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Alfaxalone

Grade

Anaesthesia

  • Alfaxalone: 1-6 mg/kg can be administered incrementally by slow IV injection over one or two minutes to gently induce the desired plane of anaesthesia. 

Subsequent Treatment

  • Intubation: In clinical settings, animals are usually intubated, or a supraglottic device is placed to allow volatile agents to be employed for anaesthetic maintenance.

  • Maintenance: Surgical anaesthesia generally lasts less than 15 minutes, so patients are maintained either through volatile agents or further doses of alfaxalone administered as slow bolus doses.

  • TIVA—Maintenance: Incremental IV Alfaxalone or a CRI can be administered according to the information provided below in indication 3 (TIVA).

ASA Status

  • ASA 1 & 2 (Low-Risk Patients): These protocols only suit  ASA 1 and 2 patients. 

  • ASA 3 & 4 (High-Risk Patients): Clinicians are encouraged to tailor their practices to suit the issues encountered in ASA 3 & 4 and address them throughout the peri-anaesthetic period so that clients understand the additional challenges these patients face. 

Technique

  • Preparation: Preoxygenation, sedation, and analgesic agents reduce the Alfaxalone induction dose and improve patient welfare and anaesthetic safety. Suitable intubation equipment should be available. 

  • Induction: The induction dose is administered incrementally by slow IV injection over one or two minutes to gently induce the desired plane of anaesthesia. Avoid rapid IV administration, as apnea, hypotension, and reflex tachycardia can result. One manufacturer advises up to  4 mg/kg in suitably premedicated rabbits and up to 5 mg/kg in unpremedicated animals. However, lower doses can be safely used in suitably premedicated animals using many dosing protocols provided within this monograph.

  • Stabilisation: Allow 20-25 seconds for the patient to respond to each dosing increment. Premedicated animals require significantly lower doses, and animals need time to stabilise. 

  • Duration: Surgical anaesthesia generally lasts less than 15 minutes.

  • Maintenance: Patients requiring surgery or prolonged interventions are maintained either through volatile agents or further doses of alfaxalone administered as slow bolus doses.

Additional Medications and Support

  • Premedication: Preoxygenation, sedation and analgesic agents reduce the Alfaxalone induction dose and improve patient welfare and anaesthetic safety. 

  • Multimodal Use: Multimodal use achieves balanced narcosis, analgesia, and muscle relaxation, improves anaesthetic safety and avoids deep levels of central brain depression. 

  • Multimodal Protocols: Dosing schedules in this monograph detail the use of opiates, midazolam and α2 adrenergic agonists before or alongside Alfaxalone.

Patient Preparation

  • Preparation: Rabbits benefit from premedication, IV access and preoxygenation before Alfaxan induction.

  • Suitable Handling: Ensure rabbits are kept away from predator contact, smell and excessive noise

  • Intubation: In clinical settings, animals are usually intubated, or a supraglottic device is placed to allow volatile agents to be employed for anaesthetic maintenance and to manage apnoea or any induction crisis that may occur.

Therapeutics

Therapeutics

  • Clinical Properties: Alfaxalone is a neuroactive steroid with sedative and general anaesthetic properties.

  • Analgesia: Alfaxalone has no analgesic properties.

  • Administration: Alfaxalone may be administered intravenously or intramuscularly.  Rapid intravenous induction has the potential to induce apnoea and should be reserved for cases where intubation is anticipated. Multimodal agents should be administered separately in fresh syringes. 

Sole Use 

  • Sole use as an induction agent is NOT RECOMMENDED in rabbits. 

MultiModal Use

  • Multimodal use achieves balanced narcosis, analgesia, and muscle relaxation, improves anaesthetic safety, and avoids deep levels of central brain depression. The dosing schedules elsewhere in this monograph cover the use of opiates, midazolam and α2 adrenergic agonists.

  • During clinical studies in rabbits, the veterinary medicinal product was used safely with the following premedicant combinations: (i) medetomidine hydrochloride in combination with buprenorphine hydrochloride or butorphanol tartrate, and (ii) midazolam hydrochloride in combination with buprenorphine hydrochloride or butorphanol tartrate (SPC Data).

Treatment Goals

  • Safe, stable anaesthesia.

Treatment End Points

  • Safe completion of any planned procedure.

Efficacy Profile

  • Comparative risk of death or other adverse outcomes, such as inadequate depth or duration of surgical anaesthesia or sedation, remain poorly investigated.

Therapeutic Monitoring

  • Anaesthetised rabbits should be monitored using standard safe anaesthetic monitoring techniques and procedures. These are often locally established protocols.

Adverse Effects

  • CNS: Minor excitatory effects (Muscle twitching/tremors) at induction have been noted in rabbits (SPC Data).

  • Respiratory: Respiratory depression and apnea may occur with rapid IV injection or excessive dose. In rabbits, oxygenation prior to administration is essential in order to reduce the risk of life-threatening hypoxaemia post-induction, which can occur secondary to respiratory depression or apnoea.

  • Cardiac: Cardiodepressant and vasodilatory effects of inhalant anaesthetics may result in hypotension.

  • Algesia: The analgesic properties of alfaxalone are limited. Therefore, appropriate peri-operative analgesia should be provided in cases where procedures are anticipated to be painful.

Contraindications

Datasheet contraindications include: 

  • Incompatible Induction Agents: Do not combine with other intravenous anaesthetic agents (Propofol and Thiopentone). 

  • Hypersensitivity: Do not use on animals with hypersensitivity to the active substance or any other excipients.

  • Neonates: The safety of the veterinary medicinal product in animals less than 16 weeks of age has not been verified. Use with caution.

Reproductive Safety

  • Pregnancy: Safety has not been established in cases where pregnancy is to be continued. However, studies using alfaxalone in pregnant rabbits demonstrated no harmful effects on the treated animals' gestation or their offspring's reproductive performance.

  • Lactation: Safety has not been verified in lactating animals. 

  • Male Fertility: Safety has not been verified

  • Female Fertility: Safety has not been verified

  • Neonates: Safety has not been verified.

Significant Interactions

  • Injectable induction agents: Avoid use alongside propofol and thiopentone.

  • Premedicatnts: Use alongside common rabbit premedications (typically acepromazine, atropine, butorphanol, dexmedetomidine, diazepam, NSAIDs, medetomidine, methadone, midazolam, morphine and xylazine) is relatively safe, provided dose adjustments are being made to moderate potential cumulative CNS depression.  

Alternative Products and Protocols

A variety of alternative and complementary anaesthetic agents are presented here. When anaesthetising rabbits, we recommend users consider the multimodal use of agents such as those with links below:

Formulations

  • Injection: 10 mg/ml solution.

Evidence

Evidence Base

Rabbit Anaesthesia 

  1. Bradley, M.P., Doerning, C.M., Nowland, M.H., Lester, P.A., 2019. Intramuscular Administration of Alfaxalone Alone and in Combination for Sedation and Anesthesia of Rabbits (Oryctolagus cuniculus). J Am Assoc Lab Anim Sci 58, 216–222. https://doi.org/10.30802/AALAS-JAALAS-18-000078

  2. Bradley, M.P., Doerning, C.M., Nowland, M.H., Pasloske, K., Lester, P.A., 2022. Evaluation of alfaxalone total intravenous anesthesia in rabbits (Oryctolagus cuniculus) premedicated with dexmedetomidine or dexmedetomidine and buprenorphine. Vet Anaesth Analg S1467-2987(22)00013–7. https://doi.org/10.1016/j.vaa.2022.01.006

  3. Calero Rodriguez, A., van Zeeland, Y.R., Schoemaker, N.J., de Grauw, J.C., 2021. Agreement between invasive and oscillometric arterial blood pressure measurement using a high-definition oscillometric device in normotensive New Zealand White rabbits using two different anaesthetic protocols. Vet Anaesth Analg 48, 679–687. https://doi.org/10.1016/j.vaa.2021.03.016

  4. Engbers, S., Larkin, A., Rousset, N., Prebble, M., Jonnalagadda, M., Knight, C.G., Pang, D.S.J., 2017. Comparison of a Supraglottic Airway Device (v-gel®) with Blind Orotracheal Intubation in Rabbits. Front Vet Sci 4, 49. https://doi.org/10.3389/fvets.2017.00049

  5. Gil, A.G., Silván, G., Villa, A., Illera, J.C., 2012. Heart and respiratory rates and adrenal response to propofol or alfaxalone in rabbits. Vet Rec 170, 444. https://doi.org/10.1136/vr.100573

  6. Grint, N.J., Smith, H.E., Senior, J.M., 2008. Clinical evaluation of alfaxalone in cyclodextrin for the induction of anaesthesia in rabbits. Vet Rec 163, 395–396. https://doi.org/10.1136/vr.163.13.395

  7. Marín, P., Belda, E., Laredo, F.G., Torres, C.A., Hernandis, V., Escudero, E., 2020. Pharmacokinetics and sedative effects of alfaxalone with or without dexmedetomidine in rabbits. Res Vet Sci 129, 6–12. https://doi.org/10.1016/j.rvsc.2019.12.015

  8. Marsh, M.K., McLeod, S.R., Hansen, A., Maloney, S.K., 2009. Induction of anaesthesia in wild rabbits using a new alfaxalone formulation. Vet Rec 164, 122–123. https://doi.org/10.1136/vr.164.4.122

  9. Navarrete-Calvo, R., Gómez-Villamandos, R.J., Morgaz, J., Manuel Domínguez, J., Fernández-Sarmiento, A., Muñoz-Rascón, P., López Villalba, I., Del Mar Granados, M., 2014. Cardiorespiratory, anaesthetic and recovery effects of morphine combined with medetomidine and alfaxalone in rabbits. Vet Rec 174, 95. https://doi.org/10.1136/vr.101293

  10. Raulic, J., Leung, V.S., Doss, G.A., Graham, J.E., Keller, K.A., Mans, C., Sadar, M.J., Vergneau-Grosset, C., Pang, D.S., 2021. Development and Testing of a Sedation Scale for Use in Rabbits (Oryctolagus cuniculus). J Am Assoc Lab Anim Sci 60, 549–555. https://doi.org/10.30802/AALAS-JAALAS-21-000002

  11. Reabel, S.N., Queiroz-Williams, P., Cremer, J., Hampton, C.E., Liu, C.-C., da Cunha, A., Nevarez, J.G., 2021. Assessment of intramuscular administration of three doses of alfaxalone combined with hydromorphone and dexmedetomidine for endoscopic-guided orotracheal intubation in domestic rabbits (Oryctolagus cuniculus). J Am Vet Med Assoc 259, 1148–1153. https://doi.org/10.2460/javma.20.07.0402

  12. Roan, R., 2009. Use of alfaxalone in rabbits. Vet Rec 164, 188. https://doi.org/10.1136/vr.164.6.188-a

  13. Rousseau-Blass, F., Pang, D.S., 2020. Hypoventilation following oxygen administration associated with alfaxalone-dexmedetomidine-midazolam anesthesia in New Zealand White rabbits. Vet Anaesth Analg 47, 637–646. https://doi.org/10.1016/j.vaa.2020.04.012

  14. Tutunaru, A.C., Sonea, A., Drion, P., Serteyn, D., Sandersen, C., 2013. Anaesthetic induction with alfaxalone may produce hypoxemia in rabbits premedicated with fentanyl/droperidol. Vet Anaesth Analg 40, 657–659. https://doi.org/10.1111/vaa.12071

Unpremedicated Anaesthesia

  1. Gardhouse, S., Sanchez, A., 2022. Rabbit Sedation and Anesthesia. Veterinary Clinics of North America: Exotic Animal Practice 25, 181–210. https://doi.org/10.1016/j.cvex.2021.08.012

  2. Gil, A.G., Silván, G., Villa, A., Illera, J.C., 2012. Heart and respiratory rates and adrenal response to propofol or alfaxalone in rabbits. Vet Rec 170, 444. https://doi.org/10.1136/vr.100573

  3. Marín, P., Belda, E., Laredo, F.G., Torres, C.A., Hernandis, V., Escudero, E., 2020. Pharmacokinetics and sedative effects of alfaxalone with or without dexmedetomidine in rabbits. Res Vet Sci 129, 6–12. https://doi.org/10.1016/j.rvsc.2019.12.015

Expert Opinion

  1. 1317822  Extrapolation of pharmacological properties in man and veterinary species. Some material employed in collating the data displayed here was taken from veterinary product datasheets or extrapolated from pharmacology texts.


Monograph Details

Monograph Details

Analysis Criteria

  • Species: Rabbit

  • Active Substance: Alfaxalone

  • Indication: Anaesthesia

  • Dosing Suggestion: 1-6 mg/kg, slow IV

Consensus Resources

  • Monograph Location: Alfaxalone Rabbit

  • Reference Location: 

  • Monograph Document Folder: 

PICO and V-Grade Resources

  • Monograph Analysis Worksheet: 

Consensus Team

  • Monograph Authors: S McArthur; TBA (last updated 20/03/2024)

  • Monograph Editors: TBA (last updated 20/03/2024)

Monograph Contact

  • For permissions and further information about the Veterinary Consensus Initiative (VCI), please get in touch with us via Stuart McArthur B Vet Med MRCVS; Email: stuart.mcarthur@me.com

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