Isoflurane

Registered South African indications:

• General anaesthesia

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other halogenated anaesthetics
• Known or suspected genetic susceptibility to malignant hyperthermia

Cautions

• Pregnancy
• Breastfeeding
• Hepatic impairment
• Elderly
• Known or risk factors for QT prolongation
• Mitochondrial disorders
• Exposure to halogenated anaesthetics within the last 3 months
• Myasthenia gravis
• Increased intracranial pressure
• Reactive airways disease
• Hypovolaemia
• Hypotension
• Debilitated patients
• Coronary artery disease
• Obstetric procedures
• Duchenne muscular dystrophy
• Children younger than 2 years

Forms avail. in SA and covered in this monograph: liq

General anaesthesia

• Inhaled (liq): Initial: 0.5-3%; Maintenance: 0.5-2.5% when used in combination with nitrous oxide and oxygen; Concentrations up to 3.5% may be used when given with oxygen alone OR 2.5% when given with nitrous oxide; Recovery: Reduce to 0.5% near the end of surgical procedure; MAC: 1.2%

Hypnotic dose of intravenous induction agent is recommended to avoid coughing, breath holding or laryngeal spasm

To only be used in specific isoflurane vaporisers

See adult dosage

Pregnancy

• Caution; evidence of risk
• There are no or limited amount of data from the use of isoflurane in pregnant women. Studies in animals have shown reproductive toxicity. Isoflurane should only be used during pregnancy if the benefit outweighs the potential risk
• Isoflurane, like other inhalational agents, has relaxant effects on the uterus with the potential risk for uterine bleeding. Clinical judgement should be observed when using isoflurane during obstetric anaesthesia. Consideration should be taken to use the lowest possible concentration of isoflurane in obstetrical operations

Breastfeeding

• Caution
• It is not known whether isoflurane/metabolites are excreted in human milk. Because many agents are excreted in human milk, caution should be exercised when isoflurane is administered to a breastfeeding woman

Renal Impairment

• No dose adjustment recommended

Hepatic Impairment

• Caution; no dose adjustment recommended

Elderly

• Caution; dose adjustment recommended
  Dose adjustments are patient profile dependant
  Lower concentrations are usually required to maintain surgical anaesthesia due to decreased MAC (Minimum alveolar concentration) values
  Age, co-morbidities, heart rate, respiratory rate and blood pressure amongst other factors, also need to be considered when determining dosage

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Agitation
• Delirium
• Mood altered
• Seizures
• Mental impairment

Cardiovascular Disorders

• Arrhythmias
• Bradycardia
• Cardiac arrest
• QT prolongation
• Tachycardia
• Chest pain 
• Torsade de pointes
• Hypotension
• Haemorrhage

Respiratory Disorders

• Bronchospasm 
• Dyspnoea 
• Wheezing
• Respiratory depression
• Laryngospasm

Gastrointestinal Disorders

• Ileus
• Nausea and vomiting

Hepatobiliary Disorders

• Hepatic necrosis
• Hepatocellular injury
• Increased blood bilirubin

Genitourinary Disorders

• Increased serum creatinine 
• Decreased serum urea 

Endocrine and Metabolic Disorders

• Hyperkalaemia
• Increased blood glucose
• Malignant hyperthermia 

Musculoskeletal Disorders

• Myoglobinuria
• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders

• Facial oedema
• Contact dermatitis
• Rash

Immune, Blood and Lymphatic System Disorders

• Carboxyhaemoglobinaemia
• Anaphylactic reaction
• Hypersensitivity

• Sympathomimetics
• Non-selective monoamine oxidase inhibitors
• Beta blockers
• Isoniazid
• Epenephrine
• Neuromuscular blocking agents
• Opioids
• Narcotic premedication 
• Benzodiazepines
• Calcium antagonists
• Nitrous oxide

• Isoflurane concentrations
• Oxygen concentration

Isoflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Isoflurane also activates calcium-dependent adenosine triphosphatase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. Also appears to bind the D subunit of adenosine triphosphate synthase and nicotinamide adenine dinucleotide dehydogenase. Isoflurane also binds to the gamma-aminobutyric acid receptor, the large conductance calcium-activated potassium channel, the glutamate receptor and the glycine receptor.

Liquid 100ml

• Aerrane (AstraZeneca) originator
• Isofor 100% (Safeline)

Liquid 250ml

• Forane (Abbvie) originator
• Isofor (Safeline)
• Isoflurane USP (Safeline)