Despite advances in pharmacotherapy, electroconvulsive therapy (ECT) remains the main treatment option in psychiatry. It can be used primarily when urgent treatment is needed for severe psychiatric diseases or secondarily after failure or intolerance to pharmacotherapy [1]. This modality is based on electrical stimulation of brain tissues and creating an epileptic seizure. The quality and duration of the seizure triggered by ECT were associated with the effectiveness of the procedure. Although seizure duration is accepted as a standard to determine therapeutic efficacy, and a motor seizure typically lasting a minimum of 20-25 seconds was suggested [2]; recent guidelines or articles suggest that a minimum of 15 seconds seizure duration is enough or that seizure duration is not as important as the quality of the seizure [3].

The ‘unmodified’ ECT technique was initially applied with a high incidence of musculoskeletal complications. Various modifications, including general anesthesia and muscle relaxation, are used to increase the safety and acceptability of ECT by the patient. Neuromuscular blockade is required to control excessive muscle contractions during ECT [4]. The aims of their use are reduction of motor activity to avoid injuries, minimal interference with seizure activity, and prompt recovery of spontaneous ventilation without residual paralysis [5]. Succinylcholine is used to be the classic agent for ECT, due to its rapid onset and short duration of action. However, its use may also be accompanied by serious adverse effects due to its metabolism by plasma pseudocholinesterase; severe prolongation of the neuromuscular blockade can occur in patients with pseudocholinesterase deficiency or genetic abnormality [6]. Moreover, succinylcholine has many side effects, such as myalgia, an increase in plasma potassium, and an increase in intragastric and intraocular pressures [7,8]. When succinylcholine is contraindicated, a nondepolarizing neuromuscular blocking agent has to be used. Rocuronium, which is increasingly used in ECT as an alternative to succinylcholine, is a neuromuscular blocking agent with a steroidal structure, with an effect of moderate duration, and is characterized by nondepolarizing properties [9]. Unlike succinylcholine, rocuronium does not lead to serious side effects, such as myalgia, headache, intragastric pressure, increased intraocular pressure, risk of malignant hyperthermia, or hyperkalemia [9]. Sugammadex is a selective relaxant binding agent indicated for the reversal of moderate to deep neuromuscular block with a high affinity for rocuronium [10].

Today, the combination of rocuronium and sugammadex may be an alternative to succinylcholine since several reports demonstrated that sugammadex produced a complete and rapid reversal of induced neuromuscular blockage without other safety concerns [11,12]. The body of evidence was heterogeneous with regards to the patient population and the doses of rocuronium-sugammadex and succinylcholine, and the outcomes that were reported [10]. Literature indicates that there was also limited information on the combined use of rocuroniumsugammadex and propofol versus succinylcholine and propofol combination on seizure variables, recovery, and adverse effects in ECT applications [11-16]. The evidence was obtained from the studies conducted in adult patients undergoing ECT using different dose combinations of rocuronium, sugammadex, and succinylcholine [11-16].

Saricicek et al. [13] compared 0.3 mg kg^-1 rocuronium and 4 mg kg^-1 sugammadex combination with 1 mg kg^-1 succinylcholine for ECT anesthesia and reported reduced myalgia and headache after ECT, faster recovery, and comparable motor seizure duration in rocuronium group. Kadoi et al. [14] reversed the deep neuromuscular blockade in patients who were treated with 0.6 mg kg^-1 of rocuronium using various doses of sugammadex (4, 8, and 16 mg kg^-1, respectively) and compared with succinylcholine and showed no significant difference in seizure duration between the groups. Comparing the combination of 0.6 mg kg^-1 rocuronium and 4 mg kg^-1 sugammadex or 1 mg kg^-1 succinylcholine in ECT anesthesia, Koksal et al. [15] found prolonged seizure duration, sufficient muscle relaxation, and early recovery during ECT in the rocuronium group. Hoshi et al. [16] showed that the patients who were given 0.6 mg kg^-1 rocuronium and antagonized with 16 mg kg^-1 sugammadex for ECT anesthesia, recovered from the muscle relaxation faster than did the patients who were given 1 mg kg^-1 succinylcholine and reported a longer seizure duration with rocuronium compared with succinylcholine. In a case report, Postaci et al. [11] reported no agitation during neuromuscular recovery in a patient switched to a combination of 0.4 mg kg^-1 rocuronium and 2 mg kg^-1 sugammadex instead of 0.5 mg kg^-1 succinylcholine after severe agitations during the recovery period of all his five consecutive ECT sessions. In a patient with pseudocholinesterase deficiency and treated with low dose succinylcholine (0.24±0.23 mg kg^-1) for the first seven ECT sessions, and with rocuronium (0.52±0.02 mg kg^-1) and 200- 400 mg sugammadex for other eight sessions, Takazawa et al. [17] reported that the recovery time from muscle relaxation after succinylcholine administration was remarkably longer than that after rocuronium-sugammadex administration.

We present here a retrospective study covering the time interval when rocuronium was used as a suitable alternative muscle relaxant for ECT when succinylcholine was not available in Turkey. The manufacturer shortage of succinylcholine, the standard neuromuscular blocking agent for ECT in Turkey, has occurred for the past year. In its absence, practitioners have been forced to use alternative agents, such as rocuronium-sugammadex. Although limited, the small quantity of heterogenous evidence suggests that the clinical effectiveness of rocuronium with sugammadex in patients requiring rapid sequence induction was not different or better compared with succinylcholine [10]. However, the potential benefits associated with sugammadex may not be sufficient to offset its high cost, which may limit its widespread use [18]. It is obvious that seizure duration is an important parameter in the selection of different muscle relaxants and anesthetic drugs in ECT [19-21]. Hence, we aimed to compare seizure variables in patients who underwent ECT after administration of either rocuroniumsugammadex or succinylcholine as a muscle relaxant with propofol anesthesia.

A total of 134 patients were evaluated (73 males and 61 females). The sample’s mean age was 33.65±10.48 years (mean± standard deviation [SD]; range, 18-63 yr), and the BMI was 26.66±6.15 kg/m² (mean±SD). The demographic and clinical characteristics of the patients are summarized in Table 1, with no significant difference between the groups (p>0.05) except for smoking status (p=0.02).

All of the variables for the first ECT session are presented in Table 2. The groups showed no significant differences either in values of HR, SBP, DBP, and SpO2 at 15 minutes following the ECT procedure. The EEG seizure duration was comparable in the rocuronium group (55.09±36.11 s) and the succinylcholine group (47.00±26.33 s), and there was no statistically significant difference between the two groups (p=0.432). Duration of motor seizure activity after succinylcholine and rocuronium amounted to 33.15±17.35 s and 36.61± 19.46 s, respectively, with no statistically significant difference (p=0.329). In addition to the abovementioned values, no significant difference was detected in values for seizure energy between the two groups (p=0.330) (Table 2). The adverse effects are also presented in Table 2. There were no major complications or death during or after ECT. There were no differences between the two groups of muscle relaxants in terms of overall adverse effects (p=0.376).

The clinical response to treatment was evaluated with the CGI-I scale between the two groups. Clinical response to treatment evaluated with the CGI-I scale is shown in Table 2. Rocuronium-sugammadex was comparable to succinylcholine in terms of clinical efficacy (p=0.075). At the end of the acute treatment stage, 28 patients (42.4%) improved and 38 patients (57.6%) partly improved in the rocuronium-sugammadex group, while 36 patients (52.9%) improved, 29 patients (42.6%) partly improved, and 3 patients (4.4%) did not improve in the succinylcholine group based on CGI-I scores.

In this retrospective study, which included the time interval in which rocuronium was used as an alternative muscle relaxant suitable for ECT due to manufacturer shortage of succinylcholine, we found that the use of rocuronium-sugammadex as a neuromuscular blocker instead of succinylcholine during ECT with propofol anesthesia produces similar results in terms of seizure variables at the first session and overall adverse effects. The clinical efficacy of ECT measured by CGI-I in both groups was comparable. Therefore, the combination of rocuronium-sugammadex may be an alternative to succinylcholine for ECT. However, the required dose of sugammadex in this clinical situation is not well established, rocuronium-sugammadex is much more expensive than succinylcholine therefore the cost of sugammadex continuous to be an important factor that limits its use [10,18]. Even at low doses, the combination of rocuronium-sugammadex seems to be an ideal alternative in ECT anesthesia when seizure duration, the incidence of side effects, and hemodynamic parameters are taken into account, especially in cases where succinylcholine is contraindicated [17].

Hemodynamic parameters were similar in both groups. The postoperative period was generally uneventful in both groups, and the patients were discharged from the post-anesthesia care unit approximately 60 minutes later. There were no major complications or death during or after ECT. No adverse effects, such as nausea, vomiting, myalgia, or headache occurred with either muscle relaxants. We routinely use succinylcholine with propofol anesthesia in our ECT clinics, the data is clearly in favor of use of rocuronium-sugammadex, especially when succinylcholine is not available.

Rocuronium (0.6-1.2 mg kg^-1) typically produces a complete neuromuscular block within 2 minutes, as compared with an average of 1 minute with 1 mg kg^-1 succinylcholine [16,28]. However, at this dose, rocuronium has a longer duration of action, making it inappropriate for use in ECT where rapid recovery of neuromuscular function is required [16]. Rocuronium 0.3 mg kg^-1 IV dose is half of the recommended intubating dose for rocuronium [29,30]. A previous report by Turkkal et al. [31] using subjective tools to assess the recovery from neuromuscular blockade, showed that 0.3 mg kg^-1 rocuronium was suitable for ECT in a crossover study in which they compared 13 patients given 0.3 mg kg^-1 rocuronium or 1 mg kg^-1 succinylcholine for ECT. Saricicek et al. [13] compared 0.3 mg kg^-1 rocuronium and 4 mg kg^-1 sugammadex combination with 1 mg kg^-1 succinylcholine for ECT anesthesia and found that the recovery from neuromuscular blockade was faster in the rocuronium-sugammadex group compared to succinylcholine. In a case study, Postaci et al. [11] used 0.4 mg kg^-1 rocuronium, and 2 mg kg^-1 sugammadex and reported that the ECT seizure parameters of the patient were more effective and recovery times shorter than in sessions in which succinylcholine was applied. Another study [32] showed that neuromuscular recovery time was significantly longer in patients treated with low-dose rocuronium 0.25 mg kg^-1 and low-dose sugammadex 0.5 mg kg^-1 compared to patients treated with low-dose succinylcholine 0.5 mg kg^-1 for bronchoscopy. We use routinely 0.5 mg kg^-1 IV succinylcholine with 1 mg kg^-1 IV propofol for induction anesthesia in the ECT unit [33]. Based on the fact that only partial paralysis is required for ECT, we used a rocuronium dose of 0.3 mg kg^-1 and a sugammadex dose of 1.5 mg kg^-1 [25,26] in this study. However, it should not be forgotten that despite all its superior properties, the expensiveness of sugammadex in today’s conditions still means a very high cost for ECT when repetitive applications are taken into account, and this is an important factor limiting the use of sugammadex as a routine reversal agent [10,18]. We suggest that use of lowdose sugammadex in this clinical situation to reverse 0.3 mg kg^-1 rocuronium block may reduce cost.

The quality and duration of the induced seizure by ECT have been associated with the efficacy of the procedure [34]. Duration of seizure is a parameter that is measured during the ECT session and is thought to be an indicator of quality. There are several reports evaluating the effects of rocuronium versus succinylcholine on seizure variables of ECT [11,13-17,31]. In their cross-over study, Turkkal et al. [31] reported that motor seizure duration was greater after 0.3 mg kg^-1 rocuronium compared with 1 mg kg^-1 succinylcholine (33 and 24 s, respectively) and suitable for ECT. They stated that this difference may be due to the electrical stimulation given after the cessation of fasciculations in the succinylcholine group, and the electrical stimulation 90 s after the muscle relaxant administration in the rocuronium group. The authors interpreted that this situation may have caused higher serum levels of propofol in the succinylcholine group, and as a result, the patients in the succinylcholine group were still under the influence of the central nervous system depressant effect, while the patients in the rocuronium group might have been freed from the depressant effect of propofol, resulting in longer motor seizures. Koksal et al. [15] interpreted that this prolongation in seizure duration in the rocuronium group might be related to the decreased effectiveness of propofol since ECT was applied later in rocuronium-administered patients. Similarly, Hoshi et al. [16] reported a longer seizure duration with rocuronium compared with coadministration of succinylcholine. The authors suggested that a possible explanation might be minor differences in the state of hyperventilation before electrical stimulation. In addition, they stated that it may be possible that the number of ECT sessions affected the seizure duration due to the improvement in the depressive state caused by ECT [35]. On the other hand, Kadoi et al. [14] compared rocuronium with 0.6 mg kg^-1 and different doses of sugammadex and 1 mg kg^-1 of succinylcholine in propofol anesthesia and found no significant difference in seizure duration among all groups. Takazawa et al. [17] reported succinylcholine below the normal application dose (0.24±0.23 mg kg^-1) in the first seven ECT sessions in a schizophrenic patient with pseudocholinesterase deficiency, rocuronium (0.52±0.02 mg kg^-1) in the next six ECT sessions, and to reverse the block, 200-400 mg sugammadex was used and they reported that seizure duration was not different between succinylcholine and rocuronium-sugammadex. They interpreted that improvement in a depressive state with ECT may affect seizure duration, therefore, the use of rocuronium after succinylcholine may mask ECT seizure duration, which is likely to be longer with rocuronium administration. Saricicek et al. [13] compared 1 mg kg^-1 propofol anesthesia together with 0.3 mg kg^-1 rocuronium-1.5 mg kg^-1 sugammadex combination and 1 mg kg^-1 succinylcholine for ECT anesthesia and reported that the patients in the two groups did not show a significant difference in terms of motor seizure duration. We compared retrospectively the seizure variables of the first session in patients who underwent ECT after administration of rocuronium-sugammadex or succinylcholine as a muscle relaxant with propofol anesthesia. Consistent with several previous studies [13-15,17], there were no significant differences in seizure variables between the rocuronium group and the succinylcholine group and the duration of EEG seizures in both groups was also in clinically effective ranges.

The limitation of this study was its retrospective nature and, therefore, all of the variables affecting seizure duration could not be taken into account such as concomitant medications affecting the seizure duration. Moreover, we did not present the recovery times from muscle relaxation between succinylcholine and rocuronium-sugammadex, because neuromuscular monitoring during treatments was assessed but not recorded for all sessions. Adequate recovery of postoperative neuromuscular function cannot be guaranteed without objective neuromuscular monitoring.

In conclusıon, the main finding of the current study is the potential of rocuronium-sugammadex as an alternative to succinylcholine with comparable seizure during for ECT. However, further randomized and controlled studies are needed to compare these two muscle relaxants in terms of all factors affecting the success of ECT. A well-conducted economic evaluation of sugammadex would help reduce the uncertainty about the cost-effectiveness of sugammadex in the context [10].