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Effects of Dexmedetomidine with Different Opioid Combinations in Dogs

Effects of dexmedetomidine combined with commonly administered opioids on clinical variables in dogs

Nishimura LT, Auckburally A, Santilli J, Vieira BHB, Garcia DO, Honsho CS, de Mattos-Junior E
American Journal of Veterinary Research, 79(3), pp. 267 275. (doi:10.2460/ajvr.79.3.267) (PMID:29466048)


What did the research find?

The objective of the study was to evaluate the effects of dexmedetomidine combined with commonly administered opioids in dogs. The research found:

  • Similar cardiorespiratory depression when dexmedetomidine was combined with any of the opioids included in the study. 
  • Monitoring of ventilation and oxygenation is recommended, particularly when a combination of dexmedetomidine and meperidine or methadone is used. 
  • Superior sedation was achieved when dexmedetomidine was combined with meperidine or methadone compared to dexmedetomidine alone or in combination with the rest of opioids included in the study.
  • Antinociceptive effects were difficult to interpret because of sedation, but they appeared to be better when dexmedetomi¬dine was combined with butorphanol, methadone, morphine, or nalbuphine.


How was it conducted?

Eight healthy, 24-month-old beagles, habituated to both environment and research team, where used in the study. Water and food were withheld for 6 hours before the start of the investigation.

Dogs were randomly assigned to receive the 7 predefined treatments with a minimum washout interval of 7 days between treatments. The treatments consisted of:

  1. dexmedetomidine (0.01 mg/kg) 

And the same dose of dexmedetomidine combined with:

  1. butorphanol (0.15 mg/kg) 
  2. meperidine (5 mg/kg)
  3. methadone (0.5 mg/kg)
  4. morphine (0.5 mg/kg)
  5. nalbuphine (0.5 mg/kg) 
  6. tramadol (5 mg/kg)

Opioid doses were selected based on equipotent analgesic doses used in other studies (Mastrocinque and Fantoni, 2003; Mainte et al. 2009).

Variables were measured before drug administration (time 0; baseline) and every 15 minutes after drug administration for 120 minutes. Measured variables included:

  • Cardiopulmonary, blood gas, and electrolyte values - heart rate, cardiac rhythm, blood pressure, respiratory rate, blood pH, PaCO2, PaO2, arterial oxygen saturation, base excess and electrolyte concentrations.
  • Sedative effects - evaluated and scored separately by 3 examiners blinded to the treatments administered. 
  • Antinociceptive effects – withdrawal reflex to heat stimulation (60oC metallic probe in interdigital space for a maximum 5 of seconds).


Why is this study important?

Dexmedetomidine has more potent sedative and analgesic effects than the racemate medetomidine but can cause dose-dependent cardiopulmonary depression. Combinations of opioids and alpha2-adrenoerceptor agonists are often used in veterinary medicine and can lead to supra-additive or synergic antinociceptive and sedative effects. This study is relevant because opioids form the basis of pain management in dogs and are commonly used in veterinary practice, but information on efficacy of certain opioids, such as nalbuphine and tramadol, have been less evaluated. The authors of the study hypothesised that dexmedetomidine in combination with any of the opioids would result in superior antinociception and sedation but would cause similar cardiopulmonary depression, compared with results for administration of dexmedetomidine alone. The results of the study confirmed the authors hypothesis. 

In the paper, previous studies are compared with the current study. We have provided a summary of the parameter comparison in this table:

Measured ParameterPrevious studies suggest…Current study suggests…
Arterial blood pressureReduction (dexmedetomidine + buprenorphine, methadone, morphine, or tramadol)Not detected
Heart rateVagally mediated bradycardia (opioids)
Reduction (opioids + alpha2-adrenorecptor agonists)
No difference in heart rate or AMP among treatments
ArrythmiaNot reported (dexmedetomidine + meperidine, methadone, morphine, or tramadolSome cardiac arrhythmias were detected (all treatments), but not clinically relevant. There were no differences among treatments
HypoxemiaEffects of opioids on oxygenation in dogs differ among reports. High doses of methadone (1.0 mg/kg) administered IV to conscious dogs can cause hypoxemia result of ventilation-perfusion impairmentSignificant but not clinically relevant reductions in PaO2, particularly when dogs received dexmedetomidine with methadone or mepivacaine. Due to impaired alveolar ventilation and ventilation-perfusion.
SedationImproved when dexmedetomidine is administered with methadone or morphine (compared with dexmedetomidine given alone or in combination with tramadol)
Improved when a combination of dexmedetomidine and meperidine is administered (compared with dexmedetomidine administered alone)
Adding butorphanol (0.2 mg/kg) to medetomidine improves sedation in dogs
Sedation was observed for all treatments for up to 60 minutes after injection. Superior sedation observed in dogs administered dexmedetomidine + mepivacaine or dexmedetomidine + methadone

Link to the full article: http://eprints.gla.ac.uk/14155...

Want to know more about opioids? Read Persperctives on Premeds - Opioids by Karen Heskin. 

Article by
Carol Atkinson
BVMS, MBA

Marketing Manager

Originally published: Thursday, 31st May 2018
Last updated: Thursday, 14th June 2018

References

Maiante, A.A., Teixeira Neto, F.J., Beier, S.L., Corrente, J.E. and Pedroso, C.E.B.P. 2009. Comparison of the cardio‐respiratory effects of methadone and morphine in conscious dogs. Journal of veterinary pharmacology and therapeutics32(4): 317-328.

Mastrocinque, S. and Fantoni, D.T. 2003. A comparison of preoperative tramadol and morphine for the control of early postoperative pain in canine ovariohysterectomy. Veterinary anaesthesia and analgesia. 30(4): 220-228.

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