ISOFLURANE Inhalation vapour Ref.[9251] Active ingredients: Isoflurane

Source: Medicines & Healthcare Products Regulatory Agency (GB)  Revision Year: 2019  Publisher: Piramal Critical Care Limited, Suite 4, Ground Floor, Heathrow Boulevard East Wing, 280 Bath Road, West Drayton, UB7 0DQ, United Kingdom

Pharmacodynamic properties

Pharmacotherapeutic group: Nervous system; anaesthetic; general; Halogenated hydrocarbons
ATC code: N01AB06

Isoflurane is a general inhalational anaesthetic which provides rapid induction of anaesthesia and also rapid recovery. Although slight pungency may limit the rate of induction, excessive salivation and tracheo-bronchial secretions are not stimulated. Pharyngeal and laryngeal reflexes are diminished quickly. Levels of anaesthesia change rapidly with Isoflurane. Heart rhythm remains stable. Spontaneous respiration becomes depressed as depth of anaesthesia increases and should be closely monitored.

During induction there is a decrease in blood pressure which returns towards normal with surgical stimulation.

Blood pressure tends to fall during maintenance in direct relation to depth of anaesthesia, due to peripheral vasodilation, but cardiac rhythm remains stable. With controlled respiration and normal PaCO2, cardiac output tends to be maintained despite increasing depth of anaesthesia, primarily through a rise in heart rate. With spontaneous respiration, the resulting hypercapnia may increase heart rate and cardiac output above awake levels.

Cerebral blood flow remains unchanged during light isoflurane anaesthesia but tends to rise at deeper levels. Increases in cerebrospinal fluid pressure may be prevented or reversed by hyperventilating the patient before or during anaesthesia. Electro-encephalographic changes and convulsion are extremely rare with isoflurane.

Isoflurane appears to sensitise the myocardium to adrenaline to an even lesser extent than Enflurane. Limited data suggest that subcutaneous infiltration of up to 50ml of 1:200,000 solution adrenaline does not induce ventricular arrhythmias, in patients anaesthetised with isoflurane.

Muscular relaxation may be adequate for some intra-abdominal operations at normal levels of anaesthesia, but should greater relaxation be required small doses of intravenous muscle relaxants may be used. All commonly used muscle relaxants are markedly potentiated by isoflurane, the effect being most profound with non- depolarising agents. Neostigmine reverses the effects of non-depolarising muscle relaxants but has no effect on the relaxant properties of isoflurane itself. All commonly used muscle relaxants are compatible with isoflurane.

Isoflurane may be used for the induction and maintenance of general anaesthesia. Adequate data are not available to establish its place in pregnancy or obstetric anaesthesia other than for caesarean section.

Relatively little metabolism of isoflurane occurs in the human body. In the post operative period only 0.17% of the isoflurane taken up can be recovered as urinary metabolites. Peak serum inorganic fluoride values usually average less than 5µmol/litre and occur about four hours after anaesthesia, returning to normal levels within 24 hours. No signs of renal injury have been reported after isoflurane administration.

Pharmacokinetic properties

MAC (Minimum Alveolar Concentration in man):

Age100% Oxygen70%N~2~O
26 ± 41.280.56
44 ± 71.150.50
64 ± 51.050.37

Preclinical safety data

Published studies in animals (including primates) at doses resulting in light to moderate anaesthesia demonstrate that the use of anaesthetic agents during the period of rapid brain growth or synaptogenesis results in cell loss in the developing brain that can be associated with prolonged cognitive deficiencies. The clinical significance of these nonclinical findings in not known.

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