ECT, Neuromuscular Blockade
Conditions
Keywords
Succinylcholine, Rocuronium, ECT
Brief summary
Electroconvulsive therapy (ECT) is the transcutaneous application of small electrical stimuli to the brain to produce generalized seizures for the treatment of selected psychiatric disorders such as severe depression. The aim of ECT is to induce a therapeutic tonic seizure where the person loses consciousness and has convulsions. Patients need general anesthesia and neuromuscular blockade to treat pain and avoid excessive tonic clonic motor contraction that might be associated with compression fractures. Neuromuscular blocking drugs (NMBD) are, therefore, administered after induction of general anesthesia to induce neuromuscular blockade. Despite the importance of NMBDs to provide optimal conditions for ECT treatment, the optimal NMBD dose to achieve acceptable neuromuscular blockade without excessive or untoward effects has not previously been identified in any study and in a prospective randomized fashion. The aim of this study is, therefore, to identify the optimal NMBD dose of two commonly used neuromuscular blocking agents (succinylcholine and rocuronium) in order to optimize the muscle strength modulation during ECT that facilitates ECT with the minimal side effects.
Detailed description
Patients, who consent to participate in the study, will randomly receive either succinylcholine or rocuronium by utilizing the Dixon's up and down technique. For patient safety, the first dose of either agent will be defined by the anesthesiologist providing care, and subsequent doses will be incrementally increased or decreased by 10% based on the assessment of a psychiatrist blinded to dose, who uses a dichotomous scale to assess the quality of the ECT (acceptable and not acceptable). The investigators will switch to the second compound as soon as the patient has received one neuromuscular blocking agent dose that resulted in 'acceptable muscle relaxation', and another dose that resulted in 'unacceptable' conditions'. Acceleromyography will be used for monitoring neuromuscular transmission. Following induction of general anesthesia, the TOF-Watch SX will be calibrated (mode 1, 50 mA), and train-of-four (TOF) stimulation (every 15 seconds) will be initiated and maintained until recovery of the T1 to 100% baseline. Non-invasive blood pressure, heart rate, peripheral oxygen saturation (SpO2), and time to recovery of spontaneous breathing will be measured during the procedure. In addition the investigators will measure stimulation parameters used to initiate ECT, as well as the duration of seizure as well as the entire procedure time.
Interventions
DRUGSuccinylcholine
Succinylcholine will be given during the series of ECT treatments. The initial dose will be defined by the anesthesiologist in charge for clinical care. The Dixon's up and down method will be used in consecutive treatments. The investigators will switch to the second compound as soon as the patient has received one neuromuscular blocking agent dose that resulted in 'acceptable muscle relaxation', and another dose that resulted in 'unacceptable' conditions'.
DRUGRocuronium
Rocuronium will be given during the series of ECT treatments. The initial dose will be defined by the anesthesiologist in charge for clinical care. The Dixon's up and down method will be used in consecutive treatments.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Adult patients (age 18-80) scheduled for ECT treatment at the MGH
Exclusion criteria
* Contraindication to the use of neuromuscular blocking drugs (e.g. allergy, preexisting muscular disease, and history of malignant hyperthermia) * Malnutrition, general weakness * Neurological or neuromuscular disease, including paralysis * Liver disease with liver function test 2x greater than upper normal limit * Kidney disease with eGFR\<60 * Electrolyte abnormalities with values outside of the normal range * Pregnancy * Cardiac disease or abnormal EKG * Medications that affect seizure threshold or blood pressure response * Unwilling to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Optimal Dose of Neuromuscular Blocking Agent During ECT | Up to six weeks following inclusion | The optimal dose of muscle neuromuscular blocking is defined as the lowest dose of either compound that predicts 'acceptable' control of muscle strength during ECT. Assessment of the primary end point is based on a dichotomous scale 'acceptable' and 'not acceptable' control of muscle strength during ECT, and the two assessors will be blinded to the dose of neuromuscular blocking agent. The optimal dose was identified for each subject, and results were reported as the average of all lowest doses collected in the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Compound Specific Differences in Time to Recovery From Neuromuscular Blockade | Up to six weeks following inclusion | The investigators defined the compound specific differences in time to recovery from neuromuscular blockade - i.e., recovery of spontaneous breathing and recovery of the twitch height to baseline. |
| Differences in Seizure Duration Between Compounds | Up to six weeks following inclusion | Observational reports suggest that differences in seizure duration might exist depending on the neuromuscular blocking agents used to accomplish muscle strength control during ECT. |
Countries
United States
Participant flow
Recruitment details
45 hospitalized patients aged 24-80 admitted for a series of ECT treatments at a frequency of 3/week were enrolled. 14 were excluded (1 received rocuronium in error, 1 received succinylcholine in error, 1 withdrew consent, 2 did not complete series of ECT, and in 9 twitch monitoring problems resulted in non-captured or disqualified data.
Pre-assignment details
Patients were randomized to either succinylcholine or rocuronium during their first ECT. During each subsequent ECT ( 2 days apart) patients received a 10% higher (if insufficient paralysis) or lower dose (if sufficient or excessive paralysis) until the minimum effective dose was identified. Then the second NMBA was tested for subsequent ECTs.
Participants by arm
| Arm | Count |
|---|---|
| Succinylcholine and Rocuronium All study participants | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Neuromuscular Blocking Agent: | Protocol Violation | 1 | 1 |
| First Neuromuscular Blocking Agent: | Technical error or incomplete ECT series | 6 | 5 |
| First Neuromuscular Blocking Agent: | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Succinylcholine and Rocuronium |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants |
| Age, Continuous | 52 Years STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 45 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 45 | 0 / 45 |
| serious Total, serious adverse events | 0 / 45 | 0 / 45 |
Outcome results
Primary
Optimal Dose of Neuromuscular Blocking Agent During ECT
The optimal dose of muscle neuromuscular blocking is defined as the lowest dose of either compound that predicts 'acceptable' control of muscle strength during ECT. Assessment of the primary end point is based on a dichotomous scale 'acceptable' and 'not acceptable' control of muscle strength during ECT, and the two assessors will be blinded to the dose of neuromuscular blocking agent. The optimal dose was identified for each subject, and results were reported as the average of all lowest doses collected in the study.
Time frame: Up to six weeks following inclusion
| Arm | Measure | Value (MEAN) |
|---|---|---|
| NMBA: Sux | Optimal Dose of Neuromuscular Blocking Agent During ECT | 0.85 mg.kg-1 |
| NMBA- Rocuronium | Optimal Dose of Neuromuscular Blocking Agent During ECT | 0.41 mg.kg-1 |
Secondary
Compound Specific Differences in Time to Recovery From Neuromuscular Blockade
The investigators defined the compound specific differences in time to recovery from neuromuscular blockade - i.e., recovery of spontaneous breathing and recovery of the twitch height to baseline.
Time frame: Up to six weeks following inclusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NMBA: Sux | Compound Specific Differences in Time to Recovery From Neuromuscular Blockade | 9.7 minutes | Standard Deviation 3.5 |
| NMBA- Rocuronium | Compound Specific Differences in Time to Recovery From Neuromuscular Blockade | 19.5 minutes | Standard Deviation 5.7 |
Secondary
Differences in Seizure Duration Between Compounds
Observational reports suggest that differences in seizure duration might exist depending on the neuromuscular blocking agents used to accomplish muscle strength control during ECT.
Time frame: Up to six weeks following inclusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NMBA: Sux | Differences in Seizure Duration Between Compounds | 27 Seconds | Standard Deviation 14 |
| NMBA- Rocuronium | Differences in Seizure Duration Between Compounds | 31 Seconds | Standard Deviation 11 |