INTRAVENOUS INDUCTION OF ANAESTHESIA IN DOGS, CATS AND PET RABBITS
In this article Karen Heskin, Veterinary Technical Manager for Jurox UK and Carl Bradbrook, RCVS & European Veterinary Anaesthesia and Analgesia Specialist and President of the Association of Veterinary Anaesthetists, consider the three most commonly used intravenous anaesthetic induction agents for cats, dogs and pet rabbits in the UK. To complement this discussion three useful summaries are available to download as quick reference guides.
ROUTES OF ADMINISTRATION FOR INDUCTION AGENTS
Dependent on the drug(s) selected, the animal and clinical presentation, and the proposed procedure, there are several common routes for induction agent administration: intravenous (IV); intramuscular (IM); and subcutaneous (SC) (see Table 1. For a downloadable summary of Routes of Administration please click here). Other routes exist but will not be covered in this article.
The intravenous route is advantageous as the dose of the induction agent can be controlled and titrated to effect, and lower doses of drugs may be possible compared to intramuscular or subcutaneous administration.
Intramuscular administration e.g. combinations such as the “triple”, are generally one dose, pre-determined mixtures that cannot be titrated to effect to suit individual patient requirements, and individual responses can vary widely. Time to onset, peak effect and recovery are slower than IV administration (Seymour & Gleed, 1999) and larger doses are often required when compared to intravenous induction.
The intramuscular route for induction of anaesthesia does have a place in some circumstances, but careful assessment of the drug(s) should be performed prior to use as not all products are suitable, or licenced, for administration via this route.
In the rabbit if intramuscular induction of anaesthesia is necessary, the lumbar epaxial muscles should be the site of choice. There are reports of self-mutilation and abscess formation following administration into the muscles of the hind limbs (Harcourt-Brown & Chitty, 2013; Martin & Kirsipuu, 2017).
The subcutaneous route for induction of anaesthesia has similar issues to the IM route:
- Inability to titrate to effect based on the individual patient’s response
- Wide variability in response
- Larger dose generally required than for intravenous induction
- Slower onset of action
- Potential for prolonged recovery
(Seymour & Gleed, 1999)
This table may be downloaded here.
Inhalation induction for dogs, cats and rabbits using volatile agents such as isoflurane and sevoflurane is not recommended in any circumstance:
- The procedure is distressing for the patient and can result in stage II excitement and the release of endogenous catecholamines.
- Breath holding during volatile induction may be observed, especially in rabbits, even following the administration of premedicants (Meredith & Lord, 2014). In rabbits, if the animal refuses to breathe (potentially for up to 3 minutes), cardiorespiratory collapse may occur (Flecknell et al, 1999).
- Relatively high oxygen flow rates are required
- The use of volatile agents for induction poses the risk of exposure of clinic personnel and the environment to the vapours.
INDUCTION OF ANAESTHESIA: INTRAVENOUS AGENTS
Alfaxalone and propofol are the most commonly used IV induction agents in dogs and cats, although ketamine may also be used.
The basic clinical features of these agents will be explored below but for full technical details reference should be made to the appropriate SPC and the latest relevant publications.
The following are summary tables that may be downloaded for further information and quick reference. Please click on the title to access the download:
- Summary of the Basic and Clinical Characteristics of Alfaxalone, Propofol and Ketamine
- SPC comparison of Alfaxan Multidose, propofol (with and without preservative), and ketamine
ALFAXALONE (ALFAXAN® MULTIDOSE)
(Please click here to download the SPC)
In the UK alfaxalone is currently licenced for intravenous induction of anaesthesia in the dog, cat and pet rabbit, and for the maintenance of anaesthesia for up to 60 minutes (via bolus or constant rate infusion) in the dog and cat. It is a neuroactive steroid molecule solubilised in an inert cyclodextrin carrier. It has a neutral pH and accidental perivascular administration is non-irritant. Alfaxalone acts at the GABAA receptor causing hyperpolarisation, muscle relaxation and unconsciousness. It can be used with all commonly administered classes of premedicants e.g. opioids, alpha-2 agonists, phenothiazines and benzodiazepines (please click Perspectives on Premeds – Opioids; Perspectives on Premeds – Alpha-2 Agonists; Perspectives on Premeds – Phenothiazines (acepromazine); and Benzodiazepines for further details and downloadable summaries).
Alfaxalone has a similar molecular structure to progesterone and, as a consequence, follows similar metabolic pathways allowing predictable elimination. Despite the similarity to progesterone alfaxalone has no reported hormonal activity.
Alfaxalone characteristically provides a smooth induction with minimal stage II excitation.
When used as recommended there is minimal depression of the cardiovascular system with only marginal changes to blood pressure (the baroreceptor reflex is not thought to be depressed). Following administration, a compensatory increase in heart rate is frequently observed (Muir et al, 2008; Okushima et al, 2014).
If alfaxalone is administered slowly there is a low incidence of apnoea (Grint et al, 2008; Muir et al, 2008; Muir et al, 2009, Schnell et al, 2014). In a study by Keates and Whittem (2012) it required 2.5 times more alfaxalone than propofol (based on the SPC dose) to cause the same degree of apnoea in dogs. Despite this, preoxygenation is recommended for patients with pre-existing disease or for reasons identified during pre-anaeasthetic examination. In situations where it is necessary to preserve oxygen supplies the routine preoxygenation of healthy dogs and cats is not essential provided appropriate and conscientious patient monitoring is performed. If preoxygenation is performed a facemask should be utilised wherever possible. Flow-by preoxygenation is an option in difficult patients, although it is less effective than administration via facemask (Ambros et al, 2018). The AlfaxanMultidose SPC states preoxygenation is essential in pet rabbits prior to induction of anaesthesia.
A summary of the article by Keates and Whittem (2012) can be accessed here.
Alfaxalone provides good muscle relaxation and this may be beneficial during endotracheal intubation, especially in pet rabbits and brachycephalic patients.
Transition to volatile maintenance agents is uneventful and recoveries are rapid and smooth.
A full induction dose of alfaxalone will provide a suitable depth and duration of anaesthesia to allow intubation for approximately:
- 8-12 minutes in the dog
- 20-25 minutes in the cat
- 10 minutes in the rabbit (Gil et al, 2012)
However, as with all induction agents, there will be individual variation.
Alfaxalone is rapidly and predictably eliminated. The plasma elimination half-life is:
- Dog: 25 minutes
- Cat: 45 minutes
- Rabbit: 44-46 minutes
This permits a smooth recovery with minimal hangover effects.
Alfaxalone has a wide safety margin: 10, 5 and 3 times the SPC dose have been administered to the dog, cat and rabbit respectively, and all patients recovered fully (Muir et al, 2008; Muir et al, 2009, Schnell et al, 2014).
Alfaxalone is not analgesic and adequate pain relief should be provided as necessary.
Dose of Alfaxan Multidose
For further details please see the downloadable
- Dose Guide for Dogs and Cats
- User Guide for the Induction and Maintenance of Anaesthesia in the Dog and Cat
- Dose Guide for Pet Rabbits
- User Guide for the induction of Anaesthesia in the Pet Rabbit
The following are the recommended doses for premedicated patients. The product should be administered slowly and to effect until stage III anaesthesia, characterised by muscle relaxation, loss of reflexes and ease of intubation, has been achieved. It may not be necessary to administer the full dose:
- Dog: 2mg/kg IV
- Cat: 5mg/kg IV
- Rabbit: 2mg/kg IV*
*The current (2020) Jurox UK recommendation is to prepare 2mg/kg for the premedicated rabbit. This is lower than the SPC dose of 4mg/kg. If additional product is required this can be drawn up as necessary (Grint et al, 2009; Gil et al, 2012; Tunitari et al, 2013; Meredith, 2015; Engbers et al, 2017; Fisher & Graham, 2018; Gomes et al, 2018; Swisher et al, 2018; Hedley et al, 2019).
Please see the Dose Guide for Pet Rabbits; User Guide for the induction of Anaesthesia in the Pet Rabbit for further details.
Alpha-2 agonist dose-sparing
If alpha-2 premedication has been administered, the patient is well sedated, or the animal is debilitated, there may be considerable dose sparing and the calculated dose may therefore be reduced. Some reports suggest up to an average of 70% dose sparing following alpha-2 premedication.
Please see Perspectives on Premeds – Alpha-2 Agonists for further information and a downloadable summary of alpha-2 agonists.
Increased circulation time with alpha-2 agonists
If alpha-2 agonists have been administered prior to induction of anaesthesia an increase in circulation time may be observed. Alfaxalone should therefore be administered over a longer period of time than described in the User Guides, and depth of anaesthesia closely monitored.
Please see Perspectives on Premeds – Alpha-2 Agonists for further information.
Recommended administration technique:
For specific details on the administration of Alfaxan Multidose for induction of anaesthesia in the dog, cat and rabbit and the maintenance of anaesthesia in the dog and cat please see the downloadable:
- Dose Guide for Dogs and Cats
- User Guide for the Induction and Maintenance of Anaesthesia in the Dog and Cat
- Dose Guide for Pet Rabbits
- User Guide for the Induction of Anaesthesia in the Pet Rabbit
Depth of anaesthesia monitoring should continue throughout the anaesthetic and until the patient has fully recovered.
Propofol is an alkyl phenol that modulates the GABAA receptor of the central nervous system. It is insoluble in aqueous solution and is therefore formulated in an oil-water phospholipid emulsion containing soya bean oil, egg phosphatide and glycerol. The unpreserved formulation has been shown to support microbial growth (Strachan et al, 2008). Preserved versions commonly contain benzyl alcohol. It has a pH of approximately 7.
Metabolism is hepatic (and possibly in the lungs (Matot et al, 1993), kidneys & gastrointestinal tract) via glucuronidation and hydroxylation. Recovery is due to redistribution and metabolism.
Propofol should be administered slowly and to effect. Pain on administration has been reported in the human literature (Desousa, 2016) and some animals may demonstrate discomfort on intravenous injection.
Hypotension, with reduced systemic vascular resistance and cardiac output, is the most prominent haemodynamic effect. The baroreceptor reflex is thought to be depressed producing an attenuation of the normal reflex increase in heart rate. Hypotension may be profound and careful monitoring is vital, especially in hypovolaemic or already hypotensive patients (Dugdale, 2010; Duke-Novakovski et al, 2016).
As with other induction agents, apnoea is a potential side-effect (Keates & Whittem, 2012; Meredith & Lord, 2014). Although the specific product SPC should be referred to with regards speed of administration, it has been recognised that slow administration of propofol will minimise the cardiorespiratory effects observed following rapid injection (Glowaski & Wetmore, 1999). As for alfaxalone, preoxygenation prior to propofol administration is recommended for patients with pre-existing disease or for reasons identified during pre-anaesthetic examination. Equipment for rapid control of the airway should be readily available following the administration of all induction agents.
Some formulations of propofol are not recommended for prolonged maintenance of anaesthesia and may have an upper maximum maintenance dose limit (please refer to the specific propofol SPC). If propofol is used for the maintenance of anaesthesia intermittent positive pressure ventilation is often necessary (Duke-Novakovski et al, 2016) and monitoring of ventilation is recommended using capnography.
Alpha-2 agonist dose-sparing and increased circulation time
If alpha-2 premedication has been administered, or the patient is very well sedated, there may be considerable dose sparing and the calculated dose of propofol may therefore be reduced. Alpha-2s may also increase in circulation time and the propofol should therefore be administered over a longer period of time.
Propofol is not analgesic and appropriate pain relief should be provided as necessary.
Propofol is licensed for the induction of anaesthesia in dogs and cats but not in rabbits, and therefore off-label use consent must be obtained prior to use in the rabbit.
Ketamine is an NMDA (N-methyl-D-aspartate) antagonist with additional action at glutamate, opioid (acting as a mu antagonist and kappa agonist) and nicotinic & muscarinic cholinergic receptors (Dugdale, 2010; Duke-Novakovski et al, 2016).
Solutions tend to be acidic (pH 3.5-5.5) which may result in pain following intramuscular injection (Dugdale, 2010; Duke-Novakovski et al, 2016).
There is approximately 50% protein binding with a slower onset of action following intravenous administration (60-90 seconds) when compared to other agents, and 10-15 minutes when administered intramuscularly. As a result, intravenous induction of anaesthesia is slower than with alfaxalone or propofol and titrating to effect can be more problematic.
Initial redistribution is followed by hepatic metabolism to produce the clinically active norketamine. This metabolite has 10-30% of the potency of ketamine (Duke-Novakovski et al, 2016). In the dog there is further metabolism via glucuronidation followed by renal excretion. In the cat both ketamine and norketamine are excreted via the kidney without further metabolism. Reduced renal function and/or repeated dosing or prolonged infusions may delay recovery and cause hallucinations and excitement. The half-life of ketamine is generally considered to be approximately 1-2 hours (Hanna, 1987; Dugdale, 2010; Duke-Novakovski et al, 2016).
Ketamine causes dissociative anaesthesia with profound analgesia and amnesia but muscle tone, including pedal, ocular & laryngeal reflexes, is maintained or increased. This can make endotracheal intubation and monitoring of anaesthetic depth challenging, especially in rabbits (Duke-Novakovski et al, 2016; Santos et al, 2016). There may be hypersensitivity to sound following ketamine administration (Dugdale, 2010).
It is not recommended to use ketamine as a single agent to induce anaesthesia. The quality of induction is improved by combining with other drugs e.g. alpha 2 agonists, benzodiazepines (see specific SPC for details).
Ketamine may cause a degree of post-induction apnoea (Dugdale, 2010) and respiratory depression (Lerche et al, 2000). Irregular breathing patterns may occur with periods of breath holding followed by short episodes of hyperventilation (Duke-Novakovski et al, 2016).
The increased muscle tone and respiratory depression that follow ketamine administration can make initial anaesthetic monitoring difficult although this will be reduced if alpha-2 agonists are administered or once maintenance with an inhalation agent has been achieved. The poor muscle relaxation and muscle fasciculation can interfere with some monitoring devices (Duke-Novakovski et al, 2016). The eyes, which do not rotate downwards and remain open following ketamine administration, must be protected with a suitable lubricant or by taping the eyelids closed (Allweiler, 2016).
Increased cardiac output, heart rate and blood pressure, via stimulation of the sympathetic nervous system, may be observed even in healthy animals. This produces an increase in myocardial oxygen demand, which can be detrimental to patients with pre-existing cardiac disease and may result in decompensation (Allweiler, 2016). Care should also be taken in hypovolaemic or dehydrated patients (Dugdale, 2010; Duke-Novakovski et al, 2016). Conversely, in severely compromised animals, or when used with other sedatives, ketamine can induce cardiovascular depression and hypotension (Duke-Novakovski et al, 2016).
Ketamine can increase salivation with the potential for upper airway or endotracheal tube/supraglottic airway device obstruction and “silent” aspiration (Duke-Novakovski et al, 2016).
Ketamine is not recommended as a sole anaesthetic agent: it can lead to a transient increase in intraocular pressure, although this effect can be attenuated somewhat by the concurrent administration of phenothiazines, alpha-2 agonists or benzodiazepines (Duke-Novakovski et al, 2016). There is minimal sedation if ketamine is used alone.
If an alpha-2 agonist has been used in conjunction with ketamine the antagonism of the alpha-2 agonist should be delayed by approximately 45 minutes in the cat and rabbit. Excitation, tremors and muscle rigidity may occur following alpha-2 antagonism if the ketamine is still clinically active as both the sedative and analgesic actions provided by the alpha-2 agonist will be “reversed”.
The individual SPCs should be referred to and the most recent editions of formularies, manuals and texts should be consulted for current information on the use ketamine IV for induction of anaesthesia.
SUMMARY TABLES AND FURTHER INFORMATION
The following are summary tables that may be downloaded for further information and quick reference. Please click on the title to access the download.
Originally published: Wednesday, 27th May 2020
Allweiler S (2016). How to improve anaesthesia and analgesia in small mammals. Vet Clin Exotic Anim. 19, 361-377
Ambros B., Valentina Carrozzo M. & Jones T. (2018). Desaturation times between dogs preoxygenated via face mask or flow-by technique before induction of anesthesia. Vet Anaesth Analg, 45: 452-458
Desousa K.A. (2016). Pain on propofol injection: Causes and remedies. Indian journal of pharmacology. 48(6): 617-623.
Duke-Novakovski T., de Vries M. & Seymour C. (eds) (2016). BSAVA Manual of Canine and Feline Anaesthesia & Analgesia. 3rd Edition. British Small Animal Veterinary Association, Gloucester, UK
Dugdale A (2010). In: Veterinary Anaesthesia: Principles to Practice. Wiley-Blackwell, Chichester, UK
Engbers S., Larkin A., Rousset N., Melanie Prebble M., Jonnalagadda M., Knight K.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
Fisher P & Graham J (2018). Chapter 10: Rabbits. In: Exotic Animal Formulary: 5th edition. Carpenter J.W. (ed). Elsevier, St. Louis, Missouri
Flecknell P.A., Roughan J.V. et al (1999). Induction of anaesthesia with sevoflurane and isoflurane in the rabbit. Laboratory Animals 33: 41-46
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
Glowaski & Wetmore, 1999: ‘Propofol: Application in veterinary sedation and anaesthesia’, Clinical Techniques in Small Animal Practice (14)1 1-9
Gomes F.E, de Matos R. & Ledbetter E. (2018). Phacoemulsification of bilateral cataracts in two pet rabbits. Open Vet J 8(2): 125-130
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
Hanna R.M. (1987). Pharmacokinetic studies of ketamine HCL in the cat. PhD thesis. Washington State University, ProQuest Dissertations Publishing, 8724295
Harcourt-Brown F & Chitty J (eds) (2013). BSAVA Manual of Rabbit Surgery, Dentistry and Imaging. British Small Animal Veterinary Association, Gloucester, UK
Hedley J., Stapleton N., Muir C., Priestnall S. & Smith K. (2019). Cutaneous botryomycosis in two pet rabbits. J Exot Pet Med 28: 143-14
Keates H, & Whittem T. (2012). Effect of intravenous dose escalation with alfaxalone and propofol on occurrence of apnoea in the dog. Res Vet Sci 93: 904–906
Lerche P., Reid J. & Nolan A.M. (2000). Comparative study of propofol or propofol and ketamine for the induction of anesthesia in dogs. Vet Rec 146: 571–574.
Martin M & Kirsipuu V. (2017). Rabbit Anaesthesia. Institutional Animal Care and Use Committee, Cornell University.
Matot I., Neely C.F., Katz R.Y. & Neufeld G. R. (1993). Pulmonary uptake of propofol in cats. Effect of fentanyl and halothane. Anaesthesiology 78: 1157-1165
Meredith A (ed) (2015). In: BSAVA Small Animal Formulary, 9th edition – Part B: Exotic Pets. British Small Animal Veterinary Association, Gloucester, UK
Meredith A & Lord B (eds) (2014). In: BSAVA Manual of Rabbit Medicine. British Small Animal Veterinary Association, Gloucester, UK
Muir W., Lerche P., Wiese A., Nelson L., Pasloske K. & WhittemT. (2008). Cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in dogs. Vet Anaesth Analg. 35.
Muir W., Lerche P., Wiese A., Nelson L., Pasloske K. & Whittem T. (2009). The cardiorespiratory and anesthetic effects of clinical and supraclinical doses of alfaxalone in cats. Vet Anaesth Analg. 36: 42–54
Okushima S., Vettorato E & Corletto F. (2014). Chronotropic effect of propofol or alfaxalone following fentanyl administration in healthy dogs. Vet Anaesth Analg.
Santos M., Vinuela A., Vela A.A. & Tendillo F. J. (2016). Single syringe ketamine-propofol for induction of anaesthesia in rabbits. Vet Anaesth Analg 43: 561-565
Seymour C & Gleed R (eds) (1999). In: BSAVA Manual of Small Animal Anaesthesia & Analgesia. 2nd ed. BSAVA, Gloucester, UK
Schnell M., Weiss C., Heit M., Whittem T., Pasloske K. & Whittem T. (2014). Margin of safety of the anaesthetic Alfaxan®-CD RTU in dogs at 0, 1, 3 and 5x the intravenous dose of 2 mg/kg. Poster presentation. Jurox Pty Ltd
Strachan F.A., Mansel J.C. & Clutton R.E. (2008). A comparison of bacterial growth in alfaxalone, propofol and thiopental. JSAP 49: 186-190
Swisher S., Lennox A. & Blair L. (2018). Successful removal of a tracheal foreign body secondary to nasograstric tube placement in a rabbit (Oryctolagus cuniculus). J Exot Pet Med 27: 32–35
Tutunari A.C., Sonea A., Drion P., Serteyn D. & Sandersen C. (2013). Anaesthetic induction with alfaxalone may produce hypoxemia in rabbits premedicated with fentanyl/droperidol. Assoc Vet Anaesth & American College of Vet Anesth Analg 40: 650–659
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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...