Sojourn Mechanism of Action

Pharmacology: Sevoflurane is an inhalation anaesthetic agent for use in induction and maintenance of general anaesthesia. Administration has been associated with a smooth, rapid loss of consciousness during inhalation induction and a rapid recovery following discontinuation of anaesthesia. Minimum alveolar concentration (MAC) of sevoflurane in oxygen reported for a 40-year-old adult is 2.1%. The MAC of sevoflurane decreases with age and with the addition of nitrous oxide.
Induction is accomplished with a minimum of excitement or of signs of upper respiratory irritation, no evidence of excessive secretions within the tracheobronchial tree and no central nervous system stimulation. The times for induction and recovery were reduced in paediatric patients who received sevoflurane in clinical studies.
Emergence and recovery are particularly rapid. Therefore, patients may require early post-operative pain relief.
As with all other inhalation agents sevoflurane depresses cardiovascular function in a dose related fashion. No evidence of seizure has been documented.
Sevoflurane had minimal effect on intracranial pressure (ICP) and preserved CO₂, responsiveness in patients with normal ICP. Its safety has not been investigated in patients with a raised ICP. Sevoflurane should be administered cautiously in conjunction with ICP-reducing manoeuvres such as hyperventilation in those patients who are at risk for elevations of ICP.
The low solubility of sevoflurane in blood should result in alveolar concentrations which rapidly increase upon induction and rapidly decrease upon cessation of the inhaled agent.
In humans <5% of the absorbed sevoflurane is metabolised. The rapid and extensive pulmonary elimination of Sevoflurane minimises the amount of anaesthetic available for metabolism. Sevoflurane is metabolised via cytochrome p450 (CYP)2E1 resulting in the production of hexafluoroisopropanol (HFIP) with release of inorganic fluoride and carbon dioxide (or a one carbon fragment). HFIP is then rapidly conjugated with glucuronic acid and excreted in the urine.
The metabolism of sevoflurane may be increased by known inducers of CYP2E1 (e.g. Isoniazid and alcohol), but it is not inducible by barbiturates.
Transient increases in serum inorganic fluoride levels may occur during and alter Sevoflurane anaesthesia. Generally, concentrations of inorganic fluoride peak within 2 hours of the end of sevoflurane anaesthesia and return within 48 hours to pro-operative levels.