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Department of Anaesthesia, Groote Schuur Hospital, Valkenberg Hospital and the University of Cape Town, South Africa
Address correspondence to Dirk van Zijl, MBChB, FCA, Department of Anaesthesia, Groote Schuur Hospital and the University of Cape Town, Anzio Road Observatory 7925, Cape Town, South Africa. Address e-mail to dirkath{at}mweb.co.za.
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Abstract |
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Introduction |
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Remifentanil is a synthetic opioid providing intense analgesia of rapid onset and short duration. It attenuates the hemodynamic response to such intense stimuli as laryngoscopy and tracheal intubation at a dose of 1.0 µg/kg (9,10). Magnesium sulfate (MgSO4) has not been studied in the setting of ECT. MgSO4 not only inhibits catecholamine release but also limits the pressor response to tracheal intubation at a dose of 30 mg/kg (11–13).
The purpose of this study was to compare the effects of remifentanil 1.0 µg/kg and MgSO4 30 mg/kg versus placebo in attenuating the unwanted autonomic responses to ECT. Our hypothesis was that remifentanil and MgSO4 could both limit the hypertensive response to ECT but that remifentanil may be associated with bradycardia.
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Methods |
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Each patient was randomly assigned to be allocated twice into each of the 3 IV test groups: placebo control, MgSO4 30 mg/kg, or remifentanil 1.0 µg/kg. To achieve a rapid measurement of arterial blood pressure without distortions from artifact induced by the convulsion, a manual oscillotonometer was used. This precluded the measurement of mean arterial pressure (MAP). Heart rate was recorded from an electrocardiogram (ECG). Systolic (SBP) and diastolic arterial blood pressures, heart rate, and oxygen saturation values were recorded on arrival for the ECT and then at 0, 1, 3, and 10 min after the end of the ECT-induced seizure. After IV access was established, patients were administered oxygen for 3 min. No premedication or anticholinergics were administered. Thiopental 4 mg/kg was given over 10 s, followed by an IV injection of the study drug over 30 s, followed by succinylcholine 0.5 mg/kg and 5 mL of 0.9% saline to flush the line. Over the next 45 s the patients were all manually ventilated with 12 breaths of 100% oxygen before the ECT stimulus was administered.
A suprathreshold electrical stimulus was delivered via bifrontotemporal electrodes with a Thymatron Dual Graph (Somatics LLC, Lake Bluff, IL) to produce seizure duration of approximately 30 s. The magnitude of the energy setting for ECT stimulus was predetermined by age and weight for each patient's first ECT and by subsequent seizure duration for the following ECTs. One more electrical stimulus at a higher energy level was given immediately after the initial stimulus (at the psychiatrist's discretion) if the seizure duration was not long enough. The electroencephalogram (EEG) trace was recorded continuously from the two frontal electrodes. The duration of the EEG seizure was recorded from the EEG trace, and peak heart rate was recorded during the convulsion from the ECG. Visual diaphragmatic movement was used to assess the apnea time from induction of anesthesia to spontaneous ventilation. Manual ventilation was performed if arterial saturation values decreased to less than 90%. Side effects and adverse events were noted before discharge back to the ward.
A pilot study revealed that the SBP increase induced by ECT was approximately 30%. It was considered that a clinically relevant effect would be a 50% reduction in this increase. Power calculations based on these figures with an assumed sd of 25 mm Hg indicated that we would need 33 ECT sessions in each group. We aimed for 40 for a comfortable margin of error. Data were analyzed with Statistica (StatSoft Inc., Tulsa, OK) Version 6 statistical software running under Windows ME. Data from all three groups were compared among groups and on a time base within groups using repeated-measures analysis of variance, with P values <0.05 considered statistically significant. Fisher's least significant difference test was used to identify individual data point differences where primary analysis showed such differences to exist. Data are presented as mean ± sd and numbers (n).
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Results |
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All patients received the same weight-related hypnotic and muscle relaxant dose for each of their anesthetics. Hemodynamic and arterial saturation data are displayed in Table 1. Compared with the control group, patients in both the remifentanil and the MgSO4 groups had a statistically significant (P < 0.05) attenuation of the increase in SBP at 0, 1, and 3 min after the ECT seizure with no difference in SBP recorded at 10 min. Remifentanil, but not MgSO4 or placebo, attenuated the heart rate increase at 1 and 3 min. The mean time from induction of anesthesia to resumption of spontaneous ventilation in the placebo group was 203 (± 53) s; MgSO4 was 207 (± 38) s, and remifentanil 297 (± 81) s. Remifentanil caused a statistically significant prolongation in the return of spontaneous ventilation (mean, 90 s) compared with the other two groups, with no other adverse respiratory effects. The mean ECT-induced seizure duration time was 33 (± 14) s with no difference among the 3 groups. There was also no difference among groups in the peak heart rate recorded during the convulsion (P = 0.6).
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Adverse events included one 43-yr-old depressed female patient receiving fluoxetine who had an increased arterial blood pressure of 140–170/90–105 mm Hg on every presentation for ECT (although it was not increased on the ward). She developed multiple ventricular premature beats immediately after each seizure that accompanied significant increases in post-ECT arterial blood pressure. Her heart rate decreased to 36 bpm when the arterial blood pressure increased to 270/130 mm Hg immediately postseizure on one occasion when remifentanil was the trial drug. There were three additional episodes of bradycardia <60 bpm at time 0, one of which was in this patient, in the placebo group. Altogether, there were 4 episodes of bradycardia in the placebo group and 5 in the remifentanil group. The only episode of a heart rate of <60 bpm (56 bpm) in the MgSO4 group occurred at 10 min in a patient whose starting heart rate was 60 bpm.
In 3 of the 115 sessions, a repeat stimulus was required because the initial seizure was too short and in one case an additional 100 mg of thiopental was given to stop a seizure that had continued for more that 60 s. At 4 ECT sessions (at least once in each group), there were technical difficulties resulting in the delay of the seizure stimulus being delivered of between 10 and 90 s.
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Discussion |
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MgSO4 is used as a drug in a variety of clinical situations including tachyarrhythmias, myocardial and neuronal ischemia, preeclampsia, tocolysis, and hemodynamic control in pheochromocytoma, and in the management of autonomically unstable conditions such as tetanus (19,20). A bolus of 30 mg/kg given on induction of anesthesia and an IV infusion of 10 mg · kg–1 · h–1 for the duration of the operation has been shown to reduce intraoperative anesthetic and analgesic requirements during ophthalmic surgery (21). In a dose of 40 mg/kg it has been shown to be very effective in attenuating the pressor response to tracheal intubation in preeclamptic patients undergoing cesarean delivery (12,13). Muscle weakness is only a problem if combined with nondepolarizing muscle relaxants or in very large doses. MgSO4 has no reported major side effects if used in a dose less than 50 mg/kg (12,21). MgSO4 does not enhance succinylcholine neuromuscular blockade (22).
MgSO4 has vagolytic qualities (23,24) but although there was an increase in heart rate in this group post-ECT compared with remifentanil, the difference did not achieve statistical significance. However, this was the only group in which there were no episodes of heart rate <60 bpm immediately after the convulsion, and this may be an advantage in young patients and others at risk of bradycardia during ECT.
Three studies have examined the use of remifentanil in the setting of ECT (25–27). In the first (25), the administration of remifentanil (1 µg/kg) in combination with methohexital was reported to increase seizure duration in elderly patients undergoing ECT. The dose of the hypnotic used was not standardized and the effect of remifentanil on the hemodynamic effects of ECT was not investigated. In a similar study (26), remifentanil (1 µg/kg) combined with a 35% reduction in the methohexital dose increased the seizure duration by 40% in middle-aged patients undergoing ECT. Smith et al. (26) did not mention the timing of the ECT stimulus or the exact time sequence of the hemodynamic recordings and only commented that peak heart rate in the remifentanil-methohexital group was more rapid than in the methohexital group (although less hypnotic drug was used with remifentanil) and that there was no difference in the peak MAP post-ECT between the two groups.
In the third study (27) patients were randomized to receive remifentanil boluses of 25, 50, or 100 µg, or saline. This was given immediately after a standard methohexital dose during four consecutive ECT treatments. Labetolol was used as rescue antihypertensive medication. The duration of motor seizure activity was not significantly different among the four groups. The 100-µg bolus group, but not the others, had significantly lower pre-ECT SBP and smaller increases in post-ECT MAP compared with control. Recart et al. (27) measured heart rate and arterial blood pressures at 1-min intervals after induction of anesthesia, but there was a delay of 3 min from induction to ECT stimulus and only the pre-ECT and peak post-ECT MAP were compared. Their patients received a mean dose of 1.3 µg/kg, with a wide range of 1 to 2 µg/kg. They noted that only a bolus of 100 µg had any antihypertensive properties. Although these investigators did record hemodynamic data with respect to ECT stimulus in the presence of remifentanil, they did not show duration of effect with respect to administration or ECT stimulus.
Although our study did show that both remifentanil and MgSO4 attenuated SBP at 0, 1, and 3 minutes post-ECT, the diastolic arterial blood pressures were not affected and our methodology did not allow us to monitor the MAP. Heart rate was only decreased at 1 and 3 minutes post-ECT with remifentanil and MgSO4 had no significant effect on heart rate. We only used one dose of remifentanil and MgSO4 and our finding must be considered in that context. Our finding also only has application in a baseline anesthetic of 4 mg/kg of thiopental and succinylcholine 0.5 mg/kg.
Our study has confirmed the work of Recart et al. (27) that remifentanil does not influence seizure duration when a standard hypnotic dose is used. Andersen et al. (25) and Smith et al. (26) both showed increases in seizure duration, but these investigators reduced the dose of methohexital by 40% and 35%, respectively, in their remifentanil group compared with their control group, who received methohexital alone. Sedative hypnotic drugs possess dose-related anticonvulsant properties, and any reduction in dose would be expected to decrease seizure threshold (28).
An additional confounding factor when comparing ECT trials is whether glycopyrrolate has been used prophylactically. The Royal College of Psychiatrists Guidelines for Anesthesia for ECT recommends the omission of anticholinergic drugs (29). One review recommends the routine use of glycopyrrolate 0.1–0.3 mg IV for all ECT sessions to reduce oral secretions and bradycardia (8). Smith et al. (26) administered succinylcholine 1.0 mg/kg and Recart et al. (27) 1.2 mg/kg and both used glycopyrrolate 0.2 mg before anesthetic induction. Most of the previous hemodynamic studies have used these large doses of succinylcholine and glycopyrrolate as part of their standard anesthetic technique, which may have had an influence on their results. We used a succinylcholine dose of 0.5 mg/kg, which is the dose recommended for ECT by the Royal College of Psychiatrists. In our experience, this dose does not result in excessive secretions. Glycopyrrolate was therefore omitted. MgSO4 has been shown to have vagolytic properties and this may negate the need for glycopyrrolate entirely (23,24).
Patients in our study tended to be younger than in many previous studies. Recart et al. (27) describe a mean age of 53 ± 14 yr (range, 36–82 yr), with all the indications for ECT being chronic depression. The mean age of our patients was 36 ± 11 yr, and the oldest was 57 yr. Psychosis was the main indication for ECT in our study population, whereas most studies have examined ECT in depression. The elderly are more at risk for hypertension and ischemic heart disease and this may also have influenced our results.
Time to spontaneous ventilation in most of the previously published studies using a larger dose of succinylcholine has varied from 5 to 10 min. The mean time to spontaneous ventilation in our study for all groups was approximately 4 minutes, and even with the prolonged return of spontaneous ventilation in the remifentanil group, all patients were breathing within 6 minutes of anesthetic induction, with no respiratory complications.
In conclusion, we have shown that both remifentanil and MgSO4 can be used to attenuate the SBP response associated with ECT. Seizure duration was not reduced, which is an important consideration in the context of the primary aim of the therapy. The increased time to spontaneous ventilation in the remifentanil group was expected, but this should not be of clinical importance. In patients such as the elderly and those with ischemic heart disease, in whom attenuation of the tachycardic response to ECT is considered important, remifentanil may be advantageous. Because MgSO4 has less effect on heart rate, it might offer advantages over remifentanil in patients at risk for post-ECT bradycardia.
The authors would like to thank Sr. Lorraine Adendorff and the Staff of Valkenberg Hospital.
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Footnotes |
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GlaxoSmithKline donated the remifentanil used in this trial.
Accepted for publication June 28, 2005.
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