Use of alpha-2 agonists in general anesthesia (Proceedings)

Alpha-2 agonists have achieved widespread popularity in veterinary medicine for their sedative and analgesic properties.  They can be valuable adjuncts in anesthetic protocols.  Clinical effects of alpha adrenergic agents include sedation, analgesia, respiratory depression, cardiovascular depression, muscle relaxation, and vasoconstriction.  They are reversible.  There are several choices of alpha adrenergic drugs available to the small animal practitioner.  Xylazine, an alpha-2 agonist with mixed alpha-1 and local anesthetic effects as well as alpha-2 selectivity, has been used by veterinarians for many years in a variety of species.  Medetomidine, a more alpha-2 selective drug, became popular during the past twenty years for small animal use.  Recently, dexmedetomidine, has been released to the US market to replace medetomidine.  Medetomidine is an equal mix of two optical enantiomers-dexmedetomidine is the dextrorotary enantiomer which is thought to possess all of the pharmacologic activity of medetomidine.  Dexmedetomidine is supplied as 0.5 mg/ml, which allows clinicians to use the same volume of drug in dosing regimes previously utilizing medetomidine.  The focus of this talk will be concerned with the use of dexmedetomidine in small animal anesthesia practice.

Patient selection is a very important consideration with the use of dexmedetomidine in anesthetic protocols.  The drug provides an optimal amount of sedation, analgesia and muscle relaxation, but also brings moderate to severe bradycardia, peripheral vasoconstriction with attendant hypertension, and reduced cardiac output.  Vital organ blood flow is also compromised.   Animals with underlying cardiovascular disease or vital organ compromise such as renal or liver disease are not good candidates for the addition of alpha-2 agonists in the anesthetic protocol.

The increase in systemic vascular resistance produced by dexmedetomidine and the reflex bradycardia it induces is one of the more confounding aspects of this drug use.  Bradycardia can be significant, with heart rates as low as 28-32 beats per minute.  It is one thing to impose this level of cardiac depression on a sedated patient: it is a more complicated situation when the addition of further cardiac depression is imposed with general anesthesia, regardless of the type of additional anesthetic agents.  Inhalant anesthetics produce reductions in cardiac output.  They also are potent vasodilators, which may improve conditions when dexmedetomidine is used.  Nevertheless, we do not recommend the routine use of anticholinergics such as atropine or glycopyrrolate to treat bradycardia produced by dexmedetomidine because of the significant systemic vascular resistance produced by the drug.  If the bradycardia produced by dexmedetomidine is deemed necessary to treat, complete or partial reversal with atipamezole (a highly alpha-2 specific antagonist) can be done. Atipamezole administration will also reverse the analgesia and sedation produced by dexmedetomidine.  It may be noticed that cats do not usually experience as significant a level of bradycardia with dexmedetomidine use as the dog.

Excellent sedation can be achieved at less than label doses of dexmedetomidine.  The drug is labeled for body surface area dosing by the manufacturer, but can also be given on a per kg basis.  It can be used as a premedicant for inhalant general anesthesia, where it serves to greatly decrease the amount of induction agent needed as well as decrease the level of inhalant needed to maintain anesthesia.  It can be used as part of injectable anesthetic regimes, one example of which is  in Table 1.  Dexmedetomidine can be administered in microdoses for treatment of post anesthetic emergence delirium or as a constant rate infusion intra or post op for patients with higher analgesic requirements.

Other detrimental clinical effects of dexmedetomidine include hyperglycemia, increased urine production, vomiting, decreased gastrointestinal motility, and respiratory depression. The drug is not recommended for use in patients less than 3-4 months of age, depending on species.

Table 1. Titletamine-Zolazepam-Butorphanol-Dexmedetomidine (TTDex) Combination in Dogs and Cats Desired Purpose IM Dosages of Individual Components Volume (ml/kg IM) of reconstituted TTDex Volume (ml/kg IM) of reconstituted TTDex

Tiletamine-zolazepam, 1 mg/kg

Butorphanol, 0.05 mg/kg

Dexmedetomidine, 2.5 µg/kg 0.01 Chemical restraint (profound sedation)

Tiletamine-zolazepam, 2 mg/kg

Butorphanol, 0.1 mg/kg

Dexmedetomidine, 5 µg/kg 0.02 Surgical plane of anesthesia

Tiletamine-zolazepam, 3 mg/kg

Butorphanol, 0.15 mg/kg

Dexmedetomidine, 7.5 µg/kg 0.03

*Each agent may be drawn up and given separately and given IM.  Alternatively, Telazol powder can be reconstituted using 2.5 ml of butorphanol (10 mg/ml) and 2.5 ml of dexmedetomidine as dilutents. If given IV, drug dosages should be halved