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Alfaxalone: The Newest Anesthetic Induction Agent

KREINStephanie Krein, DVM, DACVAA
angell.org/anesthesia
anesthesia@angell.org
617-541-5048

Since the introduction of anesthesia hundreds of years ago, the agents used to provide sedation, induction, and maintenance of anesthesia have become profoundly safer. Although the drugs we use today are much safer, there still exists no perfect anesthetic agent. Since propofol came onto the market, it has been the most widely used, and arguably one of the safest anesthetic induction agents used in both human and veterinary anesthesia. Alfaxalone, brand name Alfaxan, is the newest anesthetic induction agent to enter the United States market after approval by the FDA in 2014. Although it is new in this country, it has been available and used widely throughout the world since 2001. Alfaxalone is a neurosteroid that enhances the actions of GABAA, the most important inhibitory neurotransmitter in the body, to produce muscle relaxation and anesthesia. Alfaxalone comes as a clear, colorless, non-irritating, aqueous formulation and is marketed for intravenous use only, although it can be used off label and administered intramuscularly (IM) as part of a sedation protocol. Alfaxalone is a class IV controlled substance and needs to be kept in a lock box and a log sheet must be created to record the amounts used each time.
 

Krein - Alfaxolone - Alfaxan (alfaxalone), 10 mg per mlCardiovascular effects of alfaxalone

Cats: There are several different studies evaluating the effects of alfaxalone on heart rate, systemic vascular resistance, contractility and cardiac output and these studies do not all agree in their findings. The overall picture of alfaxalone in cats is that it may decrease, although usually not to a clinically significant value, heart rate, decrease systemic vascular resistance, and mildly decrease contractility and cardiac output.(1,2) When compared to propofol it is thought that alfaxalone is similar in its effects although it may maintain systemic vascular resistance better than propofol, thereby leading to higher blood pressures.

Dogs: Alfaxalone has been shown to cause an increase in heart rate and a decrease in systemic vascular resistance (although mild and still within normal physiologic range) after induction.(3) It is thought to be a useful induction agent in both healthy and hemodynamically unstable dogs.(4) In dogs with advanced heart failure, etomidate still remains the drug with minimal effects on the cardiovascular system.(3)

 

Respiratory effects of alfaxalone

Cats: A recent study has shown that alfaxalone maintains respiratory rate and end tidal CO2 at normal levels as compared to the decrease seen with propofol.(5)

Dogs: Respiratory rate has been shown to be decreased from baseline after induction with alfaxalone, but apnea is less commonly noted than with propofol.(3)

 

Induction and Recovery Quality with Alfaxalone

Cats:  Induction and recovery from alfaxalone anesthesia has been shown to be satisfactory in cats. (1,6,7) Although overall satisfactory recoveries are noted, things such as tremors, twitching, paddling and face rubbing can occur. Longer recovery times are noted with alfaxalone than with propofol (may not be true for constant rate infusions). Alfaxalone recoveries are more satisfactory than those seen with ketamine and midazolam/diazepam.

Dogs:  Induction has been shown to be smooth in dogs, although events such as myoclonus and tremors can be seen, especially in inappropriately premedicated dogs. Recovery has also been proven to be overall satisfactory with the use of alfaxalone, although events such as head shaking, excitation, and sensitivity to noise have been seen.(8)

 

Effects on other body systems:

Intracranial pressure: Although not thoroughly studied to this point, it is thought that alfaxalone is safe for use in patients with intracranial disease.(1,9)

Intraocular pressure and tear production: Alfaxalone has been shown to increase intraocular pressure to the same degree as propofol (clinical significance unknown) and to decrease tear production to a greater degree than propofol.(10,11)

Hepatic and renal: Alfaxalone does not appear to have any unwanted effects on either the hepatic or the renal system.(1)

 

Clinical use of alfaxalone

Dogs:  Alfaxalone use in dogs is associated with a smooth induction of anesthesia, minimal cardiorespiratory depression, although a decrease in systemic vascular resistance and blood pressure can be seen, and a satisfactory recovery. In dogs in which an increase in heart rate is desired, such as those with degenerative valvular disease, alfaxalone may be a more appropriate agent than propofol. Although solely labeled for intravenous administration, alfaxalone can be given IM as part of the premedication in difficult to handle dogs. Alfaxalone does not provide analgesia and adequate premedication and pain control must be used in order to provide smooth inductions and recoveries with this drug. In addition to its use both IV and IM, the author of this article has used intranasal administration to deliver alfaxalone in a Doberman with severe Von Willebrand’s disease. This technique has not been described in the literature. Alfaxalone can be used in both healthy dogs and in those less stable to provide sufficient induction into anesthesia.(4) Alfaxalone can also be used as a constant rate infusion to maintain anesthesia throughout various procedures.

Cats:  Alfaxalone use in cats is associated with a smooth induction of anesthesia, minimal cardiorespiratory depression, and a satisfactory recovery, although events such as tremors and twitching can be noted. Since cats can be difficult to handle, often requiring intramuscular sedation, alfaxalone could fill a much needed void in providing an option that has overall minimal cardiovascular effects. Cardiovascular disease often goes undiagnosed in cats, especially those that are difficult to handle, and the drugs used to sedate cats IM currently have many unwanted cardiovascular side effects. The use of an opioid, a sedative (midazolam or dexmedetomidine), and alfaxalone frequently provides a rapid and satisfactory sedation of these cats as well as a smooth recovery. It is my clinical opinion that alfaxalone causes less hypotension after induction than does propofol in cats. Alfaxalone can also be used as a constant rate infusion for maintenance of anesthesia in cats. For these reasons above alfaxalone may indeed become widely used in feline anesthesia.

Other species:  Although beyond the scope of this article, alfaxalone has been used and studied in many other species including alpacas, ruminants, rabbits, ferrets, fish, and reptiles.

 

For more information, please contact Angell’s Anesthesia Services at 617-541-5048 (anesthesia@angell.org).

 

  1. Warne LN, Beths T, Whittem T, Carter JE, Bauquier SH. A review of the pharmacology and clinical application of alfaxalone in cats. Vet J. 2015 Feb;203(2):141–8.
  2. Ribas T, Bublot I, Junot S, Beaufrère H, Rannou B, Gagnière P, et al. Effects of intramuscular sedation with alfaxalone and butorphanol on echocardiographic measurements in healthy cats. J Feline Med Surg. SAGE Publications; 2015 Jun;17(6):530–6.
  3. Rodríguez JM, Muñoz-Rascón P, Navarrete-Calvo R, Gómez-Villamandos RJ, Domínguez Pérez JM, Fernández Sarmiento JA, et al. Comparison of the cardiopulmonary parameters after induction of anaesthesia with alphaxalone or etomidate in dogs. Veterinary Anaesthesia and Analgesia. Blackwell Publishing Ltd; 2012 Jul;39(4):357–65.
  4. Psatha E, Alibhai HI, Jimenez Lozano A, Armitage Chan E, Brodbelt DC. Clinical efficacy and cardiorespiratory effects of alfaxalone, or diazepam/fentanyl for induction of anaesthesia in dogs that are a poor anaesthetic risk. Veterinary Anaesthesia and Analgesia. Blackwell Publishing Ltd; 2011 Jan 1;38(1):24–36.
  5. Campagna I, Schwarz A, Keller S, Bettschart-Wolfensberger R, Mosing M. Comparison of the effects of propofol or alfaxalone for anaesthesia induction and maintenance on respiration in cats. Veterinary Anaesthesia and Analgesia. 2015 Sep;42(5):484–92.
  6. Mathis A, Pinelas R, Brodbelt DC, Alibhai HI. Comparison of quality of recovery from anaesthesia in cats induced with propofol or alfaxalone. Veterinary Anaesthesia and Analgesia. Blackwell Publishing Ltd; 2012 May 1;39(3):282–90.
  7. Gieseg M, Hon H, Bridges J, Walsh V. A comparison of anaesthetic recoveries in cats following induction with either alfaxalone or ketamine and diazepam. N Z Vet J. 2014 May;62(3):103–9.
  8. Maney JK, Shepard MK, Braun C, Cremer J, Hofmeister EH. A comparison of cardiopulmonary and anesthetic effects of an induction dose of alfaxalone or propofol in dogs. Veterinary Anaesthesia and Analgesia. 2013 May;40(3):237–44.
  9. Warne LN, Beths T, Fogal S, Bauquier SH. The use of alfaxalone and remifentanil total intravenous anesthesia in a dog undergoing a craniectomy for tumor resection. Can Vet J. 2014 Nov;55(11):1083–8.
  10. Hasiuk MMM, Forde N, Cooke A, Ramey K, Pang DSJ. A comparison of alfaxalone and propofol on intraocular pressure in healthy dogs. Vet Ophthalmol. 2014 Nov;17(6):411–6.
  11. Costa D, Leiva M, Moll X, Aguilar A, Peña T, Andaluz A. Alfaxalone versus propofol in dogs: a randomised trial to assess effects on peri-induction tear production, intraocular pressure and globe position. Vet Rec. BMJ Publishing Group Limited; 2015 Jan 17;176(3):73–3.
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