Rocuronium-sugammadex as an alternative muscle relaxant to succinylcholine in electroconvulsive therapy: A meta-analysis

Abstract

BACKGROUND

Electroconvulsive therapy (ECT) requires optimal muscle relaxation, which is conventionally achieved with succinylcholine (SCC) despite its adverse effects. In this context, rocuronium-sugammadex (RS) has emerged as a potential alternative, but its comparative efficacy remains uncertain. Hence, this meta-analysis evaluated the recovery times, seizure duration, and safety of these agents in ECT.

AIM

To compare the recovery times, seizure duration, and side effect profiles of RS and SCC in ECT.

METHODS

PubMed, EMBASE, and Cochrane Library (from inception to June 2025) were systematically searched for randomized and observational studies comparing RS with SCC in ECT. The primary outcomes were seizure duration (motor/electroencephalogram) and recovery time, and the secondary outcomes included adverse events (e.g., myalgia). Pooled standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using random-effects models.

RESULTS

This meta-analysis included 7 studies involving 250 observations of patients who received RS and 282 sessions in which patients received SCC. Regarding seizure duration required for effective ECT, RS was associated with a longer duration (SMD: 0.43, 95%CI: 0.15-0.70, P < 0.05). However, this effect became nonsignificant in analyses limited to randomized controlled trials (SMD: 0.54, 95%CI: -0.17 to 1.25, P > 0.05). No significant difference was found between the groups in the recovery time (SMD: -0.51, 95%CI: -1.57 to 0.56, P = 0.277), despite trends favoring RS in three out of six studies. Qualitatively, the RS combination was associated with fewer adverse events, such as myalgia, although the reporting was inconsistent across studies. Substantial heterogeneity (I² = 89%-93%) was a key finding for recovery outcomes, likely stemming from variability in the dosing and procedural protocols.

CONCLUSION

RS is a feasible alternative to SCC for ECT, with acceptable recovery and fewer side effects without affecting the seizure duration. However, larger high-quality randomized controlled trials are necessary to statistically substantiate these findings and assess the long-term outcomes.

Key Words: Electroconvulsive therapy; Succinylcholine; Rocuronium; Sugammadex; Neuromuscular blockade; Meta-analysis

Core Tip: Based on the meta-analysis, rocuronium-sugammadex (RS) may be associated with a statistically longer seizure duration in the overall analyses, although this effect was not significant in randomized studies. No significant difference was found in recovery time compared to succinylcholine, despite some trends favoring the use of RS. Qualitatively, RS appears to have a better safety profile, with fewer adverse events such as myalgia. However, the high heterogeneity in recovery outcomes emphasizes the need for more standardized research protocols to yield more consistent and definitive conclusions.

INTRODUCTION

Electroconvulsive therapy (ECT) is an effective and potentially life-saving treatment modality for several severe psychiatric disorders, such as pharmacotherapy-resistant depression, bipolar disorder, and catatonia[1]. Introduced in 1938 by Ugo Cerletti and Lucino Bini, ECT has rapidly gained acceptance owing to its efficacy in treating conditions such as severe depression and schizophrenia, especially when alternative treatments are unavailable or ineffective[2]. The use of ECT has fluctuated with advances in pharmacological treatment and societal views, and its recently increased clinical usage is based on a better understanding of its mechanisms and parameters[3,4]. The procedure involves inducing a generalized seizure under general anesthesia, and adequate muscle relaxation to mitigate the risk of musculoskeletal injuries such as fractures and dislocations. Anesthesia for ECT is a critical component of the procedure ensuring patient safety and comfort while optimizing the therapeutic effects. Anesthesiologists must consider individual patient factors, including comorbidities and potential drug interactions, to tailor the anesthetic approach for optimal outcomes. Muscle relaxants play a pivotal role in ECT, as they prevent musculoskeletal injuries and ensure patient safety. Succinylcholine (SCC) has conventionally been used for this purpose because of its rapid onset and short duration of action; nevertheless, it has several contraindications and potential adverse effects, including hyperkalemia and malignant hyperthermia. Furthermore, it causes post-ECT myalgia and transient hyperkalemia, which can be life-threatening in certain patient populations, such as those with burns, severe trauma, or neuromuscular disorders. Other adverse effects include increased intraocular and intragastric pressure, and a rare but serious risk of malignant hyperthermia[5]. Consequently, alternative muscle relaxants such as rocuronium, atracurium, and rapacuronium are being considered, particularly in patients with specific comorbidities or contraindications to SCC[6].

In recent years, the combination of rocuronium-sugammadex (RS) has emerged as a promising alternative. Rocuronium is a non-depolarizing steroidal neuromuscular blocker known for its rapid onset, and sugammadex, is a selective relaxant-binding agent that reverses neuromuscular blockade induced by steroidal neuromuscular blocking drugs like rocuronium and vecuronium[7]. Sugammadex rapidly encapsulates and inactivates rocuronium, thereby enhancing its clinical utility. Sugammadex offers swift and predictable reversal of rocuronium-induced neuromuscular blockade, potentially facilitating faster and more complete recovery than the spontaneous metabolism of SCC or reversal with cholinesterase inhibitors[8]. This combination may mitigate the adverse effects associated with SCC and enable a controlled recovery.

Despite increasing interest and anecdotal reports of its use in ECT, a comprehensive synthesis of evidence comparing SCC with RS combination in terms of efficacy is lacking. Particularly seizure duration, which is vital for ECT effectiveness, and safety profiles in the ECT context have not been adequately investigated. Individual case reports, studies, and literature reviews have reported mixed findings regarding seizure duration and varied outcomes for adverse events and recovery times[7]. Consequently, a meta-analysis is necessary for a robust and comprehensive quantitative comparison of these studies to facilitate future research.

This meta-analysis aimed to systematically assess and compare the clinical outcomes of SCC and RS combination for muscle relaxation in patients undergoing ECT. The RS combination was hypothesized to provide similar efficacy in terms of seizure duration while offering a more favorable safety and recovery profile.

MATERIALS AND METHODS

This meta-analysis was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses. The study protocol was registered in International Prospective Register of Systematic Reviews 2025 (No. CRD420251 057315). Studies that satisfied the population, intervention, comparison, outcomes and study criteria were included (Table 1).

Table 1 Study selection criteria using the population, intervention, comparison, outcomes and study approach.

Category	Inclusion criteria	Exclusion criteria
Population	Adults (≥ 18 years) undergoing ECT for psychiatric disorders	Pediatric populations
Intervention	Rocuronium (any dose) with sugammadex reversal	Other NMBA agents (e.g., atracurium and vecuronium) or reversal without sugammadex
Comparator	Succinylcholine (any dose)	Studies without a direct succinylcholine comparison group
Outcomes	Motor/EEG seizure duration, recovery time, adverse events	Studies not reporting relevant outcomes or with insufficient data for extraction
Study design	RCTs and observational studies (cohort, case-control study and case series) with comparator arms	Case reports, reviews, editorials, conference abstracts without full data and animal studies
Language	No restriction

ECT: Electroconvulsive therapy; EEG: Electroencephalography; RCT: Randomized controlled trial; NMBA: Neuromuscular blocking agent.

Data sources and search strategy

A systematic literature search of the PubMed, Web of Science, EMBASE, Google Scholar, and Scopus databases was conducted from their inception to June 30, 2025. The search terms included: “electroconvulsive therapy”, “ECT”, and “electroshock”; interventions: "rocuronium”, “sugammadex”; and the comparator “succinylcholine”. Two reviewers manually reviewed the reference lists of the relevant review articles and included the studies to identify additional eligible studies. Both observational and randomized studies were included to maximize the evidence base, given the limited number of randomized controlled trials (RCTs).

Study selection

All search results were imported into the Zotero reference management software, and duplicates were removed. Two independent reviewers screened the titles and abstracts according to predetermined eligibility criteria. Both reviewers retrieved the full texts of the selected studies and evaluated them for final inclusion. A third reviewer was consulted to resolve any disagreements at the screening and full-text review stages via discussion or arbitration. Two reviewers independently assessed the risk of bias for each study using the mixed methods appraisal tool (MMAT), version 2018[9]. Conflicts were resolved via discussions or mediation by third-party reviewers.

Data extraction

Data were extracted using a piloted form that comprised the following elements: Study characteristics (including design, sample size, and country), patient demographics (such as age, diagnosis, and ECT parameters), intervention details (covering dosing and timing), and outcomes (expressed as mean ± SD for continuous variables and n/N for dichotomous variables).

Statistical analysis

Effect measures: For continuous outcomes, the standardized mean difference (SMD) with a 95% confidence interval (CI) was used. A random-effects model was used for all analyses, regardless of heterogeneity, as it accounted for both within-study and between-study variabilities. The Knapp-Hartung method was used for the tests and CIs. For dichotomous outcomes, the risk ratio (RR) with a 95%CI was used. Heterogeneity: Heterogeneity was assessed using τ² (restricted maximum likelihood estimator), Cochran’s Q-test, and I² statistic. For the I² statistic, a value greater than 50% indicated substantial heterogeneity.

Pre-specified subgroup analyses included comparisons between RCTs and observational studies. Sensitivity analyses were planned, excluding studies with high influence if detected using Cook’s distance (median + 6 × interquartile range). Publication bias was determined using funnel plots and Egger’s tests. Microsoft Excel was utilized for data collection. Data was analyzed using the online web tool meta-analysis online[10], and the results were verified using the Jamovi statistical software package (Version 2.6.26).

RESULTS

After protocol registration, two reviewers conducted a literature search between June 1, 2025, and June 30, 2025. They initially identified 42 records via database search. Two additional records were located in the clinical trial registries. Hence, a total of 44 records were screened (Figure 1). After removing the duplicates, the number of records was reduced to 31 articles. The initial screening excluded 10 single-case reports. Subsequently, 21 full-text articles were evaluated for eligibility, of which 14 were excluded as they failed to fulfill the inclusion criteria or reported insufficient data. Ultimately, seven studies were included in the qualitative meta synthesis, which formed the foundation for the meta-analysis (Figure 1)[11-17]. All studies were assessed for risk of bias using the MMAT, version 2018[9], and evaluations were based on the journal articles contents (Figure 2). The MMAT assessment revealed a moderate risk of bias in non-RCTs (e.g., lack of blinding). Therefore, sensitivity analyses were performed using subgroup analyses to exclude less scientifically rigorous studies before the final interpretation.

Figure 1  Meta-analysis flow diagram according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.

Figure 2 Risk of bias assessment using mixed methods appraisal tool (version 2018). QRS: Quantitative randomized studies; QNRS: Quantitative non-randomized study; QDS: Quantitative descriptive study; C: Can not say.

This meta-analysis synthesized data from 7 studies: Hoshi et al[11], Kadoi et al[12], Saricicek et al[13], Koksal et al[14], Oflezer et al[15], Moutaoukil et al[16], and Karaca Bent et al[17]. These studies encompassed 250 observations in the RS cohort and 282 in the SCC cohort (Table 2). The number of observations was contingent on the number of sessions conducted or observed in each study. In several studies, the subjects participated in multiple sessions, and they crossed over between the two groups. In studies where multiple doses were compared, the outcome data for the optimum combination, as suggested by the investigators, were used. ECT is a dynamic, multi-session intervention in which treatment parameters, concomitant medications, and clinical responses evolve across sessions. Traditional meta-analytic approaches that aggregate outcomes per subject (e.g., pre-post ECT comparisons) obscure the critical session-specific effects of pharmacotherapy. A per-event meta-analysis is methodologically and clinically imperative for ECT research because it captures the interplay between pharmacotherapy and the progression of treatment. A per-event meta-analysis is better for three main reasons: It deals with changes in drug effects over time, it considers real-world differences in clinical settings, and it increases the ability to detect rare outcomes. These studies collectively evaluated the use of RS vs SCC for muscle relaxation in patients undergoing ECT. The study designs, patient populations, anesthesia induction agents, and specific dosages of muscle relaxants varied among the included studies. The authors successfully gathered data on the efficacy of ECT by measuring seizure duration, either via electroencephalography or motor seizure, and assessing recovery from muscle relaxation in terms of time to spontaneous breathing. Owing to inconsistencies in the reporting of side effects across studies, these effects are documented in the study findings table for qualitative assessment (Table 3). A subgroup analysis of quantitative randomized studies (QRS) and nonrandomized studies was conducted, as identified by the MMAT tool.

Table 2 Study description.

Ref.	Study design	Patients/ECT sessions	R dose	SG dose	SCC dose	Induction agent	Key outcomes measured
Hoshi et al[11]	Small observational case series, non-blinded muscle relaxant selection	5 patients (every patient 3 with SCC and 4 with R + SCC)	0.6 mg/kg	16 mg/kg	1 mg/kg	Propofol 1.0 mg/kg	T1 10% and 90% recovery, time to first spontaneous breath, eye opening, seizure duration, adverse effects
Kadoi et al[12]	Clinical study, lottery system for sugammadex dose (non-blinded sugammadex administration)	17 patients(3 session with different dose of SG and 4 sessions of SCC)	0.6 mg/kg	16 mg/kg, 8 mg/kg, or 4 mg/kg	1 mg/kg	Propofol 1.0 mg/kg	T1 10% and 90% recovery, seizure duration, time to first spontaneous breath, adverse effects
Saricicek et al[13]	Randomized	45 patients	0.3 mg/kg	4 mg/kg	1 mg/kg	Propofol 1 mg/kg	Myalgia VAS, headache VAS, time to T1, T2, motor seizure duration
Koksal et al[14]	Randomized, double-blind (for drug preparation)	16 patients	0.6 mg/kg	4 mg/kg	1 mg/kg	Propofol 2 mg/kg	Spontaneous breathing time, eye opening time, time for obeying instructions, motor seizure duration, MAS and MAS 9 timing, T1 0% and T1 90% times, vital signs, side effects
Oflezer et al[15]	Single-center retrospective observational study	134 patients	0.3 mg/kg	2 mg/kg	0.5 mg/kg	Propofol 1 mg/kg	EEG seizure duration, motor seizure modification, CGI-I score, adverse effects, vital signs
Moutaoukil et al[16]	Small observational case series (prospectively collected)	4 patients	0.3 mg/kg	4 mg/kg	0.5 mg/kg	Propofol 1-1.5 mg/kg	Motor seizure modification, time to spontaneous breathing, time to eye opening, agitation, myalgia, headache, nausea/vomiting, EEG seizure duration
Karaca Bent et al[17]	Single-center observational cohort study (prospective collection, retrospective analysis)	100 adult patients	0.4 mg/kg	2 mg/kg	1 mg/kg	Propofol 1 mg/kg	Spontaneous breathing time, spontaneous eye opening, seizure duration, vital signs (BP, HR, SpO2)

ECT: Electroconvulsive therapy; SCC: Succinylcholine; R: Rocuronium; SG: Sugammadex; T1: Time to spontaneous respiration; T2: Time to eye-opening; VAS: Visual Analogue Scale; MAS: Modified Ashworth Scale; CGI-I: Global Impression Improvement; EEG: Electroencephalography; BP: Blood pressure; HR: Heart rate.

Table 3 Study findings.

Ref.	Main findings	Conclusion/recommendation
Hoshi et al[11]	Recovery: Time to spontaneous respiration 10% and 90% recovery tended to be shorter in the RS group, but the difference was not statistically significant; seizure duration: RS longer (39 seconds vs 33 seconds)	It shows potential benefits as an alternative to succinylcholine for muscle relaxation; side effects: No adverse effects were reported with either muscle relaxants
Kadoi et al[12]	Efficacy as an alternative to SCC; sugammadex (8 mg/kg) produces equally rapid recovery as SCC for 0.6 mg/kg of rocuronium	Sugammadex (8 mg/kg) produces equally rapid recovery as SCC; side effects: No adverse effects were reported
Saricicek et al[13]	Recovery: Group RS is significantly shorter for spontaneous respiration and eye-opening across all sessions; side effects: Myalgia and headache VAS scores were significantly lower in the RS group; seizure duration: No statistically significant difference was observed	It also causes reduced myalgia and headache, and faster recovery compared to succinylcholine
Koksal et al[14]	Recovery: Rocuronium + succinylcholine was significantly shorter for Modified Alderete Score 9 (7.26 minutes vs 11.26 minutes), Spontaneous eye opening (6.64 minutes vs 9.67 minutes), obeying instructions (8.10 minutes vs 11.72 minutes), spontaneous breathing (5.93 minutes vs 8.14 minutes), and time to spontaneous respiration 90% (4.87 minutes vs 9.95 minutes); onset: Group RS longer (149.40 seconds vs 111.53 seconds); seizure duration: Group RS longer (23.28 seconds vs 15.62 seconds)	Sufficient muscle relaxation and early recovery. It can be used as an alternative to succinylcholine
Oflezer et al[15]	EEG/motor seizure duration: Rocuronium + succinylcholine longer than succinylcholine (36.61 seconds vs 33.15 seconds; P = 0.002, P < 0.001 respectively); adverse effects: No major complications or deaths were reported in either group; CGI-I score: No significant difference	Similar results in terms of seizure variables and clinical outcomes can be a suitable alternative.
Moutaoukil et al[16]	Recovery: Rocuronium + succinylcholine was significantly shorter for spontaneous respiration (219 seconds vs 296 seconds) and eye opening (402 seconds vs 467 seconds); motor seizure modification: RS had a significantly higher (better) score (3.6 vs 3.0); side effects: Agitation (0% vs 16%) and myalgia (4% vs 33%) were significantly lower in the RS group; seizure duration: Comparable (40 seconds vs 38 seconds)	Efficacious alternative to succinylcholine, leading to faster recovery with less myalgia and agitation
Karaca Bent et al[17]	Recovery: RS was notably shorter for spontaneous breathing time (88.82 seconds vs 111.78 seconds), spontaneous eye opening (173.12 seconds vs 211.42 seconds), and Modified Alderete Score 9 (410.54 seconds vs 542.60 seconds); seizure duration: No significant difference	Sugammadex is an ideal alternative agent when succinylcholine is contraindicated, or anticholinesterases are not suitable; it shortens recovery time and spontaneous respiration

RS: Rocuronium-sugammadex; SCC: Succinylcholine; VAS: Visual Analogue Scale; EEG: Electroencephalography; CGI-I: Global Impression Improvement.

Seizure duration

This meta-analysis included 7 studies with 250 observations in the RS cohort and 282 in the SCC cohort to assess seizure duration (electroencephalography or motor seizures). The total observations represented all recorded sessions across the included studies rather than unique patients. Each ECT session with recorded data was considered an independent ‘observation’ for quantitative pooling. This approach maximized the available data, particularly from studies with multiple sessions or crossovers between treatment groups. When using a random-effects model with inverse variance weighting, the pooled SMD in seizure duration was 0.43, with a 95%CI of 0.15-0.7, indicating a statistically significant prolongation of seizures in the RS group compared to the SCC group (P < 0.05; Figure 3A). The quantified heterogeneity was low to moderate [τ² = 0.04 (95%CI: 0-0.45), τ = 0.20 (95%CI: 0-0.661), I² = 40.6% (95%CI: 0%-74.4%), and H = 1.20 (95%CI: 1-2.007)]. Cochran’s Q test (Q = 10.16, degree of freedom = 6, P = 0.12) confirmed low heterogeneity across studies, with effect sizes showing consistent direction and magnitude. A random-effects model with the inverse variance method was used in the analysis to compare the SMD, which revealed a statistically significant difference between the two cohorts. A subgroup analysis was performed for seizure duration, which included five studies after excluding quantitative descriptive studies. This analysis included 206 and 243 participants in the experimental (RS) and control (SCC) groups, respectively (Figure 3B). A random-effects model with the inverse variance method was employed to compare the SMD, which revealed a statistical difference between the two cohorts. The summarized SMD was 0.43, with a 95%CI of 0.15-0.7. The test for the overall effect was significant at P < 0.05. Another subgroup analysis of QRSs (Figure 3C) included 73 and 74 participants in the RS and SCC groups, respectively. Although the trend signified favorable results for the RS group, there was no statistically significant difference between the two groups. The summarized SMD was 0.54, with a 95%CI that ranged from -0.17 to 1.25. The test for the overall effect did not yield a significant effect. This subgroup analysis, focusing on studies that were not purely descriptive, continued to show a statistically significant difference (SMD: 0.43, 95%CI: 0.15-0.7), which agreed with the overall finding. This observation supports the potential impact of the RS combination on seizure duration, even after excluding certain study types. Nonetheless, despite a trend favoring the RS group, a statistically significant difference between two cohorts was not observed in the subgroup analysis focusing on randomized studies, which generally provide higher levels of evidence. The wider CI (-0.17 to 1.25) included zero, indicating that the observed effects could be attributed to chance. Preliminary data suggest that rocuronium, when reversed with sugammadex, maintains equivalent seizure duration compared to SCC. The difference in findings between the overall analysis and this specific subgroup (randomized studies) highlights the significance of the study design and warrants further investigations in the form of RCTs.

Figure 3 Forest plot comparing rocuronium-sugammadex and succinylcholine. A: Forest chart of all included studies (seizure duration); B: Subgroup analysis of studies excluding quantitative descriptive studies; C: Subgroup analysis of quantitative randomized studies; D: In terms of spontaneous breathing time. SMD: Standardized mean difference; CI: Confidence interval.

Respiratory recovery (spontaneous breathing time)

This meta-analysis evaluated recovery times in terms of spontaneous breathing resumption between the RS and SC groups across seven studies involving 398 observations (Figure 3D). One study did not reported data for recovery of respiration[15]. The pooled analysis found no statistically significant difference in recovery times (SMD: -0.51, 95%CI: -1.57 to 0.56, P = 0.2776), although the negative point estimate suggested a trend toward faster recovery with the administration of RS. Substantial heterogeneity was observed (I² = 90.8%, P < 0.01), indicating significant variability in the study outcomes. The 3 studies showed significantly shorter recovery times with RS: Saricicek et al[13] (SMD: -1.99), Koksal et al[14] (SMD: -1.24), Karaca Bent et al[17] (SMD: -0.62). By contrast one study favored SCC (Moutaoukil et al[16], SMD: 0.96), and two showed neutral effects. Significant heterogeneity was detected (P < 0.01), implying inconsistent effects in the magnitude and/or direction among the studies. The I² value demonstrated that 90.8% of the variability among the studies arose from heterogeneity rather than random chance. The τ² was 0.928, τ was 0.965, and H was 3.33. The test of heterogeneity showed a Q value of 54.43 and P < 0.01.

Although the pooled analysis did not reveal a statistically significant difference in recovery times between RS and SCC (SMD: -0.52, 95%CI: -1.57 to 0.56, P = 0.278), the negative point estimate and the fact that 3 out of 7 studies favored RS indicated a potential trend towards faster recovery. However, substantial heterogeneity (I² = 90.8%) prevented definitive conclusions. These findings should be interpreted with caution because of the inconsistent directional effects across studies and high variability in outcomes.

Publication biases

The funnel plot for both seizure duration and spontaneous breathing time did not indicate a potential publication bias. Egger’s test did not support the presence of funnel plot asymmetry (for seizure duration; intercept: 1.63, 95%CI: -2.48 to 5.75, t: 0.778, P value = 0.472; for spontaneous breathing time, (intercept: 2.75, 95%CI: -10.52 to 16.02, t: 0.406, P value = 0.705; Figure 4).

Figure 4 Funnel plots. A: Seizure duration; B: Spontaneous breathing.

Thus, RS may facilitate more rapid recovery in specific clinical settings, definitive conclusions regarding its efficacy cannot be drawn owing to the high degree of heterogeneity. Institutional protocols and patient-specific factors must be considered while selecting an agent, particularly when the safety benefits of RS, such as the avoidance of SCC’s risks of hyperkalemia and malignant hyperthermia, may outweigh minor differences in recovery time. The primary conclusion from the analysis is that although the overall data suggest a longer seizure duration with RS, this effect is not observed in RCTs. In addition, the recovery time does not show a significant difference despite observable trends, all of which are influenced by considerable heterogeneity. Further research using standardized protocols is necessary to confirm these findings.

DISCUSSION

ECT is a procedure in which small electrical currents are applied through the skin to the brain, inducing generalized seizures to treat specific psychiatric disorders. Since its introduction, the scenarios in which ECT is an effective treatment have greatly expanded[6]. Neuromuscular blockers are often administered during seizures to minimize convulsive motor activity, thereby alleviating the risk of physical injuries, such as fractures[6]. These agents induce muscle relaxation during seizures, ensuring patient safety while undergoing ECT. The optimal dose aims to avoid prolonged paralysis, which can unnecessarily delay recovery[18]. These agents induce muscle relaxation, which is crucial in clinical settings, especially when controlling the physical manifestations of seizures. A systematic review of neuromuscular blocking agents for ECT observed that non-depolarizing agents, such as rocuronium, are preferred in patients with certain comorbidities[6]. However, neuromuscular blockade must be carefully monitored and pharmacologically reversed before emergence from anesthesia to ensure patient safety during ECT owing to the prolonged duration of action. RS is increasingly being considered a viable alternative to SCC for muscle relaxation during ECT[7]. RS provides a rapid onset of action and comparable recovery, making it suitable for ECT, where a quick and effective neuromuscular blockade is required, similar to SCC[19]. This combination is considered safe for use in special populations, including pregnant women and patients allergic to SCC[20].

This meta-analysis aimed to provide the most updated synthesis incorporating quantitative analysis to compare RS with SCC for neuromuscular blockade during ECT. The findings revealed several clinically important insights that warrant careful consideration. The most prominent finding was the significant increase in seizure duration in the case with RS compared to SCC (SMD: 0.43, 95%CI: 0.15-0.70). This effect persisted even after excluding descriptive studies, suggesting the biological plausibility of these results. However, the lack of statistical significance in the subgroup analysis of QRSs suggests the need for further confirmation. The prolongation of seizure duration in ECT following the administration of RS as opposed to SCC, may be attributed to the timing of electrical stimulation in relation to propofol administration; however, the precise mechanism yet to be elucidated[15]. Nevertheless, this finding should be cautiously interpreted as it was not replicated in the subgroup analysis of randomized studies, possibly due to the limited power from smaller sample sizes in the randomized designs. The seizure duration is traditionally regarded as a crucial determinant of the efficacy of ECT, with durations of 30 seconds to 60 seconds considered optimal for ECT[21,22]. This finding has key clinical implications. In case of recovery times, the pooled analysis did not indicate statistically significant difference (SMD: -0.51, 95%CI: -1.57 to 0.56, P = 0.277); nonetheless, the direction of the effect consistently favored RS in most studies. The substantial heterogeneity (I² = 89%) suggests that institutional protocols and dosing regimens critically influence recovery profiles. Studies employing higher sugammadex doses (≥ 4 mg/kg) demonstrated more rapid recovery, aligning with pharmacokinetic principles that optimal reversal requires adequate doses of neuromuscular blocker reversal.

The safety profile emerging from our analysis presents a compelling case for the use of RS. Although quantitative synthesis was limited by inconsistent reporting, qualitative assessment revealed fewer instances of myalgia, hyperkalemia, and other SCC-associated complications in the RS group. This is particularly relevant for patients undergoing ECT, as they require multiple treatments making them vulnerable to the cumulative adverse effects. Further quantitative analysis in future randomized studies with large sample sizes is necessary to establish this.

The comparative analysis of RS for rapid sequence induction intubation has been extensively investigated, with particular emphasis on intubation conditions, recovery times, and safety profiles[23]. SCC is traditionally preferred because of its rapid onset and short duration of action; rocuronium, especially when used in conjunction with sugammadex for reversal, is a compelling alternative. SCC provides superior intubation conditions compared to rocuronium. For example, a meta-analysis indicated that SCC was associated with a 17.7% increase in excellent intubation conditions and a 5.1% decrease in unacceptable endotracheal intubation complications[24]. However, endotracheal intubation is not routinely necessitated in clinical practice for ECT. Rocuronium, when reversed with sugammadex, facilitates faster recovery of spontaneous ventilation than SCC, even when administered at higher doses[25]. The use of SCC is linked to several side effects, including hyperkalemia and malignant hyperthermia, which are significantly encountered in certain patient populations[26]. Rocuronium has been shown to be an acceptable alternative when used in combination with sugammadex. This meta-analysis provides new evidence for making informed choices between rocuronium and SCC in the context of short procedures, such as ECT.

This study has several limitations that must be acknowledged. First, the high heterogeneity, although addressed via random-effects models and subgroup analyses, means that the findings may not be generalizable across all clinical settings. Second, differences in the ECT technique (electrode placement and stimulus parameters) and anesthesia protocols (induction agents and monitoring standards) could have influenced the outcomes. Third, although funnel plots and Egger’s tests indicated the absence of significant asymmetries the predominance of small studies increases susceptibility to publication bias. Fourth, including all ECT sessions as independent data points might have introduced within-patient correlations not entirely addressed by random-effects models and the use of SMD, potentially overestimating the sample size or underestimating the variance. While this approach maximized the available data, this limitation should be considered when interpreting the pooled results.

The findings from this meta-analysis have key clinical implications. For patients at risk of SCC complications (e.g., those with neuromuscular disorders or hyperkalemia), RS appears to be a safe alternative that does not compromise seizure quality. The trend toward faster recovery, particularly with adequate sugammadex dosing, may enhance throughput in busy ECT suites. However, the specific context should be considered when implementing this approach as the learning curve for sugammadex use and cost implications are some of the practical challenges to be overcome.

Future research should prioritize large multicenter RCTs with standardized protocols to validate these findings. Dose-response relationships, long-term cognitive outcomes, and cost-effectiveness analyses warrant special attention. Furthermore, studies examining the impact of RS on ECT efficacy (e.g., remission rates) would provide beneficial clinical insights.

CONCLUSION

This meta-analysis indicates that the RS combination is a viable and safe alternative to SCC for muscle relaxation during ECT. In the overall analysis RS is associated with a longer seizure duration than SCC. It did not achieve statistical significance in the subgroup analysis of RCTs. Therefore, larger, high-quality RCTs are needed to definitively ascertain its impact on seizure quality. The pooled analysis did not identify statistically significant difference in recovery time between the two agents. However, a consistent trend favoring faster recovery with RS was observed across most studies, with considerable improvements in recovery profiles in studies employing higher sugammadex doses. This potential for expedited recovery, the qualitative observation of fewer adverse events, such as myalgia, and the avoidance of SCC’s risks (e.g., hyperkalemia and malignant hyperthermia), present a compelling safety advantage for RS. Despite substantial heterogeneity among the included studies, particularly in terms of recovery outcomes, RS emerges as a valuable option for patients undergoing ECT. Those with contraindications to SCC and those for whom a more predictable and controlled recovery is desired are likely to benefit from this approach. Nonetheless, further large-scale, methodologically rigorous RCTs with standardized protocols are warranted to confirm these findings, explore dose- response relationships, and assess long-term cognitive and cost-effectiveness outcomes in the context of ECT.