Anesth Analg 2003;96:1047-1050
© 2003 International Anesthesia Research Society
ANESTHETIC PHARMACOLOGY
The Effect of Remifentanil on Seizure Duration and Acute Hemodynamic Responses to Electroconvulsive Therapy
Alejandro Recart, MD*,
Shivani Rawal, MD*,
Paul F. White, MD PhD, FANZCA*,
Stephanie Byerly, MD*, and
Larry Thornton, MD
Departments of *Anesthesiology and Pain Management and
Psychiatry, University of Texas Southwestern Medical Center at Dallas, Texas
Address correspondence and reprint requests to Paul F. White, PhD, MD, FANZCA, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., F2.208, Dallas, TX 75390-9068. Address e-mail to paul.white{at}utsouthwestern.edu
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Abstract
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We designed this prospective, randomized, double-blinded, placebo-controlled, crossover study to evaluate the effect of different doses of remifentanil on the acute hemodynamic response and duration of seizure activity after a standardized electroconvulsive therapy (ECT) stimulus. Twenty consenting patients with major depressive disorders receiving maintenance ECT participated in this study. Eighty ECT treatments were evaluated. All patients were premedicated with glycopyrrolate 0.2 mg IV, unconsciousness was induced with methohexital 1 mg/kg IV, and muscle paralysis was produced with succinylcholine 1.2 mg/kg IV. Subsequently, patients received 1 of 3 different doses of remifentanil 25, 50, and 100 µg or saline (control) in a random sequence immediately after methohexital at 4 consecutive ECT treatments. Labetalol, in 5-mg IV boluses, was used as a rescue antihypertensive medication. A fixed suprathreshold electrical stimulus was administered to elicit a seizure, and the times from the stimulus to the cessation of the motor and electroencephalographic (EEG) seizure activity were noted. Pre- and post-ECT blood pressure values were significantly decreased in the 100-µg remifentanil group compared with the control group. The durations of motor (38 ± 9 s to 43 ± 15 s) and EEG (55 ± 29 s to 60 ± 21 s) seizure activity were not significantly different among the four groups. Similarly, recovery times to eye opening, obeying commands, and discharge from the recovery room did not differ among the four study groups. The requirement for labetalol after ECT was nonsignificantly decreased in the remifentanil groups. In conclusion, remifentanil 100 µg IV attenuated the acute hemodynamic response to ECT. Furthermore, remifentanil had no adverse effect on the duration of ECT-induced seizure activity. Finally, adjunctive use of remifentanil did not prolong recovery times or increase post-ECT side effects.
IMPLICATIONS: Remifentanil (100 µg IV) attenuated the acute hemodynamic response after electroconvulsive therapy (ECT) without adversely affecting the length of the ECT-induced seizure activity or prolonging recovery times.
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Introduction
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Electroconvulsive therapy (ECT) is often associated with transient hypertension and tachycardia immediately after the electrical stimulus. These acute hyperdynamic responses may produce serious complications in elderly patients undergoing ECT (1). As a result of the cardiovascular morbidity associated with ECT (2,3) , a wide variety of drugs have been administered in an effort to minimize the acute hemodynamic changes (2). Studies involving trimethaphan (4), nitroprusside (5), nitroglycerine (6), alfentanil (7), clonidine (8),1 propranolol (9),1 esmolol (10), labetalol (11–13) , nicardipine (13), urapidil (14), dexmedetomidine (15), and diltiazem (16) have reported varying degrees of success in attenuating the acute hyperdynamic response associated with ECT.
Remifentanil (Ultiva®) is a potent short-acting opioid analgesic that has been found to reduce blood pressure and heart rate (HR) when administered as an adjuvant during general anesthesia (17). Recently, the administration of remifentanil (1 µg/kg IV) in combination with methohexital was reported to increase the duration of seizure activity in elderly patients undergoing ECT (18). However, the effect of remifentanil in prolonging the duration of ECT-induced seizure activity was not evaluated in the presence of a standardized dose of the hypnotic drug. Furthermore, these investigations failed to assess the effect of remifentanil on the acute hemodynamic response to ECT.
We hypothesized that remifentanil would attenuate the transient hyperdynamic response to ECT in a dose-dependent fashion without interfering with the seizure activity. Therefore, we designed a prospective, randomized, placebo-controlled, crossover study to assess the effects of three different bolus doses of remifentanil (versus saline) on the acute hemody-namic response and the durations of motor and electroencephalographic (EEG) seizure activity in patients undergoing a series of ECT treatments.
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Methods
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After IRB approval at the University of Texas Southwestern Medical Center at Dallas, informed consent was obtained from 20 patients undergoing ECT treatments for chronic depression. Patients with clinically significant cardiovascular, respiratory, or hepatic disease or with a history of adverse reactions to any of the study medications were excluded from the study. Each patient received 1 of 3 different doses of remifentanil (25, 50, or 100 µg) or a placebo (saline) after the induction of anesthesia, according to a randomized, double-blinded, crossover study design. Noninvasive systolic blood pressure (SBP) and mean arterial blood pressure (MAP), HR, and oxygen saturation values were recorded before any medications were administered (i.e., baseline values) and at 1-min intervals for 10 min, then subsequently at 12, 15, 20, and 25 min after each ECT treatment. The study patients received all 4 treatments with the same general anesthetic technique at intervals of 2 days to 2 wk between successive ECT treatment sessions.
All patients received glycopyrrolate 0.2 mg IV, 2–3 min before the induction of anesthesia. Subsequently, unconsciousness was induced with methohexital 1 mg/kg IV, administered over 10–15 s. A 5-mL syringe containing an equivalent volume of either saline or remifentanil (25, 50, or 100 µg) was prepared by a researcher not involved in the data collection. The study medication was administered 30–60 s after the methohexital. On loss of responsiveness to verbal commands, a blood pressure cuff was inflated on the right leg to isolate the circulation, to assess the duration of motor seizure activity. Succinylcholine 1.2 mg/kg IV was then administered for muscle relaxation, and ventilation was assisted with a face mask and 100% oxygen.
The magnitude of the electrical stimulus used during the four study treatments was determined before the study began by using a standardized threshold titration methodology (19), where successive stimuli of increasing intensity are delivered at 30-s intervals until a generalized motor and EEG seizure is produced. After the seizure threshold was determined, a fixed suprathreshold electrical stimulus (50% above the threshold value) was delivered for each of the 4 treatment sessions at 3 min after the induction of anesthesia via bifrontotemporal electrodes with a MECTA SR1TM ECT device (MECTA Corp., Portland, OR). The EEG tracing was recorded continuously from the two frontal electrodes. The times from the ECT stimulus to the cessation of the clonic-tonic motor activity in the isolated foot (i.e., duration of the motor seizure) and to post-ictal EEG suppression (i.e., duration of the EEG seizure) were noted. If the patient manifested a sustained increase in MAP or HR (>25% above baseline values lasting >2 min) after the electrical stimulus, rescue bolus doses of labetalol (5 mg) were administered at 2-min intervals.
Psychomotor recovery was assessed as the time from delivery of the electrical stimulus until eye opening, to following simple commands, and to orientation to person, place, and time. The time to discharge from the posttreatment recovery room was determined by a nurse who was blinded to the study medication. Side effects were recorded before discharge from the facility.
Data were analyzed and compared by using repeated-measures analysis of variance followed by multiple Wilcoxon matched-pairs tests and Bonferroni’s correction for multiple comparisons, as well as one-way analysis of variance where appropriate, with P values <0.05 considered statistically significant. These data were analyzed with NCSS software (Number Cruncher Statistical Systems for Windows; NCSS, Kaysville, UT). An a priori power analysis was performed on the basis of a reported 39% prolongation in the duration of EEG seizure activity with remifentanil (18), suggesting that a minimum sample size of 18 cases per treatment group would be required. Data are presented as mean values (±SD) and numbers (n).
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Results
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Eighty ECT treatments were evaluated in 20 chronically depressed patients (5 men and 15 women). Their mean age (±SD) was 53 ± 14 yr (range, 36–82 yr), and mean body weight was 76 ± 15 kg (range, 47–105 kg). The Hamilton Rating Scale for Depression and the Mini-Mental State Examination scores were similar at all four treatment sessions (Table 1). The doses of methohexital and succinylcholine were also the same in each treatment group (Table 1).
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Table 1. Psychiatric Test Scores, Anesthetic Drugs, Duration of Motor and Electroencephalographis (EEG) Seizure Activity, and Recovery Times After Electroconvultive Therapy in the Four Treatment Groups
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Compared with the control group, no significant differences were found in the baseline hemodynamic values in the three remifentanil groups (Table 2). However, the pre-ECT treatment SBP and MAP values were significantly lower in the 100-µg remifentanil group compared with the control group (Fig. 1). In addition, the maximum change in the MAP after the ECT stimulus was smaller in the 100-µg remifentanil group compared with the control group. Although the control group received a larger total dose of labetalol (12 ± 7 mg) than the remifentanil groups (10 ± 6 mg, 8 ± 5 mg, and 7 ± 3 mg in the 25-, 50-, and 100-µg remifentanil groups, respectively), this difference was not statistically significant.
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Table 2. Hemodynamic Values at Baseline, Immediately Before (Pre-ECT), and after Electroconvulsive Therapy (ECT) (PostECT) and Labetalol Requirements in All Four Treatment Groups
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Finally, there were no significant differences in either the duration of motor or EEG seizure activity among the four study groups (Table 1). Early recovery times and discharge times were also unaffected by the addition of remifentanil 25–100 µg IV. None of the patients in this study experienced post-ECT nausea and vomiting or other anesthetic-related side effects.
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Discussion
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A recently published study (18) found a 39% increase in the duration of ECT-induced seizure activity when patients received a combination of methohexital and remifentanil compared with methohexital alone. However, the current dose-ranging study failed to demonstrate any pro- or anticonvulsant effect of remifentanil on the duration of motor or EEG seizure activity after ECT over a dosage range of 25–100 µg (0.24–2.1 µg/kg IV). The explanation for these apparently conflicting results relates to the fact that the earlier study did not standardize the dose of the hypnotic (methohexital) medication. In the study by Andersen et al. (18), the dosage of methohexital was reduced by 40% in the remifentanil group compared with their control group, which received methohexital alone (0.5 vs 0.75 mg/kg IV). Because sedative-hypnotic drugs such as methohexital and propofol possess dose-related anticonvulsant properties (20), any anesthetic-sparing effects of remifentanil would be expected to lead to a prolongation of the seizure activity after a standardized electrical stimulus. Optimizing the duration of seizure activity appears to be very important in achieving a good therapeutic response to ECT treatments (2,19) .
Remifentanil possesses acute cardiovascular depressant effects that can lead to reductions in both HR and MAP during general anesthesia (17). In this study, the immediate pre-ECT SBP and MAP values were decreased in a dose-related fashion. The HR was increased above the baseline value in all four groups because an anticholinergic drug (namely, glycopyrrolate 0.2 mg IV) was administered before the induction of anesthesia. Of importance, the peak increase in MAP after the electrical stimulus was significantly reduced in the large-dose remifentanil group. It is possible that the use of a larger dose of remifentanil (>100 µg IV) would have also blunted the transient tachycardia observed after the ECT stimulus. However, use of 150- to 200-µg doses of remifentanil in a pilot study was associated with significant hypotension immediately before the ECT stimulus and prolonged recovery times (Paul F. White, unpublished data, 2002).
Analogous to our earlier studies involving conventional antihypertensive drugs [e.g., labetalol (13), nicardipine (13), clonidine (8), and dexmedetomidine (15)], use of the potent opioid analgesic remifentanil was unable to completely block the acute hyperdynamic response to the ECT stimulus. This study could be criticized because adjunctive drugs with central and peripheral cardiovascular effects were administered before (e.g., glycopyrrolate) and after (e.g., labetalol) the ECT stimulus to minimize side effects associated with ECT (e.g., excessive oral secretions, post-ECT hypertension, and arrhythmias). However, the confounding effect of these adjunctive drugs was negated because similar doses of these drugs were administered during each of the four treatment sessions.
In conclusion, remifentanil (100 µg IV) attenuated the acute hemodynamic response to ECT under methohexital anesthesia without adversely affecting the duration of seizure activity or the recovery profile. As a result of its anesthetic-sparing effects, small doses of remifentanil (25–100 µg IV) could prove to be highly beneficial in patients with suboptimal seizure times.
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Acknowledgments
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An educational grant was received from Abbott Laboratories to purchase the study drugs used in this study.
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Footnotes
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1 Liu WS, Petty WC, Jeppsen A, et al. Attenuation of hemodynamic and hormonal responses to ECT with propranolol, Xylocaine, sodium nitroprusside or clonidine (abstract). Anesth Analg 1984;63:244. 
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Accepted for publication December 10, 2002.
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Abstract
Introduction
and 100-µg remifentanil (
) groups. *P < 0.05 compared with the control group. HR = heart rate; MAP = mean arterial blood pressure; SBP = systolic blood pressure.
