Originally published in the November 2014 issue of Veterinary Practice News Twelve years after an application was sent to the Food and Drug Administration, a new anesthetic drug, alfaxalone, just became available on the U.S. veterinary market. To better understand what it is, how it works and which precautions to use, we asked Bob Stein, DVM, Dipl. AAPM, CVA, CCRT, CVPP, CMTPT, to share some information about the drug. He has eight years of alfaxalone experience in small animal practice. Dr. Stein is the founder and webmaster of the excellent Veterinary Anesthesia and Analgesia Support Group (www.vasg.org) as well as the owner of the Animal Pain Management Center in Buffalo, N.Y., and Amherst Small Animal Hospital in Snyder, N.Y. What’s All the Excitement About? Alfaxalone’s arrival on the U.S. market is exciting because of its versatility and relative safety. It can be used on cases ranging from young and healthy patients to more challenging ones like C-sections, cardiac patients and debilitated pets. It has been many years since a new anesthetic agent was approved. Isoflurane was introduced 35 years ago. Propofol and sevoflurane were released about a quarter century ago. Common induction options include opioid/benzodiazepine combinations, ketamine/benzodiazepine combinations and propofol. The routine use of chamber and mask induction is not considered appropriate in 2014. Unlike ketamine, alfaxalone is not associated with adverse cerebral outcomes or cardiac stress. Unlike propofol, alfaxalone is not associated with respiratory depression or hypotension at normal induction doses. In addition, it is the only drug approved by the FDA for the induction and maintenance of anesthesia in both dogs and cats. Propofol, isoflurane and sevoflurane are approved for use only in canine patients. What Is Alfaxalone Chemically? It is a synthetic neuroactive steroidal anesthetic. It achieves its central effects via interactions with GABA receptors [gamma aminobutyric acid], as with most anesthetics. Is Alfaxalone a New Drug? Alfaxalone was first released on the veterinary market in the 1970s in combination with another neurosteroidal agent, alfadolone. The problem was the vehicle used at that time, a castor oil surfactant called Cremophor EL. The vehicle, not alfaxalone, was responsible for clinically significant allergic reactions, which led to its withdrawal from the market. Its brand name is Alfaxan, and it is a pure formulation of alfaxalone developed by Jurox, an Australian company with North American headquarters in Kansas City, Mo. Jurox devised a method of complexing alfaxalone to a large water soluble sugar molecule [cyclodextrin]. Alfaxan was first released for use in cats and dogs in Australia in 2000, the U.K. in 2007, Central Europe in 2008 and Canada in 2011. So there is now extensive literature from 14 years of cumulative clinical experience. Can It Be Combined With Other Induction Agents? Our anesthetic protocols are based on balanced anesthetic principles. When using propofol or alfaxalone, we can premedicate with an opioid and/or a benzodiazepine, acepromazine or dexmedetomidine if the patient is healthy. We can also administer low-dose ketamine and a benzodiazepine IV just before the main induction agent. By following these strategies, we minimize the potential for respiratory and cardiovascular depression and we reduce the cost of the induction agent. How Is Alfaxalone Used? It can be used for IM sedation, IV induction and IV anesthesia maintenance. IM administration is not recommended for healthy canine patients, as the drug is metabolized by healthy dogs at about the same rate as its absorption. However, nonaggressive dogs in a weak and debilitated state may respond to alfaxalone when it is combined with an opioid and midazolam. Is Alfaxalone An Analgesic? Alfaxalone appears to facilitate muscle relaxation, unlike the dissociative agents, but it is not considered an analgesic agent. General anesthetic gas does inhibit pain perception during its use. But it does not inhibit nociceptive induction and transmission, which can lead to sensitization of the nociceptive pathways. Therefore, an opioid such as buprenorphine, morphine, hydromorphone or fentanyl should be given as well. How Safe Is Alfaxalone? It is a very safe anesthetic agent but, like all others, excessive doses will create respiratory depression and hypotension. However, in general, respiratory depression and hypotension are less pronounced when inducing and maintaining anesthesia with alfaxalone compared to propofol, isoflurane and sevoflurane. What Is the Dosage When Given Intravenously? When effective preanesthetic medications are used, most patients can be induced with 0.5 to 2 mg/kg alfaxalone IV. What Is the Dosage When Given IM for Procedural Sedation? When combined with midazolam and an opioid, most feline patients and debilitated, nonaggressive canines can be sedated with 0.5 to 2 mg/kg alfaxalone IM combined with a benzodiazepine and an opioid. What Is the Dosage When Given as a Constant Rate Infusion? The rate goes from 1 to 10 mg/kg/hour for maintenance anesthesia. You can think of this wide range as if they were numbers on a vaporizer. If a patient shows a sudden response to surgical stimulation, you can administer a minibolus of approximately 0.5 mg/kg alfaxalone, then increase the drug delivery rate accordingly. We have used alfaxalone TIVA [total intravenous anesthesia] many times at our practice with excellent results in cases where patient blood pressures were suboptimal while under inhalant maintenance anesthesia. Is Alfaxalone Safe When Used for Long-Term TIVA Anesthesia or Repeated Short-Term Procedures in Cats? Unlike propofol, alfaxalone has qualities that lend itself to both extended duration TIVA use as well as repeat induction use over several days. We have references that describe 6½ hours of successful alfaxalone TIVA in cats. There are multiple-dose safety studies delivered over a sequence of days conducted by Jurox showing good safety. Can Alfaxalone Be Used in High-Risk Patients? Versatility is one of the great advantages of alfaxalone. There is solid support for the use of alfaxalone for C-sections, sight hounds, cardiac patients, seizure patients, pediatrics under 3 months of age, geriatrics and debilitated patients. What Precautions Should Be Taken? Alfaxalone is not risk-free. All patients should have IV access, fluid support, close monitoring by a live person with effective blood pressure and ETCO2 monitoring. In order to prevent rough recoveries, alfaxalone should not be used as a solo agent. The same could be said for ketamine, propofol and inhalant agents. Smoother recoveries are expected when anesthetic agents are used in conjunction with sedative/analgesic medications. Storage will be an interesting debate, as it contains no preservatives. In Australia and New Zealand, the label says: “Store below 30 degrees C (room temperature). Protect from light. … Contents … should preferably be used within 24 hours but may be stored if necessary at 4 degrees C for up to seven days provided contamination is avoided. Do not use broached vials if the solution is not clear, colorless and free from particulate matter.” In the U.K., the label says: “Any solution remaining in the vial following withdrawal of the required dose should be discarded.” The U.S. product label states: “Once Alfaxan has been opened, vial contents should be drawn into sterile syringes; each syringe should be prepared for single patient use only. Unused product should be discarded within six hours.” My feeling is that retention and extended use of alfaxalone presents lower risk than that presented by propofol, excluding Propoflo 28. In the end, each of us will have to make a decision about the length of product retention. Disclaimer: Dr. Zeltzman declares he has no conflicts of interest regarding the publication of this interview.
