Letters to the Editor: Letter to the Editor
To the Editor
We read with interest the recent recommendations of Mirzakhani et al1 on the minimum effective doses of muscle relaxants to abet electroconvulsive therapy. The authors have attempted to answer the question “how much is enough.” We think, however, that their conclusions must be read with considerable caution for the following reasons:
- The modification of the up and down method employed by the authors in acquiring data points within subjects has not been validated. Each patient received approximately 3 treatments with succinylcholine and 3 with rocuronium (187 treatments in 31 patients). In the Dixon’s up and down method,2,3 the sequence of eliciting positive and negative responses is repeated several times to estimate the mean and the standard error of the ED50 for each subject. The precision of the estimate is directly proportional to the sample size within each subject. Is it likely that a total of only 6 test doses will define the “optimal” dose for both drugs?
- The authors suggest that a rocuronium dose of 0.41 mg/kg (95% confidence limits [CL], 0.36–0.46 mg/kg) will result inadequate relaxation in 1 of 2 patients and that a dose of 0.57 mg/kg (95% CL, 0.51–0.61 mg/kg) will still produce unsatisfactory conditions 10% of the time. We find it highly unlikely that an “intubating dose” of rocuronium will fail to produce adequate conditions for electroconvulsive therapy in 1 of 10 subjects. Clearly, further clinical confirmation from other investigators would be highly desirable.
- The recovery times to a train-of-four ratio of 0.90 after rocuronium (19.5 ± 5.7 [standard deviation] minutes) that the authors report also need to be viewed with some skepticism. It is difficult to reconcile their observations with much of the published literature. The clinical duration (time to 25% T1 recovery) of 0.60 mg/kg rocuronium averages over 30 minutes under total intravenous anesthesia or N2O–opioid anesthesia (Table). At this level of spontaneous recovery (a train-of-four count of approximately 3), rapid antagonism of nondepolarizing residual block with neostigmine cannot be guaranteed.13–15 Available data suggest that it would be surprising if the time to satisfactory recovery after neostigmine reversal of rocuronium 0.60 mg/kg will be <35 to 40 minutes.
- It should be noted that the authors’ proposals were based on the criteria and observations of only 2 psychiatrists. Other clinicians may have different standards as to what constitutes an adequately modified seizure. A still unanswered question is what degree of neuromuscular block is required to prevent traumatic injury from an induced seizure. A seizure may appear quite vigorous yet still be sufficiently modified to be safe.
Given our concerns regarding the authors’ methodology and the disparity between their reported recovery times with the great majority of published data regarding the duration of action of rocuronium, we question the clinical utility and safety of their recommendations.
Aaron F. Kopman, MD19970 Sawgrass LaneUnit 4102Boca Raton, Floridaakopman@gmail.com
Mohamed Naguib, MB, BCh, MSc, FCARCSI, MDDepartment of General AnesthesiaAnesthesiology InstituteCleveland ClinicCleveland, Ohio
1. Mirzakhani H, Guchelaar HJ, Welch CA, et al. Minimum effective doses of succinylcholine and rocuronium during electroconvulsive therapy: a prospective, randomized, crossover trial. Anesth Analg. 2016;123:587596.
2. Dixon WJ, Mood AM. A method for obtaining and analyzing sensitivity data. J Am Stat Assoc. 1948;43:109126.
3. Dixon WJ. The up-and-down method for small samples. J Am Stat Assoc. 1965;60:967978.
4. Pino RM, Ali HH, Denman WT, Barrett PS, Schwartz A. A comparison of the intubation conditions between mivacurium and rocuronium during balanced anesthesia. Anesthesiology. 1998;88:673678.
5. Stout RG, Gan TJ, Glass PS, Silverman DG, Brull SJ. The effect of desflurane on rocuronium onset, clinical duration and maintenance requirements. Acta Anaesthesiol Belg. 2006;57:349353.
6. Wang T, Huang S, Geng G. Comparison of the duration of neuromuscular blockade following a single bolus dose of rocuronium during laparoscopic gynaecological surgery vs conventional open surgery. Anaesthesia. 2014;69:854859.
7. Cooper RA, Mirakhur RK, Maddineni VR. Neuromuscular effects of rocuronium bromide (Org 9426) during fentanyl and halothane anaesthesia. Anaesthesia. 1993;48:103105.
8. Maddineni VR, McCoy EP, Mirakur RK, McBride RJ. Onset and duration of action and hemodynamic effects of rocuronium bromide under balanced and volatile anesthesia. Acta Anaesthesiol Belg. 1994;45:4147.
9. Naguib M. Neuromuscular effects of rocuronium bromide and mivacurium chloride administered alone and in combination. Anesthesiology. 1994;81:388395.
10. Foldes FF, Nagashima H, Nguyen HD, Schiller WS, Mason MM, Ohta Y. The neuromuscular effects of ORG9426 in patients receiving balanced anesthesia. Anesthesiology. 1991;75:191196.
11. 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;22:420424.
12. Wright PM, Caldwell JE, Miller RD. Onset and duration of rocuronium and succinylcholine at the adductor pollicis and laryngeal adductor muscles in anesthetized humans. Anesthesiology. 1994;81:11101115.
13. Kim KS, Cheong MA, Lee HJ, Lee JM. Tactile assessment for the reversibility of rocuronium-induced neuromuscular blockade during propofol or sevoflurane anesthesia. Anesth Analg. 2004;99:10801085.
14. McCourt KC, Mirakhur RK, Kerr CM. Dosage of neostigmine for reversal of rocuronium block from two levels of spontaneous recovery. Anaesthesia. 1999;54:651655.
15. Kirkegaard H, Heier T, Caldwell JE. Efficacy of tactile-guided reversal from cisatracurium-induced neuromuscular block. Anesthesiology. 2002;96:4550.