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Methadone with Acepromazine - when is enough, enough?

The Effects of Three Methadone Doses Combined with Acepromazine on Sedation and some Cardiopulmonary Variables in Dogs.

Bitti, F.S., Campagnol, D., Rangel, J.P., Junior, J.S.N., Loureiro, B. and Monteiro, E.R. (2017). Veterinary anaesthesia and analgesia44(2): 237-245.

What did the research find?

Combined acepromazine-methadone administration resulted in intense sedation in most dogs. Low dose methadone (0.25 mg/kg) administered in combination with acepromazine (0.05 mg/kg) will induce short-term sedation in dogs, whereas higher doses of methadone should be administered when prolonged sedation is desired.

How was it conducted?

Six healthy, adult, cross-bred dogs, of a docile and co-operative nature, were used in this prospective, randomised study. Four sedative protocols were used, with a washout period of 1 week between each:

  • Acepromazine at 0.05mg/kg (ACP),
  • Acepromazine at 0.05mg/kg and methadone at 0.25mg/kg (AM0.25),
  • Acepromazine at 0.05mg/kg and methadone at 0.50mg/kg (AM0.50),
  • Acepromazine at 0.05mg/kg and methadone at 0.75mg/kg (AM0.75).

All drugs were administered intramuscularly (IM) and in treatment groups AM0.25, AM0.50, and AM0.75 acepromazine and methadone were mixed in a single syringe before administration minutes later.

Sedation was scored using a numeric descriptive scale (NDS: range 0-3) and simple numerical scale (SNS: range 0-10) at 15, 30, 45, 60, 75, 90 and 120 minutes and every 30 minutes thereafter until sedation scores returned to zero. This was recorded by a single observer who was familiar with the scoring systems but unaware of the treatment administered. Heart rate, invasive blood pressure, arterial blood gases and rectal temperature were measured at 15 to 30 minute intervals for 120 minutes following treatment administration.


All treatments significantly increased NDS and SNS scores in comparison with baseline. According to NDS scores, mild to moderate sedation (NDS = 1-2) was observed in most dogs following acepromazine administration, with only one out of six dogs scored as exhibiting intense sedation (NDS = 3). The addition of methadone resulted in significantly higher levels of sedation in most dogs. Increasing the dose of methadone from 0.25 to 0.50 and 0.75 mg/kg prolonged sedation in a dose-related manner but did not influence the degree of sedation. Significant changes in some of the cardiopulmonary variables (i.e. arterial pressure, pH, PaCO2 and SaO2) were identified between treatment groups, although were not considered to be of clinical significance. Rectal temperature did not change significantly within the ACP group but did differ significantly in all AM groups when compared to baseline and matched ACP timepoints.

The main adverse effects of combined acepromazine-methadone were reductions in blood pressure, mild respiratory acidosis and decreased rectal temperature. These effects were well tolerated and resolved without treatment.

Why is this important?

Acepromazine is the most commonly used phenothiazine agent in dogs. Previous reports demonstrated that intravenous (IV) or IM administration of acepromazine (0.05 - 0.1 mg/kg) resulted in mild to moderate sedation in dogs (Monteiro et al. 2008; Gomes et al. 2011). In agreement with these findings, administration of acepromazine at 0.05mg/kg alone in this study resulted in mild to moderate sedation in most cases.

Methadone is a synthetic full µ-opioid agonist which is often described in the literature as having a similar analgesic efficacy as morphine. Since methadone is a full µ-opioid agonist, it elicits a maximal response at full saturation of receptor binding sites (Inturrisi, 2002) and is both effective and indicated for the control of moderate to severe pain (Murrell, 2011). Mild to moderate sedation has also been observed after administration of methadone alone in dogs (Maiante et al. 2009).

In this study, the concurrent IM administration of acepromazine (0.05 mg/kg) with methadone resulted in heavy sedation in most dogs. Increases in methadone dose (0.25, 0.50 and 0.75 mg/kg) prolonged the sedative effect in a dose-related manner but did not influence the degree of sedation. Importantly, changes in the cardiopulmonary variables measured following drug administration in these healthy dogs were well tolerated and not deemed clinically relevant.

The authors conclude that a low dose of methadone (0.25 mg/kg) can be administered in combination with acepromazine (0.05mg/kg) to induce short-term sedation in dogs, whereas higher doses should be used when prolonged sedation is desired.

Article by
Dr. Dan Cripwell
BSc (Hons) BVSc CertAVP (EM) PgCert (VPS) MRCVS

Veterinary Technical Advisor UK
RCVS Recognised Advanced Veterinary Practitioner

Originally published: Thursday, 11th October 2018


Gomes, V.H., Monteiro, E.R., Dias, R.S., Oliveira, R.L.S.D., Silva, M.F.A.D. and Coelho, K. (2011). Comparison of the sedative effects of morphine, meperidine or fentanyl, in combination with acepromazine, in dogs. Ciência Rural.  41(8): 1411-1416.

Inturrisi, C.E. (2002). Clinical pharmacology of opioids for pain. The Clinical journal of pain18(4): S3-S13.

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.

Monteiro, E.R., Junior, A.R., Assis, H.M.Q., Campagnol, D. and Quitzan, J.G. (2009). Comparative study on the sedative effects of morphine, methadone, butorphanol or tramadol, in combination with acepromazine, in dogs. Veterinary anaesthesia and analgesia36(1): 25-33.

Murrell, J. (2011). Clinical use of methadone in cats and dogs. UK Vet Companion Animal.16(5): 56-61.

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