Current evidence on the use of sugammadex for neuromuscular blockade antagonism during electroconvulsive therapy: a narrative review
Article information
Abstract
Depression is a common mental health problem that is associated with significant disability and mortality. Electroconvulsive therapy (ECT) has been demonstrated to be effective at resolving expression of suicidal intent in patients with depression. In less acute situations, patients are usually referred for ECT after several medication trials. Neuromuscular blocking agents (NMBAs) are used to block tonic-clonic motor activity and associated physical harm during the delivery of ECT. Succinylcholine (Sch), with its rapid onset of muscle relaxation, short self-terminating duration of action, and rapid subsequent return of spontaneous ventilation, is the NMBA of choice for ECT. However, the use of Sch is problematic or contraindicated is some situations. Although non-depolarizing NMBAs can be used, the variable time to onset of adequate muscle relaxation and prolonged duration of action have limited their widespread acceptance as alternatives to Sch. Recently, however, with the widespread availability of sugammadex, a chemically modified γ-cyclodextrin that rapidly and predictably reverses the effect of non-depolarizing NMBAs, the muscle relaxation achieved by rocuronium can predictably and effectively be reversed. In situations where Sch is contraindicated or otherwise problematic, rocuronium, followed by pharmacological antagonism with sugammadex, can provide a safe and effective muscle relaxation approach comparable to that of Sch in terms of duration of action. This review provides a summary of the current state of evidence for the use of sugammadex during ECT, which should lend support to further acceptance and future studies of sugammadex in the context of ECT.
Introduction
Depression is a common mental health problem that is associated with significant disability and mortality. According to the National Institute of Mental Health, 7.1% of adults in the United States experienced at least one major depressive episode in 2017 [1]. Depression is not only expensive [2], but it is associated with substantial impairment in role functioning at work and in personal life, poor physical health, increased mortality due to various physical disorders, and suicide [3]. Electroconvulsive therapy (ECT) has been successfully used to treat severe and treatment-resistant depression [4]. Modern ECT guidelines recommend the use of muscle relaxants to modify convulsive motor activity and enhance airway management. For many decades, succinylcholine (Sch), with its visible and rapid onset, short duration of action, and spontaneous recovery, has been the preferred neuromuscular blocking agent (NMBA) for ECT. Non-depolarizing muscle relaxing agents such as mivacurium, atracurium, rapacuronium, and rocuronium have been used for ECT, but with limited enthusiasm. With the widespread availability of sugammadex, a modified γ-cyclodextrin that can rapidly and predictably reverse the effect of steroidal non-depolarizing NMBAs, we are presented with a muscle relaxation strategy that can altogether replace the use of Sch for ECT, thus alleviating some of the side effects associated with Sch, such as myalgia, bradycardia, prolonged blockade, and allergic reactions [5]. This narrative review focuses on the clinical practice of muscle relaxation, its monitoring as it pertains to ECT, and current evidence for the use of sugammadex to further improve the safety profile of ECT.
Monitoring onset of NMBA effects
In the clinical setting, the effect of NMBAs is commonly assessed by measuring the motor response to peripheral nerve stimulation, typically focusing on the adductor pollicis muscle through ulnar nerve stimulation (Fig. 1). Single-twitch stimulation is a straightforward method applicable to both depolarizing and non-depolarizing NMBAs (Fig. 2A). A single twitch depression (T1) of 11%–25% has been observed to reduce muscle contractions during ECT; however, the optimal endpoints remain uncertain [6]. In a series of studies comparing Sch to rocuronium-sugammadex for ECT, Hoshi et al. [7] and Kadoi et al. [8] utilized both rocuronium (0.6 mg/kg) and Sch (1 mg/kg) and applied electroshock stimulus after confirming that the single-twitch height (T1) was zero. Different dosages of rocuronium (ranging from 0.3 mg/kg to 1.25 mg/kg) have been utilized by various investigators, while relying on a combination of clinical signs (such as eye opening, hand grip, head lift) and peripheral nerve stimulation to assess the adequacy of neuromuscular blockade [9]. In a dose-finding crossover randomized controlled trial conducted by Mirzakhani et al. [10], the authors established that a twitch suppression > 90% is necessary for controlling motor contractions during ECT. This level of suppression was achieved using doses of Sch ranging from 0.77 to 1.27 mg/kg in 50% to 90% of patients undergoing ECT, and at doses of 0.36–0.6 mg/kg when administering rocuronium [10].

Electrodes applied over the superficially located section of the ulnar nerve are used to transmit electrical impulses from a stimulator to the ulnar nerve. The evoked muscle contraction and neurostimulatory pattern in the adductor pollicis can then be visually, tacitly or objectively assessed.

Peripheral neurostimulation patterns of depolarizing (upper row) and non-depolarizing NMBD (lower row). (A) Single twitch stimulations (blue arrows) and subsequently evoked muscle contraction patterns are similar in terms of diminishing strength over time, between depolarizing and non-depolarizing NMBD but differ in onset and recovery patterns. (B) TOF neurostimulation patterns of depolarizing (upper row) and non-depolarizing NMBD (lower row) differ in terms of strength, onset and recovery patterns when using TOF count and ratio monitoring patterns. After injection of depolarizing NMBD (Sch) the TOF-R always remains but diminishes over time with the injection of non-depolarizing NMBD’s. NMBA: neuromuscular blocking agent, TOF: train-of-four, Sch: succinylcholine.
Train of four (TOF) is another neurostimulation pattern with extensive clinical applications. In this pattern, four supramaximal electrical stimuli (T1, T2, T3, and T4) are delivered at a frequency of 2 Hz, and the number of succeeding detectable muscle contractions, known as the TOF count (TOF-C; Fig. 2B) is assessed. The disappearance of responses to electrical stimuli correlates with the depth of the neuromuscular blockade. A TOF-C of 0 corresponds to optimal conditions for intubation, indicating sufficient laryngeal muscle relaxation [11]. However, studies with a similar design investigating the correlation between TOF-C and the quality, safety, and outcomes of ECT are lacking, and the optimal level of neuromuscular blockade for ECT remains unknown [12]. The degree of pharmacological muscle relaxation is more quantitatively expressed in terms of the TOF ratio (TOF-R; Fig. 2B), in which the amplitude of the fourth response (T4) is compared to that of the first response (T1) [13]. As the neuromuscular block intensifies, the TOF-R diminishes, and fades are said to be present. The return of the TOF-R to 0.9 is representative of adequate recovery from neuromuscular blockade. Table 1 shows the criteria for assessing the neuromuscular blockade depth in terms of the TOF-C and TOF-R [13]. Although the effect of Sch at commonly used doses of 1–1.5 mg/kg is short-lived, it can be prolonged in certain situations (e.g., butyrylcholinesterase deficiency and liver disease). In most cases, neuromuscular blockade can be managed without objective neuromuscular monitoring. However, when using non-depolarizing NMBAs, neuromuscular monitoring in the form of TOF-C (qualitative) or TOF-R (quantitative) should be routinely performed [14]. To prevent residual neuromuscular blockade, intermediate-acting non-depolarizing NMBAs, such as rocuronium, need to be pharmacologically antagonized after their desired effect is no longer needed. The extremely short interval between achieving an adequate depth of neuromuscular blockade, completion of ECT, and reversal of the neuromuscular blockade allows for minimal time for spontaneous recovery from the effect of non-depolarizing NMBAs.

Suggested Classification of Depth of Block Based on Train-of-Four Count and Train-of-Four Ratio Criteria
Neuromuscular monitoring in the form of the TOF-R helps in determining the readiness, dosing, and adequacy of pharmacological antagonism of the neuromuscular blockade. For sugammadex, adequate reversal dosing should be established through objective neuromuscular monitoring. This includes administering 4 mg/kg at a post-tetanic count of 1–2, providing 2 mg/kg upon the reappearance of two twitches during TOF stimulation, administering 1 mg/kg when four twitches reappear during TOF stimulation, dispensing 0.49 mg/kg at a TOF-R ≥ 0.2, and offering 0.22 mg/kg at a TOF-R ≥ 0.5 [15].
Antagonism of neuromuscular blocking agents
The key components of the neuromuscular junction involved in neuromuscular blockade and reversal are illustrated in Fig. 3A. Mechanism of action and termination of of action of Sch is illustrated in Fig. 3B. When using non-depolarizing NMBAs such as rocuronium, two commonly available pharmacological approaches to reverse neuromuscular blockade are as follows: 1) cholinesterase inhibitors such as neostigmine and 2) γ-cyclodextrin (i.e., sugammadex). The traditional approach of using cholinesterase inhibitors (Fig. 3C) is limited by their inability to reverse deep levels of neuromuscular blockade and the need for partial spontaneous recovery of neuromuscular blockade before pharmacological antagonists can be administered. Simultaneous administration of muscarinic antagonists, such as glycopyrrolate, is required to block the unwanted muscarinic effects (bronchospasm, bradycardia, and intestinal hypermotility) of cholinesterase inhibitors. Administration of “full dose” cholinesterase inhibitors in patients who have spontaneously recovered or who are close to full recovery (defined as a TOF-R > 0.90) can also have detrimental effects and provoke paradoxical weakness. This highlights the need for judicious execution of neuromuscular blockade reversal guided by objective monitoring of neuromuscular blockade depth.

Neuromuscular junction and basic elements of neuromuscular transmission, neuromuscular blocking agent induced blockage of neuromuscular transmission and antagonism of neuromuscular blockade. (A) Normal neuromuscular transmission. The presynaptic action potential triggers voltage gated Ca2++ channels with a resultant influx of Ca2++ into the presynaptic nerve ending, followed by mobilization and release of Ach into the synaptic cleft. Released Ach binds with postsynaptic nicotinic Ach receptors with an ensuing depolarization of the muscle bundle. Ach in the NMJ is metabolized by the enzyme Acetylcholinesterase (blue horseshoe) present within the NMJ thus terminating its effect. (B) Mechanism of action and termination of action of Sch: Panel B (Left) side Succinylcholine adheres to the nACh receptors on the motor end plate inducing depolarization of the membrane causing a brief period of clinically evident muscle fasciculation. This is followed by a continuous disruption of further nerve muscle transmission. Panel B (right) spontaneous recovery from Sch blockade occurs by dissociation of Sch from the nACh receptors and subsequent metabolism of Sch by butyrylcholinesterase present in the plasma. (C) Mechanism of action of Non depolarizing NMBD e.g., rocuronium (red dots) Panel C (Left): Rocuronium produces a competitive block at the nAChR preventing Ach from binding to the receptor, thus disrupting neuromuscular transmission and muscle contraction. Panel C (right)Pharmacological reversal in the form of acetylcholinesterase inhibitors prevents the breakdown of Ach resulting in an increase in Ach quantity in the NMJ and overwhelming the competitive block and making the Ach again available for bondage with Ach. (D) Mechanism of action of Non depolarizing NMBD e.g., rocuronium (red dots) Panel D (Left): Rocuronium produces a competitive block at the nAChR preventing Ach from binding to the receptor, thus disrupting neuromuscular transmission and muscle contraction. Panel D (Right) Sugammadex (green truncated cones) in the plasma has an extremely high affinity to bind rocuronium. This bondage reduces rocuronium concentration in the plasm resulting in a concentration dependent movement of rocuronium out of the NMJ and termination of the effect of rocuronium. NMJ: neuromuscular junction, Sch: Succinylcholine.
Another approach to neuromuscular blockade antagonism is the use of sugammadex, a synthetic molecule specifically designed to form high-affinity host–guest inclusion complexes with steroidal NMBAs (Fig. 3D). The binding affinity between sugammadex and steroidal non-depolarizing NMBAs depends on the blockers used in the following order from highest to lowest: rocuronium > vecuronium > pancuronium. Sugammadex binds to rocuronium in the plasma, rendering it unavailable for binding to acetylcholine (Ach) receptors in the synaptic cleft. For every 25 million rocuronium molecules bound in a rocuronium–sugammadex inclusion complex, only one complex is estimated to disassociate [15]. As the free drug concentration decreases in the plasma, a concentration gradient that moves the steroidal NMBA out of the neuromuscular junction and away from the nicotinic Ach receptors is established, terminating the effect of the NMBA [16,17]. These complexes are then renally excreted. Other categories of NMBAs, such as Sch and benzylisoquinoliniumes (i.e., atracurium, cisatracurium, and mivacurium) lack the molecular framework to bind and form host–guest complexes with sugammadex; therefore, sugammadex-induced reversal of these medications does not occur [15].
Dosage and monitoring of sugammadex during ECT
With the widespread use of sugammadex, the muscle relaxation achieved by rocuronium can be predictably and effectively reversed in patients undergoing ECT. This is a safe and effective muscle relaxation approach with a clinical effectiveness comparable to that of Sch. Even profound neuromuscular blockade achieved with rocuronium can be rapidly reversed with an appropriate dose of sugammadex. Table 2 presents the results of studies comparing the clinical effectiveness of rocuronium-sugammadex (ROC-SUG) to Sch for ECT [7,8,18–21]. Rocuronium administered at a dose of 0.6 mg/kg provides muscle relaxation comparable to Sch at a dose of 1 mg/kg both in terms of time to onset and depth of blockade. This was demonstrated by Hoshi et al. [7] in a non-randomized crossover trial and later by Kadoi et al. [8] in a trial with a similar design. Time to adequate muscle relaxation, as assessed by T1 0%, was similar between the two groups in both trials. Kadoi et al., in a separate trial, compared the effect of three different dosages of sugammadex on the antagonism of rocuronium and noted that the recovery time with sugammadex was statistically shorter than that with Sch at a dose of 16 mg/kg sugammadex but statistically longer at a dose of 4 mg/kg sugammadex. In a separate study, Kadoi et al. [19] noted prolonged recovery times after the administration of sugammadex in patients aged > 70 years compared to those aged < 50 years; however, this trial lacked a comparative Sch arm. In the non-ECT setting, a dose of 4 mg/kg sugammadex to antagonize muscle relaxation achieved with 0.6 mg/kg rocuronium has been found to provide depth, onset, and recovery characteristics of neuromuscular blockade similar to that with Sch [22,23]. Methodological variability in the assessment of muscle relaxation and subsequent antagonism endpoints limit our ability to compare findings from the trials listed in Table 2. Some investigators utilized clinical endpoints, such as spontaneous eye opening or time to first spontaneous breath, while others utilized objective neuromuscular monitoring to determine the adequacy and antagonism of neuromuscular blockade. Two inferences can be drawn from these trials. First, the muscle relaxation and recovery profile of ROC-SUG is comparable to that of Sch and meets the muscle relaxation requirement of the ECT procedure. Second, objective neuromuscular monitoring should be performed to determine the dosage of sugammadex and adequacy of recovery from muscle relaxation.
Use of rocuronium + sugammadex when succinylcholine is contraindicated
Sch is the NMBA of choice for ECT. Unfortunately, its side effects preclude its use in certain clinical situations, such as pseudocholinesterase deficiency, hyperkalemia, malignant hyperthermia, neuroleptic malignant syndrome (NMS), and catatonia. Sch has the potential to cause dangerous elevations in serum potassium levels related to the upregulation of Ach receptors and increased efflux of potassium during depolarization in cases of immobility and neuromuscular disorders, such as direct muscle injury, upper or lower motor neuron damage, neuromyopathies, and toxic muscle injury [24]. Of significant relevance is catatonia, which can lead to short-term and prolonged immobility. Sch-induced hyperkalemia has been reported to occur within as little as 5 days of immobility, which can then trigger fatal arrhythmias, such as torsade de pointes and ventricular fibrillation, leading to cardiac arrest [25,26]. Sch is metabolized by butyrylcholinesterase, and its use in patients with both congenital and acquired butyrylcholinesterase deficiency can result in prolonged neuromuscular blockade [27–29]. In patients with NMS, the use of Sch can induce hyperkalemia, and given the overlapping pathogenetic mechanisms between NMS and malignant hyperthermia, patients with NMS could be susceptible to malignant hyperthermia; thus, avoiding administration of Sch in patients with NMS is recommended [30–33].
Alternatives to Sch include mivacurium, a short-acting non-depolarizing NMBA; however, its side effects (hypotension and bronchospasm) and metabolism by pseudocholinesterase limit its usefulness [34]. It is also not a viable option in cases of butyrylcholinesterase deficiency, where the use of Sch is also contraindicated. Atracurium has been used as an alternative to Sch, but the termination of its effect does not align with the duration of the average ECT procedure [6]. Rapacuronium, a short-acting non-depolarizing NMBA, was withdrawn from the market because of the extremely high incidence of bronchospasm [35]. On the other hand, sugammadex, with its ability to reverse even profound rocuronium-induced neuromuscular blockade, is a more appropriate alternative when the use of Sch is unfavorable.
Table 3 provides data on neuromuscular blockade with rocuronium and antagonism with sugammadex when Sch is contraindicated [27–31,36–39]. Although the published data are mostly in the form of case reports, they demonstrate that ECT can be safely performed using rocuronium followed by the sugammadex muscle relaxation approach. As noted in Table 3, the dosages of both rocuronium and sugammadex used by the authors in these case reports vary widely. In addition, the means used to assess the adequacy of neuromuscular blockade and the effectiveness of reversal is widely variable, with only a few studies utilizing objective neuromuscular monitoring. Consistent with expert consensus [14,40], we advocate for the use of weight-based dosing of the NMBA followed by objective neuromuscular monitoring to guide sugammadex dosing and to determine the adequacy of antagonism (i.e., TOF-R of 0.9).
Use of rocuronium + sugammadex to reduce ECT-related adverse events
The adverse effects of ECT can be broadly classified into general medical adverse effects (dental and tongue injuries, headaches, and myalgia) and cognitive adverse effects (amnesia, confusion, and agitation) [41,42]. Myalgia is commonly experienced post-ECT and can occasionally be severe and debilitating. Myalgia, headache, and sore throat are the known side effects of Sch. The exact mechanism of myalgia after ECT is unclear; however, both Sch-induced fasciculations and ECT-induced seizures have the potential to cause muscle damage and associated pain. Data regarding the role of Sch in post-ECT myalgia are conflicting. In a study comparing serum myoglobin levels as a marker of muscle injury, investigators unexpectedly found higher levels of myoglobin in patients receiving Sch for intubation compared to patients receiving Sch before undergoing ECT [43]. In the non-ECT setting, the use of rocuronium and sugammadex has been associated with a significantly lower incidence of sore throat compared to the use of Sch [23]. In a randomized controlled trial comparing the incidence of headaches and myalgia in patients undergoing ECT, Saricicek et al. noted a significantly lower incidence of myalgia and headaches in patients receiving ROC-SUG compared to patients receiving Sch [21]. Table 4 provides a list of other studies on the role of rocuronium and sugammadex use on reducing ECT-related adverse events [21,29,44].

Studies and Case Reports Conducted on the Role of Rocuronium + Sugammadex in Reducing ECT-related Adverse Events
The incidence of other ECT-related adverse effects, such as arrhythmia and postictal agitation, may be reduced with ROC-SUG compared to Sch [39,44]. However, these potential benefits have only been described in case reports and need to be substantiated in larger trials.
Safety profile of sugammadex
Hypersensitivity and anaphylaxis
In 2008, sugammadex was approved for use in Europe. Owing to safety concerns related to hypersensitivity reactions, including anaphylaxis, risk of coagulopathy, and cardiac conduction abnormalities, the US Food and Drug Administration (FDA) delayed the approval of sugammadex in the United States until 2015, when comprehensive safety data became available [45]. The 2015 FDA briefing release on sugammadex reported 273 cases of anaphylaxis among 11.5 million sugammadex exposures, demonstrating that the risk of anaphylaxis associated with sugammadex was comparable to that of other perioperative pharmacological interventions [46]. Following FDA approval of sugammadex in the United States, emerging data suggested a higher risk of hypersensitivity reactions, particularly at higher doses such as 16 mg/kg compared with 4 mg/kg. This led to the speculation of a dose-response relationship for these reactions [47]. Hypersensitivity reactions to sugammadex triggered by repeat dosing over a short interval have also been described in the literature [48], which is particularly concerning for repeat ECT sessions.
The rocuronium-sugammadex inclusion complex has also been noted to demonstrate novel antigenicity that is not observed with the individual constituents of rocuronium and sugammadex. Two retrospective observational studies revealed incidences of anaphylaxis attributable to sugammadex and the sugammadex–rocuronium complex at 0.02% and 0.04%, respectively [49]. Understanding the association between sugammadex use and hypersensitivity reactions, including anaphylaxis, is a complex challenge due to the limitations of previous studies. Inconsistencies in defining these reactions and a lack of standardized diagnostic criteria have contributed to difficulties in accurately assessing rates of anaphylaxis. Additionally, issues such as underestimation of cases in retrospective studies, variability in skin testing timing, and uncertainties regarding the causative agent, whether sugammadex alone or in combination with rocuronium, further complicate the analysis. The storage conditions required for sugammadex, particularly avoidance of exposure to light, introduce additional factors that may influence its allergenic potential.
The potential risks of sugammadex-induced hypersensitivity and anaphylaxis are well-known, and the role of sugammadex in ECT continues to be studied. The use of sugammadex will undoubtedly continue to expand, and a state of vigilance is required to recognize and manage instances of hypersensitivity and anaphylaxis.
Anticoagulation effects after administration of sugammadex
A self-resolving increase of up to 25% in prothrombin time (PT) and activated partial thromboplastin time (aPTT) has been reported in healthy volunteers after sugammadex administration [50]. However, in follow-up clinical trials, this increase in coagulation parameters was clinically irrelevant. Similarly, no clinically relevant effect of sugammadex on platelet aggregation was observed in healthy volunteers [51]. The increase in PT and aPTT observed after administration of sugammadex may be an in vitro effect of sugammadex on phospholipids present in coagulation assays, and thus may only artificially prolong these measurements [52].
Special considerations
Pregnancy, lactation, and use of sugammadex in women of reproductive age
Treatment of new-onset or recurrent severe psychiatric symptoms such as major depression or psychosis during pregnancy may be limited due to the teratogenic concerns of psychotropic medications during the first trimester and the toxicity or withdrawal effects of these medications in the later stages of pregnancy. Although ECT is a rapid and effective treatment option in such situations, ECT-related maternal and fetal risks, such as the risk of abortion and neonatal respiratory depression, need to be considered. In pregnant females administered sugammadex for the reversal of steroidal NMBAs, encapsulation of other steroid moieties, such as progesterone, and its potential to affect the maintenance of pregnancy has been theorized [53]. Although animal studies are encouraging, human studies on this subject are lacking [54].
The potential failure of hormonal contraceptives in females of childbearing age receiving sugammadex has also been widely debated in the medical literature. The consequences of an unintended pregnancy can be devastating medically, emotionally, and financially. In vitro studies indicate the potential for sugammadex to bind progesterone and decrease hormone levels to an extent equivalent to missing doses of hormonal contraception; however, additional pharmacokinetic-pharmacodynamic modeling does not lend support to this interaction [55]. Patients undergoing ECT can be repeatedly exposed to sugammadex during treatment, and the additive effect of this exposure, if any, is currently unknown [37]. Considering this, the drug manufacturer recommends that patients taking hormonal contraceptive agents be counselled to use non-hormonal contraceptive methods for at least 7 days after exposure to sugammadex. There is a dearth of evidence regarding the pharmacokinetic behavior of sugammadex in lactating women and its transfer into breast milk. However, enteral absorption in infants is unlikely.
Elderly population
Elderly patients are more susceptible to adverse events related to the use of NMBAs. Although a delayed recovery pattern has been noted in patients aged > 65 years, this increase in time to recovery from neuromuscular blockade when using rocuronium-sugammadex was not found to be statistically or clinically significant across several clinical trials [56]. Overall, sugammadex is well tolerated in this patient group and no dose adjustment is required for elderly patients.
Renal impairment
In subjects with normal creatinine clearance, sugammadex, along with the rocuronium-sugammadex inclusion complex, is predominantly excreted renally, with sugammadex exhibiting a 2-h elimination half-life. However, in individuals with mild, moderate, and severe renal impairment, the elimination half-life of sugammadex extends to 4, 6, and 19 h, respectively [57]. Prolonged exposure to sugammadex and the ROC-SUG complex due to impaired renal elimination increases the risk of hypersensitivity reactions, disassociation of the ROC-SUG complex, and the potential for recurarization. Notably, the US FDA advises against the use of sugammadex in patients with a glomerular filtration rate (GFR) below 30 ml/min owing to safety concerns. The use of sugammadex is discouraged in cases where renal elimination is compromised. Incorporating high-flux dialysis in patients with severe renal impairment may effectively reduce the plasma concentrations of sugammadex and the ROC-SUG complex, thus offering potential preventive measures against postoperative complications related to neuromuscular blockade [58]. Findings from numerous prospective case-control studies, retrospective investigations, and case reports, including some within the ECT literature, regarding the administration of sugammadex in patients with an estimated GFR < 30 ml/min indicate a notably favorable safety profile of sugammadex in reversing the effects of rocuronium [37,59]. More data is needed to optimize the use of sugammadex in this patient population but initial reports are encouraging. Quantitative neuromuscular monitoring to confirm the depth of neuromuscular blockade and determine the dosing of reversal agents are important when considering the use of ROC-SUG in patients with end-stage renal disease.
Obesity
Obesity has a significant effect on a patient’s body composition (adipose versus lean body mass), which, in turn, affects the pharmacokinetics of medications. Body size metrics can help guide dose selection and administration. Although a quicker reversal of neuromuscular blockade is observed with the administration of sugammadex based on actual body weight than with dosing based on ideal body weight (IBW), it has been argued that with adequate neuromuscular monitoring, dosing based on IBW is adequate and clinically appropriate [60].
Pharmacoeconomics of sugammadex
The introduction and adoption of sugammadex for the reversal of neuromuscular blockade during general anesthesia has been heavily influenced by drug costs and economic evaluations. Data available from numerous randomized clinical trials indicate that rocuronium-sugammadex use results in a faster and more predictable return to adequate neuromuscular function [61]. The use of sugammadex, in comparison with neostigmine, has been shown to result in shorter operating room and recovery room stays and decreased rates of intensive care admissions related to residual neuromuscular blockade [62]. As the clinical benefits of sugammadex have begun to be recognized, cost-effectiveness modelling has evolved to incorporate these benefits [63]. The economic benefits of sugammadex are particularly evident when considering the overall costs associated with operating room time. As our understanding and clinical experience with sugammadex has expanded, its broader implications for healthcare efficiency and patient safety have become clearer. Shifting costs of alternative medications (cholinesterase inhibitors and Sch), either driven by industry or resulting from changes in health policy, can impact the cost-effectiveness of one muscle relaxation approach to another [64]. Budgetary constraints in hospitals and pharmacies may lead to decisions favoring cheaper drugs, overlooking indirect benefits such as improved patient throughput, reduced postoperative complications, and enhanced overall patient safety. A recent budgetary impact analysis in the United States on the net costs of reversal agents and overall cost offsets via a reduction in postoperative pulmonary function with the use of sugammadex demonstrated a cost saving of up to $309 with the use of sugammadex vs neostigmine or spontaneous recovery [65]. Although sugammadex is more expensive per dose compared to neostigmine, the time saved in the operating room can offset the higher drug cost: using sugammadex can translate to $50–$100 saved per minute, depending on the type and complexity of surgery. The rapid recovery and cumulative time savings of rocuronium-sugammadex translate into enhanced operational efficiency and productivity along with improved patient outcomes. These factors collectively highlight sugammadex as a valuable and cost-effective option for neuromuscular blockade reversal [63,65].
Future directions and recommendations regarding the use of rocuronium and sugammadex in patients undergoing ECT
Muscle relaxants were introduced to clinical medicine almost 80 years ago [13]. Since then, our understanding of these agents and their antagonists has greatly increased. Sugammadex is a welcome addition to the anesthesiologist’s armamentarium. Its role in managing neuromuscular blockade and safe anesthesia practice is increasing. In terms of ECT, preliminary work has been conducted to determine how rocuronium, when antagonized with sugammadex, compares to the well-established muscle relaxant Sch (Table 2). In side-by-side trials comparing Sch with ROC-SUG, longer seizure durations were noted in the ROC-SUG group with similar doses of hypnotic agents. Although the exact reason for this difference has not been elucidated, the longer time required to achieve adequate muscle relaxation when rocuronium is used compared with Sch provides both an opportunity to manually hyperventilate the patient for a longer period and a decline in hypnotic-induced electroencephalogram suppression as the muscle relaxant takes effect [66]. Future randomized controlled trials comparing muscle relaxants in ECT are necessary to elucidate whether rocuronium reversed by sugammadex is consistently and substantially better tolerated than Sch. Such trials will provide higher-quality data on the incidence of post-ECT myalgia, headaches, and postictal agitation for rocuronium-sugammadex vs. Sch and data regarding the difference in the length of recovery according to these muscle relaxation approaches.
While many unknowns still remain, the advent of sugammadex in ECT has been a welcome development, allowing practitioners to use rocuronium when Sch is contraindicated or otherwise problematic (Table 3). For decades we have allowed patients to tolerate the known side effects of ECT, including at times intolerable myalgia. Now we can offer patients the option of a different medication during the procedure to ease their discomfort. Indeed, it may be time to re-evaluate our approach to muscle relaxation during ECT altogether. ECT has progressively become safer and more tolerable over the decades. The next step in the development of this highly effective procedure could be that rocuronium reversed by sugammadex becomes the new standard of care. Larger studies are required to explore the use of rocuronium in combination with sugammadex in practice. We also need psychiatrists and anesthesiologists practicing ECT to become more comfortable with administering and monitoring these medications in combination.
Notes
Funding
None.
Conflicts of Interest
No potential conflict of interest relevant to this article was reported.
Data Availability
Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.
Author Contributions
Vivek Arora (Conceptualization; Methodology; Writing – original draft)
Laurence Henson (Writing – review & editing)
Sandeep Kataria (Writing – review & editing)