Comparison between the effects of propofol and etomidate on motor and electroencephalogram seizure duration during electroconvulsive therapy.
Abstract: An ideal anaesthetic for electroconvulsive therapy (ECT) should have rapid onset and offset with no effect on seizure duration, and provide cardiovascular stability during the procedure. Propofol is commonly used, even though it has been shown to shorten seizure duration which might affect the efficacy of ECT. Etomidate has been advocated as an alternative. This prospective, randomised, single-blind, crossover study was conducted to compare the effects of etomidate (Etomidate-[R]Lipuro, B. Braun Ltd, Melsungen, Germany) and propofol (Diprivan[R], AstraZeneca, UK) on seizure duration as well as haemodynamic parameters in patients undergoing ECT. Twenty patients aged between 18 and 70 years were recruited. Group I received etomidate 0.3 mg/kg for the first course of ECT (Group IA) and propofol 1.5 mg/kg for the second ECT (Group IB), while Group II received propofol for the first ECT (Group IIA) and etomidate for the second ECT (Group IIB). There was a washout period of two to three days in between procedures. Parameters recorded included motor seizure duration, electroencephalogram seizure duration, blood pressure and heart rate. Analysis demonstrated neither period effect nor treatment period interaction. Etomidate was associated with a significantly longer motor and electroencephalogram seizure duration compared with propofol (P <0.01). Neither drug demonstrated consistent effects in suppressing the rise in heart rate or blood pressure during ECT. Myoclonus and pain on injection were the most common adverse effects in etomidate group and propofol group respectively. Etomidate is a useful anaesthetic agent for ECT and should be considered in patients with inadequate seizure duration with propofol.

Key Words: electroconvulsive therapy, seizure duration, propofol, etomidate
Article Type: Clinical report
Subject: Propofol (Dosage and administration)
Propofol (Comparative analysis)
Etomidate (Comparative analysis)
Etomidate (Dosage and administration)
Electroencephalography (Usage)
Electroencephalography (Health aspects)
Electroconvulsive therapy (Health aspects)
Epilepsy (Care and treatment)
Epilepsy (Research)
Authors: Tan, H.L.
Lee, C.Y.
Pub Date: 09/01/2009
Publication: Name: Anaesthesia and Intensive Care Publisher: Australian Society of Anaesthetists Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 Australian Society of Anaesthetists ISSN: 0310-057X
Issue: Date: Sept, 2009 Source Volume: 37 Source Issue: 5
Topic: Event Code: 310 Science & research
Geographic: Geographic Scope: Malaysia Geographic Code: 9MALA Malaysia
Accession Number: 208535191
Full Text: The use of electroconvulsive therapy (ECT) for the treatment of psychiatric disorders dates back to 1937 (1). Since then, its indication has become more diversified and includes the vast majority of major depressive disorders, bipolar mood disorders and even post-partum psychosis (1-4.) Electroconvulsive therapy is considered to be one of the important treatment modalities available. It has the advantage of producing a more rapid response compared to conventional treatment, an important consideration in the management of patients with suicidal tendencies (2,3,5).

Anaesthesia is required for the safe and effective conduct of ECT. Methohexitone, initially proposed by the American Psychiatric Association as the anaesthetic agent of choice for induction of anaesthesia in patients undergoing ECT (6), is no longer available in Malaysia and many parts of the world. In its place, propofol is now extensively used as an induction agent for ECT. Propofol has been shown to reduce cognitive dysfunction following ECT, but it also significantly shortens the seizure duration (7,8). This might affect the efficacy of ECT, given that seizures that last at least 20 to 25 seconds are considered necessary for an antidepressant effect (9,10). Etomidate has good cardiovascular stability and produces rapid recovery. It has also been shown to prolong seizure duration in patients undergoing ECT (11-13), and has been suggested as an alternative anaesthetic agent for the procedure (11,14-16). This study was conducted to compare the effects of etomidate and propofol on motor and electroencephalogram (EEG) seizure duration in patients undergoing ECT. The haemodynamic effects of both drugs during ECT were also compared.

MATERIALS AND METHODS

Following Institutional review Board approval, this prospective, randomised, single-blind, crossover study was carried out on 20 ASA I or II patients aged between 18 and 70 years and scheduled for ECT. Patients with anticipated difficult airway and a history of allergy to either of the anaesthetic agents or related compounds were excluded, as were those who refused to participate in the study. Assessment of the treating psychiatrist was sought and surrogate consent was obtained for patients deemed not competent to provide their own consent. Anaesthesia was conducted by anaesthetists with a minimum of six months' experience in anaesthesia and data was collected by an independent observer.

The patients were randomly allocated into two groups. Group I received etomidate (Etomidate-[R]Lipuro, B. Braun Ltd, Melsungen, Germany) for the first course of ECT (Group IA) and propofol (Diprivan[R], AstraZeneca, UK) for the second course of ECT (Group IB), while Group II received propofol for the first ECT (Group IIA) and etomidate for the second ECT (Group IIB). There was a washout period of two to three days between the procedures. Ten patients were recruited into each group.

Patients were fasted overnight and no sedative premedication was administered prior to the procedure. The procedure was carried out in the treatment room of the psychiatric ward. An intravenous cannula was inserted on the dorsum of the hand and a blood pressure cuff was applied on the ipsilateral arm. The patients' heart rate, blood pressure, Sp[O.sub.2] and electrocardiogram were monitored throughout the procedure and recorded pre-induction, post-induction and every three minutes thereafter for 12 minutes.

Depending on group allocation, anaesthesia was induced with either intravenous propofol 1.5 mg/kg (premixed with 40 mg of lignocaine) or etomidate 0.3 mg/kg. After loss of responsiveness to verbal command, another blood pressure cuff over the contralateral arm was inflated to 50 mmHg above the systolic blood pressure to isolate the forearm muscles from the effects of intravenous suxamethonium 0.5 mg/kg which was then administered. Ventilation was accomplished with 100% oxygen via facemask. A bite-block was inserted just prior to delivery of the ECT stimulus, which was given one minute after administration of suxamethonium. The ECT stimulus was delivered by Thymatron[TM] System II (SOMATICS Inc., Lake Bluff, IL, USA), and the procedure was performed according to standards approved at our institution and in agreement with the American Psychiatric Association guidelines (6). Motor seizure duration was recorded as the time interval between ECT stimulus and cessation of tonic-clonic motor activity in the isolated upper limb, while EEG seizure duration was recorded as the interval between ECT stimulus and post-ictal EEG suppression.

After cessation of the seizure, the patients were ventilated with 100% oxygen via facemask until return of adequate spontaneous breathing. They were then placed in the recovery position and monitored in a designated post-anaesthesia care area for 30 minutes prior to discharge to the ward.

Any adverse events which occurred during the procedure were documented. These included pain on injection, allergic reaction, myoclonus or abnormal movement, oxygen desaturation (Sp[O.sub.2] <95%), brady- or tachycardia (change of heart rate of 20% from baseline) and hypo- or hypertension (change of mean arterial pressure [MAP] of 20% from baseline).

Rescue therapy, if required, would be as follows: intravenous atropine 0.4 mg for bradycardia lasting more than 30 seconds and associated with hypotension; intravenous ephedrine 6 mg for hypotension (MAP below 20% of baseline); and intravenous diazepam 5 mg for electrical seizure duration greater than 120 seconds (17).

The [alpha] value was set at 0.05 and power of study at 80%. The mean and standard deviation for the motor and electrical seizure duration was obtained from a previous study by Avmarov (11). Using the power and sample size software calculator nQuery Advisor, a sample size of seven in each arm was obtained. Allowing for a dropout rate of 30%, the sample size in each arm would be 20. Data analysis was done using t-test for parametric data and general linear model18 for the haemodynamic parameters.

As this study used a cross-over design, the period effect and treatment by period interaction was calculated using a method as described by Altman (19), before determining the treatment effect (20,21). A period effect is noted when the underlying condition or ability to respond to treatment changes from one period to the next. A treatment by period interaction is noted when a difference occurs in response to treatment in the first period compared with the second period, most commonly seen because an effect from active treatment is carried over into the outcome measurements of the next period. In a crossover design, responses to treatment are suspected if any period or treatment by period interaction effects are noted (22).

RESULTS

The groups were comparable in terms of age, weight, height and body mass index as illustrated in Table 1.

Being a crossover trial, analyses for the period effect and treatment period interaction were performed. No period effect was demonstrated (P value of 0.072 and 0.362 for motor and electrical seizure respectively), indicating that the seizure duration was not affected on repeated administration of both drugs. There was also no treatment period interaction (P value of 0.474 and 0.857 for motor and electrical seizure respectively) indicating an absence of carry-over effect. This meant that there was no difference in response to treatment in the first period compared with the second period.

As results for both period and treatment period interaction were not significant, we proceeded to analyse the treatment effect. As shown in Table 2, etomidate had a significantly longer mean seizure duration compared to propofol for both the motor and electrical components (P <0.01). It was also noted that the standard deviation for etomidate was comparatively greater for all categories.

[FIGURE 1 OMITTED]

Haemodynamic parameters are shown in Figures 1 and 2. There was no significant difference in baseline MAP and heart rate between the groups. No significant hypo- or hypertension was observed in either group post-induction. In both groups, etomidate did not attenuate the hypertensive response associated with ECT and resulted in significantly higher mean MAP post-ECT at three minutes. Propofol in Group IB demonstrated higher mean MAP post-ECT compared to Group IIA. In Group I, none of the subsequent mean MAP values showed significant difference from baseline value. In Group II, both subgroups demonstrated significant increase in mean MAP at nine and 12 minutes, while increase in mean MAP at three and six minutes was only significant in the etomidate group, Group IIB.

[FIGURE 2 OMITTED]

There was no difference in heart rate between the groups post-induction. There was significant tachycardia for both the subgroups in Group I at three and nine minutes. All the four subgroups demonstrated similar degrees of tachycardia at 12 minutes.

Eight out of 20 patients who received etomidate developed either myoclonus (n=6) or pain on injection (n=2). Six out of 20 patients who received propofol demonstrated either pain on injection (n=5) or abnormal movement (n=1). The most prominent side-effect was therefore myoclonus with etomidate, not observed in patients receiving propofol. None of the patients showed significant desaturation during the procedure.

DISCUSSION

ECT has a well-established role in the management of patients who have not responded to psychopharmacological treatment (2-4). Many studies documenting the efficacy of ECT for depressive illness have been published, finding ECT superior to 'sham' ECT and to medications in the treatment of patients with severe depressive illness (3), particularly those with psychotic and suicidal symptoms (5).

Electroconvulsive therapy, performed in geographically dispersed locations outside the operating rooms, requires scheduling and staffing for anaesthetics which are quite different from those in the operating rooms (23). The procedure itself consists of programmed electrical stimulation of the central nervous system to initiate seizure activity. In terms of haemodynamic effects, seizure activity causes an initial parasympathetic discharge, later followed by sympathetic discharge (24). The parasympathetic discharge is manifested as bradycardia, rarely asystole (25), premature atrial and ventricular contractions, or a combination of these abnormalities. The sympathetic discharge is associated with tachycardia, hypertension, premature ventricular contractions and, rarely, ventricular tachycardia. Electrocardiogram changes, including ST-segment depression and T-wave inversion (26), presumed to be secondary to the sympathetic discharge, may also be seen after ECT, without biochemical evidence of myocardial infarction (27).

With the introduction of intravenous anaesthetic agents, neuromuscular blockade and assisted or controlled ventilation with 100% oxygen in 1963, anaesthesia has brought ECT into a new dimension in terms of patient comfort as well as amnesia during the procedure (1,28). The perfect induction agent for ECT would ensure rapid unconsciousness, be painless on injection, have no haemodynamic effects, would not affect seizure duration or amplitude, provide rapid recovery and be inexpensive (28).

The search for an ideal anaesthetic agent for ECT has been an ongoing process. Most of the anaesthetic agents used have anticonvulsant properties because of their effects on the gamma-aminobutyric acid receptors (29,30). The efficacy of ECT requires knowledge of anaesthetic precepts, understanding of the interaction between anaesthetic drugs and seizure activity, and awareness of the physiological effects of ECT as well as the treatment of those effects (31).

Historically, because of its short duration of action and minimal effect on seizure threshold, methohexitone is the most popular intravenous anaesthetic for ECT (32). Psychomotor functions recover more quickly after administration of methohexitone compared with thiopentone33, with the seizure duration being reduced or comparable in the thiopentone group (34). Low doses of methohexitone (e.g. 0.5 to 1.0 mg/kg) have even been reported to provoke convulsions in patients with epilepsy (35).

Propofol has been used as an induction agent for ECT, as it is an ultrashort-acting anaesthetic agent with good recovery profile, including an earlier return of cognitive function (9). Its potent anticonvulsant properties may be problematic for certain seizure-resistant individuals. Ketamine reportedly increases the duration of electrically induced seizures and has thus been recommended for patients with an increased seizure threshold (36). However, its drawbacks include a slower induction, delayed recovery and increased incidence of nausea and ataxia during recovery compared to methohexitone (37). The enhanced haemodynamic response and resultant inrease in intracranial pressure make ketamine less desirable than methohexitone and propofol for routine ECT treatments (38).

In the past decade, there has been a resurgence of interest in etomidate, especially with the introduction of the drug in lipid formulation designed to reduce the problems of thrombophlebitis, pain on injection and haemolysis (39). Etomidate has good cardiovascular stability and allows rapid recovery. It has also been shown to prolong seizure duration in elderly seizure-resistant patients undergoing ECT (10) and has been suggested as an alternative anaesthetic agent for the procedure (13,16). Interestingly, there have been case reports of spontaneous seizure after administration of etomidate for ECT (40,41). However, etomidate-induced seizures are an exceedingly rare event and should not alter usual ECT practice for patients without risk for seizure (40).

For several years, etomidate has been under-utilised due to its feared complications of adrenal suppression and anaphylaxis. There have been studies showing increased risk of adrenal suppression following single doses of etomidate in critically injured patients (42), haemodynamically unstable patients (43), patients with septic shock (44) and patients undergoing emergency surgery (45). ryding questioned the wisdom of using etomidate in ECT, since immunosuppression could be present in mostly susceptible, elderly depressive patients, possibly not eating, inactive and with self-neglect (46). Our study, conducted on 20 ASA I or II patients, did not address the issue of adrenal suppression and hence it may not be appropriate to extrapolate our results to the patient groups depicted by ryding. Earlier studies by Fragen (47) and Wagner (48), however, found that in healthy adults undergoing elective surgery, the adrenal-suppressive effects of etomidate were reversible and lasted less than 24 hours (<6 hours in most cases). In a recently published prospective observational study, Tekwani et al found no statistically significant increase in hospital length of stay or mortality in patients given etomidate for rapid-sequence intubation (49). They concluded that their data did not support suggestions that the use of etomidate for intubation in the emergency department be abandoned.

As an induction agent widely used for patients undergoing ECT, propofol has been shown to reduce cognitive dysfunction following ECT, but also significantly shortens the seizure duration (7,8). Attempts have been made to use smaller doses of propofol in order to minimise its effect on seizure duration. Avmarov et al suggested that a dose of 0.75 mg/kg could shorten the seizure duration in comparison with methohexitone (11). However, it was doubtful whether such a low dose would be adequate to induce anaesthesia without significant risk of awareness or recall. Avmarov et al also compared different doses of 0.75 mg/kg, 1 mg/kg and 1.5 mg/kg of propofol with 0.15 mg/kg, 0.2 mg/kg and 0.3 mg/kg of etomidate (11). They found no significant dose-related differences in motor and EEG seizure durations with different doses of etomidate. Based on the above, we opted to use propofol 1.5 mg/kg and etomidate 0.3 mg/kg for induction of anaesthesia in this study, doses regarded as approximately "equihypnotic" by Avmarov (11).

It has been suggested that monitoring of EEG bispectral index scores (BIS) during ECT may be useful in ensuring adequate depth of anaesthesia. This is especially so when low doses of induction agents are used in an attempt to minimise effects on seizure duration. Using BIS monitoring, Sartorius et al investigated the influence of anaesthetic drugs on seizure adequacy or on treatment success (50). They found significant correlations for pre-ECT BIS versus motor response time, seizure concordance, ictal coherence and peak heart rate, and concluded that controlling BIS-levels before stimulation may have an additional effect on treatment success.

In our study, both the motor and EEG seizure duration demonstrated neither period effect nor treatment by period interaction. Differences in the mean motor seizure duration might suggest the possibility of a period effect, even though it was not significant statistically. This could be attributed to a lack of clear end-point in measurement of motor seizure duration as compared to EEG seizure duration. The possibility of a period effect was convincingly rejected by examining the EEG seizure duration, the gold standard for measuring seizure activity. The washout period of two to three days was adequate as no carry-over effects were demonstrated. This was expected, as both induction agents used were ultrashort-acting anaesthetic agents.

The standard deviation of seizure duration in patients receiving etomidate spread through a bigger range compared to propofol. It was possible that patients could manifest widely differing pharmacodynamic responses in the context of seizure duration to etomidate. Etomidate produced a significantly longer seizure duration compared with propofol in both electrical and motor seizures. The motor and electrical seizure duration for etomidate may extend beyond 100 seconds. It would confer benefit to patients who are seizure-resistant or have inadequate seizure duration. On the other hand, care should be taken in anticipation of prolonged seizure of two minutes or longer. This is of sufficient concern for the psychiatrist to terminate the seizure after discussion with an anaesthetist (17). This could mean that the advantage of the etomidate group in having longer seizure duration is offset by the possibility of having a prolonged seizure. The longest seizure duration was 120 seconds in our study and termination of seizure was not necessary.

We checked for period effect and period by treatment interaction for the patient's baseline blood pressure in Groups I and II. We noted that there was period effect but no period by treatment interaction, signifying no carry-over effect due to treatment. The mean MAP during the second procedure was consistently lower in both groups. We hypothesise that the higher blood pressure during the first ECT might be attributed to anxiety and higher sympathetic activity. By the time the patient came for the second ECT, anxiety level would be much reduced with knowledge from the previous experience.

Avmarov reported that propofol conferred better protection against untoward hypertensive responses to ECT compared to etomidate (11). Our results showed that the mean MAP readings were higher with etomidate post-ECT at three minutes in both groups, and at six and nine minutes in Group II. However, the results were not significant in the etomidate treatment group in Group IA, though the mean MAP was higher than propofol at six, nine and 12 minutes. This could be due to the high level of variability between the baseline and MAP post-ECT for Group I. Group IB demonstrated a significant rise in mean MAP post-ECT at three minutes, and thus we could not conclude that propofol conferred better protection in attenuating hypertensive response post-ECT. Based on our results, we concluded that neither drugs demonstrated consistent effects in suppressing the rise in blood pressure post-ECT.

Analysis of the mean heart rate in comparison with the baseline reading showed that the increase in heart rate at three minutes post-ECT was significant in Group I and bordered on being significant (P=0.05) in Group II. Both the drugs did not demonstrate consistent effects in suppressing the rise in heart rate post-ECT. Even though there were significant differences in mean heart rate at nine and 12 minutes for Group I and at 12 minutes for Group II, no conclusion could be made as many of the patients had started to regain consciousness by then.

This lack of difference in cardiovascular effects between the two study drugs is in agreement with rosa, who compared propofol, etomidate and thiopentone during ECT (51). However, Gazdag found that during the treatment, the mean MAP was increased by 8.1 mmHg by propofol and 18.3 mmHg by etomidate (52). The authors concluded that propofol was more effective in attenuating the seizure-induced increase in MAP than etomidate, and supported the use of propofol in patients with greater cardiovascular risk. This is in contrast with the review by Folk et al, who recommended that etomidate may be considered in patients with decreased cardiac output (28). These differences could be attributed to different characteristics of population studied--depressive disorders in Rosa's study, schizophrenia in Gazdag's study and a heterogenous group in our study. Because the biochemical bases of schizophrenia differ from that of depression, the influence of these biochemical differences on electrophysiologic variables and possibly haemodynamic effects cannot be ruled out.

Myoclonus was the most prominent side-effect of the etomidate group, consisting of 30% of patients who received the induction agent. Our figures were lower than the reported incidence of 50 to 80% in unpremedicated patients (29). It would be tempting to assume that seizure activity might have occurred post-etomidate resulting in manifestation of myoclonus. However, EEG recorded at the time of myoclonus failed to demonstrate epileptic paroxysms or ictal spiking (30); instead it usually showed slow a-waves indicating deep anaesthesia of the patients (29). One possible explanation for the occurrence of myoclonus is the transient disinhibition of subcortical structures during the transition from consciousness to unconsciousness (29).

Pain on injection with etomidate occurred in only two out of 20 patients (10%) in our study. It is well recognised that etomidate dissolved in lipofundin has an almost physiological osmolality and is devoid of pain on injection, postoperative thrombophlebitis or haemolytic effects (29,39). This is in contrast with the earlier formulation using propylene glycol as solvent, which may cause direct injury resulting in pain and venous sequelae (53). At the time of our study, the Propofol-[R]Lipuro (B. Braun Ltd, Melsungen, Germany) formulation was not yet available in our hospital. Our study with propofol (Diprivan[R], AstraZeneca, UK) mixed with lignocaine was associated with pain on injection in eight out of 20 patients (25%). Even though our figures compared favourably with reported incidence of 32 to 67% (54), it would be reasonable to expect the incidence to reduce even further with propofol in an emulsion of long- and medium-chain triglycerides, as reported by rau et al (55).

CONCLUSION

Etomidate was associated with a significantly longer motor and EEG seizure duration compared to propofol during ECT. Neither drug demonstrated consistent effects in suppressing the rise in heart rate or blood pressure following ECT.

REFERENCES

(1.) Selvin BL. Electroconvulsive therapy. Anesthesiology 1987; 67:367-387.

(2.) Potter WZ, Rudorfer MV. Electroconvulsive therapy--a modern medical procedure. N Engl J Med 1993; 328:882-883.

(3.) Fink M, Taylor MA. Electroconvulsive therapy: evidence and challenges. JAMA 2007; 298:330-332.

(4.) Lisanby SH. Electroconvulsive therapy for depression. N Engl J Med 2007; 357:1939-1945.

(5.) Dettling M, Anghelescu I, Bajbouj M, Guevara-Cuellar CA, Pineda-Canar CA, Torri A et al. Electroconvulsive therapy for depression. N Engl J Med 2008; 358:645-646.

(6.) American Psychiatric Association Task Force on ECT. The practice of electroconvulsive therapy. recommendations for treatment, training and privileging, 2nd ed. American Psychiatric Press, Washington, DC 2002.

(7.) Fredman B, D'Etienne J, Smith I, Husain MM, White PF. Anesthesia for electroconvulsive therapy: effects of propofol and methohexital on seizure activity and recovery. Anesth Analg 1994; 79:75-79.

(8.) Geretsegger C, Rochowanski E, Kartnig C, Unterrainer AF. Propofol and methohexital as anesthetic agents for electroconvulsive therapy (ECT): a comparison of seizure-quality measures and vital signs. J ECT 1998; 14:28-35.

(9.) Rasimas JJ, Stevens SR, Rasmussen KG. Seizure length in electroconvulsive therapy as a function of age, sex, and treatment number. J ECT 2007; 23:14-16.

(10.) Ilivicky H, Caroff SN, Simone AF. Etomidate during ECT for elderly seizure-resistant patients. Am J Psychiatry 1995; 152:957-958.

(11.) Avramov MN, Husain MM, White PF. The comparative effects of methohexital, propofol, and etomidate for electroconvulsive therapy. Anesth Analg 1995; 81:596-602.

(12.) Stadtland C, Erfurth A, Ruta U, Michael N. A switch from propofol to etomidate during an ECT course increases EEG and motor seizure duration. J ECT 2002; 18:22-25.

(13.) Saffer S, Berk M. Anesthetic induction for ECT with etomidate is associated with longer duration than thiopentone. J ECT 1998; 14:89-93.

(14.) Catherine D, Anil Kr, Howard JI, Stanley NC. Augmentation of seizure induction in electroconvulsive therapy: A clinical reappraisal. J ECT 2002; 18:118-125.

(15.) Hughes RL. More on etomidate and ECT. Anaesthesia 2006; 61:407.

(16.) Ibrahim FI, Aldridge C. Etomidate and ECT. Anaesthesia 2006; 61:192.

(17.) Lock T. The ECT Handbook. The Second report of the royal College of Psychiatrists' Special Committee on ECT. Freeman CP, ed. London: Royal College of Psychiatrists 1995. p. 79-80.

(18.) Chan YH. Biostatistics 301. Repeated measurement analysis. Singapore Med J 2004; 45:354-368.

(19.) Altman DG. Practical Statistics for Medical research. London: Chapman and Hall/CRC 1990. p. 467-471.

(20.) Senn S. Cross-over Trials in Clinical Research. 35-82. John Wiley & Sons Ltd, Chichester 2002; p. 35-82.

(21.) Woods Jr, Williams JG, Tavel M. The two-period crossover design in medical research. Ann Intern Med 1989; 110:560-566.

(22.) Abernethy AP, Currow DC, Frith PA, Fazekas BS, McHugh A, Bui C. randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea. BMJ 2003; 327:523-528.

(23.) Dexter F, Macario A, Cowen DS. Staffing and case scheduling for anesthesia in geographically dispersed locations outside of operating rooms. Curr Opin Anaesthesiol 2006; 19:453-458.

(24.) Saito S. Anesthesia management for electroconvulsive therapy: hemodynamic and respiratory management. J Anesth 2005; 19:142-149.

(25.) McCall WV. Asystole in electroconvulsive therapy: report of four cases. J Clin Psychiatry 1996; 57:199-203.

(26.) Conckey GH, Conti Cr. Electroconvulsive therapy-induced transient T-wave inversions on ECG. Clin Cardiol 1995; 18:418-420.

(27.) Dec Jr GW, Stern TA, Welch C. The effects of electroconvulsive therapy on serial electrocardiograms and serum cardiac enzyme values. A prospective study of depressed hospitalized inpatients. JAMA 1985; 253:2525-2529.

(28.) Folk JW, Kellner CH, Beale MD, Conroy JM, Duc TA. Anesthesia for electroconvulsive therapy: a review. J ECT 2000; 16:157-170.

(29.) Ostwald P, Doenicke AW. Etomidate revisited. Curr Opin Anaesthesiol 1998; 11:391-398.

(30.) Doenicke AW, Roizen MF, Kugler J, Kroll H, Foss J, Ostwald P. Reducing myoclonus after etomidate. Anesthesiology 1999; 90:113-119.

(31.) Wagner KJ, Mollenberg O, rentrop M, Werner C, Kochs EF. Guide to anaesthetic selection for electroconvulsive therapy. CNS Drugs 2005; 19:745-758.

(32.) O'Flaherty D, Giesecke AH. Electroconvulsive therapy and anesthesia. Curr Opin Anesthesiol 1991; 4:436-440.

(33.) Korttila K, Linnoila M, Ertaman P, Hakkinen S. recovery and simulated driving after intravenous anesthesia with thiopental, methohexital, propanidid or alphadione. Anesthesiology 1975; 43:291-299.

(34.) Dew RE, Kimball JN, Rosenquist PB, McCall WV. Seizure length and clinical outcome in electroconvulsive therapy using methohexital or thiopental. J ECT 2005; 21:16-18.

(35.) Modica PA, Tempelhoff r, White PF. Pro- and anticonvulsant effects of anesthetics (Part 2). Anesth Analg 1990; 70:433-444.

(36.) rasmussen KG, Jarvis Mr, Zorumski CF. Ketamine anesthesia in electroconvulsive therapy. Convuls Ther 1996; 12:217-223.

(37.) McInnes EJ, James NM. A comparison of ketamine and methohexital in ECT. Med J Aust 1972; 1:1031-1032.

(38.) Ding Z, White PF. Anesthesia for electroconvulsive therapy. Anesth Analg 2002; 94:1351-1364.

(39.) Doenicke A, Roizen MF, Hoernecke R, Mayer M, Ostwald P, Foss J. Haemolysis after etomidate: comparison of propylene glycol and lipid formulations. Br J Anaesth 1997; 79:386-388.

(40.) Griffeth BT, Mehra A. Etomidate and unpredicted seizures during electroconvulsive therapy. J ECT 2007; 23:177-178.

(41.) Nicoll K, Callender J. Etomidate-induced convulsion prior to electroconvulsive therapy. Br J Psychiatry 2000; 177:373.

(42.) Cotton BA, Guillamondegui OD, Fleming SB, Carpenter rO, Patel SH, Morris Jr JA et al. Increased risk of adrenal insufficiency following etomidate exposure in critically injured patients. Arch Surg 2008; 143:62-67.

(43.) Lundy JB, Slane ML, Frizzi JD. Acute adrenal insufficiency after a single dose of etomidate. J Intensive Care Med 2007; 22:111-117.

(44.) Jackson WL Jr. Should we use etomidate as an induction agent for endotracheal intubation in patients with septic shock? A critical appraisal. Chest 2005; 127:1031-1038.

(45.) Morris C, McAllister C. Etomidate for emergency anaesthesia; mad, bad and dangerous to know? Anaesthesia 2005; 60:737-740.

(46.) Ryding FN. Etomidate and ECT. Anaesthesia 2006; 61:192.

(47.) Fragen RJ, Shanks CA, Molteni A, Avram MJ. Effects of etomidate on hormonal responses to surgical stress. Anesthesiology 1984; 61:652-656.

(48.) Wagner RL, White PF. Etomidate inhibits adrenocortical function in surgical patients. Anesthesiology 1984; 61:647-651.

(49.) Tekwani KL, Watts HF, Rzechula KH, Sweis RT, Kulstad EB. A prospective observational study of the effect of etomidate on septic patient mortality and length of stay. Acad Emerg Med 2009; 16:11-14.

(50.) Sartorius A, Munoz-Canales EM, Krumm B, Krier A, Andres FJ, Bender HJ et al. ECT anesthesia: the lighter the better? Pharmacopsychiatry 2006; 39:201-204.

(51.) rosa MA, Rosa MO, Marcolin MA. Fregni F. Cardiovascular effects of anesthesia in ECT: a randomized, double-blind comparison of etomidate, propofol, and thiopental. J ECT 2007; 23:6-8.

(52.) Gazdag G, Kocsis N, Tolna J, Ivanyi Z. Etomidate versus propofol for electroconvulsive therapy in patients with schizophrenia. J ECT 2004; 20:225-229.

(53.) Doenicke AW, Roizen MF, Hoernecke R, Lorenz W, Ostwald P. Solvent for etomidate may cause pain and adverse effects. Br J Anaesth 1999; 83:464-466.

(54.) Nathanson MH, Gajraj NM, Russell JA. Prevention of pain on injection of propofol: a comparison of lidocaine with alfentanil. Anesth Analg 1996; 82:469-471.

(55.) Rau J, Roizen MF, Doenicke AW, O'Connor MF, Strohschneider U. Propofol in an emulsion of long- and medium-chain triglycerides: the effect on pain. Anesth Analg 2001; 93:382-384.

H. L. Tan *, C. Y. Lee([dagger])

Department of Anaesthesia and Intensive Care, Kuala Lumpur Hospital, Kuala Lumpur, Malaysia

* M.D. (UKM), M.Med. (Anaesth.) UKM, Clinical Specialist.

([dagger]) M.B., B.S., M.Med. (Anaesth.) U.K.M., F.A.N.Z.C.A., Clinical Professor, Consultant Anaesthesiologist, Department of Anaesthesiology and Intensive Care, Faculty of Medicine, National University of Malaysia.

Address for reprints: Dr C. Y. Lee, Department of Anaesthesiology and Intensive Care, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur, Malaysia.

Accepted for publication on April 6, 2009.
Table 1

Demographic data and psychiatric disorder, values expressed as
mean [+ or -] SD or number (%) where appropriate

                              Group I              Group II
                              (n=10)               (n=10)

Age (y)                       32.8 [+ or -] 10.9   33.0 [+ or -] 9.0
Weight (kg)                   57.3 [+ or -] 14.1   52.5 [+ or -] 11.6
Height (m)                    1.6 [+ or -] 0.1     1.6 [+ or -] 0.1
Body mass index               22.2 [+ or -] 4.1    21.7 [+ or -] 4.1
(kg/[m.sup.2])
Race
  Malay                       5 (50%)              4 (40%)
  Chinese                     2 (20%)              4 (40%)
  Indian                      3 (30%)              1 (10%)
  Others                      0 (0%)               1 (10%)
Diagnosis
  Schizophrenia               3 (30%)              4 (40%)
  Bipolar mood disorder       2 (20%)              4 (40%)
  Major depressive disorder   1 (10%)              1 (10%)
  Brief psychotic disorder    1 (10%)              1 (10%)
  Schizophreniform disorder   2 (20%)              0 (0 %)
  Post partum psychosis       1 (10%)              0 (0 %)

Table 2
Motor and electrical seizure duration, values expressed as
mean [+ or -] SD

                            Motor seizure         Electrical seizure
                            duration (s)          duration (s)

Group I    IA: etomidate    61.9 [+ or -] 37.4    73.1 [+ or -] 43.6
(n=10)     IB: propofol     28.2 [+ or -] 14.0    39.3 [+ or -] 14.6

Group II   IIA: propofol    20.9 [+ or -]  5.5    29.5 [+ or -] 12.6
(n=10)     IIB: etomidate   43.4 [+ or -] 20.1    67.2 [+ or -] 37.4
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