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
Pharmacotherapeutic group: Nervous system; anaesthetics; general; Halogenated hydrocarbons
ATC code: N01AB07
Desflurane is one of a family of halogenated methyl ethyl ethers, which are administered by inhalation, producing a dose-related temporary loss of consciousness and of pain sensations, suppression of voluntary motor activity, reduction of autonomic reflexes, and depression of respiration and the cardiovascular system.
Other members of the series include enflurane and isoflurane which are halogenated with chlorine as well as fluorine. Desflurane is halogenated exclusively with fluorine.
As suggested by its structure, the diffusion coefficient of gas in the blood for desflurane (0.42) is lower than all available volatile anaesthetics (isoflurane has 1.4 blood-gas partition coefficient), and slightly lower than nitrous oxide (0.46). These data indicate that desflurane would meet the need for an agent characterised by rapid recovery.
Animal studies have shown more rapid induction and awakening with desflurane than from isoflurane anaesthesia, with similar cardiovascular profile. EEG monitoring did not detect epileptogenic or other central nervous system undesirable effects during the desflurane-anaesthesia, and concomitant use of adjuvant medicinal products produced no unanticipated or toxic EEG responses.
Clinical studies to date evaluating myocardial ischemia, infarction and death as outcome parameters have not established that the coronary arteriolar property of desflurane is associated with coronary steal or myocardial ischemia in patients with coronary artery disease.
Studies in pigs susceptible to malignant hyperthermia indicated that desflurane is a powerful trigger for malignant hyperthermia.
Pharmacological effect of desflurane is dose-dependent.
As predicted from its physiochemical profile, pharmacokinetic studies in animals as in man indicate that desflurane washes into the body more rapidly than other volatile anaesthetics, and allows faster induction. It also washes out of the body more rapidly allowing quick recovery and flexibility in adjustment of the depth of anaesthesia.
Desflurane is eliminated via the lungs, undergoing only minimal metabolism (0.02%), hence low potential for toxicity.
The pharmacological effect is proportional to the inspired concentration of desflurane. The main adverse effects are exacerbations of the pharmacological action.
The MAC (minimum alveolar concentration) decreases with increasing age. A reduction of dose is recommended in hypovolemic, hypotensive and weak patients, as indicated in section 4.4.
Non-clinical data on acute and subchronic toxicity of desflurane show that it triggers in a concentration-dependent manner a predictable and controllable depression of respiration and circulatory system. There was no development of organ specific toxicity with desflurane in this case.
In swine, desflurane did not sensitize the myocardium to exogenously administered epinephrine. Desflurane appears to produce coronary vasodilation at arteriolar level in selected animal models, in a similar fashion to that of isoflurane. In an animal model simulating coronary artery disease with conscious, chronically instrumented dogs, desflurane does not appear to divert blood from collateral dependent myocardium to normally perfused areas (“coronary steal”).
Embryotoxicity studies in which rats and rabbits were administered desflurane during the phase of organogenesis showed embryo toxic effects after an exposure period of 4 MAC-hours a day (approximately 40 cumulative MAC hours). No adverse reaction was detected after an exposure period of 10 cumulative MAC hours.
In rats, during gestation and lactation, increased post-implantation loss and reduction in weight-gain of offspring was observed after a maternal exposure period of 4 MAC hours/per day. During this same period, maternal exposure of 1 MAC hour/day did not cause adverse effects. All of the adverse effects observed on the foetus or offspring were limited to groups where maternal toxicity (death and reduced weight gain) occurred, that is, the effects on the offspring may reflect the pharmacological effect of desflurane on the female animal.
The fertility of male and female rats was reduced at an exposure of 4 MAC hours/day. The effects were limited to those dose-groups, in which maternal toxicity was observed.
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 is not known.
A detailed investigation by in-vivo and in-vitro studies revealed no evidence of mutagenic properties of desflurane.
Long-term studies on carcinogenicity of desflurane were not carried out.
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