Postoperative analgesic effects of either a constant rate infusion of fentanyl, lidocaine, ketamine, dexmedetomidine, or the combination lidocaine-ketamine-dexmedetomidine after ovariohysterectomy in dogs



      To evaluate the postoperative analgesic effects of a constant rate infusion (CRI) of either fentanyl (FENT), lidocaine (LIDO), ketamine (KET), dexmedetomidine (DEX), or the combination lidocaine-ketamine-dexmedetomidine (LKD) in dogs.

      Study design

      Randomized, prospective, blinded, clinical study.


      Fifty-four dogs.


      Anesthesia was induced with propofol and maintained with isoflurane. Treatments were intravenous (IV) administration of a bolus at start of anesthesia, followed by an IV CRI until the end of anesthesia, then a CRI at a decreased dose for a further 4 hours: CONTROL/BUT (butorphanol 0.4 mg kg−1, infusion rate of saline 0.9% 2 mLkg−1 hour−1); FENT (5 μg kg−1, 10 μg kg−1hour−1, then 2.5 μg kg−1 hour−1); KET (1 mgkg−1, 40 μg kg−1 minute−1, then 10 μg kg−1minute−1); LIDO (2 mg kg−1, 100 μg kg−1 minute−1, then 25 μg kg−1 minute−1); DEX (1 μgkg−1, 3 μg kg−1 hour−1, then 1 μg kg−1 hour−1); or a combination of LKD at the aforementioned doses. Postoperative analgesia was evaluated using the Glasgow composite pain scale, University of Melbourne pain scale, and numerical rating scale. Rescue analgesia was morphine and carprofen. Data were analyzed using Friedman or Kruskal–Wallis test with appropriate post-hoc testing (p < 0.05).


      Animals requiring rescue analgesia included CONTROL/BUT (n = 8), KET (n = 3), DEX (n = 2), and LIDO (n = 2); significantly higher in CONTROL/BUT than other groups. No dogs in LKD and FENT groups received rescue analgesia. CONTROL/BUT pain scores were significantly higher at 1 hour than FENT, DEX and LKD, but not than KET or LIDO. Fentanyl and LKD sedation scores were higher than CONTROL/BUT at 1 hour.

      Conclusions and clinical relevance

      LKD and FENT resulted in adequate postoperative analgesia. LIDO, CONTROL/BUT, KET and DEX may not be effective for treatment of postoperative pain in dogs undergoing ovariohysterectomy.


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        • Anil SS
        • Anil L
        • Deen J
        Challenges of pain assessment in domestic animals.
        J Am Vet Med Assoc. 2002; 220: 3313-3319
        • Bell RF
        • Dahl JB
        • Moore RA
        • et al.
        Peri-operative ketamine for acute post-operative pain: a quantitative and qualitative systematic review (Cochrane review).
        Acta Anaesthesiol Scand. 2005; 49: 1405-1428
        • Boscan P
        • Pypendop BH
        • Solano AM
        • et al.
        Cardiovascular and respiratory effects of ketamine infusions in isoflurane-anesthetized dogs before and during noxious stimulation.
        Am J Vet Res. 2005; 66: 2122-2129
        • Columbano N
        • Secci F
        • Careddu GM
        • et al.
        Effects of lidocaine constant rate infusion on sevoflurane requirement, autonomic responses, and postoperative analgesia in dogs undergoing ovariectomy under opioid-based balanced anesthesia.
        Vet J. 2012; 193: 448-455
        • Ebert B
        • Mikkelsen S
        • Thorkildsen C
        • et al.
        Norketamine, the main metabolite of ketamine, is a non-competitive NMDA receptor antagonist in the rat cortex and spinal cord.
        Eur J Pharmacol. 1997; 333: 99-104
        • Firth AM
        • Haldane SL
        Development of a scale to evaluate postoperative pain in dogs.
        J Am Vet Med Assoc. 1999; 214: 651-659
        • Gutierrez-Blanco E
        • Victoria-Mora JM
        • Ibancovichi-Camarillo JA
        • et al.
        Evaluation of the isoflurane-sparing effects of fentanyl, lidocaine, ketamine, dexmedetomidine, or the combination lidocaine-ketamine-dexmedetomidine during ovariohysterectomy in dogs.
        Vet Anaesth Analg. 2013; 40: 599-609
        • Holton LL
        • Scott EM
        • Nolan AM
        • et al.
        Comparison of three methods used for assessment of pain in dogs.
        J Am Vet Med Assoc. 1998; 217: 685-690
        • Holton LL
        • Reid J
        • Scott EM
        • et al.
        Development of a behavior-based scale to measure acute pain in dogs.
        Vet Rec. 2001; 148: 525-531
        • Kehlet H
        • Dahl JB
        The value of “multimodal” or “balanced analgesia” in postoperative pain treatment.
        Anesth Analg. 1993; 77: 1048-1056
        • Lervik A
        • Haga HA
        • Ranheim B
        • et al.
        The influence of a continuous rate infusion of dexmedetomidine on the nociceptive withdrawal reflex and temporal summation during isoflurane anaesthesia in dogs.
        Vet Anaesth Analg. 2012; 39: 414-425
        • Lin GY
        • Robben JH
        • Murrell JC
        • et al.
        Dexmedetomidine constant rate infusion for 24 hours during and after propofol or isoflurane anaesthesia in dogs.
        Vet Anaesth Analg. 2008; 35: 141-153
        • MacDougall LM
        • Hethey J
        • Livingston A
        • et al.
        Antinociceptive, cardiopulmonary, and sedative effects of five intravenous infusion rates of lidocaine in conscious dogs.
        Vet Anaesth Analg. 2009; 36: 512-522
        • Marret E
        • Rolin M
        • Beaussier M
        • et al.
        Meta-analysis of intravenous lidocaine and postoperative recovery after abdominal surgery.
        Br J Surg. 2008; 95: 1331-1338
        • Mathews K
        • Kronen PW
        • Lascelles D
        • et al.
        Guidelines for recognition, assessment and treatment of pain: WSAVA global pain council members and co-authors of this document.
        J Small Anim Pract. 2014; 55: E10-E68
        • McCarthy GC
        • Megalla SA
        • Habib AS
        Impact of intravenous lidocaine infusion on postoperative analgesia and recovery from surgery. A systematic review of randomized controlled trials.
        Drugs. 2010; 70: 1149-1163
        • Mich PM
        • Hellyer P
        Objective, categoric methods for assessing pain and analgesia.
        in: Gaynor JS Muir III, WW Handbook of Veterinary Pain Management. 2nd edn. Mosby Elsevier, China2009: 78-109
        • Mion G
        • Villevieille T
        Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings).
        CNS Neurosci Ther. 2013; 19: 370-380
        • Murrell JC
        • Hellebrekers LJ
        Medetomidine and dexmedetomidine: a review of cardiovascular effects and antinociceptive properties in the dog.
        Vet Anaesth Analg. 2005; 32: 117-127
        • Ortega M
        • Cruz I
        Evaluation of a constant rate infusion of lidocaine for balanced anesthesia in dogs undergoing surgery.
        Can Vet J. 2011; 52: 856-860
        • 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. 2006; 33: 97-103
        • Pozzi A
        • Muir WW
        • Traverso F
        Prevention of central sensitization and pain by N-methyl-D-aspartate receptor antagonist.
        J Am Vet Med Assoc. 2006; 228: 53-60
        • Sano T
        • Nishimura R
        • Kanazawa H
        • et al.
        Pharmacokinetics of fentanyl after single intravenous injection and constant rate infusion in dogs.
        Vet Anaesth Analg. 2006; 33: 266-273
        • Sarrau S
        • Jourdan J
        • Dupuis-Soyris F
        • et al.
        Effects of postoperative ketamine infusion on pain control and feeding behavior in bitches undergoing mastectomy.
        J Small Anim Pract. 2007; 48: 670-676
        • Slingsby LS
        • Waterman-Pearson AE
        The post-operative analgesic effects of ketamine after canine ovariohysterectomy – a comparison between pre- or post-operative administration.
        Res Vet Sci. 2000; 69: 147-152
        • Smith LJ
        • Bentley E
        • Shih A
        • et al.
        Systemic lidocaine infusion as an analgesic for intraocular surgery in dogs: a pilot study.
        Vet Anaesth Analg. 2004; 31: 53-63
        • Steagall PVM
        • Teixeira FJ
        • Minto BW
        • et al.
        Evaluation of the isoflurane-sparing effects of lidocaine and fentanyl during surgery in dogs.
        J Am Vet Med Assoc. 2006; 229: 522-527
        • Thomson AH
        • Elliot HL
        • Kelman AW
        • et al.
        The pharmacokinetics and pharmacodynamics of lignocaine and MEGX in healthy subjects.
        J Pharmacokinet Biopharm. 1987; 15: 101-115
        • Uilenreef JJ
        • Murrell JC
        • McKusick B
        • et al.
        Dexmedetomidine continuous rate infusion during isoflurane anaesthesia in canine surgical patients.
        Vet Anaesth Analg. 2008; 35: 1-12
        • Valtolina C
        • Robben JH
        • Uilenreef J
        • et al.
        Clinical evaluation of the efficacy and safety of a constant rate infusion of dexmedetomidine for postoperative pain management in dogs.
        Vet Anaesth Analg. 2009; 36: 369-383
        • Van Oostrom H
        • Doomenbal A
        • Schot A
        • et al.
        Neurophysiological assessment of the sedative and analgesic effects of a constant rate infusion of dexmedetomidine in the dog.
        Vet J. 2011; 190: 338-344
        • Wagner AE
        • Walton JA
        • Hellyer PW
        • et al.
        Use of low doses of ketamine administered by constant rate infusion as an adjunct for postoperative analgesia in dogs.
        J Am Vet Med Assoc. 2002; 221: 72-75
        • Wilcke JR
        • Davis LE
        • Neff-Davis CA
        • et al.
        Pharmacokinetics of lidocaine and its active metabolites in dogs.
        J Vet Pharmacol Ther. 1983; 6: 49-58