Action And Clinical Pharmacology: Compared with thiamylal and thiopental, methohexital is at least twice as potent on a weight basis, and its duration of action is only about half as long. Although the metabolic fate of methohexital in the body is not clear, the drug does not appear to concentrate in fat depots to the extent that other barbiturate anesthetics do. Thus, cumulative effects are fewer and recovery is more rapid with methohexital than with thiobarbiturates. In experimental animals, the drug cannot be detected in the blood 24 hours after administration.
Methohexital differs chemically from the established barbiturate anesthetics in that it contains no sulfur. Little analgesia is conferred by barbiturates; their use in the presence of pain may result in excitation.
I.V. administration of methohexital results in rapid uptake by the brain (within 30 seconds) and rapid induction of sleep. With single doses, the rate of redistribution determines duration of pharmacologic effect. Metabolism occurs in the liver through demethylation and oxidation. Side-chain oxidation is the most important biotransformation involved in termination of biologic activity. Excretion occurs via the kidneys through glomerular filtration.
Indications And Clinical Uses: For i.v. induction of anesthesia prior to the use of other general anesthetic agents.
For i.v. induction of anesthesia and as an adjunct to subpotent inhalational anesthetic agents (such as nitrous oxide in oxygen) for short surgical procedures; methohexital may be given by infusion or intermittent injection.
For use along with other parenteral agents, usually narcotic analgesics, to supplement subpotent inhalational anesthetic agents (such as nitrous oxide in oxygen) for longer surgical procedures.
As i.v. anesthesia for short surgical, diagnostic, or therapeutic procedures associated with minimal painful stimuli (see Precautions).
As an agent for inducing a hypnotic state.
Contra-Indications: In patients in whom general anesthesia is contraindicated, in those with latent or manifest porphyria, or in patients with a known hypersensitivity to barbiturates.
Manufacturers’ Warnings In Clinical States: This drug should be administered by persons qualified in the use of intravenous anesthetics. Cardiac life support equipment must be immediately available during use of methohexital.
As with all potent anesthetic agents and adjuncts, this drug should be administered only by those trained in the administration of general anesthesia, the maintenance of a patent airway and ventilation and the management of cardiovascular depression encountered during anesthesia and surgery.
Because the liver is involved in demethylation and oxidation of methohexital and because barbiturates may enhance pre-existing circulatory depression, severe hepatic dysfunction, severe cardiovascular instability, or a shock-like condition may be reason for selecting another induction agent.
Psychomotor seizures may be elicited in susceptible individuals.
Prolonged administration may result in cumulative effects, including extended somnolence, protracted unconsciousness, and respiratory and cardiovascular depression. Respiratory depression in the presence of an impaired airway may lead to hypoxia, cardiac arrest and death.
The CNS-depressant effect of methohexital may be additive with that of other CNS depressants, including ethyl alcohol and propylene glycol.
Danger of Intra-arterial Injection: Unintended intra-arterial injection of barbiturate solutions may be followed by the production of platelet aggregates and thrombosis, starting in arterioles distal to the site of injection. The resulting necrosis may lead to gangrene, which may require amputation. The first sign in conscious patients may be a complaint of fiery burning that roughly follows the distribution path of the injected artery; if noted, the injection should be stopped immediately and the situation re-evaluated. Transient blanching may or may not be noted very early; blotchy cyanosis and dark discoloration may then be the first sign in anesthetized patients. There is no established treatment other than prevention. The following should be considered prior to injection: 1. The extent of injury is related to concentration. Concentrations of 1% methohexital will usually suffice; higher concentrations should ordinarily be avoided. 2. Check the infusion to ensure that the catheter is in the lumen of a vein before injection. Injection through a running i.v. infusion may enhance the possibility of detecting arterial placement; however, it should be remembered that the characteristic bright-red color of arterial blood is often altered by contact with drugs. The possibility of aberrant arteries should always be considered.
Postinjury arterial injection of vasodilators and/or arterial infusion of parenteral fluids are generally regarded to be of no value in altering outcome. Animal experiments and published individual case reports concerned with a variety of arteriolar irritants, including barbiturates, suggest that one or more of the following may be of benefit in reducing the area of necrosis: arterial injection of heparin at the site of injury, followed by systemic anticoagulation; sympathetic blockade (or brachial plexus blockade in the arm); intra-arterial glucocorticoid injection at the site of injury, followed by systemic steroids. A recent case report (nonbarbiturate injury) suggests that intra-arterial urokinase may promote fibrinolysis, even if administered late in treatment. If extravasation is noted during injection of methohexital, the injection should be discontinued until the situation is remedied. Local irritation may result from extravasation; s.c. swelling may also serve as a sign of arterial or periarterial placement of the catheter.
Precautions: General: Maintenance of a patent airway and adequacy of ventilation must be ensured during induction and maintenance of anesthesia with methohexital solution. Laryngospasm is common during induction with all barbiturates and may be due to a combination of secretions and accentuated reflexes following induction or may result from painful stimuli during light anesthesia. Transient apnea may be noted during induction, which may impair pulmonary ventilation; the duration of apnea may be longer than that produced by other barbiturate anesthetics. Cardiorespiratory arrest may occur. I.V. administration of methohexital is often associated with hiccups, coughing, and/or muscle twitching, which may also impair pulmonary ventilation.
Following induction, temporary hypotension and tachycardia may occur.
Recovery from methohexital anesthesia is rapid and smooth. The incidence of postoperative nausea and vomiting is low if the drug is administered to fasting patients. Postanesthetic shivering has occurred in a few instances.
The usual precautions taken with any barbiturate anesthetic should be observed with methohexital. The drug should be used with caution in patients with asthma, obstructive pulmonary disease, severe hypertension or hypotension, myocardial disease, congestive heart failure, severe anemia, or extreme obesity.
Methohexital should be used with extreme caution in patients with status asthmaticus.
Caution should be exercised in debilitated patients or in those with impaired function of respiratory, circulatory, renal, hepatic or endocrine systems.
Information for the Patient: Occupational Hazards: When appropriate, patients should be instructed as to the hazards of drowsiness that may follow use of methohexital. Outpatients should be released in the company of another individual, and no skilled activities, such as operating machinery or driving a motor vehicle, should be engaged in for 8 to 12 hours.
Laboratory Tests: BSP and liver function studies may be influenced by administration of a single dose of barbiturates.
Drug Interactions: Barbiturates may influence the absorption and elimination of other concomitantly used drugs, such as phenytoin, halothane, anticoagulants, corticosteroids, ethyl alcohol and propylene glycol-containing solutions.
Pregnancy: Reproduction studies have been performed in rabbits and rats at doses up to 4 and 7 times the human dose respectively and have revealed no evidence of impaired fertility or harm to the fetus due to methohexital. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Labor and Delivery: Methohexital has been used in cesarean section delivery but, because of its solubility and lack of protein binding, it readily and rapidly traverses the placenta.
Lactation: Caution should be exercised when methohexital is administered to a nursing woman.
Children: Safety and effectiveness in children have not been established.
Adverse Reactions: Side effects associated with methohexital are extensions of pharmacologic effects and include: Cardiovascular: circulatory depression, thrombophlebitis, hypotension, peripheral vascular collapse and convulsions in association with cardiorespiratory arrest.
Respiratory: respiratory depression (including apnea), cardiorespiratory arrest, laryngospasm, bronchospasm, hiccups and dyspnea.
Neurologic: skeletal muscle hyperactivity (twitching), injury to nerves adjacent to injection site and seizures.
Psychiatric: emergence delirium, restlessness and anxiety may occur, especially in the presence of postoperative pain.
Gastrointestinal: nausea, emesis and abdominal pain.
Allergic: erythema, pruritus, urticaria, and cases of anaphylaxis have been reported rarely.
Other: Other adverse reactions include pain at injection site, salivation, headache and rhinitis.
Drug Abuse and Dependence: Methohexital is a Schedule G drug, it may be habit-forming.
Symptoms And Treatment Of Overdose: Symptoms: The onset of toxicity following an overdose of i.v. administered methohexital will be within seconds of the infusion. If methohexital is administered rectally or is ingested, the onset of toxicity may be delayed. The manifestations of an ultrashort-acting barbiturate in overdose include CNS depression, respiratory depression, hypotension, loss of peripheral vascular resistance and muscular hyperactivity ranging from twitching to convulsive-like movements. Other findings may include convulsions and allergic reactions. An acute allergic reaction to methohexital may include erythema, pruritus, urticaria, rhinitis, dyspnea, hypotension, anxiety, abdominal pain and peripheral vascular collapse. Following massive exposure to any barbiturate, pulmonary edema, circulatory collapse with loss of peripheral vascular tone, and cardiac arrest may occur.
Treatment: Establish an airway and ensure oxygenation and ventilation. Resuscitative measures should be initiated promptly. For hypotension, i.v. fluids should be administered and the patient’s legs raised. If desirable increase in blood pressure is not obtained, vasopressor and/or inotropic drugs may be used as dictated by the clinical situation.
For convulsions, diazepam i.v. and phenytoin may be required. If the seizures are refractory to diazepam and phenytoin, general anesthesia and paralysis with a neuromuscular blocking agent may be necessary.
Protect the patient’s airway and support ventilation and perfusion.
Meticulously monitor and maintain, within acceptable limits, the patient’s vital signs, blood gases, serum electrolytes, etc. Absorption of drugs from the gastrointestinal tract may be decreased by giving activated charcoal, which, in many cases, is more effective than emesis or lavage; consider charcoal instead of or in addition to gastric emptying. Repeated doses of charcoal over time may hasten elimination of some drugs that have been absorbed. Safeguard the patient’s airway when employing gastric emptying or charcoal.
Dosage And Administration: Preanesthetic medication is generally advisable. Methohexital sodium may be used with any of the recognized preanesthetic medications, but the phenothiazines are less satisfactory than the combination of an opiate and a belladonna derivative.
Facilities for assisting respiration and administering oxygen are necessary adjuncts for i.v. anesthesia.
Preparation of Solution: Follow diluting instructions exactly.
Diluents: Do not use diluents containing bacteriostats. Sterile Water for Injection is the preferred diluent. Five percent Dextrose Injection or 0.9% Sodium Chloride Injection may be used. (Brietal Sodium is not compatible with Ringer’s Lactate Solution.)
Dilution Instructions: For a 1% solution (10 mg/mL), contents of vials should be diluted as follows: 500 mg vials – add 50 mL of diluent.
Solutions of methohexital should be freshly prepared and used promptly. Reconstituted solutions are chemically stable at room temperature for 24 hours.
For continuous drip anesthesia, prepare 0.2% solution by adding 500 mg of drug to 250 mL of diluent. For this dilution, recommended solvents are either 5% glucose solution or isotonic (0.9%) sodium chloride solution instead of distilled water in order to avoid extreme hypotonicity.
Administration: Methohexital is administered i.v. in a concentration of no higher than 1%. Higher concentrations markedly increase the incidence of muscular movements and irregularities in respiration and blood pressure. Dosage is highly individualized; the drug should be administered only by those completely familiar with its quantitative differences from other barbiturate anesthetics.
Methohexital may be dissolved in Sterile Water for Injection, 5% Dextrose Injection, or Sodium Chloride Injection. For induction of anesthesia, a 1% solution is administered at a rate of about 1 mL/5 seconds. Gaseous anesthetics and/or skeletal-muscle relaxants may be administered concomitantly. The dose required for induction may range from 50 to 120 mg or more but averages about 70 mg. The induction dose usually provides anesthesia for 5 to 7 minutes.
The usual dosage in adults ranges from 1 to 1.5 mg/kg. Data on dosage requirements in children are not available.
Maintenance of anesthesia may be accomplished by intermittent injections of the 1% solution or, more easily, by continuous i.v. drip of a 0.2% solution. Intermittent injections of about 20 to 40 mg (2 to 4 mL of a 1% solution) may be given as required, usually every 4 to 7 minutes. For continuous drip, the average rate of administration is about 3 mL of a 0.2% solution/minute (1 drop/second). The rate of flow must be individualized for each patient. For longer surgical procedures, gradual reduction in the rate of administration is recommended (see discussion of prolonged administration in Warnings). Other parenteral agents, usually narcotic analgesics, are ordinarily employed along with methohexital during longer procedures.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Compatibility: Solutions of Brietal Sodium should not be mixed in the same syringe or administered simultaneously during i.v. infusion through the same needle with acid solutions, such as atropine sulfate, metocurine iodide injection and succinylcholine chloride.
Reduction of pH by addition of acidic compounds may cause free barbituric acid to be precipitated.
The soluble sodium salts of barbiturates are the forms used for i.v. administration. Solubility is maintained only at a relatively high (basic) pH.
Availability And Storage: Each rubber-stoppered vial of dry powder contains: methohexital sodium 500 mg/50 mL formulated with anhydrous sodium carbonate 30 mg. Preservative-free.
BRIETAL SODIUM® Lilly Methohexital Sodium Anesthetic