In preventing nausea, sugammadex outperformed neostigmine without significant risk elements; (2) Application of sugammadex reducesd the dose of opioids compared with neostigmine; (3) Sugammadex reduced the incidence of nausea when the time of drug administration was T2 reappeared on TOF or in non-laparoscopic surgery, but not T4 and laparoscopic surgery; (4) Sugammadex nearly lowered nausea rates in both children and adults, even with neostigmine dosages up to 40 μg/kg, and even those exceeding 40 μg/kg; (5) Sugammadex decreased the occurrence of bradycardia and urinary retention; (6) Sugammadex could reduce the T0.9 time, the time of extubation and the time in PACU.

It has been determined that the use of neostigmine in doses above 2.5 mg increases the risk of PONV

sugammadex was associated with decreased nausea and vomiting scores upon arrival in the PACU, likely due to its rapid restoration of neuromuscular strength

We found that administering sugammadex when T2 reappeared on the TOF is more effective in reducing the incidence of PONV, indicating that using antagonists at this point may be a better strategy, although the underlying mechanism warrants further investigation

Citation

Zeng J, Cao Q, Hong A, Gu Z, Jian J, Liang X. Comparative efficacy of sugammadex and neostigmine in postoperative nausea and vomiting management: a meta-analysis of randomized controlled trials. J Anesth. 2025 Apr 28. doi: 10.1007/s00540-025-03498-7. Epub ahead of print. PMID: 40293461.

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