A comparison of dexmedetomidine with propofol versus esmolol with propofol to attenuate the hemodynamic stress responses after electroconvulsive therapy.

BACKGROUND: Modified electroconvulsive therapy (ECT) under anesthesia is an important modality in the treatment of severe, persistent depression; bipolar disorder and schizophrenia; especially in cases resistant to pharmacologic therapy. AIM: The aim of the present study is to compare the effects of dexmedetomidine and esmolol on patients' hemodynamics, motor seizure duration, and recovery times following ECT.
MATERIALS AND METHODS: Ninety cases aged between 18 and 50 years of the American Society of Anesthesiologists grade I and II; were randomly divided into three groups of 30 each. Group A received normal saline (placebo), Group B received dexmedetomidine 1 μg/kg, and Group C received esmolol 1 mg/kg; followed by induction with propofol 1 mg/kg and muscle relaxation with succinylcholine 0.75 mg/kg. Hemodynamic parameters at baseline, after study drug infusion, after induction, and after ECT application were recorded at different time intervals. The motor seizure duration using arm isolation method and recovery times using postanesthesia discharge scoring system were noted.
RESULTS: The maximum increase in hemodynamic parameters was seen following the ECT current application. Post-ECT rise in mean arterial blood pressure and heart rate in dexmedetomidine group was significantly less as compared to esmolol and control group at 2, 4, 6, and 8 min using unpaired t-test. There was no significant difference in motor seizure activity duration, emergence, and recovery times among the three groups.
CONCLUSIONS: Both dexmedetomidine and esmolol attenuate the hyperdynamic response to ECT without affecting the seizure duration, but dexmedetomidine has a more favorable response in view of stable vitals, smooth emergence and no adverse effect on recovery duration.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Electroconvulsive therapy (ECT) is a well-established treatment for severe depression in patients who do not respond to pharmacotherapy. Nowadays, almost all the ECT procedures are performed under general anesthesia; also known as modified ECT. However, it is commonly associated with acute hyperdynamic responses, including initial parasympathetic response followed by transient hypertension and tachycardia due to the release of catecholamines in the body. During the sympathetic response, systolic blood pressure may increase by 30%–40% and heart rate (HR) may increase by 20% (or more).[1] These responses may be harmful to patients with ischemic heart disease, hypertension, and cerebrovascular disease. To attenuate this stress response, many pharmacological agents such as beta blockers, calcium channel blockers, α-2-agonists, direct-acting vasodilators, and local anesthetics were tried.[23456] Dexmedetomidine is a centrally acting highly specific α-2 adrenergic agonist with α2:α1 binding selectivity ratio of 1620:1 compared to 220:1 for clonidine. The advantages of intravenous (IV) dexmedetomidine as premedicant in anesthesia include sedation, analgesia, anxiolysis, and improved hemodynamic stability. It also effectively reduces the requirement of anesthetics.[7] Esmolol hydrochloride is a rapid onset, ultra-short acting β1 cardioselective adrenergic receptor antagonist administered only intravenously. It has a distribution half-life of 2 min and an elimination half-life of 9 min. After an initial dose of 0.5 mg/kg intravenously; over 60 s, its full therapeutic effect comes in 5 min, and its action ceases within 10–30 min following the discontinuation of drug. It thus appears quite suitable for use during a short-lived stress procedure such as laryngoscopy, tracheal intubation, or ECT.

For ECT, the optimal seizure duration remains unclear. As per psychiatry point of view, an adequate motor seizure is defined as the one that lasts more than 25–30 s. Too short (<10 s) or too long (>120 s) may reduce clinical efficacy.[1] The objectives of anesthesia to be kept in mind for modified ECT include rapid loss of consciousness, attenuation of hemodynamic responses, avoidance of gross movements, minimal interference with seizure, prompt, smooth and early recovery of spontaneous ventilation and consciousness. Furthermore, early ambulation and discharge to home should be considered.

Therefore, the present study was designed to compare the effects of dexmedetomidine and esmolol (followed by induction with propofol and muscle relaxation by succinylcholine) in attenuating the hemodynamic stress responses, motor seizure activity duration, and recovery times in patients who underwent modified ECT.

MATERIALS AND METHODS

After ethical committee clearance 90 cases, belonging to the American Society of Anesthesiologists Classes I and II, aged 18–50 years diagnosed with major depressive disorder (suicidal patients), schizophrenia, catatonia (in which first-line treatment failed), or bipolar disorder were included in the study. Patients with atrioventricular conduction block greater than first degree, history of major illness such as tuberculosis, bronchial asthma, hypertension, recent stroke, acute respiratory disorder, raised intracranial pressure from any cause, HR <50 bpm, systolic blood pressure (SBP) <90 mmHg or history of drug allergy to interventional drugs and pregnant females were excluded from the study. The study population was randomly divided into three groups (Groups A, B, and C) with thirty cases in each group. Preanesthetic evaluation was done thoroughly. Airway assessment using Mallampati grading; eye examination to rule out papilledema and other routine investigations were done. Chronic antidepressant medications were continued. The patient was kept nil by mouth for 6 h. On arrival of the patient in the ECT/operating room, a 20-gauge cannula was inserted, and an infusion of Ringer lactate was started. Multiparameter monitors were attached to record HR, noninvasive measurements of SBP, diastolic blood pressure (DBP), mean arterial blood pressure (MAP), continuous electrocardiogram monitoring, and oxygen saturation. After a stabilization period of 5 min, baseline vitals were taken. Group A received normal saline (placebo); Group B received dexmedetomidine 1 μg/kg (total volume 20 ml over 10 min); and Group C received esmolol 1 mg/kg (total volume 20 ml over 3 min) before induction using syringe pumps. Preoxygenation was done for 3 min through face mask with Bain's circuit. General anesthesia was induced with IV propofol 1 mg/kg till the loss of eyelash reflex. Then, tourniquet of the second arm was inflated, and succinylcholine 0.75 mg/kg IV was administered for neuromuscular relaxation. When fasciculations subsided, and adequate muscle relaxation was obtained, an oral soft bite block was placed in the mouth to avoid tongue bite. Psychiatrist was allowed to place bitemporal electrodes over forehead and a brief pulse stimulus of 90–120 volts maintenance electroconvulsive therapy current for 2 ms was given to produce seizures. The effectiveness of ECT current was verified by the appearance of tonic–clonic seizures. The controlled or assisted ventilation was continued with 100% oxygen until patient resumed adequate spontaneous breathing. The HR, SBP, DBP, and MAP were recorded at 0, 2, 4, 6, 8, 10 min, and thereafter every 5 min till 30 min and then every 15 min; following the ECT current. The duration from the ECT stimulus to the cessation of clonic tonic motor activity in the isolated arm was recorded using clinical method. The time from the end of succinylcholine administration until spontaneous breathing, eye opening, and obeying commands were recorded.

Patients were assessed for side effects such as nausea, vomiting, hypotension/hypertension, respiratory depression after the electrical stimulus and were discharged from the postanesthetic care unit to the psychiatry department according to postanesthesia discharge scoring system (PADSS) criteria.

Analysis

Data analysis was carried out using the SPSS package (IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp). Quantitative variables were presented as mean ± standard deviation and the differences were assessed using an independent sample t-test. Qualitative variables were presented as numbers and percentages, and Chi-square test was used for comparison. The alternative hypothesis was assumed, and value of P ≤ 0.05 was considered to be statistically significant.

RESULTS

The mean age, weight, and gender were comparable among the three groups as shown in Table 1.

Table 1

Demographic data

The baseline variables were comparable in all the three groups as shown in Table 2.

Table 2

The intergroup comparison of baseline vitals

Results were analyzed using unpaired t-test at various time intervals. There was a significant rise in HR at the time of ECT (P < 0.01) and it was maximum in control group about 29% (22 bpm) followed by esmolol group, i.e., about 14% (11 bpm) followed by dexmedetomidine group, which showed the least increase in mean HR, i.e., only 2% (2 bpm) from the baseline values. Also after dexmedetomidine infusion, a significant reduction in HR was noted, which was about 6% (5 bpm). Hence, the HR was stable and near to baseline at most of the times in Group B (dexmedetomidine group) [Table 3].

Table 3

Postelectroconvulsive therapy changes in heart rate in Group A, B, and C at different time interval

Similar to increase in HR, maximum rise in mean blood pressure was seen at the time of ECT application and it was maximum for control group, i.e., about 35.24% (30 mmHg); followed by esmolol group, i.e. 23% (30 mmHg); followed by dexmedetomidine group, which showed the least increase, i.e., 6.11% (6 mmHg) only; when compared to baseline values.

As stated above, parallel trends were seen in SBP and DBP. All the significant changes in hemodynamic variables (P < 0.01) were confined to 8–10 min following ECT current application; after which no significant variation was seen.

There was no significant difference in duration of motor seizure activity (Group A – 27.26 ± 3.68, Group B – 28.7 ± 3.27, Group C – 28.7 ± 3.81). In addition, recovery times were similar in all the groups (Group A – 508.26 ± 11.4 sec, Group B – 508.63 ± 10.37 sec and Group C – 507.86 ± 9.63 sec). Patients were shifted to the ward or were ready to go home when they met discharge criteria according to PADSS.

A minimum score of 7/8 or achieving same preoperative status is must before transferring the patient to a Phase 3 recovery area or home. Our patients were ambulatory and could be discharged to home after around 25–30 min, but we observed the patients for 60 min to check for any side effect of our interventional drugs as well as the procedure.

DISCUSSION

ECT induces generalized tonic–clonic epileptic seizure. The patients coming for ECT has already been taking a variety of anti-psychotic medications which makes them prone to even more exaggerated cardiovascular responses. However, the ideal pretreatment regimen to attenuate the acute hemodynamic response after ECT has not been identified. In our study, post-ECT hyperdynamic responses were significantly less in the dexmedetomidine group at 0, 2, 4, 6, and 8 min as compared with Group A and Group C. These observations were similar to the findings of Shams and El-Masry[7] and Begec et al.[8] Optimum motor seizure duration has been used to assess the effectiveness of modified ECT. Fu and White[9] have reported that dexmedetomidine slightly extended the seizure activity duration during ECT but our findings were similar to those of Shams and El-Masry,[7] Mizrak et al.,[10] Cohen and Stewart,[11] and Dodawad[12] who found no significant differences in the duration of seizures in their studies comparing the use of dexmedetomidine with the control population.

In addition, our results were parallel to the studies carried out by Saito et al.,[13] Howie et al.[14] and Weinger et al.[15] who found no significant differences in the duration of seizures, comparing the use of esmolol versus control group before ECT. Motor seizure duration, time to spontaneous breathing and obeying commands were comparable among all the groups.

Apart from stable hemodynamics, we observed that dexmedetomidine also reduced the post-ictal emergence agitation, panic and restlessness in the patients following the therapy. Emergence was clear, without any confusion and smooth. At the same time, duration of motor seizures was preserved, and recovery was not prolonged. No patient experienced headache, respiratory depression, hypoxemia, bradycardia, hypotension, jaw pain, and muscle spasms. Esmolol has a very fast onset of action (2 min) while dexmedetomidine has a little delayed onset of action and has to be given by infusion. To make double blinding possible many authors gave esmolol also in similar fashion as dexmedetomidine, but this may decrease the efficacy of esmolol as it is rapidly cleared from the body. To avoid this bias and rather than making drug (esmolol) less effective, we changed the anesthesiologist in last minute after giving one drug in bolus form and other as infusion, which is a preferred technique.[16]

ECT procedures are frequently performed in an outpatient setting; therefore, the anesthetic agents used should have rapid recovery profiles. In the present study, dexmedetomidine and esmolol did not prolong the recovery times. These drugs may be superior to other drugs for ECT because of their short half-life and wide therapeutic indices. However, the implications of these findings require further investigation.

CONCLUSION

Both dexmedetomidine and esmolol attenuate the hyperdynamic response to ECT without affecting the seizure duration, but dexmedetomidine has a more favorable response in view of stable vitals, smooth emergence, and no adverse effect on recovery duration.

Limitations

The monitoring of seizure duration by observing tonic–clonic activity and not using electroencephalogram (EEG) was a limitation of our study because EEG seizure duration activity may be longer than motor seizure activity.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.