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Clinical Trial
. 2014 Sep;55(9):875-85.

Effects of acepromazine or methadone on midazolam-induced behavioral reactions in dogs

Bradley T Simon  1 , Elizabeth M Scallan  1 , Carlo Siracusa  1 , Amy Henderson  1 , Meg M Sleeper  1 , M Paula Larenza Menzies  1
Affiliations
Clinical Trial

Effects of acepromazine or methadone on midazolam-induced behavioral reactions in dogs

Bradley T Simon et al. Can Vet J. 2014 Sep.

Abstract
in English, French

This study evaluated whether acepromazine or methadone reduced behavioral parameters, overall excitement, and activity associated with midazolam administration to healthy dogs. Dogs received midazolam (M) alone [M: 0.25 mg/kg body weight (BW)] or with methadone (MM) (MM: 0.75 mg/kg BW) or acepromazine (MA) (MA: 0.03 mg/kg BW) or saline (S) solution alone, all intramuscularly. Two blinded observers evaluated behavioral parameters using video recordings 30 min before and after injection of drugs. Accelerometery was used to evaluate "total activity counts" (TAC) at baseline and post-treatment. Post-treatment excitement scores were significantly higher in M and MA compared to baseline, M and MM compared to S, and M compared to MA. Behavioral parameters showed significantly higher proportions of "pacing" post-treatment in all groups receiving midazolam, and "restlessness," "chewing/licking," and "sniffing" in M. No significant differences were found for TAC at baseline and post-treatment. Midazolam-induced paradoxical behavioral changes (excitation, panting, pacing, restlessness, licking/chewing, and vocalization) were not prevented by acepromazine or methadone in healthy dogs.

Effets de l’acépromazine ou de la méthadone sur les réactions comportementales induites par le midazolam chez les chiens. Cette étude a évalué si l’acépromazine ou la méthadone réduisait les paramètres comportementaux, le niveau d’excitation général et l’activité associée à l’administration de midazolam chez des chiens en santé. Les chiens ont reçu le midazolam (M) seul (M : 0,25 mg/kg poids corporel [PC]) ou avec de la méthadone (MM) (MM : 0,75 mg/kg PC) ou de l’acépromazine (MA) (MA : 0,03 mg/kg PC) ou une solution saline (S) seule, tous administrés par voie intramusculaire. Deux observateurs à l’aveugle ont évalué les paramètres comportementaux à l’aide d’enregistrements vidéo 30 minutes avant et après l’injection des médicaments. Un accéléromètre a été utilisé pour évaluer les «numérations de l’activité totale» (NAT) comme données de référence et après le traitement. Les notes d’excitation après le traitement étaient significativement supérieures pour M et MA comparativement aux données de référence, M et MM comparativement à S et M comparativement à MA. Les paramètres comportementaux ont montré des proportions significativement supérieures de «va-et-vient» après le traitement dans tous les groupes qui avaient reçu midazolam et une «agitation», de «mastication et léchage» et de «reniflement» dans M. Aucune différence significative n’a été constatée pour NAT aux données de référence et après le traitement. Les changements comportementaux paradoxes induits par le midazolam (excitation, halètement, va-et-vient, agitation, lèchage et mastication et vocalisation) n’ont pas été prévenus par l’acépromazine ni la méthadone chez les chiens en santé.(Traduit par Isabelle Vallières).

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Figures

Figure 1
Figure 1
A — Schematic drawing depicting the study kennel (1 — entrance; 2 — individual; 3 — barricade; 4 — video camera) used to evaluate behavioral parameters of the dogs in the study. B — Photograph of the view obtained from the video recording of a dog during the acclimation period prior to the recording of behavioral parameters.
Figure 2
Figure 2
Proportion of restlessness manifestations (in percentage) that were present (black bars) or absent (white bars), observed by 2 blinded investigators from the evaluation of 2-minute long videos of dogs receiving midazolam (A; group M; n = 4), midazolam and methadone (B; group MM; n = 5), midazolam and acepromazine (C; group MA; n = 5), and saline (D; group S; n = 5), all IM, obtained 20 and 10 min prior (Pre10 and Pre20, respectively) and 10, 20, and 30 min after (Pst10, Pst20, and Pst30, respectively) drug administration. a, b, and * — significantly different (i.e., P < 0.05) from values obtained at Pre10 and Pre20 within treatment group and with group S at the evaluated time point, respectively, by means of Chi-squared tests.
Figure 3
Figure 3
Proportion of pacing manifestations (in percentage) that were present (black bars) or absent (white bars), observed by 2 blinded investigators from the evaluation of 2-minute long videos of dogs receiving midazolam (A; group M; n = 4), midazolam and methadone (B; group MM; n = 5), midazolam and acepromazine (C; group MA; n = 5) and saline (D; group S; n = 5), all IM, obtained 20 and 10 min prior (Pre10 and Pre20, respectively) and 10, 20, and 30 min after (Pst10, Pst20, and Pst30, respectively) drug administration. a, b, and * — significantly different (i.e., P < 0.05) from values obtained at Pre10 and Pre20 within treatment group and with group S at the evaluated time point, respectively, by means of Chi-squared tests.
Figure 4
Figure 4
Proportion of vocalization events (in percentage) that were present (black bars) or absent (white bars) observed by 2 blinded investigators from the evaluation of 2-minute long videos of dogs receiving midazolam (A; group M; n = 4), midazolam and methadone (B; group MM; n = 5), midazolam and acepromazine (C; group MA; n = 5) and saline (D; group S; n = 5), all IM, obtained 20 and 10 min prior (Pre10 and Pre20, respectively) and 10, 20, and 30 min after (Pst10, Pst20, and Pst30, respectively) drug administration. b and * — significantly different (i.e., P < 0.05) from values obtained at Pre20 within the same group and with group S at the evaluated time point, respectively, by means of Chi-squared tests.
Figure 5
Figure 5
Proportion of chewing/licking events (in percentage) that were present (black bars) or absent (white bars) observed by 2 blinded investigators from the evaluation of 2-minute long videos of dogs receiving midazolam (A; group M; n = 4), midazolam and methadone (B; group MM; n = 5), midazolam and acepromazine (C; group MA; n = 5) and saline (D; group S; n = 5), all IM, obtained 20 and 10 min prior (Pre10 and Pre20, respectively) and 10, 20, and 30 min after (Pst10, Pst20, and Pst30, respectively) drug administration. a, b, and * — significantly different (i.e., P < 0.05) from values obtained at Pre10 and Pre20 within treatment group and with group S at the evaluated time point, respectively, by means of Chi-squared tests.
Figure 6
Figure 6
Proportion of sniffing manifestations (in percentage) that were present (black bars) or absent (white bars) observed by 2 blinded investigators from the evaluation of 2-minute long videos of dogs receiving midazolam (A; group M; n = 4), midazolam and methadone (B; group MM; n = 5), midazolam and acepromazine (C; group MA; n = 5) and saline (D; group S; n = 5), all IM, obtained 20 and 10 min prior (Pre10 and Pre20, respectively) and 10, 20, and 30 min after (Pst10, Pst20, and Pst30, respectively) drug administration. a, b, and * — significantly different (i.e., P < 0.05) from values obtained at Pre10 and Pre20 within treatment group and with group S at the evaluated time point, respectively, by means of Chi-squared tests.
Figure 7
Figure 7
Proportion of panting events (in percentage) that were present (black bars) or absent (white bars) observed by 2 blinded investigators from the evaluation of 2-minute long videos of dogs receiving midazolam (A; Group M; n = 4), midazolam and methadone (B; Group MM; n = 5), midazolam and acepromazine (C; Group MA; n = 5) and saline (D; Group S n = 5), all IM, obtained 20 and 10 min prior (Pre10 and Pre20, respectively) and 10, 20, and 30 min after (Pst10, Pst20, and Pst30, respectively) drug administration. * — significantly different (i.e., P < 0.05) from values obtained in group S at the evaluated time point by means of Chi-squared tests.
Figure 8
Figure 8
Box-plots displaying the median or 50th percentile, the 25th percentile (lower box), the 75th percentile (upper box), the interquartile ranges (whiskers) and outliers (circles) of excitation scores (0 — no excitement to 3 — severe excitement) over time (Pre10 and Pre20, 10 and 20 min after commencing experiments, respectively; Pst10, Pst20, and Pst30, 10, 20, and 30 min after treatment, respectively) of dogs (n = 5) receiving midazolam 0.25 mg/kg (A — group M), midazolam 0.25 mg/kg BW together with methadone 0.75 mg/kg BW (B — group MM), midazolam 0.25 mg/kg BW together with acepromazine 0.03 mg/kg BW (C — group MA) and saline 0.125 mL/kg BW (D — group S); all IM. * — significantly different (i.e., P < 0.025) from values obtained at Pre10 and Pre20 (a and b, respectively) within the same group and from values obtained in groups MA and S (# and *, respectively) at the evaluated time point, by means of Kruskal-Wallis one-way ANOVA on ranks tests and Bonferroni corrections.
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