Halothane

Usage

• Halothane is indicated for the induction and maintenance of general anesthesia.
• Pharmacological classification: Inhalation anesthetic.
• Mechanism of action: Halothane acts on the central nervous system to produce a dose-dependent depression of consciousness, leading to unconsciousness and analgesia. It affects multiple ion channels, depressing nerve conduction, breathing, and cardiac contractility. Its immobilizing effects are attributed to its binding to potassium channels in cholinergic neurons, as well as binding to NMDA and calcium channels.

Alternate Names

• Fluothane (brand name, no longer available in the US)

How It Works

• Pharmacodynamics: Halothane depresses the central nervous system, causing unconsciousness and analgesia. It also relaxes skeletal muscle, suppresses salivary, bronchial, and gastric secretions, and dilates the bronchioles.

• Pharmacokinetics:

  • Absorption: Absorbed rapidly through the lungs upon inhalation.
  • Distribution: Distributes widely throughout the body, with higher concentrations in tissues with high blood flow and lipid content, like the brain, liver, and adipose tissue. It also crosses the placenta and enters breast milk.
  • Metabolism: Primarily metabolized in the liver by CYP2E1, and to a lesser extent by CYP3A4 and CYP2A6, producing trifluoroacetic acid, bromide, and chloride salts via oxidative pathways. A small amount is metabolized via reductive pathways.
  • Elimination: Primarily eliminated through the lungs (60-80% unchanged) with the remainder excreted in urine and feces as metabolites.

• Mode of action: Halothane primarily acts by enhancing the activity of GABA_A receptors, the major inhibitory neurotransmitter receptors in the central nervous system. This leads to hyperpolarization of neurons and reduces neuronal excitability. Halothane also inhibits NMDA receptors, further contributing to its anesthetic effects.

• Receptor binding, enzyme inhibition, or neurotransmitter modulation: Enhances GABA_A receptor activity and inhibits NMDA receptor activity.

• Elimination pathways: Primarily pulmonary excretion (unchanged) with a smaller portion excreted in urine and feces as metabolites.

Dosage

Standard Dosage

Adults:

• Induction: 0.5% to 3% v/v in oxygen or a mixture of nitrous oxide and oxygen, increased gradually as needed.
• Maintenance: 0.5% to 1.5% v/v, adjusted according to patient response and the flow rate used.

Children:

• Induction: 1.5% to 2% v/v.
• Maintenance: 0.5% to 1.5% v/v.
• Pediatric safety considerations: Halothane is generally avoided in children undergoing outpatient dental procedures due to the risk of postoperative nausea and vomiting. Close monitoring of respiratory and cardiovascular function is crucial in pediatric patients.

Special Cases:

• Elderly Patients: Start with lower doses and titrate carefully due to potential age-related decreases in organ function.
• Patients with Renal Impairment: Dose adjustments may be necessary, although specific guidelines are limited due to primarily pulmonary elimination. Close monitoring is required.
• Patients with Hepatic Dysfunction: Halothane is generally avoided in patients with pre-existing liver disease or a history of halothane-induced hepatitis due to the increased risk of hepatotoxicity. If use is unavoidable, use lower doses and monitor liver function closely.
• Patients with Comorbid Conditions: Consider specific conditions and potential drug interactions.

Clinical Use Cases

• Intubation: Halothane can be used to facilitate intubation by relaxing the airway muscles.
• Surgical Procedures: Can be utilized for a wide range of surgical procedures requiring general anesthesia.
• Mechanical Ventilation: Halothane can be used in patients requiring mechanical ventilation to facilitate sedation and muscle relaxation.
• Intensive Care Unit (ICU) Use: May be used for short-term sedation and anesthetic management in the ICU setting.
• Emergency Situations: Limited role in emergency situations, mainly superseded by newer agents with better safety profiles.

Dosage Adjustments

• Dosage adjustments may be necessary based on patient response, underlying medical conditions, and concomitant medications.

Side Effects

Common Side Effects:

• Nausea
• Vomiting
• Chills
• Headache
• Postoperative shivering
• Bradycardia
• Hypotension
• Respiratory depression

Rare but Serious Side Effects:

• Hepatotoxicity (halothane hepatitis)
• Malignant hyperthermia
• Cardiac arrhythmias (ventricular arrhythmias)
• Cardiac arrest
• Respiratory arrest

Long-Term Effects:

• Chronic liver damage (with repeated exposure)

Adverse Drug Reactions (ADR):

• Malignant hyperthermia
• Severe hepatotoxicity

Contraindications

• Hypersensitivity to halothane
• Personal or family history of malignant hyperthermia
• History of unexplained jaundice or pyrexia following previous halothane exposure
• Raised intracranial pressure
• Patients with known or suspected genetic predisposition to malignant hyperthermia
• Children under 18 years of age undergoing outpatient dental surgery

Drug Interactions

• Epinephrine: Increased risk of ventricular dysrhythmias.
• Suxamethonium (succinylcholine): Increased risk of malignant hyperthermia.
• Non-depolarizing muscle relaxants: Potentiates their effects.
• Aminoglycosides: Enhanced muscle relaxant effects.
• Tubocurarine: Increased hypotension.
• Sympathomimetics, aminophylline, theophylline, and tricyclic antidepressants: Increased risk of arrhythmias.
• Hypotensive agents (e.g., hexamethonium bromide, trimetaphan camsilate): Potentiates their effects.
• Ketamine: Prolonged recovery from anesthesia.
• Alcohol: Increased CNS depression.
• Many other medications

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Not established. Use only if potential benefit justifies the potential risk to the fetus. Halothane reduces uterine muscle tone and increases the risk of postpartum hemorrhage.
• Breastfeeding: Halothane is excreted in breast milk. Breastfeeding should be interrupted for 24 hours after halothane anesthesia.

Drug Profile Summary

• Mechanism of Action: Inhaled anesthetic, enhances GABA_A activity, inhibits NMDA receptors.
• Side Effects: Nausea, vomiting, chills, headache, hepatotoxicity, malignant hyperthermia, cardiac arrhythmias.
• Contraindications: Malignant hyperthermia susceptibility, previous halothane-induced jaundice/pyrexia, raised intracranial pressure.
• Drug Interactions: Epinephrine, suxamethonium, non-depolarizing muscle relaxants, aminoglycosides, sympathomimetics.
• Pregnancy & Breastfeeding: Not established for pregnancy, interrupt breastfeeding for 24 hours.
• Dosage: Induction: Adults: 0.5-3%, Children: 1.5-2%; Maintenance: Adults/Children: 0.5-1.5%.
• Monitoring Parameters: Pulse, blood pressure, oxygen saturation, end-tidal CO2, temperature (for malignant hyperthermia).

Popular Combinations

• Halothane can be used with nitrous oxide and oxygen to enhance anesthesia and reduce the required concentration of halothane.

Precautions

• General Precautions: Careful patient history (prior anesthetic reactions), monitor liver function tests.
• Specific Populations: Avoid or use with caution in patients with liver or kidney disease, pregnant women, and breastfeeding mothers.
• Lifestyle Considerations: Avoid alcohol for at least 24 hours after anesthesia. Restrict driving and operating machinery for at least 24 hours.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Halothane?

A: Induction: Adults: 0.5-3%, Children: 1.5-2%; Maintenance: Adults/Children: 0.5-1.5%. Dosage should be adjusted based on patient response and clinical situation.

Q2: What are the major side effects of Halothane?

A: Nausea, vomiting, shivering, hepatotoxicity, malignant hyperthermia, cardiac arrhythmias.

Q3: In which patients should Halothane be avoided?

A: Patients with malignant hyperthermia susceptibility, previous halothane-induced jaundice/pyrexia, raised intracranial pressure.

Q4: Can Halothane be used during pregnancy?

A: Only if absolutely necessary and the benefits outweigh the potential risks to the fetus.

Q5: Is it safe to breastfeed while using Halothane?

A: Interrupt breastfeeding for 24 hours after halothane anesthesia.

Q6: What are the signs of malignant hyperthermia associated with Halothane?

A: Muscle rigidity, tachycardia, tachypnea, cyanosis, arrhythmias, unstable blood pressure, hyperthermia.

Q7: What are the drug interactions of Halothane?

A: Interacts with epinephrine, suxamethonium, non-depolarizing muscle relaxants, aminoglycosides, sympathomimetics, and many other medications. Consult a comprehensive drug interaction database before administering halothane.

Q8: How is Halothane metabolized?

A: Primarily metabolized in the liver by CYP2E1, and to a lesser extent by CYP3A4 and CYP2A6.

Q9: How is Halothane eliminated from the body?

A: Primarily eliminated unchanged through the lungs.

Q10: What is the mechanism of action of Halothane?

A: Halothane enhances the activity of GABA_A receptors and inhibits NMDA receptors, leading to CNS depression and anesthesia.