Steroid Agents

Introduction

The only available steroid anaesthetic for use in veterinary patients is alfaxalone. It is a progesterone derived neurosteroid.

Mechanism of Action

Neurosteroids act similarly to other anaesthetic agents by acting at the GABAa receptor chloride channels to enhance the inhibitory effect of GABA. This produces hypnosis and muscle relaxation.

Pharmacological Considerations

Alfaxalone is available as either a single agent solution at 10mg/ml, or in combination with alfadolone with polyoxyethylated castor oil as a solvent. Alfaxalone can be administered intravenously and intramuscularly, though the efficacy of intramuscular injection is species dependant - do not rely on intramuscular injection of alfaxalone to sedate or induce anaesthesia in dogs. It has a rapid onset of action, inducing anaesthesia with 30-60 seconds when given intravenously. Its duration of action is dose dependent. If given intramuscularly, onset of anaesthesia is within 7-10 minutes. Recovery occurs due to a combination of metabolism via and redistribution.

The formulation of alfaxalone in cyclodextrin has a volume of distribution after a single injection of a clinical dose in dogs and cats of 2.4 L/kg and 1.8 L/kg, respectively. In cats, the mean terminal plasma elimination half-life (t1/2) for alfaxalone is approximately 45 minutes for a 5 mg/kg dose. Mean plasma clearance for a 5 mg/kg dose is 25.1 ± 7.6 mL/kg/min. In dogs, the mean terminal plasma elimination half-life (t1/2) for alfaxalone is approximately 25 minutes for a 2 mg/kg dose. Plasma clearance for a 2 mg/kg dose is 59.4 ± 12.9 mL/kg/min. (Product literature)

Drug Interactions

Alfaxalone in cyclodextrin has been used safely after administration of an extremely wide range of premedication and peri-operative drugs. Dose dependant CNS depression can be accentuated by administration of sedatives and analgesics. Alfaxalone should not be administered concurrently with other intravenous anaesthetic induction drugs, but has been used safely as an induction agent prior to maintenance with halothane, isoflurane, sevoflurane and desflurane. It should not be mixed in the same syringe as other medications, as the cyclodextrin has a propensity to bind other chemicals. If a need exists to dilute the alfaxalone in cyclodextrin solution, it has been shown to be stable in 0.9% Saline for up to 7 days. Slight absorbtion to plastic of giving sets has been recognised, though this appears to be of no clinical significance.

Contraindications and Side Effects

Cardiovascular Effects

• At clinical doses, and employing the concepts of balanced anaesthesia, alfaxalone in cyclodextrin causes little cardiovascular effect, however a dose dependent decrease in arterial blood pressure thought to be due to myocardial contractility and stroke volume can be recognised at supra-clinical doses.

Respiratory Effects

• Minimal respiratory effects. Rapid intravenous administration can produce a short period of apnoea, therefore when using the IV route alfaxalone should be administered steadily over a period of 60 seconds (e.g. 1/4 dose every 15 seconds) while assessing the depth of anaesthesia achieved.

Other Effects

• Administration of the combination product (alfaxalone/aldalone) solubilised in Cremophor EL is associated with adverse effects. In cats hyperaemia or oedema of the ears and forepaws is observed in over half of animals; and in dogs it can induce an anaphylactoid reaction with histamine release leading to a fall in arterial blood pressure, urticaria and skin erythema. Its association with histamine release means it is contraindicated in animals with conditions such as asthma or mast cell tumours.

These adverse effects are not experienced in cats or dogs following administration of the aqueous cyclodextrin formulation of alfaxalone, which is Cremophor-free.

Uses

Alfaxalone can be used for induction and maintenance of anaesthesia in dogs and cats.