Alfaxalone
**Alfaxalone** is a neuroactive steroid molecule that functions as a rapid-acting central nervous system depressant and general anesthetic. It is primarily used for the induction and maintenance of anesthesia in veterinary patients. **Clinical Pearls & Pharmacological Profile:** * **Formulation Evolution:** The modern formulation (Alfaxanยฎ) uses 2-hydroxypropyl-beta-cyclodextrin (HPCD) as a solubilizing agent. This is a significant improvement over the historical product (Saffanยฎ), which contained polyethoxylated castor oil (Cremophor EL) and caused severe histamine release and anaphylaxis, particularly in cats. * **Cardiorespiratory Effects:** While generally considered to have a wide safety margin, alfaxalone can cause dose-dependent respiratory depression and post-induction apnea, especially if administered rapidly IV. Cardiovascular parameters are typically well-maintained, though compensatory tachycardia may occur. * **Analgesia:** Alfaxalone provides **negligible analgesic effects**. It must be combined with appropriate pure analgesics (e.g., opioids) for painful procedures. * **Recovery:** Recovery is generally rapid and smooth due to its short half-life and lack of accumulation, but patients can experience psychomotor excitement (paddling, vocalization, twitching) if stimulated or if inadequate premedication/analgesia was provided.
Mechanism: Alfaxalone exerts its anesthetic effects by interacting with **GABA_A (gamma-aminobutyric acid type A) receptors** in the central nervous system. * **Mechanism:** It binds to specific transmembrane domains on the GABA_A receptor complex. * **Pathway:** Binding โ Enhances the binding of the inhibitory neurotransmitter GABA to the receptor โ Increases the frequency and duration of **chloride (Clโป) ion channel** opening โ Influx of chloride ions into the neuron โ **Hyperpolarization** of the postsynaptic cell membrane โ Inhibition of neural action potential transmission โ Dose-dependent CNS depression (ranging from sedation to general anesthesia).
Dosing by species
- Anesthesia Induction (Premedicated) ยท 3 mg/kg ยท IV ยท once ยท Administer over first 60 seconds to effect. If intubation not possible, one further similar dose may be administered.
- Anesthesia Induction (Unpremedicated) ยท 2 mg/kg ยท IV ยท once ยท Administer over first 60 seconds to effect.
- Anesthesia Induction (Alternative) ยท 1-2 mg/kg ยท IV ยท once ยท Slowly over 20-30 seconds while assessing degree of anesthesia.
- Anesthesia Maintenance (CRI, Premedicated) ยท 0.1-0.12 mg/kg/minute ยท IV ยท CRI ยท Up to 1 hour ยท Equivalent to 6-7 mg/kg/hour.
- Anesthesia Maintenance (CRI, Unpremedicated) ยท 0.13-0.15 mg/kg/minute ยท IV ยท CRI ยท Up to 1 hour ยท Equivalent to 8-9 mg/kg/hour.
- Anesthesia Maintenance (Bolus, Premedicated) ยท 1-1.2 mg/kg ยท IV ยท q10m ยท Up to 1 hour ยท Administer every 10 minutes as needed.
- Anesthesia Maintenance (Bolus, Unpremedicated) ยท 1.3-1.5 mg/kg ยท IV ยท q10m ยท Up to 1 hour ยท Administer every 10 minutes as needed.
- Anesthesia Maintenance (Alternative Bolus) ยท 5-12 mg/kg total dose ยท IV ยท incremental ยท 5-7 mg/kg total for short procedures; 8-12 mg/kg total for longer procedures.
- Anesthesia Induction ยท 5 mg/kg ยท IV ยท once ยท Premedicated or unpremedicated. Administer over first 60 seconds to effect.
Routes of administration
Contraindications
- Concurrent use with other injectable general anesthetic agents (e.g., propofol, thiopental)
- Situations where endotracheal intubation, positive pressure ventilation, and oxygen support are unavailable
- Animals less than 12 weeks of age (safety not established)
Adverse effects
- Respiratory depression
- Post-induction apnea
- Hypotension (dose-dependent)
- Cardiac arrhythmias (primarily secondary to hypoxemia/hypercapnia)
- Psychomotor excitement during recovery (especially if unstimulated or lacking premedication)
Drug interactions
- CNS Depressants (e.g., acepromazine, opioids, alpha-2 agonists, benzodiazepines) ยท Potentiates the CNS and respiratory depressant effects. Significantly reduces the required induction and maintenance doses of alfaxalone.
- Propofol ยท Should not be used concurrently according to the manufacturer label.
- Thiopental ยท Should not be used concurrently according to the manufacturer label.
- Other IV anaesthetic agents ยท Increased risk of severe CNS and respiratory depression ยท major
- Premedicants (e.g., sedatives, opioids) ยท Synergistic CNS depression; significantly reduces the required induction dose of alfaxalone ยท moderate
- Opioids (e.g., methadone, buprenorphine) ยท Synergistic CNS depression; reduces the required induction dose of alfaxalone. ยท moderate
- Alpha-2 agonists (e.g., dexmedetomidine) ยท Profound synergy; significantly reduces alfaxalone dose requirements and may exacerbate cardiovascular and respiratory depression. ยท major
- Phenothiazines (e.g., acepromazine) ยท Enhanced sedation and increased risk of hypotension. ยท moderate
- Opioids (e.g., butorphanol, methadone) ยท Synergistic CNS depression; significantly reduces the required induction dose of alfaxalone. ยท moderate
- Benzodiazepines (e.g., midazolam) ยท Synergistic CNS depression; reduces alfaxalone dose requirements. ยท moderate
Monitoring
- Level of anesthesia / CNS depression (jaw tone, palpebral reflex)
- Respiratory rate, rhythm, and depth (capnography and pulse oximetry highly recommended due to apnea risk)
- Cardiovascular status (heart rate, ECG rhythm, blood pressure)
- Body temperature (monitor for hypothermia during anesthesia)
Overdose
Overdoses up to 25 mg/kg primarily result in severe cardiorespiratory depression. **Clinical Signs of Toxicity:** * Severe hypoventilation and prolonged apnea * Hypotension * Cardiac arrhythmias **Treatment:** * Immediate endotracheal intubation and positive pressure ventilation with 100% oxygen. * Cardiovascular support (IV fluids, vasopressors/inotropes if hypotension is severe). * Continuous monitoring until the drug is metabolized and cleared.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.