Optimal Dose of Succinylcholine and Rocuronium for Electroconvulsive Therapy (ECT)

Optimal Control of Muscle Strength for Electroconvulsive Therapy: A Comparison of Succinylcholine Versus Rocuronium-induced Neuromuscular Blockade

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.

Study Overview

• Status: Completed
• Conditions: Neuromuscular Blockade; ECT
• Intervention / Treatment: Drug: Succinylcholine; Drug: Rocuronium

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Succinylcholine first, then Rocuronium; Cross-over randomized controlled, assessor blinded clinical trial.	Drug: Succinylcholine; 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'.; Other Names: Suxamethonium; Drug: Rocuronium; 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.
Experimental: Rocuronium first, then succinylcholine; Cross-over randomized controlled, assessor blinded clinical trial.	Drug: Succinylcholine; 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'.; Other Names: Suxamethonium; Drug: Rocuronium; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to six weeks following inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to six weeks following inclusion
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.	Up to six weeks following inclusion

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Matthias Eikermann, MD, PhD, Massachusetts General Hospital; Principal Investigator: Ala Nozari, MD, PhD, Mass. General Hospital

Publications and helpful links

General Publications

• 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 Jan;46(1):49-51. doi: 10.1007/BF03012514.
• 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 Dec;20(8):589-93. doi: 10.1016/j.jclinane.2008.06.006.
• Wagner KJ, Mollenberg O, Rentrop M, Werner C, Kochs EF. Guide to anaesthetic selection for electroconvulsive therapy. CNS Drugs. 2005;19(9):745-58. doi: 10.2165/00023210-200519090-00002.
• Eikermann M, Hunkemoller I, Peine L, Armbruster W, Stegen B, Husing J, Peters J. Optimal rocuronium dose for intubation during inhalation induction with sevoflurane in children. Br J Anaesth. 2002 Aug;89(2):277-81. doi: 10.1093/bja/aef177.
• Miguel RV, Soto R, Dyches P. A double-blind, randomized comparison of low-dose rocuronium and atracurium in a desflurane anesthetic. J Clin Anesth. 2001 Aug;13(5):325-9. doi: 10.1016/s0952-8180(01)00282-3.
• Reynolds LM, Lau M, Brown R, Luks A, Fisher DM. Intramuscular rocuronium in infants and children. Dose-ranging and tracheal intubating conditions. Anesthesiology. 1996 Aug;85(2):231-9. doi: 10.1097/00000542-199608000-00002.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): July 1, 2013
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: September 20, 2011
• First Submitted That Met QC Criteria: September 26, 2011
• First Posted (Estimate): September 28, 2011

Study Record Updates

• Last Update Posted (Estimate): June 2, 2015
• Last Update Submitted That Met QC Criteria: June 1, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: ECT; Rocuronium; Succinylcholine
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Neuromuscular Agents; Neuromuscular Nondepolarizing Agents; Neuromuscular Blocking Agents; Neuromuscular Depolarizing Agents; Rocuronium; Succinylcholine
• Other Study ID Numbers: 2010P001154