Uforane

Approved Indications:

• Induction of General Anesthesia: Isoflurane is widely used for initiating general anesthesia in surgical procedures.
• Maintenance of General Anesthesia: It is commonly administered to maintain anesthesia after induction with intravenous agents.

Important Off-Label / Clinically Accepted Uses:

• Status Asthmaticus (Refractory): Inhaled isoflurane has been used in intensive care settings for life-threatening asthma unresponsive to conventional therapy.
• Refractory Status Epilepticus: As an adjunct in patients unresponsive to anticonvulsants and requiring anesthetic suppression of brain activity.

Route: Inhalation via vaporizer with calibrated delivery

Adults:

• Induction of Anesthesia: 1.5% to 3% inspired concentration, typically following IV induction agents.
• Maintenance of Anesthesia: 1% to 2.5% inspired concentration, adjusted to desired depth of anesthesia.

Pediatrics:

• Induction: 1.5% to 3% is typical; lower concentrations if pre-medicated.
• Maintenance: 1% to 2.5%, titrated as needed based on patient response and surgical stimulation.

Elderly:

• Reduced dosage required due to increased sensitivity.
• Minimum Alveolar Concentration (MAC) decreases by ~6% per decade after age 40.

Renal/Hepatic Impairment:

• No specific dose adjustment; use with caution. Monitor organ function in prolonged use.

Notes:

• Use only with calibrated vaporizers designed for isoflurane.
• Administer in combination with oxygen or oxygen/nitrous oxide mixtures.
• Avoid closed-circuit systems unless specifically equipped for anesthetic agent monitoring.

Isoflurane acts primarily at the central nervous system by enhancing inhibitory neurotransmission and attenuating excitatory neurotransmission. It positively modulates GABA-A receptors, increasing chloride ion influx and causing neuronal hyperpolarization. It also affects potassium channels (e.g., TREK-1), NMDA receptors, and glycine receptors. These combined effects result in a decrease in neuronal excitability, leading to hypnosis, amnesia, and muscle relaxation characteristic of general anesthesia.

• Absorption: Rapidly absorbed via the lungs due to high volatility and controlled vaporization.
• Onset of Action: 7–10 minutes for surgical anesthesia after induction.
• Distribution: Widely distributed with high lipid solubility; crosses the blood-brain barrier.
• Metabolism: Less than 0.2% is metabolized hepatically (mostly unchanged).
• Metabolites: Trifluoroacetic acid and fluoride ions (clinically insignificant in most cases).
• Elimination: >99% eliminated unchanged via exhalation.
• Half-life: Not applicable due to rapid pulmonary elimination and low metabolism.
• MAC (Minimum Alveolar Concentration):
• Adults (age 40): ~1.15%
• Elderly: Lower MAC (~0.9% or less)
• Pediatrics: Higher MAC (~1.6–1.8%)

• Pregnancy: Category C (FDA historical). No adequate human studies; use only if benefits outweigh potential fetal risks. Animal studies show adverse effects at high doses.
• Labor & Delivery: Isoflurane may cause uterine relaxation and increased bleeding; not recommended for obstetric anesthesia.
• Lactation: Isoflurane is rapidly eliminated and not significantly excreted in breast milk. It is generally considered safe when breastfeeding resumes after maternal recovery from anesthesia.

• Primary Class: Inhalational General Anesthetic
• Subclass: Halogenated Ether Anesthetic (Volatile)

• Known hypersensitivity to isoflurane or other halogenated inhalational agents
• History of malignant hyperthermia
• Patients with known or suspected susceptibility to malignant hyperthermia
• Severe hepatic dysfunction following prior exposure to halogenated anesthetics

• Malignant Hyperthermia: Life-threatening reaction requiring immediate discontinuation and treatment with dantrolene.
• Hypotension: Monitor blood pressure closely; dose-dependent vasodilation can occur.
• Respiratory Depression: May cause respiratory acidosis, especially with deep anesthesia.
• Hepatotoxicity: Use with caution in repeated exposures; rare cases of fulminant hepatic failure reported.
• Intracranial Pressure: Isoflurane can increase cerebral blood flow and intracranial pressure; use with caution in neurosurgical patients.
• Cardiac Arrhythmias: Can sensitize the myocardium to catecholamines.

Common Side Effects:

• Respiratory: Cough, breath-holding, respiratory depression
• Cardiovascular: Hypotension, bradycardia, arrhythmias
• Gastrointestinal: Nausea, vomiting (especially post-op)
• Neurological: Emergence agitation, shivering

Serious or Rare Side Effects:

• Malignant Hyperthermia
• Fulminant hepatic necrosis
• Anaphylactic reaction
• Increased intracranial pressure

Onset & Severity:

• Most side effects are dose-dependent and occur during or shortly after anesthesia. Severe effects such as malignant hyperthermia may occur rapidly and require immediate intervention.

Major Interactions:

• Non-selective beta-agonists (e.g., epinephrine): Increased risk of arrhythmia due to myocardial sensitization
• Calcium channel blockers: May exacerbate hypotension
• Neuromuscular blocking agents: Potentiates muscle relaxation effects
• CNS depressants (e.g., opioids, benzodiazepines): Additive CNS and respiratory depression
• Enzyme Interactions: Minimal hepatic metabolism; not significantly affected by CYP450 induction or inhibition

• Anesthesia Guidelines (ASA 2024): Isoflurane remains a recommended agent for maintenance in general anesthesia due to its cardiovascular stability and low metabolism.
• Malignant Hyperthermia Screening: Updated clinical protocols advise preoperative genetic risk screening in patients with a family history of anesthesia-related complications.
• Environmental Regulation (2024): Increased awareness of greenhouse gas impact of volatile anesthetics like isoflurane; recommendations favor minimal-flow anesthesia techniques to reduce environmental exposure.

• Storage Temperature: Store below 30°C (86°F)
• Humidity/Light: Protect from direct sunlight; store in tightly sealed amber-colored bottles
• Handling Precautions:
• Use with calibrated vaporizers only
• Do not refrigerate or freeze
• Stability: Chemically stable under normal conditions; avoid contamination with water or incompatible materials