Pharmacotherapeutic group: Inhalation anaesthetic

ATCvet code: QN 01 AB 08

Sevoflurane is an inhalational anaesthetic agent, having a light odour, for induction and maintenance of general anaesthesia. The Minimum Alveolar Concentration (MAC) of sevoflurane in dogs is 2.36%. Multiples of MAC are used as a guide for surgical levels of anaesthesia, which are typically 1.3 to 1.5 times the MAC value.

Sevoflurane produces unconsciousness by its action on the central nervous system. Sevoflurane produces only modest increases in cerebral blood flow and metabolic rate, and has little or no ability to potentiate seizures. Sevoflurane may increase intracranial pressure at concentrations of 2.0 MAC and above under normal partial pressures of carbon dioxide (normocapnia), but intracranial pressure has been shown to remain within normal range at sevoflurane concentrations of up to 1.5 MAC if hypocapnia is induced by hyperventilation.

Sevoflurane has a variable effect on heart rate, which tends to increase from baseline at low MAC and fall back with increasing MAC. Sevoflurane causes systemic vasodilation and produces dose-dependent decreases in mean arterial pressure, total peripheral resistance, cardiac output and possibly the strength of myocardial contraction and speed of myocardial relaxation.

Sevoflurane has a depressive effect on respiration characterised by a fall in ventilation frequency. Respiratory depression may lead to respiratory acidosis and respiratory arrest (at sevoflurane concentrations of 2.0 MAC and above) in spontaneously breathing dogs.

Concentrations of sevoflurane below 2.0 MAC result in a small net increase in total liver blood flow. Hepatic oxygen delivery and consumption were not significantly altered at concentrations up to 2.0 MAC.

Sevoflurane administration adversely affects the autoregulation of renal blood flow in dogs. As a result, renal blood flow falls in a linear fashion with increasing hypotension in sevoflurane anaesthetised dogs. Nevertheless, renal oxygen consumption, and hence renal function, are preserved at mean arterial pressures above 40 mmHg.

A minimal amount of sevoflurane is required to be dissolved in the blood before the alveolar partial pressure is in equilibrium with the arterial partial pressure because of the low solubility of sevoflurane in blood (blood/gas partition coefficient at 30°C is 0.63 to 0.69). During sevoflurane induction, there is a rapid increase in alveolar concentration towards the inspired concentration, with the ratio of inspired to end-tidal concentration of sevoflurane reaching a value of 1 within 10 minutes. Anaesthetic induction is correspondingly rapid and the depth of anaesthesia changes rapidly with changes in anaesthetic concentration.

Sevoflurane is metabolised to a limited extent in the dog (1 to 5%). The principle metabolites are hexafluoroisopropanol (HFIP) with release of inorganic fluoride and CO2. Fluoride ion concentrations are influenced by the duration of anaesthesia and the concentration of sevoflurane. Once formed, HFIP is rapidly conjugated with glucuronic acid and eliminated as a urinary metabolite. No other metabolic pathways for sevoflurane have been identified. In dogs exposed to 4% sevoflurane for 3 hours, mean peak maximum serum fluoride concentrations of 20.0 ± 4.8 μmol/l have been observed after 3 hours of anaesthesia. Serum fluoride fell quickly after anaesthesia ended and had returned to baseline by 24 hours post-anaesthesia.

The elimination of sevoflurane is biphasic in nature, with an initial rapid phase and a second, slower phase. Parent compound (the dominant fraction) is eliminated via the lungs. The half-life for the slow elimination phase is approximately 50 minutes. Elimination from blood is largely complete within 24 hours. The elimination time from adipose tissue is more prolonged than from the brain.