Orally administered clonidine (0.2-0.3 mg) has been reported to decrease the acute hypertensive response to electroconvulsive therapy (ECT) without prolonging early recovery. This preliminary study was designed to evaluate the acute hemodynamic effects of the investigational alpha2-adrenergic agonist, dexmedetomidine, in patients undergoing a series of ECT treatments.
Six patients undergoing a series of three to six consecutive ECT treatments were studied according to a randomized, double-blind, placebo-controlled protocol All patients received either saline or dexmedetomidine, 0.5 or 1.0 microg/kg intravenously, 10-30 min before induction of anesthesia for ECT using a standardized anesthesia protocol. In addition to assessing the cardiovascular variables, the duration of seizure activity, degree of sedation, and time to discharge from the Phase I recovery unit were assessed.
Although dexmedetomidine produced dose-related increases in the level of sedation before the ECT procedure, it failed to decrease the peak blood pressure and heart rate responses after the ECT treatment. The 0.5 and 1.0 microg/kg doses of dexmedetomidine prolonged the times to orientation and to discharge from the Phase I unit.
The results of this pilot study suggest that dexmedetomidine (0.5-1.0 microg/kg given intravenously) is not beneficial in controlling the acute hyperdynamic response after ECT.
ELECTROCONVULSIVE therapy (ECT) is an effective treatment for severe depressive disorders that are resistant to antidepressive medication. However, this treatment is commonly associated with acute hyperdynamic responses, including transient hypertension and tachycardia, immediately after the ECT stimulus is delivered. [small alpha, Greek]2-Adrenergicagonists have been reported to attenuate stress-induced sympathoadrenal responses to painful surgical stimuli and to improve intraoperative hemodynamic stability. 
Dexmedetomidine is an investigational, highly selective, [small alpha, Greek]2-adrenergicagonist with a more favorable pharmacokinetic profile than clonidine. Clonidine, a mixed [small alpha, Greek]2-adrenergicagonist and antagonist, has been reported to have a beneficial effect on the hyperdynamic response to ECT. [3,4]Therefore, a small pilot study was designed to evaluate the effect of pretreatment with dexmedetomidine on the acute hemodynamic response, level of sedation, duration of seizure activity, and recovery times in outpatients undergoing ECT. The primary objective of the study was to determine whether dexmedetomidine could decrease the hyperdynamic response without producing side effects (e.g., arrhythmias, excessive sedation, prolonged recovery).
Materials and Methods
After obtaining approval from the institutional review board and written informed consent, six patients were investigated using a randomized, double-blind, placebo-controlled crossover study design. Patients taking tricyclic antidepressant drugs were excluded. The study medication consisted of dexmedetomidine, 0.5 or 1.0 [micro sign]g/kg, or normal saline (in a total volume of 0.4 ml/kg). It was infused intravenously 10-30 min before ECT using a standardized anesthetic technique consisting of 0.1 to 0.2 mg glycopyrrolate and 10 mg labetalol, both given intravenously, followed by 1 mg/kg methohexital and 1.3-1.5 mg/kg succinylcholine, both given intravenously. The electrical stimulus was administered 2 min after induction of anesthesia. Three of the patients received both doses of dexmedetomidine either 10 or 30 min before induction of anesthesia on separate occasions to evaluate the effect of the timing of the drug administration on the acute hemodynamic response to ECT. Noninvasive mean arterial pressure, electrocardiogram, heart rate, and oxygen saturation data were recorded immediately before any medication was administered and subsequently at 1- to 2-min intervals for up to 10 min after the electrical stimulus and then at 5-min intervals until the patient was discharged from the recovery unit.
The magnitude of the electrical stimulus was maintained at a constant level for each study patient. An electroencephalographic trace was recorded continuously from two frontal cutaneous electrodes. The times from the electrical stimulus to the cessation of the clonic-tonic motor activity in the “isolated” foot (i.e., duration of motor seizure) and to postictal electroencephalographic suppression (i.e., electroencephalographic duration of seizure) were noted. The times to eye opening, orientation, and discharge from the Phase I recovery unit (using the standard modified Aldrete criteria) also were recorded. The patient's level of sedation was assessed by a blinded observer before administration of the study drug, immediately before induction of anesthesia, when entering the recovery unit, and at discharge using a 10-cm visual analog scale, on which 0 represents wide awake and 10 represents almost asleep. Data were analyzed and compared using repeated-measures analysis of variance, with probability values < 0.05 considered statistically significant. All data are reported as mean +/− SD unless otherwise indicated.
Twenty-four ECT treatments were evaluated in six elderly patients (age, 73 +/− 4 yr; weight, 70 +/− 13 kg; height, 177 +/− 5 cm). In the three patients who received both doses of dexmedetomidine on two separate occasions, the acute hemodynamic responses to the electrical stimulus were similar when the drug was administered 10 min versus 30 min before induction of anesthesia. In all patients, the mean arterial pressure and heart rate values were unchanged after the 5-min infusion of the study drug but increased significantly 1 to 2 min after the electrical stimulus. There were no differences in the hemodynamic variables between the pretreatments with dexmedetomidine (0.5 or 1.0 [micro sign]g/kg given intravenously) and saline either before or after the ECT treatments (Table 1). In addition, the times for the peak mean arterial pressure and heart rate values to return to the pretreatment baseline values were similar for all three pretreatment regimens (data not shown).
Although there were no significant differences in the duration of seizure activity among the three pretreatment groups, the motor and electroencephalographic seizures were slightly longer after pretreatment with dexmedetomidine. In addition, the sedation scores on the visual analog scale were increased in a dose-related fashion after pretreatment with dexmedetomidine compared with saline. Times to orientation and discharge from the recovery unit after ECT also were significantly longer when the patients received dexmedetomidine. Finally, no untoward cardiovascular side effects were observed either before or after the ECT treatments.
Dexmedetomidine has been reported to produce dose-dependent decreases in blood pressure and heart rate as a result of its agonistic effect at the [small alpha, Greek]2-adrenergicreceptor. [5-7]A 2-[micro sign]g/kg preinduction dose of dexmedetomidine reduced the hemodynamic response to tracheal intubation and decreased the anesthetic requirement. Because the hyperdynamic response to ECT is associated with an acute increase in concentrations of epinephrine and norepinephrine in plasma, [9,10]we hypothesized that this [small alpha, Greek]2-adrenergicagonist also would be effective in modifying the ECT-evoked hyperdynamic response.
Dexmedetomidine is a more highly selective and potent [small alpha, Greek]2-adrenergicreceptor agonist than clonidine. [1,2]Although clonidine did not alter the duration of ECT-induced seizure activity, these data suggest that dexmedetomidine tended to prolong the duration of seizure. A study involving a larger number of patients is required, however, to determine whether this difference is statistically significant. Although similar doses of dexmedetomidine have been reported to be effective in modifying the acute hemodynamic response to tracheal intubation, a single 0.5- or 1.0-[micro sign]g/kg intravenous dose of dexmedetomidine failed to decrease the peak mean arterial pressure and heart rate values after ECT. Although a larger dose of dexmedetomidine might have effectively blunted the transient hyperdynamic response after ECT, the intrinsic sedative effects of the drug probably would have resulted in an even further prolongation of the recovery time in this elderly patient population. In addition, the risk of untoward cardiovascular side effects (e.g., severe bradycardia) increases when larger doses of dexmedetomidine are administered. [1,2]
A dose of dexmedetomidine (0.5 or 1.0 [micro sign]g/kg given intravenously), which produced an increased level of preanesthetic sedation and prolonged recovery, failed to modify the acute hyperdynamic response immediately after ECT. These preliminary data suggest that dexmedetomidine would not be a useful anesthetic adjuvant during ECT.
The authors thank Dr. M. Husian in the Department of Psychiatry and the nurses in the Psychiatric Unit at Zale Lipshy University.