Methohexital 500mg powder for solution for injection vials

BackgroundElectroconvulsive therapy (ECT) is a widely used treatment for depression, but the choice of the anesthetic that is used for induction may affect both clinical outcomes and the occurrence of adverse effects (AEs). Propofol and methohexital are frequently used in Finland, yet their relative impact on treatment efficacy and AEs remains uncertain.MethodsWe conducted a systematic literature review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases were searched up to January 21, 2025. Studies comparing propofol and methohexital in adult patients receiving ECT for depression and utilizing numeric scales for depression assessment were included. The primary outcome was the clinical treatment response, defined by the number of ECT sessions required to achieve remission. The secondary outcome was the variation of AEs associated with ECT between comparator groups. We included eight studies in the final analysis with 194 patients in the propofol group and 198 patients in the methohexital group. Five of the studies were randomized controlled trials and three were retrospective cohort studies. Three randomized controlled trials with 131 patients: 62 (47%) in propofol group and 69 (53%) in methohexital group were included in meta-analysis.ResultsThe number of ECT sessions required for recovery did not differ between groups. All studies demonstrated effective alleviation of depression through ECT, regardless of anesthetic choice. However, AEs were inconsistently reported, and a comprehensive overview of the topic was not possible.ConclusionsLow-quality evidence suggests equal efficacy of propofol compared to methohexital with regard to clinical remission of depression after ECT.Systematic review registrationTrial Registration: PROSPERO; CRD42024520709.Editorial commentThis systematic review and meta-analysis presents the available but limited and low-quality evidence in this study area, and supports an interpretation that propofol and methohexital have similar efficacy when facilitating electroconfulsive therapy as treatment for depression, to relieve depression symptoms.

Abstract licence: CC BY

GABA (γ-aminobutyric acid) receptors are constituents of many inhibitory synapses within the central nervous system. They are formed by 5 subunits out of 19 various subunits: α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3. Two main subtypes of GABA receptors have been identified, namely GABAA and GABAB. The GABAA receptor (GABAAR) is formed by a variety of combinations of five subunits, although both α and β subunits must be included to produce a GABA-gated ion channel. Other subunits are γ, δ, ε, π, and ϴ. GABAAR has many isoforms, that dictate, among other properties, their differing affinities and conductance. Drugs acting on GABAAR form the cornerstone of anesthesia and sedation practice. Some such GABAAR agonists used in anesthesia practice are propofol, etomidate, methohexital, thiopental, isoflurane, sevoflurane, and desflurane. Ketamine, nitrous oxide, and xenon are not GABAR agonists and instead inhibit glutamate receptors-mainly NMDA receptors. Inspite of its many drawbacks such as pain in injection, quick and uncontrolled conversion from sedation to general anesthesia and dose-related cardiovascular depression, propofol remains the most popular GABAR agonist employed by anesthesia providers. In addition, being formulated in a lipid emulsion, contamination and bacterial growth is possible. Literature is rife with newer propofol formulations, aiming to address many of these drawbacks, and with some degree of success. A nonemulsion propofol formulation has been developed with cyclodextrins, which form inclusion complexes with drugs having lipophilic properties while maintaining aqueous solubility. Inhalational anesthetics are also GABA agonists. The binding sites are primarily located within α+/β- and β+/α- subunit interfaces, with residues in the α+/γ- interface. Isoflurane and sevoflurane might have slightly different binding sites providing unexpected degree of selectivity. Methoxyflurane has made a comeback in Europe for rapid provision of analgesia in the emergency departments. Penthrox (Galen, UK) is the special device designed for its administration. With better understanding of pharmacology of GABAAR agonists, newer sedative agents have been developed, which utilize "soft pharmacology," a term pertaining to agents that are rapidly metabolized into inactive metabolites after producing desired therapeutic effect(s). These newer "soft" GABAAR agonists have many properties of ideal sedative agents, as they can offer well-controlled, titratable activity and ultrashort action. Remimazolam, a modified midazolam and methoxycarbonyl-etomidate (MOC-etomidate), an ultrashort-acting etomidate analog are two such examples. Cyclopropyl methoxycarbonyl metomidate is another second-generation soft etomidate analog that has a greater potency and longer half-life than MOC-etomidate. Additionally, it might not cause adrenal axis suppression. Carboetomidate is another soft analog of etomidate with low affinity for 11β-hydroxylase and is, therefore, unlikely to have clinically significant adrenocortical suppressant effects. Alphaxalone, a GABAAR agonist, is recently formulated in combination with 7-sulfobutylether-β-cyclodextrin (SBECD), which has a low hypersensitivity profile.

Abstract licence: CC BY-NC

BackgroundPharmacologic angiotensin axis blockade (AAB) has been associated with profound hypotension following anesthetic induction with propofol. To combat this problem, investigators have attempted to withhold angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) preoperatively, or evaluated the effects of different induction agents in conferring greater hemodynamic stability. To date, methohexital has not been compared with the most commonly used induction agent, propofol. Hence, the primary objective was to study the hypothesis that methohexital confers a better hemodynamic profile than propofol for anesthetic induction, in patients receiving AAB. The secondary objective was to investigate the postinduction levels of serum neurohormones in an attempt to explain the mechanisms involved.MethodsForty-five adult, hypertensive patients taking ACEi or ARB and scheduled for elective, noncardiac surgery completed the study. Patients were randomized to receive equi-anesthetic doses of either propofol or methohexital for anesthetic induction. Hemodynamic variables were measured and blood samples were drawn before induction and for 15 minutes afterwards.ResultsMethohexital resulted in less hypotension compared with propofol (P = .01), although the degree of refractory hypotension was similar (P = .37). The postinduction systolic blood pressure (P = .03), diastolic blood pressure (P ConclusionWhile methohexital was shown to confer greater hemodynamic stability in patients taking ACEi/ARB, the measured hormone levels could not explain the mechanism for this effect.

Abstract licence: CC BY-NC-ND

BackgroundThe ideal hypnotic agent for electroconvulsive therapy (ECT) is still under debate and previous studies comparing etomidate and methohexital have produced conflicting results. This retrospective study compares etomidate and methohexital as anesthetic agents in continuation and maintenance (m)ECT with regard to seizure quality and anesthetic outcomes.MethodsAll subjects undergoing mECT at our department between October 1st, 2014 and February 28th, 2022 were included in this retrospective analysis. Data for each ECT session were obtained from the electronic health records. Anesthesia was performed with either methohexital/succinylcholine or etomidate/succinylcholine. Standard seizure quality parameters, anesthesiological monitoring data, pharmacological interventions and side-effects were recorded.Results573 mECT treatments in 88 patients were included (methohexital n = 458, etomidate n = 115). Seizures lasted significantly longer after using etomidate (electroencephalography: +12.80 s [95 %-CI:8.64-16.95]; electromyogram +6.59 s [95 %-CI:4.14-9.04]). Time to maximum coherence was significantly longer with etomidate (+7.34 s [95 %-CI:3.97-10.71]. Use of etomidate was associated with longer procedure duration (+6.51 min [95 %-CI:4.84-8.17]) and higher maximum postictal systolic blood pressure (+13.64 mmHg [95 %-CI:9.33-17.94]). Postictal systolic blood pressure > 180 mmHg, the use of antihypertensives, benzodiazepines and clonidine (for postictal agitation), as well as the occurrence of myoclonus was significantly more common under etomidate.ConclusionsDue to longer procedure duration and an unfavorable side effect profile, etomidate appears inferior to methohexital as an anesthetic agent in mECT despite longer seizure durations.

Abstract licence: CC BY