Ketofol, Again
Out on PubMed, from researchers in Chongqing, China, is this study:Subanesthetic dose of ketamine for the antidepressant effects and the associated cognitive impairments of electroconvulsive therapy in elderly patients-A randomized, double-blind, controlled clinical study.
Brain Behav. 2020 Dec 11:e01775. doi: 10.1002/brb3.1775. Online ahead of print.PMID: 33305900
The abstract is copied below:
Objectives: We previously confirmed that low-dose ketamine, as an adjunctive anesthetic for electroconvulsive therapy (ECT) in adult patients with depression, accelerates the effects of ECT and reduces the ECT-induced learning and memory deficits. This study explored the efficacy and safety of low-dose ketamine in elderly patients with depression.
Methods: Elderly patients with depression (N = 157) were randomly divided into two groups: propofol anesthesia group (group P) and propofol combined with ketamine anesthesia group (group KP). Patients in group KP were given low-dose ketamine (0.3 mg/kg) for each ECT treatment; patients in group P were given the same amount of normal saline. Depressive symptoms and global cognitive functions were assessed using the 24-item Hamilton Depression Rating Scale and Mini-Mental State Examination, respectively, at baseline, 1 day after the 1st, 2nd, 4th, and 6th ECT sessions, and 1 day after the end of the ECT course. ECT effects of and complications were recorded.
Results: In total, 67 patients in group KP and 70 in group P completed the study. After the ECT, the response and remission rates were 82.09% and 73.13%, respectively, in group KP, and 81.43% and 68.57%, respectively, in group P; there was no statistical difference between groups. However, the incidence of cognitive function impairment was lower in group KP (10.4%) than in group P (25.7%), while different electrical dose and seizure duration were required during the course of treatment between the two groups. There was no difference in the complications of ECT between groups.
Conclusions: Low-dose ketamine is safe as an adjunct anesthetic for elderly patients subjected to ECT. It has a protective effect on cognitive function and may accelerate the antidepressant effects of ECT.
Keywords: depression; elderly; electroconvulsive therapy; ketamine
2 figures from the paper:
And from the text:
The purpose of this study was to investigate the safety of intravenous low-dose ketamine (0.3 mg/kg) under propofol anesthesia, as
well as its efficacy in reducing cognitive impairments caused by ECT.
We found no significant psychotropic or hemodynamic adverse effects in patients who received ketamine during ECT. Although the
adjunctive low-dose ketamine did not affect the final response and
remission rates, the effects of ECT appeared earlier in the treatment
process. Moreover, seizure duration was longer in the early stages
of the treatment course and a lower electrical dose was required at
the end of the ECT course in patients administered with ketamine
plus propofol than in those administered only with propofol. MMSE
scores decreased at the beginning of treatment, but there was no
difference between the two groups; in addition, there was no difference at the end of the ECT course. However, the incidence of cognitive dysfunction during treatment was higher in patients who
received only propofol.
Electrocardiogram, noninvasive blood pressure measurement, and pulse oxygen saturation analysis were conducted for all subjects. Anesthesia was induced before the ECT. Patients in group P received 1.5 mg/kg propofol (Corden Pharma S.p.A, No: X17073B) and 1 mg/kg suxamethonium chloride (Shanghai Xudong Haipu Pharmaceutical Co. LTD, NO: AA151201) intravenously. The same volume saline was injected as the placebo adjunct anesthetic. Patients in group KP received 0.3 mg/kg ketamine before receiving 1.5 mg/kg propofol and 1 mg/kg suxamethonium chloride n. During the treatment, patients were supported by a mask with 100% oxygen, and a short‐acting β‐blocker was used as necessary.
Electroconvulsive therapy
ECT was conducted three times a week using Thymatron DGx ECT system (Somatics LLC, Lake, IL), with the electrode placed on both temporal sides. The first energy for ECT was determined according to the patient's age: energy percent = age × 0.5%. The stimulation energy was adjusted based on the seizure time. The energy was increased by 5% in the subsequent treatment if the seizure time was <25 s. Patients were usually subjected to 8–12 sessions of ECT, and ECT was stopped if the patients achieved the standard of remission, as described below.
ECT was conducted three times a week using Thymatron DGx ECT system (Somatics LLC, Lake, IL), with the electrode placed on both temporal sides. The first energy for ECT was determined according to the patient's age: energy percent = age × 0.5%. The stimulation energy was adjusted based on the seizure time. The energy was increased by 5% in the subsequent treatment if the seizure time was <25 s. Patients were usually subjected to 8–12 sessions of ECT, and ECT was stopped if the patients achieved the standard of remission, as described below.
The pdf is here.
This study adds to the evidence base on the characteristics of combined propofol/ketamine anesthesia for ECT in older patients (here, mean age 65). Again, a signal is identified (slightly faster response, possibly slight beneficial cognitive effects), but it is small and not clearly clinically significant. It seems somewhat self-defeating to go to the trouble of conducting a moderate-sized clinical trial and then use a cognitive assessment tool as rudimentary as the MMSE.
Yes, ketofol is a good anesthetic alternative to have in the ECT toolbox, but certainly not a game-changer.
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