INTRAMUSCULAR USE OF ALFAXALONE IN CATS
A PubMed search of “alfaxalone” and “intramuscular” produces over 200 hits with studies involving both cats and dogs, but also ranging from hedgehogs and ducks to bearded dragons and koalas. This is despite Alfaxan® Multidose not currently being licenced in the UK for intramuscular (IM) use.
This review mainly focuses on how we can utilise IM alfaxalone for sedation in cats although we also consider some published literature discussing general anaesthesia following IM administration.
AIMS OF SEDATION VIA THE IM ROUTE
In clinical practice we are occasionally required to perform IM sedation of cats where intravenous (IV) access may not initially be possible e.g. fractious animals (Grubb et al., 2013). The principal aims of IM sedation: to allow IV access; for diagnostic procedures; the administration of fluids or other drugs; or to permit IV induction of general anaesthesia.
In my experience we consider administering IM alfaxalone to cats that are difficult to handle but will tolerate an IM injection. These could be cats where an alpha-2-agonist (medetomidine or dexmedetomidine) and/or ketamine would be undesirable due to the recognised cardiovascular effects of these drugs (Robinson & Borgeat, 2016; Cremer & Ricco, 2018), or simply due to the fact that we are unsure of cardiac status and want to err on the side of caution. IM alfaxalone may also be an option in cats that have received premedication or sedation but who are still difficult to handle prior to IV cannulation. An article discussing alpha-2 agonists can be accessed here.
ADMINISTRATION OF ALFAXALONE INTRAMUSCULARLY
pH & VOLUME OF ALFAXAN® MULTIDOSE
Ideally the volumes of IM drugs should be small and non-irritant to minimise discomfort on administration. Alfaxan® Multidose has a neutral pH and does not cause pain or tissue reaction when given IV (Michou et al., 2012), intramuscularly IM (Adami et al., 2016), or by inadvertent perivascular administration.
The maximum recommended volume of any drug per IM site in cats is 0.25ml/kg. Consequently, it might be necessary to divide the dose of alfaxalone over two or more locations to minimise irritation, particularly in heavier cats. The epaxial musculature is preferred as there tends to be less discomfort at this site compared to the hind leg.
To minimise the total volumes required, and to maximise efficacy, we should aim to co-administer alfaxalone with other agents. The majority of IM alfaxalone protocols reported in the literature combine alfaxalone with an opioid, which should be selected based on clinical need (Ribas et al., 2014; Deutsch et al., 2017; Granfone et al., 2017; Reader et al, 2018; Bonagura, 2019).
It should be noted that the times to onset of action, peak effect and recovery following IM administration of sedative or anaesthetic drugs are slower than the IV route (Seymour & Gleed, 1999; Rodrigo-Mocholi et al., 2018), and the doses cannot be titrated to effect. Therefore, some animals may receive a higher dose than is actually required. Subcutaneous or accidental intra-fat injections should be avoided as the effects may be inconsistent or poor via these routes.
A download chart describing the benefits and limitations of the various routes of administration may be accessed here.
ONSET OF ACTION
Alfaxalone has a high bioavailability of 94% after IM use, meaning it is efficiently absorbed into the central compartment following administration by this route. Onset of action is rapid with mean times to lateral recumbency of 6-12 minutes (Ribas et al., 2014; Granfone et al., 2017; Reader et al., 2018; Rodrigo-Mocholi et al., 2018) and peak sedation by approximately 15 minutes post administration (Cremer & Ricco, 2018).
THE EFFECT IS DOSE DEPENDENT
The clinical effects of the IM administration of alfaxalone are dose dependent and reliable (Tamura et al., 2015; Rodrigo-Mocholi et al., 2016). Deutsch et al. (2017) administered butorphanol 0.2mg/kg plus either alfaxalone 2mg/kg or 5mg/kg via the IM route to feline patients. Both alfaxalone doses provided sedation but the recovery time with alfaxalone 2mg/kg was shorter (82 +/- 24 minutes) than for the 5mg/kg dose (127 +/- 33 minutes).
DURATION OF ACTION
Alfaxalone does not accumulate in muscle tissue however, in common with many other drugs administered IM, recovery times compared to IV are generally longer (Rodrigo-Mocholi et al., 2018) and are also dependent on concomitantly administered sedatives/opioids, the doses of each drug used, and whether any of the components are antagonised.
In studies where alfaxalone (2mg/kg) was administered in combination with butorphanol (0.2mg/kg) mean recovery times to sternal recumbency were 32–36 minutes, and 44 minutes to standing (Ribas et al., 2014; Reader et al., 2018). Higher doses of butorphanol (0.4mg/kg) appeared to delay recovery from lateral recumbency: median of 53 minutes, range 43-83. (Granfone et al., 2017). Details can be found in “Suggested IM Alfaxalone Protocols” below.
When used in combination with other drugs possessing sedative properties the typical IM alfaxalone recovery is smooth, quiet and uneventful, with minimal adverse effects (Ribas et al., 2014; Adami et al., 2016; Granfone et al., 2017; Khenissi et al., 2017; Reader et al., 2018). Details are summarised in “Suggested IM Alfaxalone Protocols” below.
PHYSIOLOGICAL EFFECTS OF INTRAMUSCULAR ALFAXALONE
CARDIOVASCULAR STABILITY WITH ALFAXALONE
Unlike other drugs commonly administered IM for sedation e.g. alpha-2 agonists, alfaxalone is not known to cause bradycardia or a reduction in cardiac output. Alfaxalone, the active ingredient in Alfaxan® Multidose, has been demonstrated by many authors, including Muir et al., (2008); Muir et al., (2009); Psatha et al., (2011); Okushima et al., (2014); Pypendop et al., (2019), to provide excellent cardiovascular stability.
At clinical doses the infrequent and mild vasodilation that may be observed following IV alfaxalone is unlikely to occur IM, therefore cardiac output, good mucous membrane colour, tissue perfusion and peripheral pulses are maintained.
It should be remembered however, that cardiovascular effects are also reliant on which other agents are concurrently administered e.g. alpha-2 agonists may cause bradycardia and/or a reduction in cardiac output; ketamine can increase cardiac output and blood pressure via stimulation of the sympathetic nervous system, even in healthy animals (Murrell, 2016), and these consequences should be considered when selecting sedation protocols. Articles discussing intravenous induction, including a brief description of ketamine, and the alpha-2 agonists may be accessed by clicking on the links.
To the author’s knowledge there have been no reported occurrences of apnoea in the literature, even when alfaxalone has been administered IM for induction of general anaesthesia (Mahdmina et al., 2020).
USE IN ALL ASA CATEGORIES
Unlike some other commonly administered sedatives and combinations that may cause unfavourable cardiovascular side effects (Murrell, 2016), alfaxalone is suitable for all American Society of Anaesthesiologists (ASA) physical status categories e.g. hyperthyroid patients; those with cardiovascular disease. As described above, this is due to the minimal effects on the cardiovascular system, and the rapid metabolism and smooth recovery associated with alfaxalone. A discussion of the ASA physical status categories may be accessed here. For a downloadable chart describing the ASA categories please click here.
ADMINISTRATION WITH OTHER PRODUCTS
Alfaxalone can be used with all commonly administered classes of premedicants e.g. opioids, alpha-2 agonists, phenothiazines and benzodiazepines (Alfaxan® Multidose SPC, 2020). Inclusion of drugs with sedative properties into the alfaxalone IM protocol produce a synergistic effect resulting in a reduced dose requirement for each drug (Cruz-Benedetti et al., 2018), and promotes a smooth recovery, as described above.
Butorphanol is an opioid with minimal cardiovascular effects at clinical doses and is mainly used for its sedative properties. Butorphanol is a relatively poor and short-lived analgesic therefore, if a procedure is, or is anticipated to be, painful the butorphanol should be substituted with either buprenorphine (mild to moderate pain) or methadone (moderate to severe pain).
THE AIMS OF IM ALFAXALONE SEDATION
There is a high level of interest in the ability of alfaxalone to be administered IM, to be absorbed effectively and to produce sedation. But we need to consider our end goals: Are we aiming for sedation to allow diagnostic and/or minor procedures? Or do we want to place an IV cannula to permit further drug administration e.g. sedation of a difficult cat as a form of premedication prior to general anaesthesia? Or is the goal to produce general anaesthesia (defined as the ability to intubate the trachea)?
Combinations obtained from recently published literature, or from personal experience, are described below with drugs doses, time to onset of sedation, duration of sedation, clinical notes & comments, and recovery times (where available).
A handy wall chart summarising the IM alfaxalone protocols described in this article may be downloaded here.
As alfaxalone is, by design, an induction agent it is recommended that intubation, pulse oximetry and the ability to provide oxygen be available at all times following IM administration, even if general anaesthesia is not planned.
SUGGESTED IM ALFAXALONE PROTOCOLS
Probably the most widely used IM alfaxalone combination for sedation of cats.
- Alfaxalone 1-3mg/kg + butorphanol 0.2-0.4mg/kg IM
- Allow approximately 10-15 minutes for the administered drugs to reach peak effect
- Duration is dose dependent: 32 minutes (lower dose range) to 53 minutes (Ribas et al., 2014; Granfone et al., 2017; Reader et al., 2018)
Suitable for e.g.
- Gaining IV access
- Diagnostic procedures including echocardiography
- Blood donation • Sedation of cats with unknown or diagnosed cardiac disease
- Sedation of difficult cats
- Prior to general anaesthesia
We mention above that an alfaxalone combination may be our first choice for a cat with undetermined cardiac disease. So how does a combination of alfaxalone and an opioid affect echocardiographic parameters? A study by Ribas et al. (2014) reported that measurements taken pre- and post- sedation (alfaxalone 2mg/kg & butorphanol 0.2mg/kg) were, in the majority, not significantly different. Heart rate decreased, but this change did not reach statistical significance in the 10 cats studied. Sedation was deep and long lasting. Prior to using this protocol for echocardiography the reader is advised to consult the full results described in the article: https://pubmed.ncbi.nlm.nih.go....
2. IM ALFAXALONE FOLLOWED BY INDUCTION OF GENERAL ANAESTHESIA
If general anaesthesia is required, and the cat is not at stage III anaesthesia following the initial IM doses of alfaxalone and opioid, a further intravenous dose of alfaxalone may be administered slowly and to effect:
- Prepare 2-3mg/kg alfaxalone
- Administer 0.5mg/kg of this dose intravenously
- Flush the cannula with saline to ensure the 0.5mg/kg has been administered
- Wait approximately 20 seconds
- Assess depth of anaesthesia
- Should the cat require additional alfaxalone the 0.5mg/kg incremental process may be repeated until intubation is possible or the full 2-3mg/kg dose has been administered
N.B. The dose of alfaxalone described in this protocol (2-3mg/kg) is lower than described in the SPC for IV induction of anaesthesia in the cat. This is due to the dose sparing effect of the IM alfaxalone (and concomitant sedative agents) on the subsequent IV induction dose (Largos-Carvajal et al., 2020).
3. IM ALFAXALONE FOLLOWING “INEFFECTIVE” SEDATION
IM alfaxalone may be an option to increase sedation to permit IV access in cats that have already received premedicant or sedative drugs but have not attained the desired level of sedation.
Dependent on the degree of sedation already present it is suggested to administer:
- Alfaxalone 1-2mg/kg IM
- Start at the lower end of this dose range
- Assess the quality of sedation after 10-15 minutes
- Repeat alfaxalone 1mg/kg IM if necessary
4. HEAVY SEDATION
For heavy sedation the following protocol is based on a study by Cremer & Ricco, (2018)
Alfaxalone 1mg/kg + dexmedetomidine 0.005mg/kg + butorphanol 0.2mg/kg IM (ADB) compared to ketamine 5mg/kg + dexmedetomidine 0.005mg/kg + butorphanol 0.2mg/kg IM (KDB)
- Peak sedation within 15 minutes in both groups
- Sedation quality equivalent in both groups
- Duration of action 90 minutes for the alfaxalone protocol - significantly shorter than the KDB group (147 minutes)
- Arterial partial pressure of oxygen maintained better in the alfaxalone group
- Recovery quality good in the alfaxalone group
The study concluded: “For shorter diagnostic procedures, alfaxalone + dexmedetomidine + butorphanol may be the better choice”.
If any of the above protocols are considered for surgical cases the butorphanol should be substituted with either buprenorphine (mild to moderate pain) or methadone (moderate to severe pain).
5. IM ALFAXALONE FOR GENERAL ANAESTHESIA
One situation where an effective IM alfaxalone combination may be desirable is in shelter medicine for the induction of general anaesthesia prior to the neutering of cats where placement of an IV cannula, the gold-standard for non-shelter cats, is rarely prioritised for healthy animals. Volatile induction is not recommended due to the stress to the cat, often resulting in stage II excitement and the release of endogenous catecholamines, the relatively high oxygen flow rates required, and the risk of volatile pollution of the workplace.
Based on studies reported in the literature the following are potentially suitable protocols:
5a. ANAESTHESIA FOR MINOR PROCEDURES
Adami et al., (2015)
Alfaxalone 2.5mg/kg + dexmedetomidine 0.014mg/kg + butorphanol 0.3mg/kg IM
- Lateral recumbency in 5 minutes (range 1–11)
- Time to interaction with observer 9.5 minutes (range 2–35) after IM atipamezole to antagonise dexmedetomidine
- The authors concluded this alfaxalone combination provided a suitable depth of anaesthesia for cats undergoing minor clinical procedures.
Khenissi et al., (2017)
Alfaxalone 3mg/kg + dexmedetomidine 0.01mg/kg + butorphanol 0.2mg/kg IM (ADB) compared to ketamine 5mg/kg + dexmedetomidine 0.01mg/kg + butorphanol 0.2mg/kg IM (KDB)
- For castration
- In the alfaxalone group (ADB) recovery to sternal recumbency following extubation: 15-30 minutes
- 9/16 alfaxalone (ADB) cats ambulatory 30 minutes post extubation compared to 2/16 KDB cats (p = 0.010)
- Alfaxalone (ADB) cats less ataxic at 120 minutes post extubation than KDB cats (p = 0.003)
- Better recovery quality following alfaxalone (ADB) combination than for the KDB group
- Cardiorespiratory parameters remained within acceptable limits in both groups
- Author’s conclusion: alfaxalone (ADB) combination was suitable for minor procedures lasting less than 1 hour.
5b. GENERAL ANAESTHESIA FOR OVARIOHYSTERECTOMY (Mahdmina et al., 2020)
Medetomidine 600μg/m2 + buprenorphine 180μg/m2 IM** followed 15 minutes later by alfaxalone 3mg/kg IM
Medetomidine 500μg/m2 + methadone 5mg/m2 IM** followed 15 minutes later by alfaxalone 3mg/kg IM
- Endotracheal intubation possible 5 minutes after alfaxalone administration
- Surgery, by a single experienced surgeon, possible in all cases
- Intraoperative cardiovascular parameters remained stable
- IM atipamezole administered 5 minutes after cessation of isoflurane (at extubation)
- Recoveries smooth and excitement-free
- 90% cats eating at 30 minutes post-extubation
- Author’s conclusion: “Both protocols provided good anaesthesia conditions for ovariohysterectomy in the cat”.
** Please note these doses are for body surface area and are presented as m2. For conversion to mg/kg please refer to relevant texts e.g. BSAVA Small Animal Formulary (Allerton, 2020).
A handy wall chart summarising the protocols described above can be downloaded here.
The aim of sedation should be to gain IV access e.g. for the induction of general anaesthesia; and/or for completion of diagnostic or minor procedures.
Alfaxalone administered IM provides rapid, dose-dependent sedation with a short duration of action. Combining with butorphanol will reduce dose requirements, an advantage in larger cats, and will assist in smoothing recovery. For painful procedures butorphanol may be replaced with buprenorphine or methadone.
The addition of other sedative agents will increase the duration of sedation and, dependent on drug(s) and doses used, may induce general anaesthesia.
Alfaxalone may be administered IM to additionally sedate cats that have not responded as desired to other sedative/premedicant protocols.
Much of the literature focuses on the IM use of alfaxalone in cats. For dogs, just as for cats, the addition of other agents is key to minimising the volume of alfaxalone required.
Keep an eye open for an article by Matt describing the intramuscular use of alfaxalone in dogs to be published soon in Anaesthesia1ST.
OFF LICENCE & CASCADE ADVICE
It should be noted that the intramuscular administration of alfaxalone (Alfaxan® Multidose) is not currently authorised in the UK. The conditions for use are listed in the SPC (Summary of Product Characteristics) which may be accessed here. It is the responsibility of the veterinary surgeon accountable for the patient to assess clinical need & the suitability of the product and use it in accordance with the prescribing cascade. Further details may be found at: https://www.gov.uk/guidance/th...
Please download the "Intramuscular alfaxalone in cats" wall chart here for a summary of the IM alfaxalone combinations and advice described in this article.
Originally published: Wednesday, 3rd February 2021
Last updated: Monday, 8th February 2021
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Peripheral venous cannulation is a common invasive procedure in small animals, but what are the best-practice insertion techniques and what can we do to avoid complications?Read On...
Paper summary: Heated intravenous fluids alone fail to prevent hypothermia in cats under general anaesthesia.
In this summary of a paper by Jourdan et al (2017) we examine the common practice of warming intravenous fluids and the effect on patient temperature.Read On...
This summary of a publication by Panti et al., examines the effect of orally administered omeprazole on gastro-oesophageal reflux in the anaesthetised dog.Read On...
In this paper we explore perceptions and opinions of Canadian pet owners about anaesthesia, pain and surgery in small animals.Read On...
How can a Veterinary version of the ASA Physical Status Classification help you achieve safer anaesthesia? To find out how watch our webinar.Read On...
This scientific paper assessed whether the American Society of Anesthesiologists (ASA) Physical Status Classification correlated with the risk of anaesthetic death in dogs and cats.Read On...
This is our third product launch this year, and the latest addition to our anaesthesia and analgesia portfolio, Methadyne, contains 10mg/ml methadone as its active ingredient. It can be administered for analgesia of moderate to severe pain in dogs and cats, to provide neuroleptanalgesia, and as part of a patient’s premedication protocol prior to general anaesthesia.Read On...
A retrospective comparison of two analgesic strategies after uncomplicated tibial plateau levelling osteotomy in dogs.
In this review we summarise a publication by Bini (2018) examining two protocols for the administration of methadone following TPLO surgery in dogs.Read On...
In this article we have identified the key clinical peer reviewed papers to support the use of Alfaxan for maintenance of Anaesthesia in Cats and Dogs.Read On...
Paper summary: Effect of benzodiazepines on the dose of alfaxalone needed for endotracheal intubation in healthy dogs
This paper examined whether a benzodiazepine, administered as a co-induction agent with alfaxalone, improved endotracheal intubation, and reduced the dose of alfaxalone, in the dogRead On...
In this article we examine why methadone could be considered the analgesic of choice for many of our patients and understand its importance in modern veterinary medicine. The article includes a link to a downloadable summary sheet.Read On...
In this article from the Perspectives on Premeds series, Karen takes us through the properties and uses of phenothiazines in modern veterinary practice.Read On...
This study looks at the effects of three methadone doses combined with acepromazine on sedation and some cardiopulmonary variables in dogs.Read On...
We have extended our anaesthesia and analgesia portfolio with the launch of AceSedate®. Containing the tried and trusted, long-acting sedative agent acepromazine as its active ingredient, AceSedate can be used for the premedication, sedation and tranquilisation of cats and dogs.Read On...
Caesarean Section Survival Guide. Part 2: Anaesthetic Protocol Selection & Peri-operative Considerations.
In this second instalment of the 2-part article, we explore premedication, induction, maintenance & monitoring, recovery and analgesia for the Caesarean section patient.Read On...
In the first instalment of this 2-part review Karen examines the physiological changes that occur during pregnancy and how those adjustments can affect the selection of anaesthetic protocols for the increasingly common Caesarean section.Read On...
No leeway for the spay: A comparison between methadone and buprenorphine for perioperative analgesia in dogs undergoing ovariohysterectomy.
This recent paper compares post-operative pain scores and requirement for rescue analgesia following premedication with methadone or buprenorphine, in combination with acepromazine or medetomidine, in 80 bitches undergoing ovariohysterectomy.Read On...
Cardiac arrest in dogs and cats is, thankfully, relatively rare. However, when it does happen it can have devastating consequences for the animal, owner and the veterinary team. This study examined the common causalities leading up to a cardiac arrest with the aim of changing protocols to improve outcomes.Read On...
In this article, Carl focuses on the benefits of introducing a safety checklist in practice to reduce patient morbidity, mortality and to improve communication between members of the veterinary team. The article contains links to the AVA safety checklist as well as a link to a customisable list that you can adapt to your practice needs.Read On...
The effects of hypothermia are very far reaching throughout the peri-anaesthetic process. In this article, James takes us through the interesting mechanisms of body cooling and warming, the clinical relevance of hypothermia and what we can do to prevent it.Read On...
All patients are exposed to the risks associated with general anaesthesia. Continuously monitoring anaesthetised patients maximises patients safety and wellbeing. In this article, Dan takes us through the common monitoring techniques that provide information about the cardiovascular status of your patient.Read On...
Despite being widely recognized in humans, postoperative nausea and vomiting (PONV), and the role of maropitant in reducing inhalational anaesthetic requirements have been poorly documented in dogs. This recent study evaluates PONV and isoflurane requirements after maropitant administration during routine ovariectomy in bitches.Read On...
Little information is available about the effect that different doses of medetomidine and butorphanol may have when using sevoflurane for maintenance of anaesthesia in dogs. This recent study evaluates heart rate and median sevoflurane concentration required at different dose rates.Read On...
In this second article of the capnography series, James provides a guide to a few of the most common traces that you will encounter during surgery. Scroll to the end of the article to download a printable capnography cheatsheet.Read On...
Pain, what a Pain! (Part 2) – Practical Tips On How To Perform Dental Nerve Blocks In Companion Animal Practice
In this second article of the Pain, what a Pain! series, Dan takes us through the LRA techniques associated with dental and oral surgery. In this article, you will find practical tips and pictures on common dental nerve blocks as well as safety concerns to consider.Read On...
This recent retrospective study looks at the cases of 185 pet rabbits admitted for sedation or general anaesthetic and evaluates the incidence and risk factors contributing to peri-anaesthetic mortality and gastrointestinal complications.Read On...
Pain, what a Pain! How Locoregional Anaesthesia can Improve the Outcome and Welfare of Veterinary Patients (Part 1)
In this first article out of a series of two, Dan takes us through an introduction and practical tips for appropriate local anaesthesia delivery. Find out why these anaesthesia techniques, that are well recognised in human medicine, have seen an increase in popularity in veterinary medicine over the recent yearsRead On...
Read the highlights of a recently published research paper that evaluates cardiorespiratory, sedative and antinociceptive effects of dexmedetomidine alone and in combination with morphine, methadone, meperidine, butorphanol, nalbuphine and tramadol.Read On...
This study evaluates the effectiveness of two methods of preoxygenation in healthy yet sedated dogs and the impact of these methods on time taken to reach a predetermined haemoglobin desaturation point (haemoglobin saturation (SpO2) of 90%) during an experimentally induced period of apnoea.Read On...