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Should I Be Using Alfaxalone?

The short answer is: Maybe.

Whenever anyone wants advice on changing up their anesthesia drug protocols, one of the first questions I ask is – Why do you want to make this change? Is there a specific issue that you are trying to resolve?

Having this background information can help me figure out if a change makes sense. If changing things up does seem like a good idea, the next step is to figure out whether the specific issue will be best resolved by bringing in a new drug or just changing how you use your familiar drugs. The solution to a recurring anesthesia-related problem might just be addressing some of the perioperative management strategies.

Sometimes adding a new drug to your anesthesia tool box does make good sense however! And alfaxalone has a couple of clinically advantageous characteristics.

Alfaxalone is a neuroactive steroid that modulates GABA A receptors, much like propofol, barbiturates, etomidate, and benzodiazepines, enhancing inhibitory synaptic transmission in the central nervous system. At high concentrations, alfaxalone can act as an agonist at the GABA A receptor. It was available in the 1980s for veterinary and human anesthesia but the solubilizing agent (a derivative of castor oil) caused systemic hypersensitivity reactions. In its new form, alfaxalone is solubilized in a cyclodextrin (hydropropyl-beta-cyclodextrin), which does not exhibit adverse systemic effects. A new formulation is also in Phase I clinical trials for humans, though a different cyclodextrin (7-sulfobutyl ether β cyclodextrin) is used in this version.

Why you might want to use alfaxalone

Alfaxalone results in minimal cardiovascular depression at typical doses in healthy patients. Some decrease in systemic vascular resistance can occur, resulting in hypotension, and this can be exaggerated if pre-existing systemic illness has created hemodynamic compromise. In addition, tachycardia is sometimes noted immediately following IV induction with alfaxalone. This may be problematic in patients for whom tachycardia will decrease cardiac output (eg severe hypertrophic cardiomyopathy or pulmonic stenosis).

A dose-dependent decrease in respiratory rate and minute ventilation occurs following alfaxalone administration. Apnea can occur but is usually of shorter duration than that which occurs following propofol administration. This effect can be minimized by titrating alfaxalone slowly to effect over 60 to 90 seconds while monitoring the patient and continuing to preoxygenate.

All in all, alfaxalone exhibits cardiorespiratory effects that are really quite similar to propofol, though maybe a bit less long-lasting in healthy dogs and cats. So, if it is not all that much kinder to the cardiorespiratory system than propofol, why bother switching?

Alfaxalone really shines when you need to achieve chemical restraint via intramuscular drug administration but want to avoid a dissociative anesthetic, for whatever reason. In cats, intramuscular administration of alfaxalone at 2.5 mg/kg will induce lateral recumbency within about 5 minutes and may last up to 30 minutes.

Intramuscular combinations to achieve heavy sedation:

Alfaxalone 1 – 2 mg/kg and opioid of choice: butorphanol 0.2 – 0.4 mg/kg hydromorphone 0.1 mg/kg methadone 0.3 – 0.5 mg/kg

Alfaxalone 1 mg/kg, midazolam 0. 2 – 0.5 mg/kg & opioid of choice

Alfaxalone 1 -2 mg/kg and dexmedetomidine 2 – 8 mcg/kg +/- opioid of choice

Many other combinations and doses are possible – these are just a jumping off point!

Because the line between sedation and anesthesia is blurry, make sure to monitor your patient’s vital signs continuously, keep them warm, supply O2 by mask, and assess whether you need to control the airway and ventilation to keep them safe.

Why you might NOT want to use alfaxalone

Rough recoveries may occur, consisting of twitching, paddling, and opisthotonus, especially if given as a sole agent.

The volume can be large for IM administration, e.g. 2 mg/kg in a typical cat will be about 1 mL. This limits its IM use to cats and small dogs.

It is controlled in the US.

It is relatively expensive in the US.

The preserved Alfaxan-28 version sometimes precipitates when mixed with other drugs, especially midazolam.

How I use alfaxalone

I most commonly reach for alfaxalone for IM administration in combination with other drugs when I need a high level of chemical restraint but do not want to use a dissociative. Then, to make it cost effective, I use the bottle up on other patients for IV inductions. Like propofol, alfaxalone should be titrated to effect & I often use a co-induction agent, such as midazolam or ketamine.

After mild to moderate sedation, I draw up 2 mg/kg alfaxalone total and administer ~0.5 mg/kg every 30 seconds or so, while preoxygenating and monitoring, until I can intubate the patient.

The Bottom Line

Alfaxalone has some nice things about it that make it a useful tool in your anesthesia armamentarium. I think of it almost like propofol I can give IM. But I do believe you can provide excellent anesthetic care without it and I do not think that it is some sort of panacea that is so much better than induction with propofol – or ketamine/midazolam for that matter – that it will improve outcomes in veterinary anesthesia.

Almost always, the largest gains in anesthesia are to be made in the monitoring and supportive care we provide for our patients, as conveyed by this quote from the developer of the MacIntosh laryngoscope blade and the first professor of anesthesia at the University of Oxford.

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