Methohexital


Article Author:
Qaisar Syed


Article Editor:
Arpan Kohli


Editors In Chief:
Kranthi Sitammagari
Mayank Singhal


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Kyle Blair
Trevor Nezwek
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Daniyal Ameen
Altif Muneeb
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes
Komal Shaheen
Sandeep Sekhon


Updated:
7/11/2019 10:55:53 PM

Indications

Methohexital belongs to a family of drugs known as barbiturates.[1] It is the preferred agent for use in electroconvulsive therapy (ECT). However, its use has also found utility in procedural sedation for cardioversion, as an induction agent for intubation in neonates, and as a sedative in imaging procedures.[2][3] Methohexital is the choice of sedative in ECT as it both reduces the seizure threshold and prolongs seizure duration. The latter is an important quality during ECT, as the duration of seizure has links to improved efficacy of ECT.[4]

Mechanism of Action

Methohexital produces its effect by potentiating the inhibitory actions of GABA on the GABA (A) receptor. At higher concentrations, methohexital directly stimulates and activates the receptor. Barbiturates bind to the GABA A receptor and increase the open duration of the GABA A receptor without having any effect on channel opening frequency or conductance. Specifically, the downstream effect is on the chloride channel, causing it to stay open for longer, causing influx. This action causes inhibitory pathways to activate in the brain and causes decreased neuronal excitability thus inducing anesthesia/sedation.[5] Research has shown the highest concentration of methohexital in the hypothalamus, globus pallidus, and the substantia nigra. Once the GABA receptor is activated, increased chloride influx causes increases the negative charge on the inside of the membrane resulting in hyperpolarization and thus post-synaptic neuron inhibition.[6] 

Methohexital is a derivative from barbituric acid which is a compound made of malonic acid and urea. The chemical formula for methohexital is 1-methyl-2-pentynyl barbituric acid. The acyclic side chain at the fifth Carbon of the benzene ring is responsible for the hypnotic activity attributed to this compound. Also, compared to barbituric acid, the nitrogen on methohexital is methylated, which does cause some excitatory effects but produces the rapid onset and short duration of action, which makes this drug so clinically useful.[6]

Administration

Methohexital has a variety of administration routes, including rectal, IV, and IM use.

Standard adult dosing for anesthesia induction is 50 to 120 mg IV as a bolus. General anesthesia maintenance calls for 20 to 40 mg IV every 4 to 7 minutes as needed. In pediatrics, general anesthesia induction dosing is 6.6 to 10 mg/kg IM injection once. Alternately, 25 mg/kg as a single dose rectally is an option.

In pediatrics, methohexital has found application in procedural sedation for obtaining imaging at doses between 0.5 mg/kg to 2.0 mg /kg.[7] The use of rectal methohexital is predominantly in the pediatric population; one study reports a dose of 30 mg/kg of 10% methohexital caused 85% of children to fall asleep.[8] The induction dose for methohexital for electroconvulsive therapy is 1.5 mg/kg.[9] 

After IV administration of methohexital, peak brain concentrations occur at the 30-second mark and steadily decline as the drug gets redistributed to other tissues. Five minutes after administration, half of the initial concentration is in the grey matter. The duration of action for methohexital is 4 to 7 minutes. Metabolism of methohexital occurs in the liver where the molecule undergoes oxidation of the side chain at carbon 5 of the benzene resulting in the inactive metabolite hydroxymethohexital. In summary, the disappearance of methohexital from the bloodstream is attributable to both liver inactivation and redistribution, but redistribution plays a greater role.[6] 

Adverse Effects

The adverse effects of methohexital include respiratory depression, apnea, hiccoughs, cardiovascular depression, and laryngospasm.[6] In critically ill patients who are preload dependent, methohexital may reduce systemic vascular resistance and cardiac output, however, the incidence of these events is low.[10] The ventilatory and cardiovascular depressant effects of methohexital are dose-dependent; however, they vary with the pre-existing disease in a patient. The respiratory depressant effect may result from both central and peripheral mechanisms. Methohexital can alter the upper airway tone resulting in obstruction, while also affecting the central respiratory system in the brainstem resulting in apnea and hypoventilation. Hypotension has also been noted during the administration of methohexital and is mediated by peripheral vasodilation with a subsequent decrease in afterload, decreased preload, and negative inotropic effect on the heart. 

It is important to note that when given in conjunction with other medications like opioids, the cardiorespiratory depressant effects of methohexital are additive. In some cases, adverse effects like restlessness, excitement, and delirium are possible. However, these are treatable with intravenous caffeine.[11] Methohexital is commonly associated with pain when injected into smaller veins; one study demonstrated that dissolving the drug in a lipid emulsion before administration resulted in the resolution of pain with no changes in potency.[12] Mean arterial pressure is not significantly affected after administration of methohexital and appears to be more hemodynamically stable when compared to other agents.[13] As methohexital is a commonly used agent during ECT, it is essential to note that it has dose-dependent anticonvulsant properties, and may adversely affect seizure procurement in a subset of patients with high seizure thresholds.[14]

Contraindications

Barbiturates like methohexital are contraindicated in acute intermittent porphyria (AIP). AIP is a deficiency of the enzyme hydroxymethylbilane synthase in the pathway for heme biosynthesis. Acute attacks are usually intermittent and manifest as severe abdominal pain, peripheral neuropathy, psychiatric symptoms, autonomic dysfunction, and hyponatremia. Methohexital is strictly contraindicated in patients with a history of AIP.[15]

Monitoring

When administering methohexital, it is crucial to know that respiratory and hemodynamic effects may occur. It is important to monitor the patient throughout the procedure and the recovery phase. Guidelines suggested by organizations state that anesthesia standards of monitoring be in place, the most important factor being that during procedural sedation, one person should be present whose job is only to monitor and sedate the patient. Monitors, including hemodynamic (Blood pressure cuff), O2 saturation (continuous pulse oximetry), ECG monitoring, End-tidal CO2 monitor, and respiratory rate monitoring should be in place. When possible, the person responsible for delivering sedation should have an unobstructed view of the patient's face, mouth, and chest wall during the procedure. To assess the depth of the anesthetic when using methohexital, it is reasonable to use a bispectral index (BIS) monitor which analyzes a continuous EEG and quantifies the hypnotic/sedative effects of the drug being administered. Before administration of methohexital, there should be appropriate airway equipment, including resuscitation equipment/medications, bag-valve-mask device, and Yankauer suction.[11]

Toxicity

High doses of methohexital are associated with seizures in the post-operative period, likely due to acute withdrawal as it is highly potent. Other symptoms of toxicity include muscle twitching, apnea, and shivering.[16]

Enhancing Healthcare Team Outcomes

Methohexital is a has a variety of uses including procedural sedation in pediatrics, electroconvulsive therapy, and as an induction agent during the delivery of anesthesia. Like all other sedatives, methohexital is best used and managed by an interprofessional team to ensure its safety.

It is essential to appropriately evaluate the patient pre-operatively and address factors like allergies, previous exposure to this drug class and adverse reactions, and pertinent medical history. It is also important to evaluate patients and their baseline status in terms of physical activity to assess their cardiopulmonary reserve. The professional administering methohexital to the patient should clearly and effectively communicate with the proceduralist in terms of dose, timing, and anticipated time needed to complete the given procedure.

Guidelines suggested by organizations state that anesthesia standards of monitoring be in place, the most important factor being that during procedural sedation one person (nurse anesthetist) should be present whose job is only to monitor the patient.

In terms of care coordination in the OR setting, it is important to know that one person does not make a team and that it is the collective effort of the anesthesiologist, surgeons, nursing, and OR personnel who make it possible to deliver care to patients safely and effectively.[17]

Methohexital is a barbiturate, and while it is a very useful agent in its applications, it is not without risks, which is why the entire interprofessional health team has to coordinate their activities when using this drug. The ordering physician (MD, DO, NP) decides as to using the drug, as well as dosing, but the pharmacist needs to verify the dosing, as well as checking any potential drug interactions Nursing will be monitoring and adminsitering the drug, and  needs to report any undue circumstances to the clinicians and/or pharmacist. With a collaborative approach, methohexital can be a safe anesthetic that serves to help the team achieve positive outcomes for the patient. [Level V]


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Methohexital - Questions

Take a quiz of the questions on this article.

Take Quiz
A 3-year-old male is undergoing an MRI scan under sedation to characterize an intracranial lesion further, to obtain optimal images. He is sedated to limit movement during the MRI. He is easily being ventilated with a bag-mask and undergoes induction with an anesthetic agent, and a tracheal tube is placed. Upon auscultation, there is a complete absence of breath sounds in bilateral lung fields. Capnography shows prolonged expiratory upstroke of the capnogram. The endotracheal tube is removed as the patient is desaturating, and bag-mask ventilation is attempted to maintain adequate ventilation. Which anesthetic agent used in induction is likely responsible for the patient's presentation?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the inactive metabolite of methohexital?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Anesthesia is induced for a 15-year-old patient undergoing tonsillectomy with a standard induction dose of methohexital. How much time does one have before you need to re-dose the medication to sustain the effects of the anesthetic?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
When conducting anesthesia for electroconvulsive therapy, which agent is the most appropriate for maximizing the effectiveness of electroconvulsive therapy (ECT) and ameliorating sympathetic response accompanied by the induced seizure?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 45-year-old female with a past medical history of acute intermittent porphyria, hypertension, and gastroesophageal reflux disease undergoes a knee replacement under general anesthesia, postoperatively she develops severe abdominal pain, hallucinations, orthostatic hypotension, and peripheral neuropathy, which of the following agents is likely responsible for her current presentation?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Methohexital - References

References

López-Muñoz F,Ucha-Udabe R,Alamo C, The history of barbiturates a century after their clinical introduction. Neuropsychiatric disease and treatment. 2005 Dec;     [PubMed]
Naulaers G,Deloof E,Vanhole C,Kola E,Devlieger H, Use of methohexital for elective intubation in neonates. Archives of disease in childhood. Fetal and neonatal edition. 1997 Jul;     [PubMed]
Wood J,Ferguson C, Best evidence topic report. Procedural sedation for cardioversion. Emergency medicine journal : EMJ. 2006 Dec;     [PubMed]
Kadiyala PK,Kadiyala LD, Anaesthesia for electroconvulsive therapy: An overview with an update on its role in potentiating electroconvulsive therapy. Indian journal of anaesthesia. 2017 May;     [PubMed]
Löscher W,Rogawski MA, How theories evolved concerning the mechanism of action of barbiturates. Epilepsia. 2012 Dec;     [PubMed]
Sedik H, Use of intravenous methohexital as a sedative in pediatric emergency departments. Archives of pediatrics     [PubMed]
Bonavia A,Verbeek T,Adhikary S,Kunselman A,Budde A,Lyn-Sue J,Mets B, A randomized controlled trial comparing methohexital and propofol for induction in patients receiving angiotensin axis blockade. Medicine. 2019 Feb;     [PubMed]
Audenaert SM,Montgomery CL,Thompson DE,Sutherland J, A prospective study of rectal methohexital: efficacy and side effects in 648 cases. Anesthesia and analgesia. 1995 Nov;     [PubMed]
Martone CH,Nagelhout J,Wolf SM, Methohexital: a practical review for outpatient dental anesthesia. Anesthesia progress. 1991 Nov-Dec;     [PubMed]
Diaz-Guzman E,Mireles-Cabodevila E,Heresi GA,Bauer SR,Arroliga AC, A comparison of methohexital versus etomidate for endotracheal intubation of critically ill patients. American journal of critical care : an official publication, American Association of Critical-Care Nurses. 2010 Jan;     [PubMed]
Westrin P, Methohexital dissolved in lipid emulsion for intravenous induction of anesthesia in infants and children. Anesthesiology. 1992 Jun;     [PubMed]
Yen T,Khafaja M,Lam N,Crumbacher J,Schrader R,Rask J,Billstrand M,Rothfork J,Abbott CC, Post-electroconvulsive therapy recovery and reorientation time with methohexital and ketamine: a randomized, longitudinal, crossover design trial. The journal of ECT. 2015 Mar;     [PubMed]
Avramov MN,Husain MM,White PF, The comparative effects of methohexital, propofol, and etomidate for electroconvulsive therapy. Anesthesia and analgesia. 1995 Sep;     [PubMed]
Tobias JD,Leder M, Procedural sedation: A review of sedative agents, monitoring, and management of complications. Saudi journal of anaesthesia. 2011 Oct;     [PubMed]
Pischik E,Kauppinen R, An update of clinical management of acute intermittent porphyria. The application of clinical genetics. 2015;     [PubMed]
Boarini DJ,Kassell NF,Coester HC, Comparison of sodium thiopental and methohexital for high-dose barbiturate anesthesia. Journal of neurosurgery. 1984 Mar;     [PubMed]
Goyal R, Surgeons and anesthesiologists: Need to communicate? Journal of anaesthesiology, clinical pharmacology. 2013 Jul;     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of PA-Hospital Medicine. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for PA-Hospital Medicine, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in PA-Hospital Medicine, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of PA-Hospital Medicine. When it is time for the PA-Hospital Medicine board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study PA-Hospital Medicine.