European Journal of Cardiovascular Medicine

Neuromuscular blocking agents (NMBAs) are a cornerstone of modern anesthetic practice, facilitating tracheal intubation, providing muscle relaxation during surgery, and optimizing surgical conditions. Rocuronium, a non-depolarizing aminosteroid NMBA, has gained widespread popularity due to its rapid onset and intermediate duration of action. Its hemodynamic stability and predictable pharmacokinetics make it an attractive alternative to other agents such as vecuronium and atracurium. However, like all non-depolarizing NMBAs, residual neuromuscular blockade (RNMB) after rocuronium administration remains a clinical concern that may result in postoperative complications including hypoxemia, upper airway obstruction, aspiration, and delayed recovery. To mitigate such risks, effective reversal of neuromuscular block is an essential component of safe anesthesia practice.^[1]

Traditionally, acetylcholinesterase inhibitors, particularly neostigmine, have been the mainstay for reversing non-depolarizing neuromuscular blockade. Neostigmine acts by inhibiting acetylcholinesterase, thereby increasing acetylcholine concentration at the neuromuscular junction, which competitively antagonizes NMBA molecules bound to nicotinic receptors. While generally effective, neostigmine has several limitations: its onset of action is relatively slow (up to 10-15 minutes), efficacy depends on the depth of neuromuscular block at the time of administration, and it is associated with muscarinic side effects such as bradycardia, increased secretions, and bronchospasm, necessitating the concurrent use of anticholinergic agents such as glycopyrrolate or atropine. Furthermore, incomplete reversal with neostigmine has been documented, particularly when administered at deeper levels of blockade.^[2]

The advent of sugammadex, a modified γ-cyclodextrin, represents a paradigm shift in the reversal of aminosteroid NMBAs, particularly rocuronium and vecuronium. Unlike neostigmine, sugammadex works by a novel mechanism: it encapsulates the NMBA molecules in a tight complex, effectively inactivating them and rapidly decreasing the free plasma concentration. This creates a concentration gradient that promotes dissociation of NMBA molecules from the neuromuscular junction into the plasma, thereby producing swift and predictable reversal, even from deep levels of blockade. Clinical trials have consistently demonstrated that sugammadex produces a much faster recovery of neuromuscular function compared to neostigmine, with recovery times to a train-of-four (TOF) ratio of ≥0.9 often within 2-3 minutes, regardless of block depth.^[3]

The clinical implications of faster and more reliable reversal are significant. Reduced incidence of RNMB translates into improved patient safety, fewer respiratory complications, and potential economic benefits by reducing recovery room time and facilitating operating room turnover. However, sugammadex is not without its own concerns. Its relatively high cost compared to neostigmine poses economic challenges, particularly in resource-limited healthcare settings. Additionally, rare but significant adverse events, including hypersensitivity reactions, anaphylaxis, and potential drug interactions (e.g., with hormonal contraceptives and anticoagulants), have been reported. Nevertheless, the safety profile of sugammadex is generally favorable, with fewer cardiovascular and muscarinic side effects compared to neostigmine.^[4]

Comparative studies between sugammadex and neostigmine have yielded valuable insights. For instance, trials have consistently shown that sugammadex provides faster reversal and fewer adverse respiratory complications in the post-anesthesia care unit (PACU). Meta-analyses have further reinforced the superiority of sugammadex in terms of recovery profile, although the magnitude of benefit in terms of hard clinical outcomes (e.g., mortality, major morbidity) remains debated. Moreover, the choice between sugammadex and neostigmine is often influenced by the patient’s comorbidities, surgical context, and institutional resources. In high-risk patients-such as the elderly, those with obesity, obstructive sleep apnea, or compromised pulmonary function-rapid and reliable reversal may be particularly advantageous.^[5]

Aim

To compare sugammadex and neostigmine for reversal of rocuronium block with respect to recovery profile and adverse events.

Objectives

1. To assess the time to recovery of neuromuscular function (TOF ratio ≥0.9) after administration of sugammadex versus neostigmine.
2. To evaluate the incidence of adverse events associated with sugammadex and neostigmine.
3. To compare overall recovery profiles and perioperative outcomes between sugammadex and neostigmine groups.

Source of Data

The study population comprised patients undergoing elective surgical procedures under general anesthesia with rocuronium-induced neuromuscular block who required pharmacological reversal at the end of surgery.

Study Design

A prospective, randomized, comparative clinical study was conducted.

Study Location

The study was carried out in the Department of Anesthesiology at a Dr Ulhas Patil Medical College, Jalgaon.

Study Duration

The study was conducted over a period of 18 months, including patient recruitment, data collection, and analysis.

Sample Size

A total of 100 patients were included in the study. Patients were randomly allocated into two equal groups:

• Group S (Sugammadex group): 50 patients received sugammadex for reversal.
• Group N (Neostigmine group): 50 patients received neostigmine with glycopyrrolate for reversal.

Inclusion Criteria

• Patients aged between 18-65 years.
• American Society of Anesthesiologists (ASA) physical status I or II.
• Patients undergoing elective surgical procedures requiring general anesthesia and neuromuscular blockade with rocuronium.
• Patients who provided informed consent.

Exclusion Criteria

• Patients with anticipated difficult airway or requiring rapid sequence induction.
• Patients with known hypersensitivity to sugammadex, neostigmine, or rocuronium.
• Patients with severe hepatic, renal, or cardiac dysfunction.
• Pregnant and lactating women.
• Patients on medications known to interfere with neuromuscular function (e.g., anticonvulsants, aminoglycosides).

Procedure and Methodology

All patients were preoperatively evaluated and assessed for eligibility. Informed consent was obtained. Standard fasting guidelines were followed. In the operating room, routine monitoring including ECG, non-invasive blood pressure, pulse oximetry, and capnography was instituted. Neuromuscular monitoring was performed using a peripheral nerve stimulator assessing TOF ratio at the adductor pollicis muscle via ulnar nerve stimulation.

General anesthesia was induced with intravenous propofol and fentanyl. Rocuronium was administered for neuromuscular block, and tracheal intubation was facilitated. Anesthesia was maintained with inhalational agents (sevoflurane or isoflurane) in a mixture of oxygen and nitrous oxide, supplemented with opioids as required.

At the end of surgery, when reversal was clinically indicated, patients were randomized to receive either:

• Group S: Sugammadex 2 mg/kg intravenously at reappearance of second TOF count.
• Group N: Neostigmine 0.05 mg/kg with glycopyrrolate 0.01 mg/kg intravenously at reappearance of second TOF count.

The primary endpoint was the time to recovery of TOF ratio ≥0.9. Secondary endpoints included hemodynamic changes, adverse events (e.g., bradycardia, bronchospasm, nausea, vomiting, hypersensitivity), and postoperative recovery characteristics.

Sample Processing

Neuromuscular monitoring data and clinical parameters were recorded intraoperatively. Postoperative follow-up in the recovery room included monitoring for adverse respiratory events, hemodynamic instability, and other complications for at least 60 minutes.

Statistical Methods

Data were entered into Microsoft Excel and analyzed using SPSS software. Quantitative variables were expressed as mean ± standard deviation and compared using the independent Student’s t-test. Qualitative variables were expressed as proportions/percentages and compared using Chi-square or Fisher’s exact test as appropriate. A p-value <0.05 was considered statistically significant.

Data Collection

A structured proforma was used to collect patient demographics, intraoperative details, reversal agent used, time to recovery of TOF ≥0.9, hemodynamic parameters, and postoperative adverse events. Data were verified for accuracy and completeness before analysis.

Table 1: Comparison of reversal outcomes and adverse-event composite (N = 100)

*Composite = any of: bradycardia, PONV, desaturation <92%, bronchospasm, residual paralysis (TOF<0.9 in PACU), hypersensitivity.

Table 1 demonstrate a clear advantage of sugammadex over neostigmine in terms of reversal efficiency and safety. The mean time to achieve a TOF ratio ≥0.9 was significantly shorter in the sugammadex group (2.6 ± 0.8 minutes) compared with the neostigmine group (12.4 ± 3.1 minutes), with a mean difference of -9.8 minutes (95% CI: -10.70 to -8.90, p < 0.0001). Similarly, extubation after reversal occurred much earlier in patients who received sugammadex (6.9 ± 1.7 minutes) compared to those who received neostigmine (13.8 ± 3.4 minutes), reflecting a mean difference of -6.9 minutes (95% CI: -7.97 to -5.83, p < 0.0001). PACU stay was also significantly shorter in the sugammadex group (38.0 ± 9.0 minutes) versus the neostigmine group (52.0 ± 12.0 minutes), with a mean difference of -14 minutes (95% CI: -18.21 to -9.79, p < 0.0001). Adverse events, considered as a composite outcome, occurred in 12% of patients given sugammadex compared to 34% in the neostigmine group, with a relative risk of 0.35 (95% CI: 0.15-0.82, p = 0.0156). 

Figure 1

Table 2: Time to recovery of neuromuscular function (TOF ≥0.9) after reversal (N = 100)

Table 2 further supports the superior efficacy of sugammadex in reversing neuromuscular block. The mean recovery time to TOF ≥0.9 was 2.6 ± 0.8 minutes with sugammadex compared to 12.4 ± 3.1 minutes with neostigmine (p < 0.0001). Importantly, 94% of patients receiving sugammadex achieved TOF ≥0.9 within 3 minutes, whereas only 6% of patients in the neostigmine group reached this target within the same timeframe (risk difference 0.88, 95% CI: 0.79-0.97, p < 0.0001). Within 5 minutes, almost all patients in the sugammadex group (98%) had recovered neuromuscular function, while only 16% in the neostigmine group had done so (p < 0.0001). Conversely, delayed recovery taking more than 10 minutes was observed in just 2% of sugammadex patients compared to 78% of neostigmine patients (relative risk 0.03, 95% CI: 0.01-0.21, p < 0.0001).

Table 3: Incidence of individual adverse events (N = 100)

The incidence of adverse events shown in Table 3 reveals a marked difference between the two groups. Bradycardia requiring intervention occurred in 18% of neostigmine patients but only 2% of sugammadex patients (RR = 0.11, 95% CI: 0.01-0.82, p = 0.0157). Postoperative nausea and vomiting (PONV) was also less frequent with sugammadex (6%) compared with neostigmine (22%), corresponding to a relative risk of 0.27 (95% CI: 0.08-0.88, p = 0.0407). Hypoxemic episodes (SpO₂ <92% in PACU) were observed in 16% of neostigmine patients versus only 2% of sugammadex patients (RR = 0.12, 95% CI: 0.02-0.92, p = 0.0309). Residual paralysis (TOF <0.9 at 15 minutes in PACU) was present in 14% of patients in the neostigmine group but absent in the sugammadex group (p = 0.0125). Bronchospasm occurred in two neostigmine patients and none in the sugammadex group, though this was not statistically significant (p = 0.495). A single case of hypersensitivity reaction was recorded in the sugammadex group, though this did not reach statistical significance. Overall, the adverse event profile strongly favors sugammadex, with fewer clinically relevant complications compared to neostigmine.

Figure 2

Table 4: Overall recovery profile and perioperative outcomes (N = 100)

Table 4, recovery quality was significantly better in the sugammadex group. The mean time to achieve an Aldrete score ≥9 was substantially shorter with sugammadex (12.7 ± 3.2 minutes) compared with neostigmine (20.4 ± 4.9 minutes), with a mean difference of -7.7 minutes (95% CI: -9.34 to -6.06, p < 0.0001). Early PACU discharge (within 60 minutes) was achieved by 88% of patients in the sugammadex group compared to 58% in the neostigmine group (risk difference 0.30, 95% CI: 0.14-0.46, p = 0.00033). Airway support interventions such as jaw thrust or oropharyngeal airway were required more often in the neostigmine group (12%) than in the sugammadex group (2%), although this difference did not reach statistical significance (p = 0.1117). One patient in the neostigmine group required re-intubation in the PACU, while none did in the sugammadex group.

In table 1, results show that sugammadex produced substantially faster and more reliable reversal than neostigmine and was associated with fewer adverse events and a smoother PACU course. The mean time to TOF≥0.9 in cohort (2.6 ± 0.8 min with sugammadex vs 12.4 ± 3.1 min with neostigmine) mirrors the magnitude and direction seen in randomized trials and meta-analyses. Yang Y et al.(2025)^[6] reported median recovery to TOF≥0.9 of 3 min (95% CI 2-3) with sugammadex versus 8 min (6-10) with neostigmine, a 5-minute advantage-very close between-group gap when expressed on the same scale. Hurford WE et al.(2020)^[7] Large evidence syntheses conclude consistently that sugammadex reverses aminosteroid block far more rapidly across depths of blockade, with fewer drug-related adverse effects-again concordant with findings. Sayed Ibrahim E et al.(2022)^[8]

Speed translated into clinical workflow benefits in study: extubation and PACU discharge occurred earlier with sugammadex (extubation -6.9 min; PACU stay -14 min), and a greater proportion of patients left PACU ≤60 min (88% vs 58%). Similar efficiency signals-shorter time to extubation, faster PACU throughput, and lower staffing costs-have been reported in economic and operations analyses, strengthening the generalizability of recovery-profile results. Motamed C et al.(2025)^[9] Although cost remains a consideration, several models suggest that time savings and reduced complication rates may offset drug acquisition costs in many settings. Ravindranath S et al.(2025)^[10]

The consistency extends to categorical recovery metrics in Table 2. In cohort, 94% of sugammadex patients achieved TOF≥0.9 within 3 min (vs 6% with neostigmine) and only 2% exceeded 10 min (vs 78%). These proportions align with trial summaries and narrative reviews highlighting the predictability of sugammadex even from deeper blocks, in contrast to the variability of neostigmine when the block is more than shallow-moderate. Bologheanu R et al.(2022)^[11] Contemporary guidance also emphasizes objective (quantitative) monitoring and a TOF ratio threshold ≥0.9 to mitigate residual paralysis-methodologic principles used in protocol and aligned with residual-paralysis outcome (0% with sugammadex vs 14% with neostigmine). Zhang Y et al.(2024)^[12]

Safety and adverse-event patterns in Table 3 likewise match the literature. We observed fewer episodes of bradycardia requiring treatment (2% vs 18%), less treated PONV (6% vs 22%), and fewer desaturation events (2% vs 16%) with sugammadex. Prior comparative reviews and meta-analyses attribute these differences to the absence of muscarinic effects and to more complete early reversal of pharyngeal and respiratory muscle function with sugammadex. Deana C et al.(2020)^[13] Importantly, the reduction of residual paralysis in sugammadex group is compatible with evidence suggesting lower rates of early postoperative pulmonary complications (POPCs)-such as hypoxemia, atelectasis, non-invasive ventilation, and re-intubation-when sugammadex is used rather than neostigmine, although the certainty of evidence varies and high-quality RCTs are still encouraged. Han J et al.(2021)^[14] PACU airway-support and re-intubation rates were low overall and not statistically different between groups, which is plausible given the study size, but the point estimates trended in the expected direction (fewer interventions with sugammadex), consistent with prior signals. Voss T et al.(2022)^[15]

Results reinforce practice recommendations that couple pharmacologic reversal with quantitative neuromuscular monitoring to reach TOF≥0.9 before extubation. The consensus statement advocates objective monitoring at the adductor pollicis and cautions that clinical tests alone are insufficient-perspectives that are reflected in protocol and outcomes. Maqusood S et al.(2024)^[16] Recent educational reviews similarly stress routine use of quantitative monitors and note that sugammadex, while not a substitute for monitoring, offers a more dependable path to complete recovery than neostigmine.

The present comparative study demonstrated that sugammadex provides a significantly faster and more reliable reversal of rocuronium-induced neuromuscular block compared to neostigmine. Patients in the sugammadex group achieved earlier recovery of TOF ratio ≥0.9, shorter extubation times, and reduced PACU stay. Moreover, the incidence of adverse events such as bradycardia, postoperative nausea and vomiting, desaturation, and residual paralysis was markedly lower with sugammadex, underscoring its superior safety profile. Overall, sugammadex ensured smoother and more predictable recovery, contributing to enhanced perioperative outcomes. While cost considerations remain a limiting factor in resource-constrained settings, its clinical benefits make sugammadex a favorable choice, particularly in high-risk patients and situations where rapid and complete reversal is crucial.

LIMITATIONS OF THE STUDY

1. The study was conducted in a single tertiary care center, which may limit the generalizability of the results to wider populations.
2. The sample size of 100 patients, though adequate for primary endpoints, may not be sufficient to detect very rare adverse events such as hypersensitivity or anaphylaxis.
3. Only ASA I-II patients were included, thereby excluding patients with significant comorbidities; outcomes may differ in higher-risk groups.
4. Cost analysis was not performed, which could have provided additional insights into the economic implications of using sugammadex versus neostigmine.
5. The follow-up period was restricted to the immediate postoperative phase, and long-term outcomes such as readmissions or late pulmonary complications were not assessed.

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