Perspectives on Premeds is a series of articles touching on different pharmacological, physiological and clinical aspects of pre-anaesthetic medication. This first article aims to provide a refresher on α2 agonists.
Alpha-2 agonists have been the subject of significant discussion within the veterinary literature. Since their initial introduction onto the veterinary market they frequently received ‘bad press’ and were associated with a number of negative user experiences. A likely explanation for this was unfamiliarity with α2 agonists together with the high dose rates initially recommended. However, as user experience and confidence has grown, the beneficial sedative and analgesic effects of α2 agonists have become extensively recognised and their use in small animal veterinary medicine is now wide spread.
α2 agonists are currently available on the UK market, namely: medetomidine, dexmedetomidineand xylazine. Xylazine has an approximately 10 times less affinity for the α2 receptor than medetomidine and dexmedetomidine, and as a result is associated with a wider range of undesirable effects in the most commonly treated small animals.
Medetomidine is a 50:50 mix of dexmedetomidineand levomedetomidine. Dexmedetomidineis the active isomer and levomedetomidine has traditionally been considered to be the inactive component. However, a recent study3 has suggested very high doses of levomedetomidine may actually reduce the sedative and analgesia effects of dexmedetomidineand enhance bradycardia. Further studies need to be performed to determine the clinical effects of the levomedetomidine isomer in the practice setting. Additionally, dexmedetomidinehas a reduced hepatic metabolic requirement as only one isomer is delivered to the liver for processing.
This article will focus on medetomidine and dexmedetomidine.
α2 agonists are widely used for their sedative and analgesic properties and are regularly incorporated into premedication protocols prior to general anaesthesia. When used for this purpose they elicit several desirable effects, these include:
- Drug sparing effects – the doses of other premedicants, induction and maintenance agents may be reduced. This effect should be considered when determining the doses of other concomitantly administered CNS depressant drugs
- Minimal respiratory depression at clinical doses
Pharmacological Effects of Alpha-2 Agonists
The α2 agonists, medetomidine and dexmedetomidine, provide profound, dose related sedation which plateaus at higher doses.
α2 agonists afford profound analgesia, effected at spinal cord level via the α2 receptors. This can help produce a smooth and stable induction, maintenance and recovery with a reduction in “swings”. The analgesic effects are short lived and generally persist for approximately 1 hour at clinical doses although sedation may continue for longer.
Peripheral vasoconstriction occurs following administration. This can initiate a biphasic alteration to blood pressure:
- Phase 1. There is an initial increase in blood pressure lasting approximately 20 minutes resulting in a compensatory decrease in heart rate and cardiac output. Cardiac output can reduce by up to 50%. This should not be an issue in healthy animals but must be considered in animals with a reduced organ reserve when blood flow to the vital tissues may be compromised.
- Phase 2. After approximately 20 minutes there is a decrease in central sympathetic tone and a reduction in peripheral vasoconstriction. As a result, blood pressure returns to normal or just below, with a normal or reduced heart rate.
Although peripheral vasoconstriction will limit heat loss there is also depression of the thermoregulatory centre giving rise to a reduction in body temperature. Animals should be closely monitored following administration of α2 agonists and warming provided where necessary.
There are significant drug sparing effects4 following the administration of α2-agonists, some authors reporting up to a 70% dose sparing effect.2 This should always be considered when administering multiple products, during intravenous induction of anaesthesia and during maintenance. The doses of concomitant drugs should be reduced accordingly.
Blood flow to the liver and the hepatic metabolism of drugs is reduced following the administration of α2 agonists. In patients with liver disease α2 agonists should be avoided if possible.
The reduction in cardiac output increases circulation time and this, together with the reduced metabolic capacity of the liver, means intravenous induction agents should be given slowly and to effect. The dose of both induction and maintenance agents may be lower than expected.
There are minimal effects on the respiratory system. However, in brachycephalics, the profound sedation can potentially lead to upper airway obstruction and caution should be exercised.
A reduction in vasopressors and renin secretion following the administration of α2-agonists causes an increased urine output. This class of drug should therefore be avoided in “blocked cats” and attention must be paid to bladder care in all patients receiving α2-agonists (and all premedicants).
A transient hyperglycaemia may be observed as a consequence of reduced insulin production.
Emesis may be observed in some individuals due to activation of the central α2 receptors. This class of drug should therefore be avoided in gastrointestinal foreign body patients.
Antagonism of alpha-2 agonists
α2 agonist sedation and analgesia are readily antagonised with atipamezole (an α2 antagonist).
Antagonism of α2 agonists will not only “reverse” the sedative effects of the drug but also the analgesic effects, so it is essential to consider administering an alternative class of analgesic to maintain pain relief.
Antagonism may be considered in some patients during the recovery period as studies have demonstrated this to be a time of high risk for anaesthetic complications.1 If atipamezole is administered intramuscularly the recovery should be smooth and uneventful although this can be dependent on the timing of antagonism and on the concomitant use of other drugs e.g. ketamine.
Antagonism is not recommended less than 45 minutes after α2 agonist administration if used in combination with ketamine, as excitable recoveries are more likely than if antagonism occurs at a later stage.2
Intravenous administration of atipamezole is “off licence” (see appropriate SPC) and may result in very rapid and excitable recoveries. Routine intravenous administration is not recommended.2, 5
The selectivity of dexmedetomidine for the alpha 2 receptor is superior to that of medetomidine suggesting it would be the drug of choice but clinical evidence is sparse, and its use is currently the preference of the individual prescribing the drug.
Summary of alpha-2 agonists
- Profound sedation (dose dependent)
- Profound analgesia (duration approximately 1 hour)
- Peripheral vasoconstriction
- Biphasic alterations to blood pressure
- Increased blood pressure (approx. 20 minutes duration)
- Followed by normal or slightly reduced blood pressure
- Significant dose sparing. Adjust the doses of concomitant drugs, induction & maintenance agents accordingly
- Potential for hypothermia (resetting of thermoregulatory centre)
- Reduced hepatic blood flow (and therefore metabolism)
- Increased circulation time and reduced cardiac output – administer intravenous agents more slowly
- May increase urine output. Care in urinary disease/“blocked” animals
- Transient hyperglycaemia
- May cause emesis. Care in GI disease/foreign bodies
- Antagonisable. Both sedation and analgesia are “reversed”. Consider alternative and multimodal pain management
Coming soon within the Perspectives on Premeds series:
- Timing and route of administration for optimal results
- ASA Physical Status
- Downloadable pre-meds characteristics table
- Which premed? – Choosing the most appropriate combination for each ASA Physical Status category (dogs and cats)
Originally published: Friday, 4th May 2018
Last updated: Thursday, 31st May 2018
- Broadbelt DC, Blisset KJ et al (2008). The risk of death: the confidential enquiry into perioperative small animal fatalities. Veterinary Anaesthesia & Analgesia 35, 365-373
- BSAVA Manual of Canine and Feline Anaesthesia and Analgesia. 3rd edition. (2016)
- Kuusela E et al (2001). Sedative, analgesic, and cardiovascular effects of levomedetomidine alone and in combination with dexmedetomidine in dogs. American Journal of Veterinary Research 62, 616-621
- Dugdale A (2010). Veterinary Anaesthesia, Principles to Practice. Wiley-Blackwell.
- BSAVA Small Animal Formulary. 9th Edition (2017).
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...