Assistant Professor of Anesthesiology, Veterinary Medicine & Biomedical Sciences, Small Animal Clinical Sciences, Texas A&M University, College Station, TX, USA
Dexmedetomidine has become increasingly popular amongst small animal veterinarians because of its ability for providing sedation, muscle relaxation, and analgesia. It is administered as a premedication prior to surgery or as a constant rate infusion (CRI) during surgery to reduce inhalant requirements and provide multimodal analgesia. We will review some of the most current literature on dexmedetomidine in small animal practice. More specifically it will focus on novel methods for administration (ultra-low dose CRI's, locoregional adjuncts, oral transmucosal), effects on the cardiopulmonary system during the perioperative period compared to acepromazine, diagnostic tests (echocardiography, radiography, biochemical and hematology), and recovery quality.
The Use of "Low Dose" Dexmedetomidine Constant Rate Infusions
Physiological consequences (decreased heart rate, cardiac output) associated with dexmedetomidine may preclude many practitioners from its use. Recently it was shown that a 0.5 mcg/kg intravenous bolus followed by a low dose constant rate infusion at 0.5 mcg/kg/h of dexmedetomidine preserved cardiopulmonary function within clinically accepted normal ranges in anesthetized dogs.1 This may be beneficial in reducing inhalant requirements and therefore adverse effects. Patients may have large variations associated with the physiological effects from dexmedetomidine and therefore each patient should be monitored closely. The effectiveness of this dose producing analgesia however is controversial.
Head-to-Head Comparison: Acepromazine versus Dexmedetomidine
Acepromazine or dexmedetomidine are commonly administered premedication agents prior to a propofol induction and inhalant-based anesthesia. Recently these two premedications were compared to determine their effects on cardiopulmonary parameters in dogs prior to the administration of propofol and isoflurane.2 The use of acepromazine or dexmedetomidine as a premedication provided no differences amongst the dose of propofol used for induction. When compared to acepromazine, dexmedetomidine maintained mean arterial pressures closer baseline values when administered prior to propofol and isoflurane. Propofol and isoflurane exacerbated acepromazine induced hypotension. Despite this hypotension observed cardiac output was well maintained with acepromazine.
Dexmedetomidine has been shown to cause bradycardia leading to reductions in cardiac output. Propofol and isoflurane after the administration of dexmedetomidine attenuated this decrease in cardiac output. Both groups maintained adequate delivery of oxygen above that of the "critical level." Neither drug prior to propofol administration (premedication phase) resulted in respiratory depression. Recovery quality was smooth and quiet with patients receiving either premedication combination.
Dexmedetomidine Use in Locoregional Anesthesia and Analgesia
The addition of dexmedetomidine to local anesthetics has been thought to prolong their duration of action via local vasoconstriction thus decreasing systemic absorption. The concept is similar to that of combing epinephrine with a local anesthetic, but with less potential adverse effects. Dexmedetomidine used when performing nerve (oral, sciatic, femoral) blocks, infiltrative blocks, and epidurals may provide longer-lasting postoperative analgesia. Thereby decreasing the need for systemically administered analgesics and inhalational anesthetics which can decrease the incidence of adverse effects including heavy sedation, aspiration, and cardiopulmonary depression. Cardiovascular changes associated with the administration of perineural dexmedetomidine are similar, albeit less of an effect, to what is seen with parenteral administration in dogs and cats. Intra-articular dexmedetomidine may improve duration and quality of analgesia in patients with joint disease.
Oral Transmucosal Administration of Dexmedetomidine
Non-compliant or fractious animals are encountered frequently in veterinary medicine. Patients may be so fractious or aggressive that an intravenous, subcutaneous, or intramuscular (IM) injection would be impossible without jeopardizing the safety of staff members. Aggressive animals may bark or hiss which allows the anesthesia provider an opportunity to spray from a distance a sedative onto the patient's oral mucosa. Dexmedetomidine appears to be an ideal pharmacological agent for oral transmucosal (OTM) absorption in cats.3 Administration of 40 mcg/kg of dexmedetomidine OTM provided equally good sedation and analgesia as the same dose administered IM in healthy cats.3 Salivation and vomiting were reported as adverse effects. The combination of a lower dose dexmedetomidine (20 mcg/kg) and buprenorphine (20 mcg/kg) administered OTM provided slightly less sedation, though adequate, for intravenous catheterization.4 A similar dose of dexmedetomidine has been shown to provide adequate sedation in healthy aggressive or anxious dogs for examination, phlebotomy, and intravenous catheter placement.5 Cardiovascular adverse effects typically noted with α2 agonists can also occur with OTM administration and therefore its use is recommended in healthy subjects. Sileo® is a new gel-formulation of dexmedetomidine used to treat fear and anxiety associated with loud noises in dogs and can be administered by pet owners at home. Sileo® is not recommended in dogs with cardiovascular, respiratory, liver or kidney diseases, shock, and stress due to extremes in temperature or fatigue. Sedation and drowsiness may be potential adverse effects.
Effects of Dexmedetomidine on Diagnostic Tests
Diagnostic tests such as biochemical and hematological analysis, echocardiography, and radiography are routinely performed in veterinary patients. To obtain this information sedation may be required in non-compliant patients. When performing sedation in these patients it is important for the clinician to be aware of how dexmedetomidine sedation combinations can alter patient's diagnostic results.
Echocardiographic and Radiographic Tests
Dexmedetomidine sedation combinations effects on echocardiography were evaluated in cats.6 The use of midazolam (0.4 mg/kg), butorphanol (0.4 mg/kg), and dexmedetomidine (5 mcg/kg) (MBD) administered IM to healthy cats resulted in significant changes in heart rate and most echocardiographic measurements. Cardiac output and stroke volume decreased after administration. Ketamine (3 mg/kg) and dexmedetomidine (5 mcg/kg) IM administration to cats altered similar parameters. Sedation was more evident with KD than MBD.
In dogs, few echocardiographic changes were noted following the administration of low dose (5 mcg/kg IM) dexmedetomidine injection when compared to a high dose (10 mcg/kg IM).7 Cardiac output and heart rate decreased in both groups. Mitral, tricuspid, aortic, and pulmonic regurgitation was noted on echocardiography in some subjects after dexmedetomidine sedation.8 Therefore, a practitioner must take these findings into consideration when diagnosing heart disease.
Radiographic changes such as increased cardiac silhouette size and median percentage width on ventrodorsal and dorsoventral views in cats and dogs has been reported following dexmedetomidine administration.8,9 These results could be misinterpreted in the patient for a differential diagnosis of cardiomegaly, when in fact the patient is clinically healthy. The reason for these changes is uncertain.
Biochemical and Hematologic Tests
The use of dexmedetomidine administered IM to healthy cats resulted in decreased packed cell volume, white blood cell count, platelets, total protein and lactate.6 The use of sedation can decrease the release of catecholamine's which can prevent contraction and the release of red blood cells from the spleen during routine physical restraint for phlebotomy in cats. Reduction in stress and muscle relaxation post injection can result in decreases in lactate concentrations. Fluid compartmental shifts to maintain cardiac output may account for the decrease in total protein. Hyperglycemia occurs following dexmedetomidine due to insulin inhibition through stimulation of α2 receptors in the ß cells of the pancreas.6 Dexmedetomidine appears to have little to no effect on coagulation tests.6,9
Dexmedetomidine and Its Effects on Recovery
The administration of low-dose dexmedetomidine immediately prior to extubation in dogs under general anesthesia decreased the incidence of poor recoveries in dogs. Despite this advantage significantly prolonged recoveries was observed.10
References
1. Pascoe PJ. The cardiopulmonary effects of dexmedetomidine infusions in dogs during isoflurane anesthesia. Vet Anaesth Analg. 2015;42(4):360–368.
2. Grasso SC, Ko JC, Weil AB, Paranjape V, Constable PD. Hemodynamic influence of acepromazine or dexmedetomidine premedication in isoflurane-anesthetized dogs. J Am Vet Med Assoc. 2015;246(7):754–764.
3. Slingsby LS, Taylor PM, Monroe T. Thermal antinociception after dexmedetomidine administration in cats: a comparison between intramuscular and oral transmucosal administration. J Feline Med Surg. 2009;11(10):829–834.
4. Santos LC, Ludders JW, Erb HN, Basher KL, Kirch P, Gleed RD. Sedative and cardiorespiratory effects of dexmedetomidine and buprenorphine administered to cats via oral transmucosal or intramuscular routes. Vet Anaesth Analg. 2010;37(5):417–424.
5. Cohen AE, Bennett SL. Oral transmucosal administration of dexmedetomidine for sedation in 4 dogs. Can Vet J. 2015;56(11):1144–1148.
6. Biermann K, Hungerbuhler S, Mischke R, Kastner SB. Sedative, cardiovascular, haematologic and biochemical effects of four different drug combinations administered intramuscularly in cats. Vet Anaesth Analg. 2012;39(2):137–150.
7. Kellihan HB, Stepien RL, Hassen KM, Smith LJ. Sedative and echocardiographic effects of dexmedetomidine combined with butorphanol in healthy dogs. J Vet Cardiol. 2015;17(4):282–292.
8. Wang HC, Hung CT, Lee WM, Chang KM, Chen KS. Effects of intravenous Dexmedetomidine on cardiac characteristics measured using radiography and echocardiography in six healthy dogs. Vet Radiol Ultrasound. 2015.
9. Volpato J, Mattoso CR, Beier SL, Coelho MM, Tocheto R, Kirsten CE, et al. Sedative, hematologic and hemostatic effects of dexmedetomidine-butorphanol alone or in combination with ketamine in cats. J Feline Med Surg. 2015;17(6):500–506.
10. Hunt JR, Slingsby LS, Murrell JC. The effects of an intravenous bolus of dexmedetomidine following extubation in a mixed population of dogs undergoing general anaesthesia and surgery. Vet J. 2014;200(1):133–139.