Secondary Logo

Journal Logo

Ambulatory Anesthesiology and Perioperative Management: Original Clinical Research Report

Minimum Effective Doses of Succinylcholine and Rocuronium During Electroconvulsive Therapy: A Prospective, Randomized, Crossover Trial

Mirzakhani, Hooman MD, PhD, MMSc*†‡§; Guchelaar, Henk-Jan PharmD, PhD§; Welch, Charles A. MD; Cusin, Cristina MD; Doran, Mary E. NP; MacDonald, Teresa O. RN; Bittner, Edward A. MD, PhD*; Eikermann, Matthias MD, PhD*#; Nozari, Ala MD, PhD*

Author Information
doi: 10.1213/ANE.0000000000001218

Electroconvulsive therapy (ECT) is a treatment in which generalized seizures are induced by transcutaneous electrical stimuli to the brain to treat specific psychiatric conditions such as major depressive or cyclothymic disorders.1,2 The quality and duration of the induced seizure by ECT have been associated with the efficacy of the procedure. Anesthetic drugs and neuromuscular blocking agents (NMBAs) are administered to ensure patient comfort and safety but need also be titrated to provide optimal conditions for the induced seizure activity during the treatment while allowing a rapid recovery on its completion.3 Because of its rapid onset and short duration of action, succinylcholine is considered the NMBA of choice for ECT; however, a nondepolarizing NMBA needs to be considered in some patients with metabolic, neuromuscular, or neurologic comorbidities or other contraindications to succinylcholine (eg, immobilization or pseudocholinesterase deficiency).4 Despite the importance of NMBAs to provide favorable conditions for ECT, the NMBA dose to achieve acceptable level of muscle contracture via the use of neuromuscular blockade without excessive or untoward effects has not been identified in a prospective randomized fashion and via the use of objective monitoring techniques.5 The aim of this study is, therefore, to identify the minimum effective starting NMBA doses of 2 commonly used neuromuscular blocking drugs (succinylcholine and rocuronium), defined as the lowest dose to provide optimized muscle strength modulation during ECT.


This crossover, randomized controlled, assessor-blinded clinical trial was conducted in the postanesthesia care unit at Massachusetts General Hospital in Boston, Massachusetts. The IRB approved the study protocol, and written informed consent was obtained from all participating patients. The study was registered before patient enrollment. Registry Url: Identifier: NCT01441960.


Two hundred twenty-seven ECT sessions were conducted in 45 hospitalized patients aged 24 to 80 years with ASA physical status I to III admitted for a series of ECT treatments at a frequency of 3 times per week. The indication for ECT in all enrolled patients was major depressive disorder or bipolar disorder, and all patients were taking psychotropic medications, including antidepressants and antipsychotics, as indicated by their psychiatric condition. Only patients within 20% of the ideal body weight were included. Exclusion criteria included age <18 years, patients with illness or medications known to influence neuromuscular transmission, significant renal or liver dysfunction, electrolyte abnormalities, and pregnant women.


The flow of patients through the study is depicted in Figure 1. After screening by the psychiatrist and anesthesiologist responsible for the clinical treatment of each patient, informed consent was obtained and patients were enrolled. After preoxygenation with 100% oxygen for 3 minutes through a facemask, anesthesia was induced with propofol (1.2 mg kg−1 IV over 5 seconds). Continuous neuromuscular transmission monitoring was applied after stabilization and baseline calibration to establish a control twitch response before NMBA injection (see the Neuromuscular Transmission Monitoring section). Succinylcholine (Quelicin®, Hospira Inc., Lake Forest, IL) 0.8 (2.67 × ED95) mg kg−1 or rocuronium-bromide (Zemuron®, Organon USA Inc., a subsidiary of Merck & Co. Inc., Roseland, NJ) 0.4 mg kg−1 (1.33 × ED95) was then administered IV over 5 seconds through an IV catheter in the arm contralateral to the side of neuromuscular transmission monitoring, which was then flushed with a 10-mL bolus of normal saline. These initial doses were selected as the median of applied succinylcholine and rocuronium doses to achieve acceptable ECT-induced motor activity in a pilot study of 10 patients. Ventilation was assisted until recovery of normal spontaneous ventilation through a facemask and an Ambu-bag with supplemental 100% oxygen.

Figure 1.
Figure 1.:
Schematic representation of the study methods. After screening for eligibility criteria, we enrolled consecutive patients who scheduled for series of ECT after consenting to participate in the study. Only captured data from patients who completed the series of treatments with reliable neuromuscular monitoring were used for analysis. ECT = electroconvulsive therapy.

After the peak effect of neuromuscular transmission blockade was established, an electrical stimulus at approximately 6× seizure threshold was delivered with right unilateral application of electrodes with a MECTA Model SR II apparatus (MECTA Corp., Portland, OR). The treating psychiatrists, blinded to the type and dose of the NMBA (see Discussion), determined the stimulus parameters for the applied ECT (level, dynamic, energy, intensity, and duration of stimulus) and the subsequent duration of seizure (Table 1). The duration of seizure was monitored by electroencephalogram (EEG) and recorded from EEG activity.

Table 1.
Table 1.:
ECT Parameters and Hemodynamic, Acceleromyographic, and Clinical Characteristics of Subjects After Muscle Relaxation with Succinylcholine or Rocuronium Under Optimized ECT-Induced Seizure Activity

Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded every 3 minutes, and the heart rate (HR) and oxygen saturation (Spo2) were monitored and recorded continuously throughout the procedure and until the patient’s full recovery. Temperature was monitored and maintained at ≥35°C. Labetalol (10–50 mg IV) or esmolol (40–80 mg IV) was administered to treat hypertension and tachycardia, when necessary.

After termination of seizure and when appropriate, as determined by the practicing anesthesiologist, the rocuronium-induced neuromuscular blockade was reversed with 50 μg kg−1 neostigmine in conjunction with 10 μg kg−1 glycopyrrolate.6 After return of normal spontaneous breathing, patients were placed in a lateral decubitus position. Neuromuscular monitoring was continued until full recovery of the neuromuscular blockade was recorded (T1 = 100% or train-of-four [TOF] ratio of >0.9 for succinylcholine and rocuronium, respectively).7

Neuromuscular Transmission Monitoring

Neuromuscular transmission was monitored using acceleromyography, and a TOF-Watch SX® monitor (Organon) was connected to a laptop computer. Before induction of anesthesia, the subject’s arm was taped in a stable and comfortable position, skin was cleansed, and surface electrodes were placed (3–5 cm apart) over the ulnar nerve at the wrist. A hand adaptor (Organon) was used to fix the thumb position to minimize the potential variability in evoked muscle contraction. The TOF-Watch was calibrated by use of the standard calibration with default supramaximal stimulation (CAL1: 10-second stimulation current of 50 mA), and ulnar nerve stimulation was resumed with single twitch stimulation at 0.1 Hz and continued till observation of <5% variation of twitch heights for 2 to 3 minutes, after which a bolus dose of the NMBA was injected.8 The same mode of stimulation was continued until the peak effect of neuromuscular transmission blockade was established (first of 3 consecutive twitches with the same/increasing value or ≥95% depression of twitch).8

After completion of the ECT-induced seizure, twitch stimulation was continued in patients who had received succinylcholine until a twitch height of 100% of control (baseline) with response variation <5% for 2 minutes was recorded.8 For rocuronium-treated patients, the mode of stimulation was changed to TOF stimulation with square wave pulses of 0.2-milliseconds duration delivered at 2 Hz every 15 seconds and continued until 3 consecutive responses with a TOF ratio ≥0.9 were recorded. All twitch height values during the recovery phase were normalized to final twitch value and were expressed as percentages of control values.8

NMBA Randomization and Crossover

Patients were assigned randomly to receive either succinylcholine or rocuronium at a standard initial dose, as listed previously, during their first ECT. During each subsequent ECT treatment (2 days apart), patients received a 10% higher (if insufficient paralysis) or lower (if sufficient or excessive paralysis) dose of the same NMBA until the minimum effective dose (MED) that resulted in acceptable neuromuscular blockade (MEDECT) was identified. When the MEDECT dose of the first NMBA was identified, each patient received the second NMBA (ie, succinylcholine if rocuronium had been administered, and vice versa) for his or her subsequent ECT treatments, and the dose was increased or decreased in 10% increments according to the same protocol until the MEDECT dose for the second NMBA was established (Supplemental Digital Content 1, Supplemental Figure 1, study design,

Quality Assessment of Neuromuscular Blockade

Table 2.
Table 2.:
Definitions of Conditions and Terms for Assessing the Quality of “Acceptable” or “Not-Acceptable” Muscle Relaxation During ECT-Induced Seizure

The quality of neuromuscular blockade during seizure was independently assessed by the use of a dichotomous scale of “acceptable” or “not acceptable” by 2 psychiatrists blinded to the dose and type of NMBA. A grading system was used to score the 2 psychiatrists’ evaluation. Each psychiatrist provided a single score based on the defined criteria for “acceptable” or “not acceptable” ECT conditions (Table 2). A summed score of ≥2 was considered as acceptable level of induced muscle relaxation. Any summed score of <2 was considered as a not acceptable level of induced neuromuscular blockade. Consequently, NMBA trials were continued until the lowest dose that provided acceptable neuromuscular blockade during induced seizure was identified.

Outcome Variables

The primary clinical outcome of the study was to define the MEDECT of succinylcholine and rocuronium for each subject to achieve our definition of an acceptable level of neuromuscular blockade. MED50ECT was, hence, defined as the smallest dose of succinylcholine or rocuronium that resulted in adequate muscle relaxation and safe application of ECT in 50% of the cases. We also provide the NMBA dose that resulted in adequate relaxation in 90% and 95% of the population (MED90ECT and MED95ECT, respectively) and the nonparametric bootstrap confidence intervals (CIs) for the upper tail distribution of the optimal doses. The measured MED50ECT of succinylcholine and rocuronium and the corresponding T1 suppression for acceptable motor activity during ECT were compared with their ED95s (median dose corresponding to >95% adductor pollicis twitch depression9), ie, m × ED95 under the conditions studied (ECT). As a coprimary outcome, the estimated CIs for each MEDECT are calculated to identify the range of MEDs for each applied NMBA for ECT.

The secondary outcome was the duration of the neuromuscular transmission blockade defined as the time to complete recovery from neuromuscular blockade after a single bolus dose of the MED50ECT, ie, return of the twitch height to its baseline if succinylcholine had been administered or TOF ratio ≥0.9 if rocuronium was used. All patients were monitored until full recovery from neuromuscular blockade (twitch height of 100% or TOF ratio ≥0.9 for succinylcholine and rocuronium, respectively).

Statistical Analysis

Data are presented as mean ± SD or (range) unless otherwise specified. On the basis of results from previous NMBA dose−response studies, we considered a minimum sample size of 24 to be adequate for the estimation of MED50ECT with 80% power and with a reasonable degree of assurance.10,11 We also used resampling and bootstrap method for estimation of MED50ECT CIs to investigate the adequacy of sample size on the estimated confidence limits (Supplemental Digital Content 2, In addition, we conducted a power analysis to determine the sample size needed for our secondary outcome parameters, ie, the duration of block and time to recovery. In our pilot data from10 patients, a 3-minute difference in recovery end points (100% twitch height recovery or TOF ≥0.9 for succinylcholine and rocuronium, respectively) with a SD of 5 minutes was observed. Assuming a normal distribution of the data, we calculated a sample size of 31 to achieve 90% power to detect a mean of paired differences of 3.0, with a known SD of differences of 5.0 and with a significance level (α) of 0.05 using a 2-sided Wilcoxon test. Accordingly, we concluded that a sample size of 31 would provide adequate power for both of our clinical outcome parameters.

All the calculations were performed using SPSS Statistics for Windows, version 19.0 (IBM Corp., Armonk, NY, 2010), PASS 11 (NCSS, LLC., Kaysville, UT), and SigmaPlot 11 (Systat Software, San Jose, CA).

Normality assumption of the measured variables was assessed using the Lilliefors test (all P > 0.12 and N = 31). The Welch t test was conducted to compare the measured variables (eg, recovery time, duration of seizure, and hemodynamic variables) obtained under succinylcholine and rocuronium conditions (P > 0.01).12,13 Cohen κ for interrater reliability was used to assess interrater reliability between the 2 assessors of motor seizure activity during ECT. The MED of NMBA was defined as the lowest dose that provided completion of ECT under our definition of acceptable conditions (MEDECT). The minimum acceptable doses obtained from the study patients (31 minimum doses for either of crossed-over groups, succinylcholine or rocuronium) were resampled 10,000 times using the nonparametric bootstrap method.14 The 25th, 50th (median), 75th, 90th, and 95th percentiles of these samples (MED25ECT, MED50ECT, MED75ECT, MED90ECT, MED95ECT, and MED99ECT, respectively) and the corresponding 95% and 99% CIs were then calculated.

Covariates included were age, ASA physical status, anesthetic dose, and the ECT parameters. A P value <0.05 (unless otherwise specified) was considered statistically significant and reported for a 2-tailed test.


Two hundred twenty-seven ECT treatments in 45 enrolled subjects were recorded. Thirty-one subjects completed their series of treatment, generating a total of 187 qualified ECTs for data analysis (Figure 1). To identify the optimal dose of each NMBA, a range of 2 to 4 observations was needed, yielding a total of 187 qualified ECTs for data analysis. The mean age and body weight of the subjects were 50 ± 8 years (range, 24–80 years, female/male: 15/16) and 80 ± 20 kg (range, 49–109 kg), respectively. Median of ASA physical status was II. There were no significant differences between the 2 groups (treated patients with succinylcholine or rocuronium) in baseline values of Spo2, HR, SBP, and DBP. The dose of propofol used to induce anesthesia was not different in the succinylcholine and rocuronium groups (100 ± 28 mg vs 105 ± 29 mg, P > 0.05). No significant difference was observed between the groups in the dose of any medications administered during ECT (eg, esmolol and labetalol).

Primary Clinical Outcome: Minimum Effective Dose of NMBA and Onset Time

MED50ECT of succinylcholine and rocuronium were 0.85 mg kg−1 (95% CI, 0.77–0.94) and 0.41 mg kg−1 (95% CI, 0.36–0.46), respectively. The MED90ECT and MED95ECT doses (the MEDs that provided optimal ECT conditions in 90% and 95% of patients, respectively) were 1.06 mg kg−1 (95% CI, 1.02–1.27) and 1.16 mg kg−1 (95% CI, 1.08–1.5) for succinylcholine and 0.57 mg kg−1 (95% CI, 0.51–0.61) and 0.59 mg kg−1 (95% CI, 0.56–0.63) for rocuronium, respectively. The range of applied MEDECT for succinylcholine and rocuronium were 0.46 to 1.22 mg kg−1 and 0.26–0.59 mg kg−1, respectively. Table 3 demonstrates 95% and 99% CI of the MED percentiles.

Table 3.
Table 3.:
Ninety-Five Percent and 99% Nonparametric Bootstrap Confidence Intervals of the Percentiles of MEDs for Succinylcholine and Rocuronium to Achieve Acceptable Induced Neuromuscular Blockade During ECT (MEDECT)

Acceptable ECT-induced seizure contracture after applying MEDECTs was achieved after 1.4 ± 0.5 minutes and 3.7 ± 1 minutes in the succinylcholine and rocuronium groups, respectively (P < 0.001). Nadir twitch suppression to achieve an acceptable controlled seizure quality (muscle activity) was 0% ± 2% (0–10, frequency of 0: 92.5%) for succinylcholine and 4% ± 6% (0–30, frequency of 0: 40%) for rocuronium. An adductor pollicis twitch suppression of 0% to 10% resulted in 100% acceptable neuromuscular blockade after succinylcholine (97.5%: 0%–4%; 2.5%: 5%–10%). When rocuronium was used, a T1 twitch value of 0% to 10% of baseline resulted in acceptable level of neuromuscular blockade in 95% of cases (60% of these patients had a T1 value of 0%–4% baseline, and 35% had T1 of 5%–10% baseline).

Secondary Clinical Outcome: Time to Recovery from Neuromuscular Blockade

Figure 2.
Figure 2.:
Time course of single twitch height (percentage baseline) after injection of succinylcholine or rocuronium (means ± SE) in optimized electroconvulsive therapy-induced seizure quality. *P < 0.05. A, Onset of action and suppression of twitch height; B, recovery of twitch height.

The time to 90% twitch recovery after succinylcholine was 9.37 ± 3.2 minutes, whereas 100% twitch recovery was obtained after 9.7 ± 3.5 (3–20) minutes (Figure 2). The time to TOF recovery >0.9 was 19.5 ± 5.7 minutes after rocuronium (Table 1).

ECT Parameters, Hemodynamic Variables, and Ancillary Data

No clinically significant differences were identified in the recorded EEG parameters or seizure quality when adequate neuromuscular blockade was obtained with rocuronium instead of succinylcholine. ECT parameters including pulse width, energy, frequency, and duration were similar in both groups (Table 1). No differences in HR, SBP, and DBP data were observed between or within the succinylcholine and rocuronium groups. Nadir Spo2, defined as the lowest recorded periprocedural oxygen saturation, was 94% ± 3% (85–100) and 92% ± 4% (79–99) for rocuronium and succinylcholine, respectively (P > 0.05).

The interrater reliability for the raters was found to be κ = 0.862 (P < 0.001; 95% CI, 0.801–0.923). Duration of motor seizure activity after succinylcholine and rocuronium amounted to 27 ± 14 and 31 ± 11 seconds, respectively (P < 0.001, Table 1).


The findings reported herein indicate that near-complete twitch suppression is required for optimal neuromuscular blockade during ECT. The MED50ECT for succinylcholine and rocuronium was 0.85 mg kg−1 (95% CI, 0.77–0.94) and 0.41 mg kg−1 (95% CI, 0.36–0.46), respectively. The time to achieve acceptable neuromuscular blockade was increased by approximately 2.3 minutes with rocuronium compared with succinylcholine, resulting in a total of approximately 12 minutes increased procedure time.

Minimum Effective Dose of Succinylcholine and Time to Onset of Maximal Effect

Although a single best dose of succinylcholine for ECT has not been identified in the literature, doses between 0.5 and 6 mg kg−1, 0.8 and 1 mg kg−1, and even up to 1.4 mg kg−1 have been recommended on the basis of the anecdotal reports, previous experience of anesthesia providers, or limited clinical studies.5,15–19 The methodologic differences of these observations, interindividual and intraindividual variability, and particularly the lack of objective assessment in most occasions could explain the wide range of the recommended effective doses of succinylcholine for ECT.

The optimal dose of an NMBA is determined not only by its pharmacodynamics but also by its clinical use and the individual patient’s preexisting medical conditions. As an example, the recommended intubating dose for rocuronium is 2 × its adductor pollicis ED95, whereas for rapid sequence intubation, a significantly greater dose of 4 × ED95 is used. Similarly, for an elderly patient with severe osteoporosis, a clinician may choose to start the ECT treatments using a greater dose of NMBA (eg, MED90ECT) to minimize the risk of insufficient neuromuscular blockade, excessive muscle contractions, and potentially bone fractures, whereas in a younger and healthier patient, MED50ECT may be more desirable because of the lower risk for complications from a “suboptimal” muscle relaxation and the benefits of a more rapid recovery from anesthesia and the procedure. The applied initial dose in both examples can then be adjusted in subsequent ECT treatments based on the initial response.

Consistent with the reports from the study by Murali et al.20 and Bryson et al.,21 our data suggest that succinylcholine doses close to 1 mg kg−1 (MED90ECT in this study) may provide acceptable ECT conditions in most patients and also highlight the importance of avoiding early application of ECT after the administration of succinylcholine (<1.4 minutes, time to onset of acceptable neuromuscular blockade), even in the absence of a twitch response to nerve stimulation. This observation also is consistent with the previous finding by Beale et al.22 that the muscle response to ulnar nerve stimulation can be extinguished long before cessation of muscle fasciculation and suggests that the time to onset of adequate relaxation for ECT is longer than the traditional 60 seconds used for rapid sequence intubation (1 mg kg−1of succinylcholine, 3.5 × its adductor pollicis ED95).23–25 This difference in time to obtain acceptable ECT conditions compared with that for endotracheal intubation may be attributed to a difference in sensitivity to succinylcholine in different muscle groups (eg, oropharynx versus extremities) but also can indicate that a deeper neuromuscular blockade is needed for acceptable ECT conditions compared with endotracheal intubation. Kopman et al.26 showed that the onset speed of succinylcholine might be dependent on the rapid plasma clearance such that, in patients with normal plasma cholinesterase activity, after an ED95 dose of succinylcholine, time to peak effect (95% twitch depression) occurs in <2 minutes (109 ± 15 seconds).

The MED90ECT of 1.06 mg kg−1 succinylcholine (≈3.5 × its adductor pollicis ED95) in our study and an induced twitch height suppression of 0% to 4% for acceptable motor seizure modification are in line with the findings by Murali et al.20, who recommended a dose of 1.0 mg kg−1 and twitch suppression to 0% to 5% of baseline. The MED95ECT (1.16 mg kg−1) has also been used in other clinical trials (1.2 mg kg−1).27–30

Duration of Paralysis and Time to Recovery After Succinylcholine

The time required for 90% twitch recovery (9.4 minutes) after succinylcholine in each subject is comparable with the reported recovery time by others after a single dose of 1 mg kg−1 (9.3 minutes).31,32 Similarly, the time required for 100% twitch recovery (9.7 minutes) in our study is similar to that in previously published pharmacokinetic studies of this NMBA (10 minutes after applying the dose of 1.0 mg kg−1).33,34 Accordingly, our data suggest that the seizure-induced release of acetylcholine into the neuromuscular junction does not significantly alter the duration of succinylcholine-induced neuromuscular blockade.

Rocuronium as an Alternative to Succinylcholine During ECT

Rocuronium is used increasingly as an alternative to succinylcholine for neuromuscular blockade during ECT, primarily in the elderly and in patients with cardiovascular and neurologic comorbidities. Immobilized patients and elderly or those who have suffered a stroke are particularly susceptible to succinylcholine-induced hyperkalemia because of depolarization of upregulated nicotinic (neuronal) α-7 acetylcholine receptors.5 Conversely, ECT is highly effective and is increasingly applied in the elderly and those with increased incidence of prolonged immobilization and higher risk of hyperkalemia.5 Nondepolarizing NMBAs do not cause hyperkalemia and can be given to these patients and those with susceptibility to malignant hyperthermia or with contraindications to succinylcholine.

Currently, rocuronium is given as a single bolus of 0.3 to 0.6 mg kg−1 before ECT treatment.5 Our result is consistent with the previous applied doses and provides the estimation of recommended initial doses in the range of 0.36 to 0.6 mg kg−1 (MED50ECT−MED99ECT). Our study also confirms that, in patients with contraindications to the use of succinylcholine,3 the rocuronium–neostigmine combination can provide a safe and relatively time-effective alternative to succinylcholine if appropriately dosed and monitored.

Minimum Effective Dose of Rocuronium and Time to Onset of Maximal Effect

The MED90ECT in our study (0.57 mg kg−1 ≈ 2 × ED95) is comparable with the dose that has been reported to induce >95% block in 98% of subjects.35,36 The time needed to achieve acceptable conditions for ECT is also consistent with previous studies, with a twitch suppression to 10% baseline after 2.9 ± 1.0 minutes and 0% after 3.7 ± 1.0 minutes. The time from NMBA injection to acceptable ECT conditions is hence approximately 2.3 minutes longer with rocuronium compared with succinylcholine. As anesthetics affect the duration of the ECT-induced convulsions, clinicians should consider this difference in time from anesthesia induction to ECT application with rocuronium versus succinylcholine and adjust the dose and timing of their hypnotic agents accordingly.

Duration of Paralysis and Time to Recovery After Rocuronium

Bevan et al.37 reported the time to 90% recovery of the first twitch (T1 90) to be >10 minutes. Consistent with their data, our study showed that a twitch value of 90% was obtained 12 minutes after rocuronium was administered; however, in the former study, the TOF ratio of 0.9 (indicating the average recovery time for induced acceptable neuromuscular blockade) was achieved 28 minutes after rocuronium-induced paralysis (0.45 mg kg−1), whereas it was recorded after only 19.5 minutes in this study. This time is also shorter than the recovery time reported by Wierda et al.38 (0.4 mg kg−1 rocuronium), but it is comparable with a recovery time of 19.4 ± 5.1 minutes reported by Lederer et al.,39 who applied 0.05 mg kg−1 neostigmine 5 minutes after injection of 0.4 mg kg−1 rocuronium.

Similarly, the observed recovery times after 0.5 to 0.6 mg kg−1 rocuronium for some subjects to achieve acceptable induced seizure activity in our study were shorter than what has been reported after a comparable dose in procedures other than ECT.40,41 This observed difference may imply that during induced convulsions, the release of acetylcholine into the neuromuscular junction may reduce the duration of the induced neuromuscular blockade from rocuronium.

In line with our findings, in an ECT study by Turkkal et al.,42 the reported recovery time for the tongue depressor test was 15 ± 2 minutes after a single dose of 0.3 mg kg−1 rocuronium and after reversal with 20 μg kg−1 of neostigmine. Of note, the tongue depressor test is considered a sensitive and practical bedside test to assess the recovery from neuromuscular blockade, and it is reported to correspond with a TOF ratio recovery to 0.8.43 These observations may indicate that the recovery time is dependent not only on the applied dose and the time at which reversal agent is given but also dependent possibly on the quality and vigor of the induced seizures. Regardless of these observations, it is prudent to use standard neuromuscular reversal criteria and monitoring before allowing the patient to emerge from anesthesia.

ECT Quality and Seizure Duration After Rocuronium Versus Succinylcholine

By using subjective tools to assess the recovery from neuromuscular blockade and as stated earlier, Turkkal et al.42 reported that motor seizure duration was greater after 0.3 mg kg−1 rocuronium compared with 1 mg kg−1 succinylcholine (33 and 24 seconds, respectively). Similarly, Hoshi et al.44 reported longer duration of seizure with rocuronium compared with succinylcholine. Our data are consistent with these previously published studies confirming a small difference in seizure duration, which may be attributed to a decline in propofol-induced EEG suppression45 after rocuronium associated with the 2-minute delay in achieving appropriate muscle relaxation. Because there is an association between clinical effectiveness of ECT and the duration of induced seizure,46 the American Psychiatric Association task force advocates seizure lengths >20 seconds for effective ECT outcome.47 This recommendation underscores the importance of titrating the dose of the NMBA to achieve an adequate neuromuscular blockade. EEG monitoring is also recommended for induced seizure monitoring,48 particularly in patients who might need greater doses of an NMBA to achieve acceptable modified seizure. Further studies are needed to assess the therapeutic effects of the cumulative seizure time in a series of ECTs using optimal doses of these NMBAs.


In a single-dose approach, an initial MED50ECT dose of each NMBA can be considered if a 50% risk of providing suboptimal relaxation as defined in this study (Table 2) is clinically acceptable. If there are clinical concerns that our definition of adequate neuromuscular blockade is insufficient for a specific patient (eg, in an elderly patient with severe osteoporosis), clinicians should instead consider an initial greater dose of each NMBA, such as an MED90ECT dose of succinylcholine at 1 mg kg−1, or rocuronium at 0.57 mg kg−1 to provide controlled seizure activity during ECT. Subsequent adjustments may be needed to further optimize the ECT response with the minimal dose of either NMBA. Accordingly, the presented data suggest that an initial succinylcholine dose of 0.85 mg kg−1 is reasonable for the first ECT session in most patients, with dose adjustments in 0.1 to 0.2 mg kg−1 increments or decrements, based on the quality of the observed motor seizure activity for each individual during subsequent treatments. As an alternative, and if clinically indicated, we suggest a 0.4 mg kg−1 bolus of rocuronium as the initial dose of the applied NMBA in healthier patients without osteoporosis. ECT should be applied after a twitch suppression of >90% is documented or, if twitch monitoring is not available, after sufficient time has been provided to ensure >90% peak effect from the administered rocuronium (ie, 3 minutes).

If excessive or insufficient neuromuscular blockade is noticed during the induced seizure, dose adjustment with 0.05 to 0.1 mg kg−1 decrements or increments is advisable. After the treatment, the rocuronium-induced neuromuscular blockade should be reversed in the regular fashion with neostigmine (50 μg kg−1). Quantitative neuromuscular transmission (NMT) monitoring should be used to evaluate adequate suppression of neuromuscular blockade, and to ensure sufficient recovery of the induced neuromuscular blockade, to minimize the risk for adverse respiratory events.5,49 Clinicians should ensure that all patients remain under close observation by appropriately trained personnel and should continue to monitor the neuromuscular function until complete recovery of the neuromuscular transmission has been verified (eg, tongue depressor test).43

A limitation of this study was our inability to completely blind the seizure quality assessors to the type of NMBA, because we could not mask the fasciculations (if significant) after succinylcholine. Moreover, this study does not systematically explore a single optimal dose for each NMBA that requires several further treatment sessions of each subject and a notably larger sample size to apply the identified MED for capturing the intrasubject variability of response to neuromuscular blockers. In general, using >1 crossover could be a better approach for defining the optimal doses of NMBAs for each patient and for determining its variability for any given patient or population.

In summary, the presented data show that a twitch suppression of >90% is required for acceptable neuromuscular blockade during ECT. The time to achieve acceptable neuromuscular blockade is increased by approximately 2.3 minutes when rocuronium is used instead of succinylcholine, resulting in an average of 12 minutes increased procedure time. When appropriately dosed and monitored, rocuronium can be a safe alternative NMBA for ECT in patients with contraindications to succinylcholine.


Name: Hooman Mirzakhani, MD, PhD, MMSc.

Contribution: This author helped design the study, conduct the study, analyze the data, and write the manuscript.

Conflicts of Interest: This author has no conflicts of interest.

Name: Henk-Jan Guchelaar, PharmD, PhD.

Contribution: This author helped write the manuscript.

Conflicts of Interest: This author has no conflicts of interest.

Name: Charles A. Welch, MD.

Contribution: This author helped conduct the study.

Conflicts of Interest: This author has no conflicts of interest.

Name: Cristina Cusin, MD.

Contribution: This author helped conduct the study and write the manuscript.

Conflicts of Interest: This author has no conflicts of interest.

Name: Mary E. Doran, NP.

Contribution: This author helped conduct the study.

Conflicts of Interest: This author has no conflicts of interest.

Name: Teresa O. MacDonald, RN.

Contribution: This author helped conduct the study.

Conflicts of Interest: This author has no conflicts of interest.

Name: Edward A. Bittner, MD, PhD.

Contribution: This author helped analyze the data.

Conflicts of Interest: This author has no conflicts of interest.

Name: Matthias Eikermann, MD, PhD.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Conflicts of Interest: Matthias Eikermann holds equity shares of Calabash Bioscience Inc., and received funding for research from MERCK.

Name: Ala Nozari, MD, PhD.

Contribution: This author helped design the study, conduct the study, and write the manuscript.

Conflicts of Interest: This author has no conflicts of interest.

This manuscript was handled by: Peter Glass, MB ChB, FFA(SA).


The authors thank all patients who participated in this study as well as Drs. Robert J. Glynn, Edward George, William J. Benedetto, Jonathan Charnin, and Sadeq Quraishi and all the postanesthesia care unit staff of the Massachusetts General Hospital for their valuable assistance and contribution during the study.


1. Rasmussen K. The practice of electroconvulsive therapy: recommendations for treatment, training, and privileging (second edition). J ECT 2002;18:589.
2. Wilkins KM, Ostroff R, Tampi RR. Efficacy of electroconvulsive therapy in the treatment of nondepressed psychiatric illness in elderly patients: a review of the literature. J Geriatr Psychiatry Neurol 2008;21:311.
3. Ding Z, White PF. Anesthesia for electroconvulsive therapy. Anesth Analg 2002;94:135164.
4. Booij LH. Is succinylcholine appropriate or obsolete in the intensive care unit? Crit Care 2001;5:2456.
5. Mirzakhani H, Welch CA, Eikermann M, Nozari A. Neuromuscular blocking agents for electroconvulsive therapy: a systematic review. Acta Anaesthesiol Scand 2012;56:316.
6. Kopman AF, Eikermann M. Antagonism of non-depolarising neuromuscular block: current practice. Anaesthesia 2009;64(Suppl 1):2230.
7. Viby-Mogensen J. Clinical assessment of neuromuscular transmission. Br J Anaesth 1982;54:20923.
8. Fuchs-Buder T, Claudius C, Skovgaard LT, Eriksson LI, Mirakhur RK, Viby-Mogensen J; 8th International Neuromuscular Meeting. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand 2007;51:789808.
9. Barash PG, Cullen BF, Stoelting RK, Cahalan MK, Stock MC. Clinical Anesthesia. 20096th ed. Philadelphia: Lippincott Williams & Wilkins, .
10. Kopman AF, Lien CA, Naguib M. Neuromuscular dose-response studies: determining sample size. Br J Anaesth 2011;106:1948.
11. Pace NL, Stylianou MP. Advances in and limitations of up-and-down methodology: a précis of clinical use, study design, and dose estimation in anesthesia research. Anesthesiology 2007;107:14452.
12. Zhou XH, Gao S, Hui SL. Methods for comparing the means of two independent log-normal samples. Biometrics 1997;53:112935.
13. Wellek S, Blettner M. On the proper use of the crossover design in clinical trials: part 18 of a series on evaluation of scientific publications. Dtsch Arztebl Int 2012;109:27681.
14. Efron B, Tibshirani R. Bootstrap methods for standard errors, confidence intervals, and other measures of statistical accuracy. Stat Sci 1986:5475.
15. Konarzewski WH, Milosavljevic D, Robinson M, Banham W, Beales F. Suxamethonium dosage in electroconvulsive therapy. Anaesthesia 1988;43:4746.
16. Fredman B, Smith I, d’Etienne J, White PF. Use of muscle relaxants for electroconvulsive therapy: how much is enough? Anesth Analg 1994;78:1956.
17. Gaines GY III, Rees DI. Electroconvulsive therapy and anesthetic considerations. Anesth Analg 1986;65:134556.
18. Pitts FN Jr, Woodruff RA Jr, Craig AG, Rich CL. The drug modification of ECT. II. Succinylcholine dosage. Arch Gen Psychiatry 1968;19:5959.
19. Cheam EW, Critchley LA, Chui PT, Yap JC, Ha VW. Low dose mivacurium is less effective than succinylcholine in electroconvulsive therapy. Can J Anaesth 1999;46:4951.
20. Murali N, Saravanan ES, Ramesh VJ, Gangadhar BN, Jananakiramiah N, Kumar SS, Christopher R, Subbakrishna DK. An intrasubject comparison of two doses of succinylcholine in modified electroconvulsive therapy. Anesth Analg 1999;89:13014.
21. Bryson EO, Aloysi AS, Popeo DM, Bodian CA, Pasculli RM, Briggs MC, Kellner CH. Methohexital and succinylcholine dosing for electroconvulsive therapy (ECT): actual versus ideal. J ECT 2012;28:e2930.
22. Beale MD, Kellner CH, Lemert R, Pritchett JT, Bernstein HJ, Burns CM, Duc T, Roy R. Skeletal muscle relaxation in patients undergoing electroconvulsive therapy. Anesthesiology 1994;80:957.
23. Ferguson A, Bevan DR. Mixed neuromuscular block: the effect of precurarization. Anaesthesia 1981;36:6616.
24. Mehta MP, Sokoll MD, Gergis SD. Accelerated onset of non-depolarizing neuromuscular blocking drugs: pancuronium, atracurium and vecuronium. A comparison with succinylcholine. Eur J Anaesthesiol 1988;5:1521.
25. Curran MJ, Donati F, Bevan DR. Onset and recovery of atracurium and suxamethonium-induced neuromuscular blockade with simultaneous train-of-four and single twitch stimulation. Br J Anaesth 1987;59:98994.
26. Kopman AF, Klewicka MM, Kopman DJ, Neuman GG. Molar potency is predictive of the speed of onset of neuromuscular block for agents of intermediate, short, and ultrashort duration. Anesthesiology 1999;90:42531.
27. Avramov MN, Stool LA, White PF, Husain MM. Effects of nicardipine and labetalol on the acute hemodynamic response to electroconvulsive therapy. J Clin Anesth 1998;10:394400.
28. Recart A, Rawal S, White PF, Byerly S, Thornton L. The effect of remifentanil on seizure duration and acute hemodynamic responses to electroconvulsive therapy. Anesth Analg 2003;96:104750.
29. Yoshino Y, Ozaki Y, Kawasoe K, Ochi S, Niiya T, Sonobe N, Matsumoto T, Ueno S. Combined clozapine and electroconvulsive therapy in a Japanese schizophrenia patient: a case report. Clin Psychopharmacol Neurosci 2014;12:1602.
30. Avramov MN, Husain MM, White PF. The comparative effects of methohexital, propofol, and etomidate for electroconvulsive therapy. Anesth Analg 1995;81:596602.
31. Kopman AF, Zhaku B, Lai KS. The “intubating dose” of succinylcholine: the effect of decreasing doses on recovery time. Anesthesiology 2003;99:10504.
32. Viby-Mogensen J. Correlation of succinylcholine duration of action with plasma cholinesterase activity in subjects with the genotypically normal enzyme. Anesthesiology 1980;53:51720.
33. Durant NN, Katz RL. Suxamethonium. Br J Anaesth 1982;54:195208.
34. Vanlinthout LE, van Egmond J, de Boo T, Lerou JG, Wevers RA, Booij LH. Factors affecting magnitude and time course of neuromuscular block produced by suxamethonium. Br J Anaesth 1992;69:2935.
35. Kopman AF, Klewicka MM, Neuman GG. Reexamined: the recommended endotracheal intubating dose for nondepolarizing neuromuscular blockers of rapid onset. Anesth Analg 2001;93:9549.
36. Meistelman C, Plaud B, Donati F. Rocuronium (ORG 9426) neuromuscular blockade at the adductor muscles of the larynx and adductor pollicis in humans. Can J Anaesth 1992;39:6659.
37. Bevan JC, Collins L, Fowler C, Kahwaji R, Rosen HD, Smith MF, de Scheepers LD, Stephenson CA, Bevan DR. Early and late reversal of rocuronium and vecuronium with neostigmine in adults and children. Anesth Analg 1999;89:3339.
38. Wierda JM, Beaufort AM, Kleef UW, Smeulers NJ, Agoston S. Preliminary investigations of the clinical pharmacology of three short-acting non-depolarizing neuromuscular blocking agents, Org 9453, Org 9489 and Org 9487. Can J Anaesth 1994;41:21320.
39. Lederer W, Reiner T, Khuenl-Brady KS. Neostigmine injected 5 minutes after low-dose rocuronium accelerates the recovery of neuromuscular function. J Clin Anesth 2010;22:4204.
40. Cooper RA, Mirakhur RK, Maddineni VR. Neuromuscular effects of rocuronium bromide (Org 9426) during fentanyl and halothane anaesthesia. Anaesthesia 1993;48:1035.
41. Schultz P, Ibsen M, Østergaard D, Skovgaard LT. Onset and duration of action of rocuronium–from tracheal intubation, through intense block to complete recovery. Acta Anaesthesiol Scand 2001;45:6127.
42. Turkkal DC, Gokmen N, Yildiz A, Iyilikci L, Gokel E, Sagduyu K, Gunerli A. A cross-over, post-electroconvulsive therapy comparison of clinical recovery from rocuronium versus succinylcholine. J Clin Anesth 2008;20:58993.
43. Kopman AF, Yee PS, Neuman GG. Relationship of the train-of-four fade ratio to clinical signs and symptoms of residual paralysis in awake volunteers. Anesthesiology 1997;86:76571.
44. Hoshi H, Kadoi Y, Kamiyama J, Nishida A, Saito H, Taguchi M, Saito S. Use of rocuronium-sugammadex, an alternative to succinylcholine, as a muscle relaxant during electroconvulsive therapy. J Anesth 2011;25:28690.
45. San-juan D, Chiappa KH, Cole AJ. Propofol and the electroencephalogram. Clin Neurophysiol 2010;121:9981006.
46. Lalla FR, Milroy T. The current status of seizure duration in the practice of electroconvulsive therapy. Can J Psychiatry 1996;41:299304.
47. American Psychiatric Association. The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training and Privileging: A Task Force Report. 2001Washington (DC): American Psychiatric Association Press, .
48. Girish K, Gangadhar BN, Janakiramaiah N. Merits of EEG monitoring during ECT: a prospective study on 485 patients. Indian J Psychiatry 2002;44:248.
49. Brull SJ, Naguib M. What we know: precise measurement leads to patient comfort and safety. Anesthesiology 2011;115:91820.

Supplemental Digital Content

Copyright © 2016 International Anesthesia Research Society