Everyone there is so positive and professional, and, although we came there for a sad reason, we are so grateful to have met all of you.
West Orange, NJ
Alfaxalone is a neurosteroid anesthetic agent used clinically to induce general anesthesia in a variety of species including dogs and cats. Although alfaxalone is classified as a steroid, it has not been shown to have glucocorticoid or mineralocorticoid activity. Like many other intravenous hypnotic agents, including propofol, etomidate, and thiopental, alfaxalone produces it’s sedative effect through interaction with the GABAA receptor. Older formulations of the drug (e.g. Saffan®) caused histamine release and other adverse reactions due to the use of a castor oil surfactant (Cremophor EL) to solubilize the alfaxalone. New formulations solubilized in 2-hydroxypropyl beta-cyclodextrin (Alfaxan®) do not have that effect and have been approved in the US for intravenous use in dogs and cats. Alfaxan® comes as a clear, preservative- free 1% solution (10 mg/ml) and is currently scheduled as a class IV controlled substance.
Alfaxalone produces smooth, rapid induction of anesthesia, excellent muscle relaxation, and a short duration of anesthesia (6 – 10 min after 2 mg/kg in unpremedicated dogs), clinically similar to propofol. In dogs, cardiovascular function is generally well maintained after an induction dose of 2 mg/kg given over 1 minute. A dose-dependent decrease in arterial blood pressure and transient increase in heart rate have been noted in dogs and tachycardia may be pronounced in some dogs. The most common side effect is dose–related respiratory depression, although this seems to be less pronounced than that seen with propofol (mean duration of apnea being 30 seconds after a dose of 2 mg/kg alfaxalone). However, decreases in PaO2 can also occur, possibly due to changes in ventilation/perfusion matching, and supplemental oxygen should be provided.
Alfaxalone has minimal cumulative effect due to it’s rapid metabolism and may be given by continuous rate infusion (4-6 mg/kg/hr), Recovery is generally uneventful. In contrast to propofol, alfaxalone is metabolized by the liver and this should be taken into account when using the drug in patient’s with severely impaired liver function.
In cats, clinically relevant doses of 2 – 5 mg/kg IV given over 1 minute in unpremedicated cats also cause dose-dependent cardiopulmonary depression. The decrease in arterial blood pressure is related to a decrease in systemic vascular resistance, with minimal changes in heart rate or cardiac output. A dose-dependent decrease in respiratory rate is the most common side effect. A decrease in PaO2 unrelated to changes in ventilation has been noted and supplemental oxygen should be provided. Occasional excitement in the recovery period has been reported in cats.
Alfaxalone is commonly used for short-term sedation or induction of anesthesia. As with most anesthetic drugs, alfaxalone may be given in combination with other sedative or anesthetic agents including opioids (butorphanol, methadone, hydromorphone, oxymorphone), benzodiazepines (midazolam, diazepam), and/ or alpha-2 agonists and the dose should be adjusted accordingly (1-2mg/kg (dogs); 2-4 mg/kg (cats) with the alfaxalone titrated to effect). In smaller patients, the alfaxalone may be diluted 1:1with sterile saline to allow more accurate dosing.
Although not approved for intramuscular use in the US, alfaxalone is clinically effective when given by this route and may be especially helpful in handling fractious or stressed cats (1-2 mg/kg when given in combination with an opioid and benzodiazepine) to allow physical examination and i.v. catheter placement. The volumes of drug required in larger dogs somewhat limits its usefulness in those patients. Alfaxalone does not provide analgesia when given alone, but may act synergistically with other analgesic agents, such as opioids. Recent reports comparing Apgar scores after Caesarian section in dogs, show improvement in scores in puppies after alfaxalone induction relative to propofol induction. In addition, alfaxalone has proved an effective anesthetic in other species including iguanas, turtles, rabbits and marmosets.
Submitted by: Sandra Z Perkowski, VMD, PhD, Dipl ACVAA
Bertelsen MF, Sauer CD. Alfaxalone anaesthesia in the green iguana (Iguana iguana). Vet Anaesth Analg 2011;38(5):461-466
Grint NJ, Smith HE, Senior JM. Clinical evaluation of alfaxalone in cyclodextrin for the induction of anesthesia in rabbits. Vet Rec 2008;163(13):395-396.
Grubb TL, Greene SA, Perez TE. Cardiovascular and respiratory effects, and quality of anesthesia produced by alfaxalone administered intramuscularly to cats sedated with dexmedetomidine and hydromorphone. J Feline Med Surg 2013;15(10):858-865.
Muir W, Lerche P, Wiese A, Nelson L, Pasloske K, Whittem T. Cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in dogs. Vet Anaesth Analg 2008;35(6):451-462.
Muir W, Lerche P, Wiese A, Nelson L, Pasloske K, Whittem T. The cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in cats. Vet Anesth Analg 2009: 36,42-54.
Doebeli A, Michel E, Bettschart R, Harnack S, Reichter IM. Apgar score after induction of anesthesia for canine cesarean section with alfaxalone versus propofol. Theriogenology 2013: 80(8): 850-854.
Tamura J, Ishizuka T, Fukui S, et al. The pharmacological effects of the anesthetic alfaxalone after intramuscular administration to dogs. J Vet Med Sci. 2015;77(3):289-296.
Whittem T, Pasloske KS, Heit MC, Ranasinghe MG. The pharmacokinetics and pharmacodynamics of alfaxalone in cats after single and multiple intravenous administration of Alfaxan at clinical and supraclinical doses. J Vet Pharmacol Ther 2008;31(6):571-579.