Anesth Analg 2001;92:1327-1330
© 2001 International Anesthesia Research Society
GENERAL ARTICLES
The Effects of Diltiazem on Hemodynamics and Seizure Duration During Electroconvulsive Therapy
Zen’ichiro Wajima, MD, PhD*,
Tatsusuke Yoshikawa, MD, PhD
,
Akira Ogura, MD, PhD
,
Kazuyuki Imanaga, MD*,
Toshiya Shiga, MD, PhD*,
Tetsuo Inoue, MD, PhD*, and
Ryo Ogawa, MD, PhD
*Department of Anesthesia, Chiba Hokusoh Hospital, Nippon Medical School, Chiba, Japan; Department of Anesthesia, Hakujikai Memorial Hospital, Tokyo, Japan; and Department of Anesthesiology, Nippon Medical School, Tokyo, Japan
Address correspondence and reprint requests to Zen’ichiro Wajima, MD, PhD, Department of Anesthesia, Chiba Hokusoh Hospital, Nippon Medical School, 1715, Kamagari, Inba-mura, Inba-gun, Chiba 270-1694, Japan. Address e-mail to HFB01245@ nifty.ne.jp.
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Abstract
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Electroconvulsive therapy (ECT) is often associated with acute hyperdynamic responses, and we hypothesize that diltiazem can blunt this response. We measured the effect of a 10-mg dose of diltiazem on heart rate and mean arterial pressure during ECT. Furthermore, we assessed seizure duration by using both the cuff method and two-lead electroencephalogram. We studied 18 patients with a randomized, double-blinded, placebo-controlled cross-over study design. Diltiazem significantly reduced heart rate and mean arterial pressure just after medication, and it also significantly reduced the increases in these variables after ECT, as compared with the placebo. The use of diltiazem was, however, associated with a shortened seizure duration, possibly making ECT less effective. Because of the reduction in seizure duration, the routine administration of diltiazem may not be advisable because it can possibly interfere with the psychotherapeutic efficacy of ECT. However, diltiazem medication for ECT is potentially useful for reducing tachycardia and hypertension in high-risk patients.
Implications: Diltiazem can blunt acute hyperdynamic responses after electroconvulsive therapy, but seizure duration is also significantly reduced, possibly making this therapy less effective.
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Introduction
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Electroconvulsive therapy (ECT) is often associated with acute hyperdynamic responses, including transient hypertension and tachycardia, immediately after the ECT stimulus is delivered. Attenuation or blockade of the acute hemodynamic and myocardial consequences of ECT may be desirable in patients with brain tumors, cardiac conduction defects or ectopy, hypertension, recent myocardial infarction or hemorrhagic stroke, and aortic or cerebral aneurysms (1). Many drugs such as nitroglycerine (2,3), nifedipine (4,5), ß-adrenergic blockers (6–15), and clonidine (16) attenuate the hyperdynamic response to ECT.
Diltiazem, a slow-channel calcium ion antagonist (calcium channel-blocking drugs), inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle, and such inhibition reduces heart rate (negative chronotropy); depresses contractility (negative inotropy); decreases conduction velocity (negative dromotropy); and dilates coronary, cerebral, and systemic arterioles (17). No reports have, however, dealt with diltiazem for ECT.
Though ß-adrenergic blockers are probably the most useful and widely used drugs for ECT (1), we hypothesized that diltiazem also can blunt the hyperdynamic response to ECT. The aim of this study was to investigate the effect of diltiazem administration on heart rate, arterial blood pressure, and seizure duration during ECT.
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Methods
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After obtaining approval from the IRB and written informed consent, 18 ASA physical status II or III patients undergoing ECT treatments for chronic depression were investigated with a randomized, double-blinded, placebo-controlled cross-over study design. Patients with unstable cardiovascular diseases; those using ß-adrenergic or other calcium-channel blocking drugs; and those with second or third degree atrioventricular block, arrhythmia, hypotension, sinus bradycardia, chronic obstructive pulmonary disease, and renal or hepatic failure were excluded from this study. Each patient received one of two different medications on different days 48 h apart to allow a washout period: placebo (normal saline) (Control group) or diltiazem (Diltiazem group). The anesthesiologists were blinded to the treatment being administered.
Mean arterial blood pressure (MAP), electrocardiographic data, heart rate (HR), and oxygen saturation values were recorded before anesthesia induction. Tonometric blood pressure was measured with a continuous noninvasive blood pressure monitor (18–20). None of the patients was premedicated. The Control group was given 10 mL of saline at a rate of 10 mL every 10 min, and the Diltiazem group was given 10 mg diltiazem in a 10-min period (0.1% diltiazem solution was injected). Unconsciousness was induced with propofol 1.5 mg/kg IV. Before the administration of succinylcholine (SCC), a tourniquet applied to the upper arm was inflated to isolate the circulation to the arm and permit an accurate assessment of the motor seizure. Upon loss of consciousness, a blood pressure cuff was applied to isolate the circulation to the arm so as to assess the duration of motor seizure activity (cuff method). Then SCC 1.5 mg/kg IV was administered, and ventilation was assisted via a face mask and oxygen. An electrical stimulus was delivered via bitemporal electrodes with a Sakai CS-1 apparatus (Sakai Medical Instruments, Tokyo, Japan) at a 110-V setting for 7 s. The magnitude of the electrical stimulus was held constant during the two ECT treatments conducted on each patient. Electroencephalographic (EEG) seizure length was also recorded by a two-channel EEG after the electrical stimulus.
Intragroup comparisons of HR and MAP were performed by two-way analysis of variance with repeated measures and paired t-tests with Bonferroni’s correction. Between-group comparisons of HR, MAP, and recovery time were made by unpaired t-tests. Between-group comparisons of motor and EEG seizure duration time were made by Mann-Whitney U-tests. A P value <0.05 was considered statistically significant.
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Results
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The 7 men and 11 women completing the study (36 ECT treatments) had an average (mean ± SD) age of 54 ± 14 yr (range, 71–22 yr), weight of 55 ± 10 kg (range, 42–79 kg), and height of 159 ± 11 cm (range, 151–181 cm).
There were no significant differences in baseline measures of HR and MAP between the two groups ( Table 1). In the Control group, the peak HR after ECT was significantly more rapid than the baseline HR (P < 0.01). In the Diltiazem group, HR was significantly slower after medication than at baseline (P < 0.05), and the peak HR after ECT was significantly more rapid than the baseline HR (P < 0.01). The HR increase after the stimulus was significantly less marked after diltiazem (P < 0.05).
In the Control group, peak MAP after ECT was significantly higher than the baseline MAP (P < 0.01). In the Diltiazem group, MAP was significantly lower after medication and before SCC than at baseline (P < 0.05 and 0.01, respectively), and peak MAP after ECT was significantly higher than baseline MAP (P < 0.01). MAP was significantly lower in the Diltiazem group after medication than in the Control group (P < 0.01). The increase in MAP, in response to the stimulus, was significantly less than that after diltiazem (P < 0.05).
Recovery time, indicated by spontaneous respiration, eye opening, and following commands, did not differ significantly between the Control and Diltiazem groups.
Motor seizure duration was significantly shorter in the Diltiazem group than in the Control group (P < 0.05) ( Fig. 1), and EEG seizure duration was also significantly shorter in the Diltiazem group than in the Control group (P < 0.05) ( Fig. 2).
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Figure 1. Motor seizure duration. The box represents the 25th through 75th percentiles, and the horizontal line within the box shows the median, marking the 50th percentile. The vertical error bars indicate the maximum and minimum. *P < 0.05 compared with the control.
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Figure 2. Electroencephalographic (EEG) seizure duration. The box represents the 25th through 75th percentiles, and the horizontal line within the box shows the median, marking the 50th percentile. The vertical error bars indicate the maximum and minimum. *P < 0.05 compared with the control.
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No complications potentially related to diltiazem occurred during this study.
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Discussion
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This study showed that diltiazem (10 milligrams), administered immediately before anesthesia, significantly reduced the increases in peak HR and MAP after ECT. However, it also significantly reduced seizure duration. Attenuation of the cardiovascular response is brought about by two effects: reduction of baseline hemodynamic values and blunting of their increases after ECT. Diltiazem blunts the hemodynamic changes associated with laryngoscopy, tracheal intubation, and extubation (21–23). Although diltiazem is an alternative for ECT, attention must be paid to its tendency to shorten seizure duration.
We chose the dose of IV diltiazem 10 milligrams because IV diltiazem 0.2 mg/kg can attenuate the hypertensive response to laryngoscopy, tracheal intubation, and tracheal extubation (21–23), and this dose is close to 10 milligrams.
ß-Adrenergic blockers are probably the most useful and widely used drugs for ECT (1). McCall et al. (8) found that 5- and 10-milligram doses of labetalol safely and effectively decreased blood pressure and the rate-pressure product (but not HR) without shortening seizure duration. Weinger et al.(12), however, showed that labetalol shortens seizure duration. Esmolol also blunted the maximal HR response and blood pressure response (9,10,12,15) [or rate-pressure product (9)]. However, esmolol shortened seizure duration (9,10,12,15). In contrast, there is a report demonstrating that esmolol does not shorten seizure duration (11). Oral clonidine produced a dose-related decrease in MAP before and after ECT and produced no significant changes in the duration of either motor or EEG seizure activity or recovery times after anesthesia, but it did not produce significant changes in HR (16). Though it is difficult to choose the optimal drug for treating hyperdynamic responses after ECT, caffeine (1) and theophylline (24) are capable of prolonging seizure duration. Thus, administering these drugs may be a good means of achieving premedication before ECT.
Swartz (25) commented that the duration of an induced ECT therapy seizure is routinely taken as an index of efficacy; however, it does not reliably reflect therapeutic impact, probably because seizure duration incompletely describes the amount of seizure activity. We could not prove the mechanism of shortening the seizure duration by diltiazem in this study, and we could not know whether the shortened seizure duration by diltiazem is associated with reduced therapeutic effect. Therefore, further investigation is needed.
In summary, a 10-milligram IV dose of diltiazem, administered immediately before anesthesia, significantly reduced the increases in peak HR and MAP seen after ECT. However, diltiazem also significantly reduced seizure duration. Although diltiazem can be useful for attenuating hemodynamic responses in patients at risk of cardiovascular complications, its effect in reducing seizure duration may interfere with the psychotherapeutic efficacy of ECT. Its use as a routine prophylactic measure may not be recommended for this reason.
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Accepted for publication December 28, 2000.
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Abstract
Introduction
