The Effects of Anesthetic Change on Electrographic Seizure Duration during Electroconvulsive Therapy

Introduction

The routine use of muscle relaxants in electroconvulsive therapy (ECT) starting in the 1950s has transformed the procedure from one with great morbidity (up to 35% vertebral fracture rate)¹ to one with few serious physical side effects.² ECT anesthesia involves short-acting general anesthetics to produce unconsciousness during the period of muscle relaxation,³ and optimal anesthetic selection is an area of active research. Beyond initial anesthetic choice, at times during the ECT course anesthesia may also be changed, in particular with the intention of modifying seizure duration in the case of excessively short or long seizures. Given this, data on a large cohort of patients who undergo a switch in anesthetic during the ECT course may provide normative data to guide anesthesiologists and psychiatrists in considering an anesthetic change. This study analyzes the effects of switching anesthetic on seizure duration during acute course ECT.

Methods

This was a single-center retrospective cohort study of patients aged 18+ receiving a first lifetime course of acute ECT from January 2000 to June 2017 and who had a change in anesthetic agent during the first twelve treatments. Treatments were performed using a Mecta Spectrum 5000Q (Tualatin, OR) with individualized seizure threshold determination⁴ and subsequent suprathreshold treatments generally delivered thrice weekly.⁵ Dose and electrode placement were chosen clinically by the treating psychiatrist. Anesthetics used were methohexital, etomidate, propofol, and thiopental, with weight-based dosing and changes in anesthetic made at the discretion of the treating physicians. Succinylcholine was used as the muscle relaxant for all patients. Seizure duration was determined by the treating psychiatrist based on two lead bifrontal or fronto-mastoid EEG with propofol given at seizure termination or 120 seconds of continued seizure activity to reduce posttreatment agitation. For the primary analysis, the log-transformed seizure duration following anesthesia switch was modeled using linear regression, with prior seizure duration, sex, age (z-score), diagnosis (major depressive disorder, bipolar disorder, other), type of ECT [bilateral, right unilateral brief pulse (RUL-BP), right unilateral ultrabrief pulse (RUL-UBP)], applied ECT charge (z-score), muscle relaxant dose (z-score), anesthesia type prior to the switch (etomidate, thiopental, propofol, methohexital), and anesthesia type following the switch (etomidate, thiopental, propofol, methohexital) as predictors using R (v. 4, Vienna, Austria). Analysis was limited to anesthesia switches observed at least 10 times.

Results

In total, 198 patients underwent anesthetic switches at mean of 6.9±3.0 treatments (Table S1). Of these patients 86 (43.4%) were men, and mean age was 48.6±15.4 years. Diagnoses were major depressive disorder (145; 73.2%), bipolar disorder (44; 22.2%), and other (9; 4.5%). At the treatment immediately preceding anesthetic switch 102 patients (51.5%) were receiving RUL-BP, 76 (38.4%) were receiving bilateral, and 20 (10.1%) were receiving right RUL-UBP treatments. Following the anesthetic switch 86 (43.4%) patients received RUL-BP, 90 (45.9%) received bilateral, and 22 (11.1%) received RUL-UBP treatments. Anesthetics prior to switching were methohexital (116; 58.6%), propofol (46; 23.2%), thiopental (26; 13.1%), and etomidate (10, 5.1%), and following the switch were methohexital (49; 24.7%), propofol (24; 12.1%), thiopental (27; 13.6%), and etomidate (98; 49.5%).

The most common switches were methohexital to etomidate (n=65), methohexital to thiopental (n=27), and propofol to methohexital (n=26). Analysis of the change in seizure duration for the treatments immediately prior to and following the anesthetic switch shows variable effects of the switches on seizure duration (Figure S1). In a linear model of seizure duration following anesthesia switch, higher applied ECT charge was associated with shorter seizure duration, while age, sex, diagnosis, and electrode placement were not significantly associated (Table 1). Longer prior seizures were associated with longer seizures following anesthesia switch. Among anesthetic switches, transition from propofol was associated with an increase in seizure duration (estimate 0.21; 95% CI 0.01-9.42; p=0.04), while transition to etomidate was likewise associated with longer seizures (estimate 0.24; 95% CI 0.05-0.44; p=0.015). Other switches were not significantly associated with change in seizure duration.

Table 1:

linear model of change in seizure duration before and after anesthetic switch.

Predictors	Estimates	CI	p
Prior seizure duration (log)	0.32	0.18 – 0.46	<0.001
Sex (male)	0.03	−0.11 – 0.18	0.646
Age (z score)	0	−0.07 – 0.06	0.978
Diagnosis
Major depressive disorder	−0.03	−0.32 – 0.25	0.814
Bipolar disorder	−0.12	−0.42 – 0.18	0.447
ECT Type
Right unilateral brief pulse	0.15	−0.04 – 0.35	0.127
Bilateral	0.09	−0.12 – 0.29	0.407
ECT charge (z score)	−0.07	−0.13 – −0.01	0.032
Muscle relaxant dose (Z score)	−0.02	−0.08 – 0.04	0.531
Anesthetic prior to switch
etomidate	0.06	−0.28 – 0.39	0.731
thiopental	0.2	−0.02 – 0.42	0.08
propofol	0.21	0.01 – 0.42	0.04
Anesthetic following switch
etomidate	0.24	0.05 – 0.44	0.015
thiopental	0.15	−0.13 – 0.43	0.29
propofol	−0.21	−0.48 – 0.07	0.142

Discussion

While there is extensive literature comparing ECT anesthetics,^6,7 the vast majority of these studies compare seizure durations among groups assigned to different anesthetics. In contrast, this study addresses switches in anesthetics for patients already undergoing ECT, a subject that has received minimal prior study. Our results compare treatments using methohexital, thiopental, etomidate, and propofol, yielding 12 potential pairwise switches of which eight occurred in 10 or more patients and are analyzed here. Both the transition from propofol and the transition to etomidate were associated with increase in seizure duration, while switches among other anesthetics were not associated with changes in seizure duration. These results largely match prior research on between-anesthetic differences, with meta-analysis indicating increased seizure duration using etomidate,⁶ and shorter seizures with propofol vs. methohexital.⁷

Overall these results suggest that with the exception of a switches in anesthetic from propofol or to etomidate, other switches are unlikely to cause significant changes in seizure duration. Our linear model further indicates that patient-level factors including age, sex, diagnosis, and ECT electrode placement do not significantly influence the change in seizure duration following anesthesia switch, while increasing the applied charge is correlated with shorter seizures as has been demonstrated previously.⁸

Strengths of this study include a large sample size. Additionally, consistency of ECT treatment team and protocols allows for clear comparisons among the patients receiving anesthetic switches, and reduces unmeasured sources of variability. The chief limitation is the retrospective cohort design, in which treatment decisions were made clinically rather than algorithmically. As a result, we are unable to assess why the treatment team decided to change anesthesia, and how the new anesthetic was chosen. As many anesthesia switches are likely made due to drug availability (for instance, many of the switches to thiopental in this study were as the result of a methohexital shortage at one point during the study period) or to avoid treatment adverse effects (e.g. cardiac events with thiopental),⁹ this study is unable to examine the full spectrum of causes or effects of these anesthesia changes. Moreover we do not have standardized records of treatment efficacy or side effects, and are unable to quantify the effects of anesthesia switch on these outcomes.

Conclusion

Based on 198 anesthetic switches during acute course ECT among methohexital, thiopental, etomidate, and propofol, the transition from propofol and the transition to etomidate were independently associated with lengthening of seizures.