Isoflurane

Usage

• Medical Conditions: Isoflurane is a general inhalation anesthetic indicated for the induction and maintenance of general anesthesia. It is used in various surgical procedures requiring general anesthesia.
• Pharmacological Classification: General inhalation anesthetic, halogenated ether.
• Mechanism of Action: Isoflurane enhances inhibitory synaptic transmission through GABA_A receptors and glycine receptors. It also inhibits excitatory synaptic transmission, possibly by NMDA receptors. The precise mechanism of action, as with other general anesthetics, remains incompletely understood.

Alternate Names

• 1-Chloro-2,2,2-trifluoroethyl difluoromethyl ether (chemical name)
• Brand Names: Forane, Terrell, Aerrane, IsoFlo, Isoflurano, and others.

How It Works

• Pharmacodynamics: Isoflurane produces dose-dependent hypnosis, amnesia, and muscle relaxation. It also has analgesic and mild cardiovascular depressant effects, leading to hypotension and decreased systemic vascular resistance. Respiratory depression occurs with increasing doses.
• Pharmacokinetics:
  • Absorption: Rapidly absorbed via the lungs.
  • Metabolism: Minimal hepatic metabolism (less than 0.2%).
  • Elimination: Primarily eliminated unchanged through the lungs. A small fraction is metabolized in the liver and excreted renally as inorganic fluoride.
• Mode of Action: Isoflurane’s primary site of action is believed to be the central nervous system (CNS). It likely modulates the activity of GABA_A receptors, glycine receptors, and NMDA receptors.
• Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Isoflurane potentiates the effects of GABA at GABA_A receptors and enhances the effects of glycine, contributing to the anesthetic effect.
• Elimination Pathways: Predominantly pulmonary excretion; minimal renal excretion.

Dosage

Standard Dosage

Adults:

• Induction: 1.5% to 3% inspired concentration with or without nitrous oxide (N₂O). Surgical anesthesia is typically achieved within 7-10 minutes.
• Maintenance: 1% to 2.5% inspired concentration with N₂O. 0.5% to 1% additional isoflurane may be required when administered with oxygen alone.

Children:

• Not recommended for inhalation induction in infants and children due to the risk of laryngospasm, breath-holding, and increased secretions.
• Maintenance dosage should be individualized.

Special Cases:

• Elderly Patients: Lower concentrations are generally required.
• Patients with Renal Impairment: Dose adjustment not typically necessary due to minimal renal excretion.
• Patients with Hepatic Dysfunction: Dose adjustment may be necessary, although metabolism is minimal.
• Patients with Comorbid Conditions: Careful titration based on individual patient response and underlying conditions.

Clinical Use Cases

• Intubation: Facilitates endotracheal intubation after anesthetic induction.
• Surgical Procedures: Used for various surgical procedures requiring general anesthesia.
• Mechanical Ventilation: Provides anesthesia during mechanical ventilation.
• Intensive Care Unit (ICU) Use: Rarely utilized due to its slower recovery profile compared to other anesthetic agents.
• Emergency Situations: Can be used in select emergency situations but requires careful monitoring.

Dosage Adjustments:

• Dose adjustments may be required based on patient response, co-administered medications, and presence of renal or hepatic dysfunction.

Side Effects

Common Side Effects:

• Hypotension
• Respiratory depression
• Nausea and vomiting
• Shivering
• Bradycardia or tachycardia

Rare but Serious Side Effects:

• Malignant hyperthermia
• Hepatic dysfunction (rarely, hepatic necrosis)
• Cardiac arrhythmias (including torsades de pointes)
• Allergic reactions

Long-Term Effects:

• Potential for slight decrease in intellectual function for a few days post-anesthesia.
• Small changes in mood may persist for up to 6 days post-anesthesia.

Adverse Drug Reactions (ADR):

• Malignant hyperthermia: A life-threatening condition characterized by muscle rigidity, hyperthermia, and metabolic acidosis. Requires immediate intervention.

Contraindications

• Hypersensitivity to isoflurane or other halogenated anesthetic agents.
• Known or suspected genetic susceptibility to malignant hyperthermia.

Drug Interactions

• Muscle Relaxants: Isoflurane potentiates the effects of neuromuscular blocking agents.
• N₂O: Reduces the MAC of isoflurane.
• Other CNS Depressants: Additive effects with other CNS depressants (e.g., opioids, benzodiazepines).
• CYP450 Interactions: Isoflurane has minimal interaction with CYP450 enzymes.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (US FDA – previous categorization). There are no adequate and well-controlled studies in pregnant women. Animal studies have shown some evidence of fetotoxicity. Use during pregnancy only if the benefit outweighs the risk.
• Breastfeeding: Caution advised. Limited data suggest that isoflurane is excreted in breast milk in small amounts. Due to its short half-life, it’s not expected to pose a significant risk to the infant. Breastfeeding can typically be resumed as soon as the mother recovers sufficiently from general anesthesia.

Drug Profile Summary

• Mechanism of Action: Enhances inhibitory neurotransmission (GABA, glycine) and inhibits excitatory neurotransmission (NMDA).
• Side Effects: Hypotension, respiratory depression, nausea, shivering, arrhythmias.
• Contraindications: Hypersensitivity, malignant hyperthermia susceptibility.
• Drug Interactions: Muscle relaxants, N₂O, CNS depressants.
• Pregnancy & Breastfeeding: Use with caution. FDA pregnancy category C (previous categorization)
• Dosage: Induction: 1.5%–3%; Maintenance: 1%–2.5%
• Monitoring Parameters: Heart rate, blood pressure, respiratory rate, oxygen saturation, end-tidal CO₂.

Popular Combinations

• N₂O: Often co-administered to reduce the MAC of isoflurane and provide additional analgesia.
• Muscle relaxants: Used for enhanced muscle relaxation during surgery.

Precautions

• General Precautions: Careful patient selection and monitoring are crucial.
• Specific Populations: Use with caution in patients with cardiovascular or respiratory disease.
• Children & Elderly: Dose adjustments based on age and physiologic status.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Isoflurane?

A: Adults: Induction - 1.5% to 3%; Maintenance - 1% to 2.5%. Pediatric and special population dosing should be individualized.

Q2: What are the common side effects of Isoflurane?

A: Common side effects include hypotension, respiratory depression, nausea, and shivering.

Q3: How is Isoflurane metabolized?

A: Minimally metabolized by the liver (<0.2%).

Q4: What are the contraindications for using Isoflurane?

A: Hypersensitivity to isoflurane or other halogenated anesthetic agents and known or suspected susceptibility to malignant hyperthermia.

Q5: Can Isoflurane be used in pregnant women?

A: Use with caution. FDA Pregnancy Category C (previous categorization). Animal studies have shown some evidence of fetotoxicity. Use only if the benefit outweighs the potential risk.

Q6: How does Isoflurane interact with muscle relaxants?

A: Isoflurane potentiates the effects of muscle relaxants, so dosages may need to be adjusted.

Q7: What monitoring parameters are important during Isoflurane anesthesia?

A: Heart rate, blood pressure, respiratory rate, oxygen saturation, and end-tidal CO₂ levels.

Q8: What is the MAC of Isoflurane?

A: 1.15% in pure oxygen; 0.5% with 70% N₂O.

Q9: Can Isoflurane be used in patients with renal dysfunction?

A: Yes, typically no dose adjustment is needed as it’s minimally excreted by the kidneys.