Hippocampal recording via the RNS system reveals marked ipsilateral activation of epileptiform activity during Wada testing.

Wada testing remains an important component of pre-surgical testing to assess the feasibility of temporal lobectomy for patients with intractable epilepsy. In this procedure, an anesthetic is injected into either internal carotid artery while memory and language testing is performed, simulating the effect of temporal lobe resection. The mechanism remains poorly understood because the hippocampal vasculature is predominantly via the posterior circulation. We recorded hippocampal EEG during bilateral methohexital Wada testing in three patients who had previously been implanted with a responsive neurostimulation system (RNS) to determine the effect of the injections on hippocampal activity. In all six injections from three patients, methohexital caused immediate, transient increases in hippocampal spikes. With at least two of these injections, the electrographic changes were consistent with electrographic seizures. In all cases, the epileptiform activity was not apparent on scalp EEG and was without obvious clinical correlate other than the negative findings expected from the anesthetic. The results demonstrate the utility of intracranial EEG during Wada testing and suggest that the elicitation of seizures or continuous spiking might contribute to dysfunction of the hippocampus during the Wada test. We hypothesize that this effect is due to disconnection and disinhibition of medial temporal structures.

Methohexital for procedural sedation of cardioversions in the emergency department.

BACKGROUND: Procedural sedation for electrical cardioversion is a common practice in the emergency department (ED). Ideal sedative properties for this procedure are a short half-life and minimal hemodynamic effects. There is limited literature examining methohexital for this use. OBJECTIVE: To compare the use of methohexital to propofol and etomidate for procedural sedation for electrical cardioversions in the ED. METHODS: This was a single-center, retrospective study of adult patients who underwent procedural sedation for electrical cardioversion in the ED between February 1, 2015 and July 31, 2020. Included patients received methohexital, propofol, or etomidate as an initial sedative agent in the ED. The primary outcome was time from initial dose of sedative to goal Aldrete score. The main secondary outcome was time from sedative agent to ED discharge. The safety outcome was the occurrence of a critical hemodynamic change requiring intervention. Outcomes were assessed using a single-factor ANOVA analysis. RESULTS: One-hundred and fifty cardioversion encounters were included with 50 encounters per cohort. The median (IQR) time (minutes) to goal Aldrete score was 10.5 (7-18.5) for methohexital, 12.0 (9-16.8) for propofol, and 11.0 (8-15) for etomidate (p = 0.863). Mean (SD) time (minutes) to discharge from the ED (n = 105) was 90.4 ± 40.4 for methohexital, 89.0 ± 57.4 for propofol, and 94.0 ± 42.5 for etomidate (p = 0.897). No difference was seen between the groups regarding hemodynamic changes requiring intervention. CONCLUSION: Methohexital was found to have a similar efficacy and safety profile when compared to propofol and etomidate when used as procedural sedation for cardioversions in the ED.

The influence of anaesthetic choice on seizure duration of electroconvulsive therapy; etomidate versus methohexital.

BACKGROUND: Many of the anaesthetic drugs used for electroconvulsive therapy have anticonvulsant properties and may influence efficacy of electroconvulsive therapy. With this study we aim to provide more information on the effect of etomidate and methohexital on seizure duration. We explore the relationship between induction drug, motor and electroencephalography seizure duration. Moreover, we study the relationship of seizure duration and number of therapies. METHODS: In this retrospective study we collected data from patient records from 2005 until 2016. Inclusion criteria were the use of etomidate and/or methohexital and documentation of dosage, electroconvulsive therapy dosage and seizure duration. Exclusion criteria were missing data on either induction drug, dosage or seizure duration. RESULTS: Thirty seven patients were analysed. The mean age was 52 years and seventy six percent were female. Most patients were suffering from affective disorders (81%). Motor and electroencephalography seizure duration were analysed in 679 and 551 electroconvulsive therapies, respectively. Compared to methohexital, motor and electroencephalography seizures under etomidate were 7 and 13 s longer, respectively. Furthermore, there was a negative association between seizure duration and number of treatment and a negative association between seizure duration and electroconvulsive therapy dosage. CONCLUSIONS: This study demonstrates significant longer motor and electroencephalography seizure duration using etomidate compared to methohexital. Etomidate might therefore increase the effectiveness of electroconvulsive therapy. Moreover, we observed a negative association between seizure duration, number of treatment and electroconvulsive therapy dosage. With this study we contribute to the available literature comparing methohexital and etomidate as induction agents for electroconvulsive therapy.

A Safety Comparison of Single-Agent Methohexital, Ketamine, or Propofol for Musculoskeletal Procedural Sedation in the Emergency Department.

BACKGROUND: The use of sedative and analgesic agents is required for procedural sedation in the emergency department (ED). Agents such as ketamine and propofol are commonly used for procedural sedation. This is likely due to clinical experience with these agents, as well as optimal pharmacologic properties when used in combination with one another. Methohexital, a barbiturate, is less frequently used due to concerns for adverse events associated with this drug class. OBJECTIVE: The objective of this study is to evaluate the safety of methohexital in comparison with ketamine and propofol when used for procedural sedation in musculoskeletal procedures. METHODS: A retrospective chart review was conducted to evaluate adult ED patients who received ketamine, propofol, or methohexital for procedural sedation from January 1, 2014 to June 30, 2020. RESULTS: Overall, a total of 43 procedures were included in the study. Procedures included shoulder relocation, elbow relocation, hip relocation, ankle reduction, radius/ulnar reduction, mandibular relocation, patellar relocation, and wrist reduction. There was a 90.6% overall procedural success rate, which was similar between groups. Overall adverse events occurred in 34.8% of patients. Respiratory depression occurred in 9.3% of patients. No incidence of respiratory depression was observed in the methohexital group, compared with 2 patients receiving ketamine and 4 receiving propofol (p = 0.44). CONCLUSION: Methohexital is a safe and effective option for procedural sedation for musculoskeletal procedures in the ED when compared with ketamine and propofol.

Advantages of methohexital over amobarbital in determining hemispheric language and memory lateralization in the Wada test - A retrospective study.

OBJECTIVE: Due to supply shortage, amobarbital, the traditional anesthetic agent in Wada testing, was replaced by methohexital in many epilepsy centers. This study aimed to compare the two barbiturates to identify possible advantages or disadvantages of methohexital as compared to amobarbital with regard to the adequacy of language and memory testing during the Wada test. METHODS: Data from 75 patients with temporal lobe epilepsy who underwent bilateral Wada tests using either amobarbital (n = 53) or methohexital (n = 22) as part of presurgical work-up were analyzed retrospectively. The two subgroups were compared regarding hemispheric language and memory lateralization results and Wada testing characteristics, and the adequacy of language and memory testing was assessed. RESULTS: We observed shorter durations of motor-, speech-, and EEG recovery after each injection in patients receiving methohexital compared to amobarbital. In addition, significantly more items could be presented during effective hemispheric inactivation in the methohexital group. Moreover, significant correlations of Wada memory scores with standard neuropsychological memory test scores could be found in the methohexital group. SIGNIFICANCE: Our findings confirm that methohexital is not only equally suitable for Wada testing but has several advantages over amobarbital. Wada testing can be performed more efficiently and under more constant hemispheric inactivation using methohexital. Furthermore, the adequacy of language and memory testing during the Wada test might be affected by the anesthetic agent used.

Methohexital-Induced Seizure in a Patient Undergoing Conscious Sedation.

BACKGROUND: Methohexital is a short-acting barbiturate used for procedural sedation in the emergency department (ED). As with other sedatives, adverse effects with methohexital include excess sedation and hypotension, but this agent can also lower the seizure threshold. We report a patient who developed a generalized seizure after administration of methohexital. CASE REPORT: A 60-year-old man presented to the ED by ambulance with chest pain and shortness of breath. Paramedics had administered adenosine for supraventricular tachycardia without conversion before arrival to the ED. He had no history of seizures. His initial vital signs in the ED included heart rate of 189 beats/min with a supraventricular rhythm, blood pressure 137/108 mm Hg, respiration 22 breaths/min, and oxygen saturation of 98% on room air. It was decided to attempt synchronized electrical cardioversion, and methohexital 1 mg/kg (120 mg) was administered over 2 min for moderate sedation. Within 15 s of methohexital administration, the patient developed a generalized seizure that lasted for 90 s. After seizure termination, he was successfully cardioverted, returned to his previous baseline level of consciousness within 20 min, and discharged without further problems with a follow-up referral to neurology. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Methohexital is a short-acting barbiturate used for moderate sedation. Its adverse effects are unique in that it can lower the seizure threshold in some patients. Alternative agents for sedation should be considered in individuals with possible seizure disorders.

A Comparison of Etomidate, Ketamine, and Methohexital in Emergency Department Rapid Sequence Intubation.

BACKGROUND: Rapid sequence intubation (RSI) is routinely used for emergent airway management in the emergency department (ED). It involves the use of induction, and paralytic agents help facilitate endotracheal tube placement. OBJECTIVE: In response to a previous national drug shortage resulting in the use of alternative induction agents for RSI, we describe the effectiveness and safety of ED RSI with ketamine or methohexital compared with etomidate. METHODS: We conducted a retrospective, single-center observational study from March 1-August 31, 2012 describing RSI with etomidate, ketamine, and methohexital. All adult patients undergoing RSI in the ED who received etomidate prior to its shortage and methohexital or ketamine during the shortage were included. RESULTS: The study included 47, 9, and 26 patients in the etomidate, ketamine, and methohexital groups, respectively. Successful intubation on the first attempt occurred in 74.5%, 55.6%, and 73.1% of the etomidate, ketamine, and methohexital groups, respectively. The mean number of intubation attempts and time to intubation seemed to be similar in all groups. At least three intubation attempts were required in 22.2% and 7.7% of the ketamine and methohexital groups, respectively, compared with none in the etomidate group. Two aspirations were observed in the etomidate group. CONCLUSION: Methohexital and etomidate had similar rates of successful intubation on the first attempt and seem to be more effective than ketamine. Etomidate may reduce the need for three or more intubation attempts. Larger, prospective studies are needed to determine if ketamine or methohexital are more effective than etomidate for RSI.

[Drugs for intravenous induction of anesthesia: barbiturates]. / Medikamente zur intravenösen Narkoseinduktion: Barbiturate.

The discovery of barbituric acid and research on its derivatives have long been of importance in advancements in modern anesthesia. Decades of clinical use of barbiturates worldwide and their abuse has led to an enormous amount of knowledge. Thiopental and methohexital are ultra-short acting derivatives of barbiturates. Their clinical application has been accompanied by an enormous increase in the knowledge of the pharmacology of cerebrally active drugs, in particular gamma-aminobutyric acid (GABAA) receptor and GABA-induced effects on nerve cell membranes. Despite the development of newer substances, thiopental still has a firm place in clinical applications. Currently it is mainly used in obstetrics for induction of cesarean sections under general anesthesia. A disadvantage, when properly used to induce anesthesia, is usually only the prolonged elimination kinetics of barbiturates. It is beneficial that barbiturates do not require side effect provoking solubilizers.

Evaluation of methohexital as an alternative to propofol in a high volume outpatient pediatric sedation service.

BACKGROUND: Propofol is a preferred agent for many pediatric sedation providers because of its rapid onset and short duration of action. It allows for quick turn around times and enhanced throughput. Occasionally, intravenous (IV) methohexital (MHX), an ultra-short acting barbiturate is utilized instead of propofol. OBJECTIVE: Describe the experience with MHX in a primarily propofol driven outpatient sedation program and to see if it serves as an acceptable alternative when propofol is not the preferred pharmacologic option. METHODS: Retrospective chart review from 2012 to 2015 of patients receiving IV MHX as their primary sedation agent. Data collected included demographics, reason for methohexital use, dosing, type of procedure, success rate, adverse events (AE), duration of the procedure, and time to discharge. RESULTS: Methohexital was used in 240 patient encounters. Median age was 4years (IQR 2-7), 71.8% were male, and 80.4% were ASA-PS I or II. Indications for MHX use: egg+soy/peanut allergy in 93 (38.8%) and mitochondrial disorder 9 (3.8%). Median induction bolus was 2.1mg/kg (IQR, 1.9-2.8), median maintenance infusion was 4.5mg/kg/h (IQR, 3.0-6.0). Hiccups 15 (6.3%), secretions requiring intervention 14 (5.8%), and cough 12 (5.0%) were the most commonly occurring minor AEs. Airway obstruction was seen in 28 (11.6%). Overall success rate was 94%. Median time to discharge after procedure completion was 40.5min (IQR 28-57). CONCLUSION: Methohexital can be used with a high success rate and AEs that are not inconsistent with propofol administration. Methohexital should be considered when propofol is not a preferred option.

Anesthetic considerations for pediatric electroconvulsive therapy.

Electroconvulsive therapy is being used more frequently in the treatment of many chronic and acute psychiatric illnesses in children. The most common psychiatric indications for pediatric electroconvulsive therapy are refractory depression, bipolar disorder, schizophrenia, catatonia, and autism. In addition, a relatively new indication is the treatment of pediatric refractory status epilepticus. The anesthesiologist may be called upon to assist in the care of this challenging and vulnerable patient population. Unique factors for pediatric electroconvulsive therapy include the potential need for preoperative anxiolytic and inhalational induction of anesthesia, which must be weighed against the detrimental effects of anesthetic agents on the evoked seizure quality required for a successful treatment. Dexmedetomidine is likely the most appropriate preoperative anxiolytic as oral benzodiazepines are relatively contraindicated. Methohexital, though becoming less available at many institutions, remains the gold standard for induction of anesthesia for pediatric electroconvulsive therapy though ketamine, propofol, and sevoflurane are becoming increasingly viable options. Proper planning and communication between the multidisciplinary teams involved in the care of children presenting for electroconvulsive therapy treatments is vital to mitigating risks and achieving the greatest therapeutic benefit.

Assessment of seizure duration and utility of using SedLine® EEG tracing in veterans undergoing electroconvulsive therapy: a retrospective analysis.

BACKGROUND: Electroconvulsive therapy (ECT) endures as a definitive treatment for refractory depression and catatonia and is also considered an effective treatment for a number of other severe psychiatric disorders (Lisanby, N Engl J Med 357:1939-1945, 2007)(Weiner and Prudic, Biol Psychiatry 73:105-106, 2013). GA is an essential component of the ECT procedure for various reasons (Lee, Jenkins and Sparkle, Life 11, 2021). Monitoring anesthetic effects on the brain is desirable as anesthetic agents affect seizure duration and recovery (Rasulo, Hopkins, Lobo, et al,  Neurocrit Care 38:296-311, 2023) (Jones , Nittur , Fleming and Applegate,  BMC Anesthesiol 21:105, 2021) (Soehle , Kayser , Ellerkmann and Schlaepfer,  BJA 112:695-702, 2013). Perioperative anesthetic effects on consciousness can be assessed with brain function monitoring using raw electroencephalogram (EEG) traces and processed EEG indices. OBJECTIVE: We examined the usefulness and utility of the SedLine® anesthetic effect monitor during ECT procedures. We hypothesized that the seizure duration as measured by the EEG tracing of the ECT machine is equivalent to the duration assessed by the SedLine® EEG tracing. A secondary objective was to describe the SedLine® patient state indices (PSI) at different phases of treatment. METHODS: Following IRB approval, we analyzed the data of the electronic medical records of 45 ECT treatments of 23 patients in an urban VA medical center between July 01, 2021, and March 30, 2022. We compared the seizure duration in minutes and seconds as measured either by the ECT machine EEG tracing or the SedLine® EEG tracing. We then collected SedLine® processed EEG indices at four different stages during the treatment. Appropriate comparative and observational statistical analyses were applied. RESULTS: There was no significant difference in measured seizure duration between the two methods examined (p < 0.05). We observed a lag of the SedLine PSI value at the time before stimulus delivery and limited PSI utility during the course of ECT. CONCLUSION: The SedLine® EEG tracing can be an alternative to the machine EEG tracing for the determination of seizure duration. The SedLine® processed EEG indices are not consistently useful before and after ECT delivery. Anesthetic effect monitoring during ECT is feasible.

Comparison of etomidate and methohexital as anesthetic agents for continuation and maintenance electroconvulsive therapy: A retrospective analysis of seizure quality and safety.

BACKGROUND: The 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. METHODS: All 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. RESULTS: 573 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. CONCLUSIONS: Due 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.

Comparison of Bolus Dosing of Methohexital and Propofol in Elective Direct Current Cardioversion.

Background Methohexital and propofol can both be used as sedation for direct current cardioversion (DCCV). However, there are limited data comparing these medications in this setting. We hypothesized that patients receiving methohexital for elective DCCV would be sedated more quickly, recover from sedation faster, and experience less adverse effects. Methods and Results This was a prospective, blinded randomized controlled trial conducted at a single academic medical center. Eligible participants were randomly assigned to receive either methohexital (0.5 mg/kg) or propofol (0.8 mg/kg) as a bolus for elective DCCV. The times from bolus of the medication to achieving a Ramsay Sedation Scale score of 5 to 6, first shock, eyes opening on command, and when the patient could state their age and name were obtained. The need for additional medication dosing, airway intervention, vital signs, and medication side effects were also recorded. Seventy patients who were randomized to receive methohexital (n=37) or propofol (n=33) were included for analysis. The average doses of methohexital and propofol were 0.51 mg/kg and 0.84 mg/kg, respectively. There were no significant differences between methohexital and propofol in the time from end of injection to loss of conscious (1.4±1.8 versus 1.1±0.5 minutes; P=0.33) or the time to first shock (1.7±1.9 versus 1.4±0.5 minutes; P=0.31). Time intervals were significantly lower for methohexital compared with propofol in the time to eyes opening on command (5.1±2.5 versus 7.8±3.7 minutes; P=0.0005) as well as at the time to the ability to answer simple questions of age and name (6.0±2.6 versus 8.6±4.0 minutes; P=0.001). The methohexital group experienced less hypotension (8.1% versus 42.4%; P<0.001) and less hypoxemia (0.0% versus 15.2%; P=0.005), had lower need for jaw thrust/chin lift (16.2% versus 42.4%; P=0.015), and had less pain on injection compared with propofol using the visual analog scale (7.2±9.7 versus 22.4±28.1; P=0.003). Conclusions In this model of fixed bolus dosing, methohexital was associated with faster recovery, more stable hemodynamics, and less hypoxemia after elective DCCV compared with propofol. It can be considered as a preferred agent for sedation for DCCV. Registration URL: https://www.clinicaltrials.gov/ct; Unique identifier: NCT04187196.

Pediatric Electroconvulsive Therapy: An Anesthesiologist's Perspective.

Proper planning and communication between psychiatry and anesthesiology teams is vital to conferring the greatest therapeutic benefit to children presenting for electroconvulsive therapy while minimizing risk. Anesthesia for the child undergoing electroconvulsive therapy should ideally provide deep hypnosis, ensure muscle relaxation to reduce injury, have minimal effect on seizure dynamics, and allow for rapid recovery to baseline neurologic and cardiopulmonary status. Unique factors for pediatric electroconvulsive therapy include the potential need for preoperative anxiolytic and inhalational induction of anesthesia, which must be weighed against the detrimental effects of anesthetic agents on the evoked seizure quality required for a successful treatment.

Superselective methohexital challenge prior to intracranial endovascular embolization.

Pharmacologic provocative testing (PT) and intraoperative neurophysiologic monitoring (IONM) both mitigate and predict risks associated with endovascular embolization procedures. We present a series of patients undergoing endovascular intracranial embolization predominantly for AVMs both under general anesthesia and awake with the use of IONM. We reviewed our database to identify all patients undergoing endovascular procedures between January 1, 2014 and January 1, 2016. Awake patients were tested with SSEP, EEG and real time neurologic examination while TcMEPs were performed in all anesthetized patients. BAEPs were performed in anesthetized patients if indicated. Methohexital was administered as an injection at a dose of 5 mg or 10 mg and repeat testing was performed if needed.Sixty-three endovascular procedures that met criteria were performed in 32 patients. 54 procedures in 28 patients were performed under general anesthesia, 9 procedures in 4 patients were performed in wakefulness. PT was negative in 61 procedures and subsequently completed embolizations without neurological sequelae. In two cases, the testing was positive and the procedure was terminated without embolization in one patient. The other patient underwent embolization at an alternative site without repeat PT. There were no new postoperative neurologic deficits after any of these procedures. Specificity of PT was 100% as none of the patients with a negative provocative test developed a new postoperative neurologic deficit after embolization. To our knowledge, this is the first review of PT with the use of neurophysiologic IONM techniques under general anesthesia. These data suggest a high specificity comparable to awake testing.

Positive pharmacologic provocative testing with methohexital during cerebral arteriovenous malformation embolization.

A middle-aged patient underwent staged endovascular embolization of a Spetzler-Martin grade V right parietal arteriovenous malformation(AVM).In the fifth endovascular embolization, after methohexital 10 mg injection into a right posterior choroidal artery feeding the AVM nidus, there was an immediate change in the electroencephalogram (EEG) with simultaneous loss of motor evoked potentials (MEPs) in the bilateral upper and lower extremities and a delayed change in somatosensory evoked potential responses (SSEPs). No embolization was made and procedure was terminated. This case demonstrates the utility of intraoperative neurophysiologic monitoring (IONM) with pharmacologic provocative testing in predicting and mitigating the risks prior to the proposed embolization.