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Drugs List
Therapeutic Indications
Dosage
Administration
Contraindications
Precautions and Warnings
Pregnancy and Lactation
Side Effects
Monograph

Dosage

Adults
Elderly
Children
Neonates
Patients with Hepatic Impairment
Additional Dosage Information

Induction

Starting concentration of 0.5% in oxygen or an oxygen/nitrous oxide mixture.
Concentrations of 1.3% to 3% usually induce surgical anaesthesia within 7 to 10 minutes.

A short acting barbiturate or other intravenous induction agent is usually given before the isoflurane mixture is inhaled to avoid excitement and due to the irritant effects on the respiratory tract. Alternatively, isoflurane with oxygen or an oxygen/nitrous oxide mixture may be used.

Maintenance

A concentration of 1% to 2.5% isoflurane with an oxygen and nitrous oxide mixture may maintain surgical levels of anaesthesia.
A higher concentration of 1.5% to 3.5% may be necessary if isoflurane is administered with pure oxygen.

For Caesarean section, 0.5% to 0.75% isoflurane in an oxygen and nitrous oxide mixture is sufficient.

Recovery

Concentration must be reduced to 0.5% at the end of the operation, or 0% during wound closure to promote a prompt recovery.
When administration of anaesthetic agents stop, air passages should be ventilated several times with 100% oxygen until the patients completely awakens.

Precautions and Warnings

Isoflurane must only be administered by an anaesthetist.
Vaporisers that have been specifically calibrated for isoflurane should be used so that the concentration of isoflurane administered is accurately controlled.
The extent of hypotension and respiratory depression can indicate the level of anaesthesia. The isoflurane concentration should be reduced in order to correct excessive falls in blood pressure.

Isoflurane is a profound respiratory depressant. Respiration must be closely monitored and assisted if necessary.

A lower concentration of isoflurane is recommended in hypovolaemic, hypotensive and debilitated patients.

Patients should be constantly monitored, including ECG, blood pressure, oxygen saturation and end-tidal carbon dioxide. Resuscitation equipment must be immediately available.

Isoflurane should be used with caution in patients with myasthenia gravis, as these patients are especially sensitive to drugs that cause respiratory depression.

Ventilation should be controlled in patients undergoing neurosurgery. Cerebral blood flow may rise during deep anaesthesia. Increased intracranial pressure or increased cerebrospinal fluid pressure may be prevented or corrected by hyperventilation of the patient before or during anaesthesia.

Use with caution in patients with increased intracranial pressure. In these patients hyperventilation may be required.

Reduced concentrations of isoflurane should be used in elderly patients for the maintenance of surgical anaesthesia.

Hepatic impairment, jaundice and fatal hepatic necrosis have been reported with the use of halogenated anaesthetics , and appear to indicate hypersensitivity. Patients with cirrhosis, viral hepatitis or another pre-existing hepatic disease may require an alternative anaesthetic agent, and not a halogenated anaesthetic. It has been reported that previous exposure to halogenated hydrocarbon anaesthetics, especially if the interval is less than 3 months, may increase the potential for hepatic injury.

As with all halogenated anaesthetics, isoflurane should be used with caution if administered repeatedly within a short period of time.

Isoflurane may irritate mucous membranes causing cough, breath-holding and laryngospasm. Use with caution in patients with a predisposition to bronchospasm.

Isoflurane acts as an irritant to mucous membranes and is therefore difficult to use if the anaesthesia is administered via a mask.

There has been increased blood loss in patients undergoing abortion and uterine curettage (scraping).

Inhaled anaesthetic agents have rarely been associated with increases in serum potassium that have led to cardiac arrhythmias and death in children during the post-operative period. The condition has occurred in patients with latent and overt neuromuscular disease, particularly Duchenne muscular dystrophy. Patients developed muscle damage with increased serum creatinine kinase concentrations and myoglobinuria. They did not show signs of malignant hyperthermia, such as muscle rigidity, rapid increase in body temperature, increased oxygen uptake and increased carbon dioxide production.
If hyperkalaemia or arrhythmias occur during isoflurane administration, these effects should be treated immediately. Patients should also be evaluated for latent neuromuscular disease.

Isoflurane has been reported to interact with dry carbon dioxide absorbents to form carbon monoxide. To reduce the risk of carbon monoxide in breathing circuits and increased carboxyhaemoglobin levels, carbon dioxide absorbents should not be allowed to dry out.

Carbon dioxide absorbents must be replaced routinely and should not become desiccated (dried out). Failure to observe this safety precaution may lead to excessive heat, smoke or fire in the anaesthetic machine.

Pregnancy - see Pregnancy section

Breastfeeding - see Lactation section

Patients must not drive or operate machinery for 24 hours after anaesthesia. Changes in behaviour and intellectual function may persist for up to 6 days after administration which should be taken into account when normal activities such as driving resume.

Patients must be accompanied home and should not consume alcohol.

Isoflurane is not recommended for the induction of anaesthesia in children under 18 years because of the occurrence of cough, breath-holding, desaturation, increased secretions, and laryngospasm.

Pregnancy and Lactation

Pregnancy

There is insufficient experience regarding the use of isoflurane during human pregnancy. Safety has not been established for administration during obstetric surgery, other than for Caesarean section where there does not seem to be any harm to the foetus, except for the possible increase in bilirubin blood levels.

Isoflurane relaxes the uterus muscle, and the lowest possible concentration should be used in obstetrical operations.

Blood losses similar to those seen with other inhalation anaesthetics have been seen in patients receiving isoflurane for abortion induction procedures.

If used during the third trimester, neonatal respiratory depression may occur.

The absence of human experience during organogenesis prevents an assessment of the risk for structural abnormalities

Animal studies have not demonstrated any adverse effects on fertility, pregnancy, delivery, or in the offspring. The relevance of these studies to humans is not known.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

One manufacturer suggests breastfeeding is withheld for 12 hours following administration.
Although there is little evidence for continuation of breastfeeding after administration of isoflurane to the mother, both Briggs and Schaefer consider that there is little risk to the nursing infant.
Toxnet suggests that due to the short serum half-life, isoflurane is not expected to be absorbed by the infant therefore no waiting period or discarding of milk is required. Breastfeeding can be resumed as soon as the mother has recovered from the general anaesthesia sufficiently to nurse.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Presentation

Liquid for inhalation of vapours containing isoflurane 99.9% w/w or 100% v/v

Drugs List

AERRANE liquid for inhalation

isoflurane volatile liquid

Therapeutic Indications

Uses

Induction and maintenance of general anaesthesia

Dosage

Isoflurane must only be administered by an anaesthetist.

Vaporisers that have been specifically calibrated for isoflurane should be used so that the concentration of isoflurane administered is accurately controlled.

Adults

Induction
Starting concentration of 0.5% in oxygen or an oxygen/nitrous oxide mixture.
Concentrations of 1.3% to 3% usually induce surgical anaesthesia within 7 to 10 minutes.

Maintenance
A concentration of 1% to 2.5% isoflurane with an oxygen and nitrous oxide mixture may maintain surgical levels of anaesthesia.
A higher concentration of 1.5% to 3.5% may be necessary if isoflurane is administered with pure oxygen.

For Caesarean section, 0.5% to 0.75% isoflurane in an oxygen and nitrous oxide mixture is sufficient.

Recovery
Concentration must be reduced to 0.5% at the end of the operation, or 0% during wound closure to promote a prompt recovery.
When administration of anaesthetic agents stop, air passages should be ventilated several times with 100% oxygen until the patients completely awakens.

Elderly

Reduced concentrations of isoflurane should be used in elderly patients for the maintenance of surgical anaesthesia.

Children

Induction
Not recommended in children under 18 years because of the occurrence of cough, breath-holding, desaturation, increased secretions and laryngospasm.

Maintenance
A concentration of 1% to 2.5% isoflurane with an oxygen and nitrous oxide mixture may maintain surgical levels of anaesthesia. An additional 0.5% to 1% may be necessary if isoflurane is administered with pure oxygen.

For Caesarean section, 0.5% to 0.75% isoflurane in an oxygen and nitrous oxide mixture is sufficient.

Neonates

Induction
Not recommended because of the occurrence of cough, breath-holding, desaturation, increased secretions and laryngospasm.

Patients with Hepatic Impairment

Patients with cirrhosis, viral hepatitis or another pre-existing hepatic disease may require an alternative anaesthetic agent, and not a halogenated anaesthetic.

Isoflurane may cause hepatic changes ranging from transient increase in hepatic enzymes to fatal hepatic necrosis in rare instances. Previous exposure to halogenated anaesthetics, particularly if within the previous 3 months, may increase the risk.

Additional Dosage Information

Premedication
Drugs used for premedication should be selected for the individual patient bearing in mind the respiratory depressant effects of isoflurane. The use of anticholinergic drugs may be advisable for inhalation induction in children.

Administration

For inhalation via a specifically calibrated vaporiser.

Contraindications

Genetic disposition towards malignant hyperthermia (known or suspected)

History of malignant hyperthermia

Hepatic impairment, jaundice, unexplained fever, leucocytosis or eosinophilia following a previous dose of a halogenated anaesthetic.

Induction of anaesthesia in children.