Research Paper| Volume 36, ISSUE 4, P369-383, July 2009

Clinical evaluation of the efficacy and safety of a constant rate infusion of dexmedetomidine for postoperative pain management in dogs



      To compare postoperative analgesia provided by a constant rate infusion (CRI) of dexmedetomidine (DMED) to that of a well-established positive control [morphine (MOR)] in critically ill dogs. The sedative, cardiorespiratory effects and clinical safety of a 24-hour DMED CRI were also evaluated.

      Study design

      Prospective, randomised, blinded, positive-controlled parallel-group clinical study.


      Forty hospitalised, client-owned dogs requiring post-operative pain management after invasive surgery.


      After surgery, a loading dose of either DMED (25 μg m−2) or MOR (2500 μg m−2) followed by a 24-hour CRI of DMED (25 μg m−2 hour−1) or MOR (2500 μg m−2 hour−1) was administered. Pain was measured using the Short Form of the Glasgow Composite Measure Pain Scale, sedation and physiological variables were scored at regular intervals. Animals considered to be painful received rescue analgesia and were allocated to a post-rescue protocol; animals which were unresponsive to rescue analgesia were removed from the study. Data were analysed with anova, two-sample t-tests or Chi-square tests. Time to intervention was analysed with Kaplan–Meier methodology.


      Forty dogs were enrolled. Twenty dogs (9 DMED and 11 MOR) did not require rescue analgesia. Eleven DMED and eight MOR dogs were allocated to the post-rescue protocol and seven of these removed from the study. Significant differences in pain scores between groups were not observed during the first 12 hours, however, DMED dogs were less (p = 0.009) painful during the last 12 hours. Sedation score over the entire 24-hour study was not significantly different between groups.

      Conclusion / Clinical Relevance

      Dexmedetomidine CRI was equally effective as MOR CRI at providing postoperative analgesia and no clinically significant adverse reactions were noted. This study shows the potential of DMED to contribute to a balanced postoperative analgesia regimen in dogs.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Veterinary Anaesthesia and Analgesia
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Arain SR
        • Ruehlow RM
        • Uhrich TD
        • et al.
        The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery.
        Anesth Analg. 2004; 98: 153-158
        • Barnhart M
        • Hubbel JAE
        • Muir WW
        Evaluation of the analgesic properties of acepromazine maleate, oxymorphone, medetomidine and a combination of acepromazine-oxymorphone.
        Vet Anaesth Analg. 2000; 27: 89-96
        • Bloor BC
        • Frankland M
        • Alper G
        • et al.
        Hemodynamic and sedative effects of dexmedetomidine in dog.
        J Pharmacol Exp Ther. 1992; 263: 690-697
        • Correa-Sales C
        • Rabin BC
        • Maze M
        A hypnotic response to dexmedetomidine, an α2 agonist, is mediated in the locus coeruleus in rats.
        Anesthesiology. 1992; 76: 948-952
        • Cullen LK
        Medetomidine sedation in dogs and cats: a review of its pharmacology, antagonism and dose.
        Br Vet J. 1996; 152: 519-535
        • Ebert TJ
        • Hall JE
        • Barney JA
        • et al.
        The effect of increasing plasma concentration of dexmedetomidine in humans.
        Anesthesiology. 2000; 93: 382-394
        • Fairbanks CA
        • Stone LS
        • Kitto KF
        • et al.
        α2-Adrenergic receptors mediated spinal analgesia and adrenergic opioid synergy.
        J Pharm Exp Ther. 2002; 300: 282-290
        • Gerlach AT
        • Dasta JD
        Dexmedetomdine: an updated review.
        Ann Pharmacother. 2007; 41: 245-254
        • Granholm MM
        • McKusick BC
        • Westerholm FC
        • et al.
        Evaluation of the clinical efficacy and safety of intramuscular and intravenous dexmedetomidine or medetomidine in dogs and their reversal with atipamezole.
        Vet Rec. 2007; 160: 891-897
        • Grimm KA
        • Tranquilli W
        • Thurmon J
        • et al.
        Duration of nonresponse to noxious stimulation after intramuscular administration of butorphanol, medetomidine, or a butorphanol-medetomidine combination during isoflurane administration in dogs.
        Am J Vet Res. 2000; 61: 42-47
        • Guedes AGP
        • Rude EP
        • Rider MA
        Evaluation of histamine release during constant rate infusion of morphine in dogs.
        Vet Anaesth Analg. 2006; 33: 28-35
        • Guedes AGP
        • Papich MG
        • Rude EP
        • et al.
        Pharmacokinetics and physiological effects of two intravenous infusion rates of morphine in conscious dogs.
        J Vet Pharmacol Ther. 2007; 30: 224-233
        • Hall JE
        • Uhrich TD
        • Barney JA
        • et al.
        Sedative, amnestic and analgesic properties of small-dose dexmedetomidine infusion.
        Anesth Analg. 2000; 90: 699-705
        • Hansen BD
        Analgesia and sedation in the critical ill.
        J Vet Emerg Crit Care. 2005; 15: 285-294
        • Hofmeister EH
        • Herrington J
        • Mazzaferro EM
        Opioid dysphoria in three dogs.
        J Vet Emerg Crit Care. 2006; 16: 44-49
        • Holton L
        • Reid J
        • Scott M
        Development of a behaviour-based scale to measure acute pain in dogs.
        Vet Rec. 2001; 28 (148): 525-531
        • Jin F
        • Chung F
        Multimodal analgesia for postoperative pain control.
        J Clin Anesth. 2001; 13: 524-539
        • Kukanich B
        • Lascelles BD
        • Papich MG
        Use of a Von Frey device for evaluation of pharmacokinetics and pharmacodynamics of morphine after intravenous administration as an infusion or multiple doses in dogs.
        Am J Vet Res. 2005; 66: 1968-1974
        • Kukanich B
        • Lascelles BD
        • Papich MG
        Pharmacokinetics of morphine and plasma concentration of morphine-6-glucuronide following morphine administration in dogs.
        J Vet Pharmacol Ther. 2005; 28: 371-376
        • Kuusela E
        • Raekallio M
        • Anttila M
        • et al.
        Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs.
        J Vet Pharmacol Ther. 2000; 23: 15-20
        • Kuusela E
        • Raekallio M
        • Vaisanen M
        • et al.
        Comparison of medetomidine and dexmedetomidine as premedicants in dogs undergoing propofol-isoflurane anesthesia.
        Am J Vet Res. 2001; 62: 1073-1080
        • Kuusela E
        • Vainio O
        • Kaistinen A
        • et al.
        Sedative, analgesic, and cardiovascular effects of levomedetomidine alone and in combination with dexmedetomidine in dogs.
        Am J Vet Res. 2001; 62: 616-621
        • Kuusela E
        • Raekallio M
        • Hietanen H
        • et al.
        24-hour Holter-monitoring in the perianaesthetic period in dogs premedicated with dexmedetomidine.
        Vet J. 2002; 164: 235-239
        • Lin G-Y
        • Robben JH
        • Murrell JC
        • et al.
        Dexmedetomidine constant rate infusion for 24 hours during and after propofol and isoflurane anaesthesia in dogs.
        Vet Anaesth Analg. 2008; 35: 141-153
        • Lucas AN
        • Firth AM
        • Anderson GA
        • et al.
        Comparison of the effects of morphine administered by constant rate infusion or intermittent intramuscular injection in dogs.
        J Am Vet Med Assoc. 2001; 218: 884-891
        • Marino DJ
        • Matthiesen DT
        • Fox PR
        • et al.
        Ventricular arrhythmias in dogs undergoing splenectomy: a prospective study.
        Vet Surg. 1994; 23: 101-106
        • Miller TL
        • Schwartz DS
        • Nakayama T
        • et al.
        Effect of acute gastric distension and recovery on tendency for ventricular arrhythmias in dogs.
        J Vet Int Med. 2000; 14: 436-444
        • Morton CM
        • Reid J
        • Scott EM
        • et al.
        Application of a scaling model to establish and validate an interval level pain scale for assessment of acute pain in dogs.
        Am J Vet Res. 2005; 66: 2154-2166
        • Muir WW
        • Woolf CJ
        Mechanism of pain and their therapeutic implications.
        J Am Vet Med Assoc. 2001; 219: 1346-1356
        • Muldoon SM
        • Freas W
        • Mahla ME
        • et al.
        Plasma histamine and catecholamine levels during hypotension induced by morphine and compound 48/80.
        J Cardiovasc Pharmacol. 1987; 9: 578-583
        • Murrell JC
        • Psatha EP
        • Scott EM
        • et al.
        Application of a modified form of the Glasgow pain scale in a veterinary teaching centre in the Netherlands.
        Vet Rec. 2008; 162: 403-408
        • Nelson LE
        • Lu J
        • Guo T
        • et al.
        The α2–adrenoceptors agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects.
        Anesthesiology. 2003; 98: 428-436
        • Ossipov MH
        • Harris S
        • Lloyd P
        • et al.
        Antinoceptive interaction between opioids and medetomidine: systemic additivity and spinal synergy.
        Anesthesiology. 1990; 73: 1227-1235
        • Pascoe PJ
        • Raekallio M
        • Kuusela E
        • et al.
        Changes in the minimum alveolar concentration of isoflurane and some cardiopulmonary measurements during three continuous infusion rates of dexmedetomidine in dogs.
        Vet Anaesth Analg. 2005; 33: 97-103
        • Reid J
        • Nolan AM
        • Hughes JML
        • et al.
        Development of the short-form Glasgow Composite Measure Pain Scale (CMPS-SF) and derivation of an analgesic intervention score.
        Anim Welf. 2007; 16: 97-104
        • Shehabi Y
        • Ruettimann U
        • Adamson H
        • et al.
        Dexmedetomidine infusion for more than 24 hours in critically ill patients: sedative and cardiovascular effects.
        Int Care Med. 2004; 30: 2188-2196
        • Shelly MP
        Dexmedetomidine: a real innovation or more of the same.
        Br J Anaesth. 2001; 87: 678-679
        • Sinclair MD
        A review of the physiological effects of alpha2-agonists related to the clinical use of medetomidine in small animal practice.
        Can Vet J. 2003; 44: 885-897
        • Tobias JD
        • Berkenbosch JW
        Sedation during mechanical ventilation in infants and children: dexmedetomidine versus midazolam.
        South Med J. 2004; 97: 451-455
        • Uilenreef JJ
        • Murrell JC
        • McKusick BC
        • et al.
        Dexmedetomidine continuous rate infusion during isoflurane anaesthesia in canine surgical patients.
        Vet Anaesth Analg. 2008; 35: 1-12
        • Ulloa HM
        • Houston BJ
        • Altrogge DM
        Arrhythmia prevalence during ambulatory electrocardiographic monitoring of beagles.
        Am J Vet Res. 1995; 56: 275-281
        • Unlugenc H
        • Gunduz M
        • Guler T
        • et al.
        The effect of pre-anaesthetic administration of intravenous dexmedetomidine on postoperative pain in patients receiving patient-controlled morphine.
        Eur J Anaesth. 2005; 22: 386-391
        • Urquhart J
        Controlled drug delivery: therapeutic and pharmacological aspects.
        J Intern Med. 2000; 248: 357-376
        • Vaha-Vahe T
        Clinical evaluation of medetomidine, a novel sedative and analgesic drug for dogs and cats.
        Acta Vet Scand. 1989; 30: 267-273
        • Vainio O
        • Vaha-Vahe T
        • Palmu L
        Sedative and analgesic effects of medetomidine in the dog.
        J Vet Pharmacol Ther. 1989; 12: 225-231
        • Venn RM
        • Grounds RM
        Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patients and clinician perceptions.
        Br J Anaesth. 2001; 87: 684-690
        • Venn RM
        • Bradshaw CJ
        • Spencer R
        • et al.
        Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit.
        Anaesthesia. 1999; 54: 1136-1142