Accepted Manuscript

Comparison of Sedation in Dogs: Methadone or Butorphanol in Combination with

Dexmedetomidine Intravenously

Toby Trimble, Rebecca J. Bhalla, Elizabeth A. Leece

PII: S1467-2987(18)30096-5
DOI: 10.1016/j.vaa.2018.03.008
Reference: VAA 261

To appear in: Veterinary Anaesthesia and Analgesia

Received Date: 16 November 2017

Revised Date: 5 March 2018
Accepted Date: 26 March 2018

Please cite this article as: Trimble T, Bhalla RJ, Leece EA, Comparison of Sedation in Dogs: Methadone
or Butorphanol in Combination with Dexmedetomidine Intravenously, Veterinary Anaesthesia and
Analgesia (2018), doi: 10.1016/j.vaa.2018.03.008.

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 ACCEPTED
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Title Comparison of Sedation in Dogs: Methadone or Butorphanol in Combination with Dexmedetomidine Intravenously

Running Title Sedation with methadone or butorphanol and dexmdt

Authors Toby Trimblea, 1Rebecca J Bhallaa, 2Elizabeth A Leeceb

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Author affiliation

a
Dick White Referrals, Six Mile Bottom, Cambridgeshire, CB8 0UH, UK

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b
Northwest Veterinary Specialists, Sutton Weaver, Cheshire, WA7 3FW, UK

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Primary author and correspondence

Toby Trimble, Small Animal Hospital, School of Veterinary Medicine, University of Glasgow, 464 Bearsden Road, Glasgow, G61 1QH,

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UK
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Email: t.trimble.1@research.gla.ac.uk

Tel: +44 (0) 7875 49628

Fax: +44 (0) 141 330 3663

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Author’s contributions

TT: Study design, data collection, data interpretation, statistical analysis and preparation of manuscript
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RB: Date collection and data interpretation and preparation of manuscript

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EL: Study design, data collection, data interpretation, statistical analysis and preparation of manuscript

Acknowledgements

The authors wish to thank Tammy Robinson and the anaesthesia staff at Dick White Referrals for their help with this study

Conflict of interest statement

The authors declare no conflict of interest

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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Abstract

Word count: 293 words

1 Objective Opioids can be combined with alpha-2-adrenoreceptor agonists to sedate

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2 dogs for radiography. The study investigated the sedative effects of methadone or

3 butorphanol in combination with dexmedetomidine in dogs undergoing stifle

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4 radiography.

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6 Study design Prospective, blinded, randomized, clinical trial

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8 Animals A total of 52 healthy dogs requiring sedation for stifle radiography were

9 enrolled
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11 Method Dogs were assessed for body condition (BCS), temperament and pain using the
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12 short-form composite measure pain scale (CMPS-SF). Dogs were randomized to receive
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13 methadone 0.2 mg kg-1 (group M) or butorphanol 0.2 mg kg-1 (group B) in combination

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14 with dexmedetomidine 2 mcg kg-1 intravenously. Sedation was assessed using a

15 numerical descriptive score, 0 (no sedation) -11 (greatest sedation), before

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16 administration and at 5, 10, 15 and 20 minutes by one blinded assessor. Onset signs of
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17 sedation, pulse rate and respiratory rates were recorded. Positioning for radiography was

18 attempted at 5 minutes. If positioning was not possible at 10 minutes, dexmedetomidine

19 2 mcg kg-1 was administered intravenously, the dog recorded as failed sedation, and

20 withdrawn from further analysis. Following normality testing, data were assessed using

21 Student t-test, Mann-Whitney test, 2 way-ANOVA and Fisher's exact test for failed
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22 sedations. Results are reported as mean ± standard deviation. Statistical significance

23 was set at p< 0.05.

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24 Results Groups were similar for sex, age, weight, BCS, temperament, and CMPS-SF.

25 The onset of sedation was faster in group B than group M (p = 0.048). Sedation scores

26 were higher in group B at 10 minutes compared to group M (p = 0.003). Failed sedation

27 occurred in twelve dogs in group M and two in group B (p = 0.002). Pulse rates were

28 lower in group B at 5 and 10 minutes (p = 0.002)

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30 Conclusion and clinical relevance Intravenous butorphanol provides more effective

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31 sedation at 10 minutes than methadone, in combination with dexmedetomidine.

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33 Keywords sedation, dexmedetomidine, methadone, butorphanol, opioid, canine

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34 Introduction

35 Sedation is required to facilitate positioning for radiography in companion animal

36 practice. Alpha-2-adrenoreceptor agonists in combination with an opioid are commonly

37 employed to achieve sedation. Methadone is a synthetic opioid with a high affinity for

38 the mu opioid receptor (MOP) and an antagonist at the N-methyl-D-aspartate (NMDA)

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39 receptor (Hall et al. 2014). It provides good analgesia and causes dose-dependent

40 sedation in dogs (Menegheti et al. 2014). Butorphanol is a synthetic opioid that acts as a

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41 full agonist of the kappa opioid receptor (KOP) and a partial antagonist of MOP

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42 (Maddison & Page 2008). It produces mild to moderate sedation in dogs, but only mild

43 analgesia lasting a short duration (Trim 1983). Methadone may offer advantages over

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44 butorphanol for sedation in dogs due to its better analgesic properties. When used in
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45 combination with acepromazine 0.05 mg kg-1 in dogs, methadone 0.5 mg kg-1 has been

46 shown to provide superior sedation when compared to butorphanol 0.15 mg kg-1 mg

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47 intravenously (IV) (Monteiro et al. 2009).

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49 We hypothesized that methadone in combination with dexmedetomidine would provide

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50 more reliable sedation than butorphanol and dexmedetomidine. The aim of the study
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51 was to compare the sedative effects of these combinations IV in dogs undergoing stifle

52 radiography.
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53 Materials and methods

54 Healthy dogs [American Society of Anesthesiologists (ASA) physical status I/II]

55 admitted for evaluation of stifle lameness and scheduled to undergo stifle radiographs

56 were enrolled into the study with prior informed owner consent. Ethical Review

57 Committee approval from the University of Nottingham School of Veterinary Medicine

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58 and Science was obtained before data collection: reference number 1163 140519. The

59 study design was prospective, blinded and randomized. The study was conducted

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60 between August and November 2014 at Dick White Referrals in Newmarket, UK.

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61 Exclusion criteria included evidence of cardiopulmonary disease, temperament

62 precluding the placement of an IV cannula dogs receiving concurrent medication except

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63 for non-steroidal anti-inflammatory drugs (NSAIDs) or aged less than 6 months. A pilot
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64 study was performed to establish that a sample size of twenty-five dogs in each group

65 would have an 80% power to detect a difference in sedation score of 1.94 at 10 minutes
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66 with a significance level of 0.05; we therefore aimed for 26 in each group to account for

67 potential drop-outs. Dogs were enrolled in the study and randomized into one of two
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68 groups, twenty-six in group M and twenty-six in group B. Randomization was achieved

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69 by computer-generated random sequence using Graphpad (GraphPad Software, Inc. La

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70 Jolla, CA, USA) by TT. Dogs had water available immediately prior to sedation but

71 were fasted on the morning of sedation.

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72 An IV cannula was placed in the left or right cephalic vein. Prior to sedation,

73 temperament was assessed using a score ranging from 0 (very relaxed) to 4 (very

74 excitable/nervous) (Maddern et al. 2010), see Appendix A. Pain was assessed using the

75 short-form composite measure pain scale (CMPS-SF) (Reid et al. 2007), body condition

76 score (BCS) assessed using the 1-9 scale (Laflamme, 1997) and body weight was

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77 recorded. Pulse rate was recorded by palpation of the dorsal pedal artery and respiratory

78 frequency (fR) was recorded by observation of chest wall excursion.

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79

Methadone 0.2 mg kg-1 IV (Comfortan 1% solution; Dechra Veterinary Products

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81 Limited, UK) in combination with dexmedetomidine 2 mcg kg-1 IV (Dexdomitor; Orion

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82 Pharma, Finland) was administered to dogs in group M. Dogs in group B received
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83 butorphanol 0.2 mg kg-1 (Alvegesic; Dechra Veterinary Products Limited, UK) in

84 combination with dexmedetomidine 2 mcg kg-1 IV. All combinations were mixed in the
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85 same syringe and the volume made up to 0.1 ml kg-1 with 0.9% saline (Aquapharm 1;

86 Animalcare, Limited, UK). Intravenous cannulas were flushed with saline prior to
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87 administration of sedative drugs. Sedative combinations were administered over 30

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88 seconds. Doses of butorphanol, methadone, and dexmedetomidine used were

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89 determined by the normal protocol used at the practice for sedation for radiography.
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90 A numerical descriptive scale (NDS) modified from Gurney et al. (2009) was used to

91 assess sedation (see Appendix B). Categories included spontaneous posture, response to

92 sound, resistance to lateral recumbency and overall appearance. Drugs were

93 administered to dogs in the radiography room with controlled levels of light, sound and

94 only an anaesthetist and a radiographer present. The same radiographer acted as the

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95 assessor for all patients and was unaware of the sedative combination administered. The

96 anaesthetist administering the sedative combination was aware of treatment group,

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97 however this was not divulged to maintain blinding. Time of onset of signs of sedation,

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98 to the nearest minute, denoted by muscle relaxation and visible drooping of the head

99 and time at which positioning was possible were recorded. Positioning for radiography

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100 was first attempted after 5 minutes, after sedation had been assessed. Positioning
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101 followed a standard protocol with views in lateral, followed by sternal recumbency,

102 followed by the other lateral recumbency, with the affected limb imaged first. Sedation
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103 and positioning were assessed by the same person who was unaware of treatment group.

104 Pulse rate (PR) by palpation of the dorsal metatarsal artery and respiratory frequency
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105 (fR) were also recorded at 0, 5, 10, 15 and 20 minutes. Respiratory frequency was
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106 recorded up to 80 breaths minute-1; if more than this it was deemed inaccurate to count
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107 so ‘panting’ was recorded.

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108 If positioning for radiography was not possible after 10 minutes, additional sedation

109 (dexmedetomidine 2 mcg kg-1 IV) was administered and the dog removed from

110 subsequent analysis and recorded as failed sedation. Sedation was assessed again 5

111 minutes after the additional dexmedetomidine had been administered and was recorded

112 as being successful or unsuccessful. At the end of the procedure, an intramuscular (IM)

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113 injection of atipamezole (Antisedan 0.5% solution; Orion Pharma) 20 mcg kg-1 was

114 administered if the patient was not able to walk unassisted. Any adverse events

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115 occurring during data collection period were recorded. Data were recorded on a paper

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116 form then entered into a Microsoft Excel spreadsheet (Microsoft Corporation, WA,

117 USA). Data analysis was carried out using Prism (GraphPad Software, Inc., CA, USA).

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118 Data were assessed for normal distribution using D’Agostino and Pearson omnibus
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119 normality test; normally distributed data were analysed using student t-test and data not

120 normally distributed analysed using Mann-Whitney U test. The PR and fR were analysed
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121 using two-way analysis of variance (ANOVA). The Fisher’s exact test was used to

122 assess failed sedations. Results are reported are mean ± standard deviation (SD) and
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123 median (range) where appropriate. The level of significance was set at p < 0.05.
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124 Results

125 A total of 52 healthy dogs requiring sedation for stifle radiography were enrolled, no

126 owners declined to enrol their animals in the study. Groups were similar for sex, age,

127 body mass, temperament score, BCS, CMPS-SF, or current NSAIDs treatment (Table

128 1). No adverse effects were observed after administration of either sedative

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129 combination.

130 Sedation results are displayed in Table 2. The time of onset of sedation was 3 (1-10)

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131 minutes for group M and 2 (1-4) minutes for group B (p = 0.049). Sedation scores were

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132 similar at 5 minutes. At 10 minutes, sedation scores were higher in group B [10 (8 –

133 11)] compared to group M [5.5 (3–9)] (p = 0.003). Failed sedation at 10 minutes and

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134 inability to position for radiography was observed more frequently in group M [46 %
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135 (12/26 dogs)] compared with group B [8 % (2/26 dogs)] (p = 0.002). After

136 administration of additional sedation, all but one dog (in group M) sedated sufficiently
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137 to facilitate positioning. Failed sedations were removed from further analysis. Sedation

138 scores between dogs were similar between the groups of remaining dogs at 15 and 20
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139 minutes. Of these dogs, three out of fourteen from group M and seven out of twenty-
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140 four from group B received atipamezole at the end of the procedure.
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142 The fR was recorded for both groups; however, interpretation was not possible because
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143 of the large number of dogs (32/52) recorded as panting (fR > 80 breaths minute-1) prior
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144 to administration of sedation. After sedation fR was similar in both groups. The PR were

145 lower in group B compared to group M at 5 and 10 minutes (Fig. 1) p < 0.05.

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146 Discussion

147 Degree of sedation at 10 minutes was greater using butorphanol in combination with

148 dexmedetomidine IV, compared to methadone. Failed sedation, where positioning

149 radiography was not possible, was observed more frequently in group M than group B.

150 This may be due to differences in sedative effects of the drug, the dose of drug

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151 administered or onset time of sedation.

152 Sedative effects are determined by the efficacy and potency of drugs. The two opioids

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153 tested in this study have different effects on MOP and KOP receptors, which explain

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154 their sedative properties. Methadone is a full MOP agonist, acting on central and spinal

155 MOP receptors, while butorphanol is a full KOP agonist and MOP antagonist

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156 (Maddison & Page 2008). In humans, sedation is generally considered as a side effect
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157 in the use of opioids. At analgesic doses, the MOP agonist morphine causes respiratory

158 depression due to decreased sensitivity of central medullary chemoreceptors to carbon

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159 dioxide. In contrast, KOP agonists are known to produce sedation without significant

160 depression of respiratory frequency or heart rate (McDonald & Lambert 2011). No
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161 studies have directly compared the sedative efficacy of methadone and butorphanol
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162 used alone in dogs, but it is possible that actions on the different opioid receptors results
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163 in different degrees of sedation. The magnitude of sedative response can also be dose-

164 dependent. Opioid potency is defined as the relative potency of an opioid compared to
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165 morphine for analgesic effect. Methadone has a relative potency to morphine of one to
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166 one and a half, and butorphanol is two to five times as potent as morphine (Epstein

167 2015). One limitation of the present study is the doses of methadone and butorphanol

168 are not equipotent. If a higher dose of methadone had been used it may have provided

169 similar sedation to that of butorphanol, as found by Monteiro et al. (2008). The dose of

170 methadone selected for the present study of 0.2 mg kg-1 was chosen as it is routinely

171 used for analgesia in the hospital, but it is lower than the licensed dose (0.5-1 mg kg-1).

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172 Lower doses of 0.1 mg kg-1 [Raekallio et al. (2009)] to 0.4 mg kg-1 [Pughibet et al.

173 (2015)] have been reported to be effective in dogs.

174 The differences observed in sedation quality may also be because of differences in the

175 time to maximal sedation since patients were allowed 10 minutes to become sedated

176 enough for radiographs, as is suitable for clinical practice. Onset of sedation is

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177 determined by route of administration and pKa of the individual drug. After IV

178 administration, maximal plasma concentration is rapidly achieved, however, the effector

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179 site concentration may lag behind this. Onset of CNS effects of opioids can be assessed

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180 using electroencephalography and pupillometry in humans and compared to plasma

181 concentrations of the measured drug. The time between effector site and plasma

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182 concentration gives an indication of equilibration time. For highly lipophilic opioids,
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183 such as fentanyl, equilibration occurs rapidly. In drugs with lower lipophilicity such as

184 morphine, this equilibration can take hours after reaching maximal plasma
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185 concentrations (Palmer & Royal 2015). This effect may explain the some of the

186 differences in onset time between different opioids. At the time of writing this effect has
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187 not been demonstrated with methadone or butorphanol, however, we postulate a similar
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188 effect may occur with butorphanol leading to the differences time of onset on sedation.
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189 The pKa of a chemical compound is the pH where the ionized and un-ionized forms are

190 in equilibrium; the un-ionized form of the drug is able to diffuse across the cell
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191 membrane. Drugs with a pKa closer to physiological pH have a higher proportion
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192 present in their un-ionized form and are thus able to cross the cell membrane more

193 quickly than those with a higher pKa. Butorphanol has a pKa of 8.6 and methadone a

194 pKa of 9.2 (Fredheim et al. 2008; KuKanich & Papich 2013), which may explain the

195 faster onset of action of butorphanol seen in this study. If sedation was insufficient after

196 10 minutes, dogs were withdrawn from the study and further sedation administered. A

197 possible limitation of the study may be that the peak effect of methadone may not have

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198 been reached during the initial 10 minutes, after which scoring occurred prior to

199 additional sedation being administered. During the design of the study, 10 minutes was

200 chosen since the onset of intravenous sedation should be rapid in the clinical situation

201 and was deemed sufficient to encompass the peak effect of both methadone and

202 butorphanol. Ingvast-Larsson et al. (2010) demonstrated peak plasma concentration is

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203 reached within 10 minutes, followed by a fast decline when administering methadone

204 0.4 mg kg-1 IV to dogs. However, time to peak effect following IV administration for

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205 either of the drugs compared in this study is not available. Kuusela et al. (2000)

demonstrated IV administration of dexmedetomidine 0.01 mg kg-1 alone reached peak

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207 effect for sedation and analgesia at 10 minutes. It is possible that if allowed further time,

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208 further sedation could have developed but this was not practical in the clinical setting.
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209 Assessment of sedation has been performed using both numeric descriptive scales

210 (NDS) and visual analogue scales (VAS). Previous work looking at sedation in dogs
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211 uses several different descriptive scales. (Gurney et al. 2009; Leppänen et al. 2006;

212 Monteiro et al. 2008; Valverde et al. 2004) Currently no validated scoring systems for
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213 sedation are available; making comparisons of different studies difficult especially when
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214 different end-points are employed. The degree of sedation may not be the only indicator
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215 of the suitability of a sedation protocol; in this study ability to perform restraint for

216 radiography was set as the clinical endpoint in addition to sedation scoring. In the
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217 current study, some dogs appeared to be moderately sedated but still resisted being
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218 positioned for radiography. Puighibet et al. (2015) found no significant difference when

219 comparing methadone (0.4 mg kg-1) to butorphanol (0.4 mg kg-1) in combination with

220 medetomidine (2.5 mcg kg-1) administered IM. These dogs were visually observed for

221 30 minutes and then an IV cannula was placed. Sedation was scored using a numeric

222 descriptive score and withdrawal reflex to noxious stimulus. The differences in results

223 in our study may reflect the differences in opioid dose, methodology of sedation

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224 scoring, use of a different alpha-2-adrenoreceptor agonist or the difference in peak

225 effect between IV and IM administration.

226 The study design was intended to minimise variation between animals. All radiographs

227 were carried out in the same room with the same lighting and sound conditions and a

228 maximum of two people present at all times. Due to superior analgesia using methadone

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229 compared to butorphanol in dogs, it was felt that methadone may improve the level of

230 sedation for stifle radiography. Pain scores in all animals in group M were low (0 [0-3])

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231 and low to moderate in group B [1 (0-7)], almost all being below the threshold

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232 suggested analgesia administration (Reid et al. 2007). For this reason, the conclusions of

233 this study can only be considered to apply to non-painful or moderately painful animals.

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234 Future studies are warranted to investigate if similar findings would be observed in
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235 painful animals.

236 Pulse rates were lower at 5 and 10 minutes in the butorphanol group. Alpha-2-
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237 adrenoreceptor agonists have been shown to decrease heart rate due to reflex

238 bradycardia associated with increased systemic vascular resistance and reduced
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239 sympathetic tone (Gómez-Villamandos et al. 2006). Bradycardia has been reported
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240 following treatment with methadone (Menegheti et al. 2014) and butorphanol (Monteiro
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241 et al. 2008; Trim 1983). As with other opioids, this can be through a centrally mediated

242 increase in vagal tone, or depressant effect on the sinoatrial and atrioventricular nodes
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243 (Hall et al. 2014). Unfortunately, other cardiovascular parameters were not recorded in
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244 this study and so it is difficult to assess any clinical significance of these findings.

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246 The low dose of dexmedetomidine 2 mcg kg-1 used in this study has been used

247 successfully at our clinic in combination with butorphanol prior to the licensing of

248 methadone, and we wanted to compare the new drug in the same clinical context. A

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249 higher dose of dexmedetomidine may have masked any differences between the two

250 opioids because of dose-dependent sedative effects.

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252 Conclusion

253 Intravenous butorphanol provides more effective sedation at 10 minutes than

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254 methadone, in combination with dexmedetomidine, for positioning of dogs undergoing

255 stifle radiography.

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256 References
257 Epstein ME (2015) Chapter 9 - Opioids, in: Handbook of Veterinary Pain Management
258 (3rd Edition), Mosby, St. Louis, USA pp. 161–195.
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260 Fredheim O, Moksnes K, Borchgrevink PC et al. (2008) Clinical pharmacology of
261 methadone for pain. Acta Anaesthesiol. Scand. 52, 879–889.
262

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263 Gómez-Villamandos RJ, Palacios C, Benítez A et al. (2006) Dexmedetomidine or
264 medetomidine premedication before propofol–desflurane anaesthesia in dogs. J. Vet.

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265 Pharmacol. Ther. 29, 157–163.
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267 Gurney M, Cripps P, Mosing M (2009) Subcutaneous pre-anaesthetic medication with
268 acepromazine–buprenorphine is effective as and less painful than the intramuscular

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269 route. J. Small Anim. Pract. 50, 474–477.
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271 Hall LW, Clarke KW, Trim CM (2014) General pharmacology of the injectable agents
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273 pp. 135–154.

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275 KuKanich B, Papich M (2013) Opioid Analgesic Drugs, in: Veterinary Pharmacology
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278 Laflamme D (1997) Development and validation of a body condition score system for
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279 dogs. Canine Pract. 22, 10-15.

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281 Leppänen MK, McKusick BC, Granholm MM et al. (2006) Clinical efficacy and safety
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283 radiography. J. Small Anim. Pract. 47, 663–669.

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285 Maddern K, Adams VJ, Hill NA et al. (2010) Alfaxalone induction dose following
286 administration of medetomidine and butorphanol in the dog. Vet. Anaesth. Analg. 37,
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289 Maddison JE, Page SW (2008) Small Animal Clinical Pharmacology (2nd Edition),
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291 McDonald J, Lambert DG (2011) Opioid mechanisms and opioid drugs, Anaesth.
292 Intensive Care Med., Pain / Pharmacology 12, 31–35.
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294 Menegheti TM, Wagatsuma JT, Pacheco AD et al. (2014) Electrocardiographic
295 evaluation of the degree of sedation and the isolated use of methadone in healthy dogs.
296 Vet. Anaesth. Analg. 41, 97–104.
297

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298 Monteiro ER, Figuero CDN, Choma JC et al. (2008) Effects of methadone, alone or in
299 combination with acepromazine or xylazine, on sedation and physiologic values in

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300 dogs. Vet. Anaesth. Analg. 35, 519–527.
301

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302 Monteiro ER, Junior AR, Assis HMQ, et al. (2009) Comparative study on the sedative
303 effects of morphine, methadone, butorphanol or tramadol, in combination with
304 acepromazine, in dogs. Vet. Anaesth. Analg. 36, 25–33.

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305
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306 Palmer P, Royal M (2015). Patient-Controlled analgesia: The Importance of Effector
307 Site Pharmacokinetics, in: Essentials of Pharmacology for Anesthesia, Pain Medicine,
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308 and Critical Care. Springer, New York, pp. 837–846.

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310 Reid J, Nolan A, Hughes J et al. (2007) Development of the short-form Glasgow
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311 Composite Measure Pain Scale (CMPS-SF) and derivation of an analgesic intervention
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312 score. Anim. Welf. 16, 97–104.

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314 Trim C (1983) Cardiopulmonary effects of butorphanol tartrate in dogs. Am. J. Vet.
315 Res. 44, 329–331.
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317 Valverde A, Cantwell S, Hernández J, et al. (2004) Effects of acepromazine on the

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318 incidence of vomiting associated with opioid administration in dogs. Vet. Anaesth.
319 Analg. 31, 40–45.

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320 Figure Legends

321 Figure 1 Comparison of post treatment pulse rate for dogs sedated with methadone

322 (group M) and butorphanol (group B) in combination with dexmedetomidine, showing

323 significantly higher pulse rate at 5 and 10 minutes after administration of sedation

324 (mean ± SD). For group details see Table 1.

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325 *p < 0.05

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331 Appendix A Temperament score (Maddern et al. 2010)

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Criteria Score
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Calm friendly dog 1

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Mildly excited and/or nervous 2

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Moderately excited and/or nervous 3

Very excited or nervous 4

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Highest possible score 4 Total:

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335 Appendix B Composite Simple Descriptive Sedation Score, modified from Gurney et

336 al. 2009.

Criteria Score

Spontaneous posture Standing 0

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Sternally recumbent 1

Laterally recumbent 2

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Response to sound (handclap) Body movement 0

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Head movement 1

Ear twitch 2

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Resistance to lateral recumbency Full (stands) 0
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Moderate restraint required 1

Mild restraint required 2

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No resistance 3
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Overall appearance No sedation apparent 0

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Mild sedation 1

Moderate sedation 2
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Well sedated 3
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Total possible sedation score 11 Total:

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Table 1 Details of 52 dogs sedated with either methadone (0.2 mg kg-1) intravenously (IV) (Group M) or butorphanol (0.2 mg kg-1) IV

(Group B) in combination with dexmedetomidine (2 mcg kg-1) IV

Group M Group B P value

16 male 10 female 13 male 13 female 0.29

Sex (n)

Age (months) 71 (8-132) n = 26 55.5 (10-131) n = 26 0.71

Body mass (kg) 20 ± 12.9 n = 26 23.5 ± 11.6 n = 26 0.31

PT
Temperament score 3 (1-4) n = 26 2.5 (1-4) n = 26 0.93

BCS 6 (4-8) n = 26 5 (3-9) n = 26 0.25

RI
CMPS-SF 0 (0-3) n = 26 1 (0-7) n = 26 0.09

Current NSAID treatment 6 n = 26 4 n = 26 0.73

SC
BCS, body condition score; CMPS-SF, short form composite measure pain scale; NSAID,

non-steroidal anti-inflammatory drug

U
AN
M
D
TE
C EP
AC

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1 Table 2 Onset of sedation, failed sedation and sedation scores for dogs sedated with

2 methadone (group M) and butorphanol (group B) in combination with dexmedetomidine.

3 Minimum sedation score zero, maximum 11. For group details refer to Table 1

Group M Group B P value

PT
Onset of sedation 3 (1-10) n = 26 2 (1-4) n = 253 0.049

(minutes)

RI
Failed sedation (n) 12/26 2/26 0.002

SC
Sedation score 5 minutes 5.5 (0-11) n = 26 7 (1-11) n = 26 0.31

Sedation score 10 minutes 5.5 (1-11) n = 26 10 (2-11) n = 26 0.003

Sedation score 15 minutes 8.5 (2-11)

Un = 14 10 (2-11) n = 24 0.12
AN
Sedation score 20 minutes 8 (3-11) n = 14 10.5 (3-11) n = 24 0.16
M
D
TE
C EP
AC

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PT
RI
U SC
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C
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