A comparison of acepromazine-buprenorphine and medetomidine-buprenorphine for preanesthetic medication of dogs

Nicola J. GrintDepartment of Veterinary Clinical Science, School of Veterinary Science, University of Liverpool, Leahurst, Neston, Wirral, CH46 7TE, England.

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Briony AldersonDepartment of Veterinary Clinical Science, School of Veterinary Science, University of Liverpool, Leahurst, Neston, Wirral, CH46 7TE, England.

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Alexandra H. A. DugdaleDepartment of Veterinary Clinical Science, School of Veterinary Science, University of Liverpool, Leahurst, Neston, Wirral, CH46 7TE, England.

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Abstract

Objective—To assess sedative and cardiopulmonary effects of premedication with a medetomidine-buprenorphine or acepromazine-buprenorphine combination in dogs anesthetized with propofol and isoflurane.

Design—Randomized controlled clinical trial.

Animals—90 dogs undergoing routine surgical and diagnostic procedures.

Procedures—Dogs were randomly assigned to 1 of 3 premedication groups: group 1 (acepromazine, 0.03 mg/kg [0.014 mg/lb], IM; buprenorphine, 0.02 mg/kg [0.009 mg/lb], IM), 2 (medetomidine, 5 μg/kg [2.3 μg/lb], IM; buprenorphine, 0.02 mg/kg, IM), or 3 (medetomidine, 10 μg/kg [4.5 μg/lb], IM; buprenorphine, 0.02 mg/kg, IM). Anesthesia was induced with propofol and maintained with isoflurane in oxygen. Simple descriptive scores for sedation were assigned 15 minutes (groups 2 and 3) and 30 minutes (group 1) after premedication administration. Basic cardiopulmonary data were recorded throughout the anesthetic period. Times to recovery from anesthesia were recorded.

Results—Sedation scores did not differ significantly among groups. Mean and diastolic blood pressures were significantly lower and heart rate was significantly higher in group 1 than in the other groups. Mean end-tidal partial pressure of CO2 was significantly lower and respiratory rate was significantly higher in group 1 than in the other groups. There were no significant differences in anesthetic recovery times between groups.

Conclusions and Clinical Relevance—Results suggested that either acepromazine or medetomidine could be used in combination with buprenorphine for premedication of dogs anesthetized with propofol and isoflurane for routine surgical and diagnostic procedures. Arterial blood pressure was better maintained with the medetomidine-buprenorphine combinations, but tissue perfusion was not investigated.

Abstract

Objective—To assess sedative and cardiopulmonary effects of premedication with a medetomidine-buprenorphine or acepromazine-buprenorphine combination in dogs anesthetized with propofol and isoflurane.

Design—Randomized controlled clinical trial.

Animals—90 dogs undergoing routine surgical and diagnostic procedures.

Procedures—Dogs were randomly assigned to 1 of 3 premedication groups: group 1 (acepromazine, 0.03 mg/kg [0.014 mg/lb], IM; buprenorphine, 0.02 mg/kg [0.009 mg/lb], IM), 2 (medetomidine, 5 μg/kg [2.3 μg/lb], IM; buprenorphine, 0.02 mg/kg, IM), or 3 (medetomidine, 10 μg/kg [4.5 μg/lb], IM; buprenorphine, 0.02 mg/kg, IM). Anesthesia was induced with propofol and maintained with isoflurane in oxygen. Simple descriptive scores for sedation were assigned 15 minutes (groups 2 and 3) and 30 minutes (group 1) after premedication administration. Basic cardiopulmonary data were recorded throughout the anesthetic period. Times to recovery from anesthesia were recorded.

Results—Sedation scores did not differ significantly among groups. Mean and diastolic blood pressures were significantly lower and heart rate was significantly higher in group 1 than in the other groups. Mean end-tidal partial pressure of CO2 was significantly lower and respiratory rate was significantly higher in group 1 than in the other groups. There were no significant differences in anesthetic recovery times between groups.

Conclusions and Clinical Relevance—Results suggested that either acepromazine or medetomidine could be used in combination with buprenorphine for premedication of dogs anesthetized with propofol and isoflurane for routine surgical and diagnostic procedures. Arterial blood pressure was better maintained with the medetomidine-buprenorphine combinations, but tissue perfusion was not investigated.

Use of appropriate preanesthetic medications is an essential component of any anesthetic protocol. Ideal preanesthetic medications provide muscle relaxation, anxiolysis, and analgesia and reduce the doses of drugs required for induction and maintenance of anesthesia.

Medetomidine is an α2-adrenergic receptor agonist licensed for use in dogs in Europe and the United States that induces sedation,1 anxiolysis, and analgesia.2,3 However, the use of α2-adrenergic receptor agonists in veterinary practice has been associated with concerns related to the potential for adverse cardiovascular effects, such as severe bradycardia and low cardiac output.3

Acepromazine is also licensed for use in dogs in Europe and the United States and acts on a wide variety of receptors, including D2-dopaminergic receptors and histamine1 receptors, to induce sedation.4 However, acepromazine's antagonist effects on α1-adrenergic receptors may promote peripheral vasodilation, resulting in a decrease in arterial blood pressure and subsequent hypotension.5 A recent study6 of 117 small animal hospitals found that approximately 90% routinely used acepromazine in combination with an opioid for preanesthetic medication of dogs and cats and that approximately 10% used medetomidine in combination with some other drug for preanesthetic medication.

Both acepromazine and medetomidine act synergistically when administered with an opioid, producing a more profound effect in combination than the effect associated with either drug alone. Antinociceptive synergism between opioids and α2-adrenergic receptor agonists has been recognized7 and may result from the similar distribution of receptors in the CNS, such that binding of α2-adrenergic and μ-opioid receptor agonists results in activation of similar signal transduction systems.5 Buprenorphine is a partial μ-opioid receptor agonist that is licensed for use in dogs and is classified as a schedule III drug in the United States (schedule IV in some states). Although not as effective an analgesic as pure μ-opioid receptor agonists, it is popular in veterinary practice because of its long duration of action and moderate sedative effects and because there are slightly less stringent controls over its use, compared with schedule II opioid drugs such as morphine.

The present study was designed to assess the suitability of using medetomidine in combination with buprenorphine for preanesthetic medication of dogs undergoing routine surgical and diagnostic procedures. Specifically, the purpose of the study reported here was to assess the sedative and cardiopulmonary effects of premedication with medetomidine-buprenorphine or acepromazine-buprenorphine combinations in dogs anesthetized with propofol and isoflurane. Our hypotheses were that sedation would be greater and arterial blood pressure would be better maintained with use of the medetomidine-buprenorphine combinations, compared with use of the acepromazine-buprenorphine combination.

Materials and Methods

Dogs examined at the University of Liverpool's Small Animal Hospital between March 2004 and March 2006 and scheduled to undergo anesthesia for routine surgical or diagnostic procedures were enrolled in the study. Dogs were included only if they were classified as ASA status 1 (healthy) or 2 (mild systemic disease)8 and if they were scheduled to be anesthetized for a surgical or diagnostic procedure that involved only a mild to moderate stimulus (ie, neutering, arthroscopy, radiography, endoscopy, and other minor procedures). Owners of all dogs included in the study signed a consent form prior to enrollment. The study was conducted with the approval of an ethics committee of the University of Liverpool

Dogs were randomly assigned to 1 of 3 groups by use of a block randomization scheme and sealed envelopes. Prior to administration of any preanesthetic medications, a complete physical examination was performed on each dog, and a sedation score ranging from 0 to 20 was assigned. The sedation score was a composite simple descriptive score (Appendix); scoring criteria were adapted from systems used in 2 previous studies.9,10 A single individual (NG) who was unaware of premedications given to any individual dog in the study assigned all sedation scores for all dogs.

Dogs in group 1 received acepromazinea (0.03 mg/kg [0.014 mg/lb], IM) and buprenorphineb (0.02 mg/kg [0.009 mg/lb], IM). Dogs in group 2 received medetomidinec (5 μg/kg [2.3 μg/lb], IM) and buprenorphine (0.02 mg/kg, IM). Dogs in group 3 received medetomidine (10 μg/kg [4.5 μg/lb], IM) and buprenorphine (0.02 mg/kg, IM). In all instances, the 2 drugs were mixed in a single syringe, and the drug combination was injected into the cervical epaxial muscle group by a veterinarian or veterinary nurse.

After administration of preanesthetic medications, dogs were observed, and any adverse effects (eg, signs of pain on injection, vomiting, muscle twitching, urination, and defecation) were noted. After 15 minutes for groups 2 and 3 and after 30 minutes for group 1, respiratory rate, pulse rate, and sedation score were again determined and recorded. These times were chosen to reflect the peak sedative effects of the drugs.5

Immediately after this assessment and in accordance with routine clinical practice at our hospital, a catheter was aseptically inserted into a cephalic vein and secured in place, and anesthesia was induced by slow IV administration of propofold until the dog's jaw was relaxed and the tongue could be held without the dog retracting it. On the basis of previous studies,11–18 predicted dose requirements for groups 1, 2, and 3 were 4.5 mg/kg (2.0 mg/lb), 3 mg/kg (1.4 mg/lb), and 1.5 mg/kg (0.7 mg/lb), respectively. In accordance with these predicted doses, propofol was infused via a precision syringe drivere at a rate of 2.25 mg/kg/min (1.0 mg/lb/min) for dogs in group 1, 1.5 mg/kg/min (0.7 mg/lb/min) for dogs in group 2, and 0.75 mg/kg/min (0.34 mg/lb/min) for dogs in group 3.

Following orotracheal intubation, anesthesia was maintained with isofluranef administered in oxygen via a nonrebreathing system appropriate for the dog's weight (ie, a parallel Lack system for dogs weighing > 10 kg [22 lb] with fresh gas flow equivalent to minute ventilation [200 mL/kg/min] and a Jackson-Rees modified Ayre's T-piece for dogs weighing < 10 kg with fresh gas flow equivalent to at least twice minute ventilation). Vaporizer settings were altered as necessary to maintain an appropriate depth of anesthesia and were recorded every 5 minutes. An appropriate depth of anesthesia was considered to be present when there was no pedal withdrawal on application of a toe pinch, there was minimal hemodynamic response to surgical stimuli, the eyes were ventrally rotated, and the jaw was relaxed. End-tidal isoflurane concentrations were not measured. Vaporizer calibration was verified at the beginning, middle, and end of the study period. Hartmann's solutiong (10 mL/kg/h, IV) was administered throughout the anesthetic period. Additional analgesia was provided by the administration of carprofenh (4 mg/kg [1.8 mg/lb], IV) if required.

Oxygen saturation was measured with a pulse oximeter and lingual transmittance probe/End-tidal partial pressure of carbon dioxide was measured with a mainstream handheld capnograph.i Indirect blood pressure measurements were obtained oscillometricallyj from the dorsal pedal artery or the palmar carpal artery. Heart rate and respiratory rate were monitored by means of digital pulse palpation and observation of the reservoir bag of the anesthetic machine. All measurements were recorded just after anesthetic induction and then at 5-minute intervals throughout the anesthetic period. In dogs that developed hypotension (ie, mean arterial blood pressure < 60 mm Hg during at least 2 consecutive measurement times), the delivered percentage of isoflurane was decreased, the rate of IV fluid administration was increased, and, for dogs in groups 2 and 3, atipamezolek was administered to antagonize the effects of medetomidine. In dogs that developed bradycardia (ie, heart rate < 30 beats/min), atropinel was administered IV (group 1) or atipamezole was administered to antagonize the effects of medetomidine (groups 2 and 3).

At the end of the surgical or diagnostic procedure in each dog, isoflurane administration was discontinued. For dogs in groups 2 and 3, if the duration of anesthesia was < 120 minutes, atipamezole (group 2, 0.025 mg/kg [0.011 mg/lb], IM; group 3, 0.05 mg/kg [0.023 mg/lb], IM) was administered at the same time that isoflurane administration was discontinued. Dogs were monitored continuously during recovery from anesthesia. Times from discontinuation of isoflurane administration to tracheal extubation, movement into sternal recumbency, and standing and walking were recorded.

Statistical analysis—Power analysis indicated that 30 dogs would be required in each group to detect a 15-mm Hg difference in mean blood pressure between groups at an α value of 0.05 and 80% power. For each dog, mean values for heart rate, respiratory rate, Petco2, vaporizer setting, Spo2, and systolic, mean, and diastolic blood pressures for the entire anesthetic period were calculated. The lowest heart rate during the anesthetic period was also identified for each dog. Data were summarized as mean and SD if normally distributed and as median and IQR (ie, 25th to 75th percentile) if not normally distributed.

Differences in outcomes between the 3 groups were examined with the χ2 test for categorical variables, 1-way ANOVA for normally distributed continuous variables, and Kruskal-Wallis test of the equality of medians for nonnormally distributed continuous variables. When ANOVA was used, post hoc comparisons were performed with the Tukey test; when the Kruskal-Wallis test was used, post hoc comparisons were performed with the Mann-Whitney test. Values of P ≤ 0.05 were considered significant. All statistical analyses were performed with commercially available software packages.m,n

Results

Ninety dogs met the criteria for enrollment in the study, with 30 dogs included in each group. Data from 2 dogs in group 1 were lost and were not included in analyses. Success of the randomization scheme was examined by comparing age, weight, sex distribution, and ASA status distribution among groups (Table 1). There were no significant differences among groups with respect to any of these variables. Dogs underwent a variety of procedures and comprised a number of breeds, with similar distributions of procedures and breeds among groups (Table 2).

Table 1

Clinical characteristics of dogs (n = 88) enrolled in a study of the sedative and cardiopulmonary effects of premedication with a medetomidine-buprenorphine or acepromazine-buprenorphine combination in dogs anesthetized with propofol and isoflurane.

VariableGroup 1 (n = 28)Group 2 (n = 30)Group 3 (n = 30)P value
Sex   0.5
   Sexually intact female656 
   Spayed female4118 
   Sexually intact male9911 
   Castrated male955 
Age (y)3.0 (1–4.4)4.8 (0.9–8.9)4.1 (0.9–8.3)0.5
Weight (kg)23.3 (16.8–30.7)23.8 (18.9–28.3)26.5 (15.7–38.6)0.6
ASA status   0.6
   1171515 
   2111515 
Anesthetic duration (min)80 (60–120)90 (72.5–147.5)90 (73.8–158.8)0.5

Data are given as number of dogs or median (IQR).

Dogs in group 1 were premedicated with acepromazine (0.03 mg/kg [0.014 mg/lb]) and buprenorphine (0.02 mg/kg [0.009 mg/lb]), IM; dogs in group 2 were premedicated with medetomidine (5 μg/kg [2.3 μg/lb]) and buprenophine (0.02 mg/kg), IM; dogs in group 3 were premedicated with medetomidine (10 μg/kg [4.5 μg/lb]) and buprenorphine (0.02 mg/kg), IM.

Table 2

Distribution of breeds and procedures for dogs in Table 1.

VariableGroup 1 (n = 28)Group 2 (n = 30)Group 3 (n = 30)
Breed   
   Mixed416
   Retriever355
   Spaniel524
   German Shepherd Dog131
   Collie163
   Terrier354
   Others1187
Procedures   
   Neutering684
   Arthroscopy*425
   Endoscopy467
   Other orthopedic223
   Other soft tissue303
   Radiography and minor procedures9128

Includes stifle, shoulder, and elbow arthroscopy.

Includes gastroscopy, colonoscopy, cystoscopy, and rhinoscopy.

See Table 1 for remainder of key.

There were no significant differences among groups with regard to sedation scores after administration of preanesthetic medications. Mean ± SD score was 10 ± 4 for dogs in group 1, 8 ± 4 for dogs in group 2, and 10 ± 5 for dogs in group 3. Median dose of propofol used for anesthetic induction was significantly (P < 0.001) lower for dogs in group 3 (median, 1.4 mg/kg [0.6 mg/lb]; IQR, 1.2 to 2.1 mg/kg [0.5 to 1.0 mg/lb]) than for dogs in group 2 (median, 2.6 mg/kg [1.2 mg/lb]; IQR, 1.7 to 3.4 mg/kg [0.8 to 1.5 mg/lb]) or group 1 (median, 2.9 mg/kg [1.3 mg/lb]; IQR, 1.7 to 3.7 mg/kg [0.8 to 1.7 mg/lb]).

Mean vaporizer setting was not significantly (P = 0.30) different among groups. Mean ± SD vaporizer settings were 1.5 ± 0.3, 1.3 ± 0.4, and 1.5 ± 0.3 for groups 1, 2, and 3, respectively.

Adverse effects identified following administration of the preanesthetic agents consisted of salivation (n = 1) and signs of pain on injection (1) for dogs in group 1; salivation (2), signs of pain on injection (1), and muscle twitching (1) for dogs in group 2; and signs of pain on injection (4), salivation (4), vomiting (3), and muscle twitching (2) for dogs in group 3.

None of the dogs required treatment for hypotension or bradycardia. Mean and diastolic blood pressures were significantly lower in group 1 than in group 2 or 3, and both mean and lowest heart rates were significantly higher in group 1 than in group 2 or 3. Systolic blood pressure did not differ significantly among groups. Respiratory rate was significantly higher in group 1 (median, 22 breaths/min; IQR, 15 to 51 breaths/min) than in group 2 (median, 14.5 breaths/min; IQR, 18 to 60 breaths/min) or group 3 (median, 15 breaths/min; IQR, 10 to 20 breaths/min). Mean Petco2 was significantly lower for dogs in group 1 (39 ± 6 mm Hg), compared with the other 2 groups (group 2, 42 ± 6 mm Hg; group 3, 43 ± 7 mm Hg; P = 0.03), although values for all dogs were within the range for normocapnia (35 to 45 mm Hg). There were no significant differences in Spo2 among groups (Table 3).

Table 3

Cardiopulmonary data for dogs in Table 1.

VariableGroup 1 (n = 28)Group 2 (n = 30)Group 3 (n = 30)P value
Systolic blood pressure (mm Hg)*106 ± 14113 ± 16116 ± 190.1
Mean blood pressure (mm Hg)*76 ± 1283 ± 1587 ± 170.03
Diastolic blood pressure (mm Hg)*52 ± 1267 ± 1568 ± 17< 0.001
Heart rate (beats/min)*88 ± 1572 ± 2075 ± 200.004
Lowest heart rate recorded (beats/min)69 ± 1655 ± 1653 ± 190.002
Petco2 (mm Hg)*39 ± 642 ± 643 ± 70.03

Data are given as mean ± SD.

Mean value for the entire anesthetic period.

See Table 1 for remainder of key.

Duration of anesthesia did not differ significantly (P = 0.5) among groups (Table 1). Seven dogs each in group 2 and group 3 received atipamezole at the end of anesthesia. There were no significant differences among groups with regard to time to tracheal extubation, time to movement into sternal recumbency, or time to standing and walking. Median times to tracheal extubation were 8 minutes (IQR, 5 to 10 minutes), 7 minutes (IQR, 5 to 10.5 minutes), and 8 minutes (IQR, 5 to 10 minutes) for groups 1, 2, and 3, respectively. Median times to sternal recumbency were 14.5 minutes (IQR, 10 to 27.5 minutes), 13 minutes (IQR, 8 to 20 minutes), and 10.5 minutes (IQR, 5.5 to 24 minutes) for groups 1, 2, and 3, respectively. Median times to standing were 35 minutes (IQR, 14 to 82 minutes), 20 minutes (IQR, 12.5 to 52.5 minutes), and 34 minutes (IQR, 17 to 62 minutes) for groups 1, 2, and 3, respectively.

Discussion

Results of the present study suggested that either acepromazine or medetomidine could be used in combination with buprenorphine for premedication of dogs anesthetized with propofol and isoflurane for routine surgical and diagnostic procedures, with similar degrees of preanesthetic sedation obtained when buprenorphine was administered IM in combination with either acepromazine or medetomidine. Blood pressure was better maintained with the medetomidine-buprenorphine combinations; however, whether this was associated with any clinically relevant benefits was not assessed. To our knowledge, this is the first study to evaluate the use of a medetomidine-buprenorphine combination for premedication of dogs. A previous study19 evaluated the use of medetomidine at 3 doses in combination with buprenorphine to induce sedation for a variety of procedures; however, general anesthesia was not induced or maintained in those animals. In the present study, the medetomidine-buprenorphine and acepromazine-buprenorphine combinations produced adequate sedation with minimal adverse effects for dogs of ASA 1 or 2 status undergoing anesthesia for procedures involving a mild to moderate stimulus. The procedures performed on dogs in the present study were similar to those that would be performed in clinical practice, including neutering, orthopedic and soft tissue surgeries, endoscopy, and routine diagnostic imaging. Therefore, we suggest that these results should be widely applicable.

In the present study, sedation scores were assessed 15 minutes after injection for dogs that received medetomidine and 30 minutes after injection for dogs that received acepromazine. These times were chosen to reflect the peak sedative effects of these drugs5 and to mirror clinical protocols used in general practice. Even after IV administration, buprenorphine does not begin to produce sedation for at least 30 minutes5; therefore, the sedative effects of buprenorphine should have had little influence on these sedation score results. There may have been a risk of dogs beginning to recover from sedation if sedation scoring of dogs in the medetomidine groups had been delayed until 30 minutes after drug administration, because the clinically useful effect of medetomidine begins to wane after this time.

The dose of acepromazine (0.03 mg/kg) administered in the present study was at the lower end of the dose range (0.03 to 0.125 mg/kg [0.014 to 0.057 mg/lb], IM, SC, or slow IV) suggested for premedication by the manufacturer and was in the middle of the dose range used in our hospital. The medetomidine doses administered were chosen to reflect current clinical use in our hospital. The higher dose (10 μg/kg) was at the lower end of the dose range (10 to 20 μg/kg [4.5 to 9.1 μg/lb], IV, IM, or SC) recommended for premedication by the manufacturer in the United Kingdom, and the lower dose (5 μg/kg) was less than the recommended dose range. Even so, there were no significant differences between the medetomidine groups with regard to sedation scores after preanesthetic medication, with both doses providing moderate to profound sedation in most dogs.

The dose of buprenorphine (0.02 mg/kg) administered in the present study was the dose that was routinely used in our hospital. Good preoperative sedation of dogs with this dose of buprenorphine in combination with acepromazine at a dose of 0.05 mg/kg, IM, has been demonstrated.20 A lower dose (0.01 mg/kg [0.005 mg/lb], IM) of buprenorphine was as effective as morphine for analgesia after arthrotomy in dogs,21 whereas after castration in dogs, a higher dose (0.02 mg/kg, IM) was associated with lower pain scores than the lower dose (0.01 mg/kg, IM).20

In the present study, differing propofol and isoflurane requirements among groups may have confounded the arterial blood pressure differences that were recorded. Intravenous administration of propofol for induction of anesthesia has been reported22 to result in transient (< 20 minutes) hypotension, although the doses used in the present study were lower than those used in the previous study. The actual doses of propofol administered in the present study were similar to predicted doses for dogs in groups 2 and 3, but were lower than predicted for dogs in group 1, possibly because the propofol was administered relatively slowly.

Isoflurane is known to cause dose-dependent cardiovascular depression.23 End-tidal isoflurane concentrations were not recorded in the present study, but mean values for vaporizer settings, which should have reflected isoflurane concentration delivered to the dogs via the nonrebreathing system, were calculated for the entire anesthetic period and did not differ significantly among groups. Dogs in all groups received isoflurane at a concentration between 1 and 1.25 times the reported minimal alveolar concentration. We conclude, therefore, that differences in arterial blood pressure between groups in the present study were mainly influenced by the preanesthetic medication (ie, medetomidine or acepromazine) and not isoflurane.

Both acepromazine and medetomidine have various effects on blood pressure in dogs. In the present study, mean and diastolic blood pressures were significantly lower in dogs given acepromazine than in dogs given medetomidine. Even though acepromazine appears to have caused a greater degree of hypotension than medetomidine did, blood pressure values in all groups were clinically acceptable. In a previous study16 comparing various doses of medetomidine in dogs (0.4, 4, and 40 μg/kg [0.2, 1.8, and 18.2 μg/lb), significant differences in mean blood pressure were identified at most times, with the highest dose resulting in higher blood pressures. Higher doses of medetomidine may result in more persistent increases in systemic vascular resistance, resulting in more prolonged hypertension.16 Tissue perfusion was not assessed in the present study, and higher arterial blood pressures associated with vasoconstriction may result in decreased peripheral tissue perfusion because of increased vascular resistance.24

Acepromazine acts peripherally as an antagonist of α1-adrenergic receptors, causing vasodilation, which may promote hypotension.5 In a previous study,24 dogs anesthetized with thiopental and isoflurane had significantly lower blood pressures if premedicated with acepromazine rather than saline solution. In a study25 in which dogs received acepromazine (0.1 mg/kg [0.045 mg/lb]) IV, there was a significant decrease in blood pressure from baseline, but systemic vascular resistance was not significantly different from the baseline value. Therefore, hypotension caused by administration of acepromazine at high doses may be not only a result of vasodilation, but also a result of depression of cardiac function.25 Despite causing hypotension, however, tissue perfusion may not necessarily be impaired by acepromazine. In the study by Bostrom et al,24 glomerular filtration rate was maintained in dogs anesthetized with thiopental and isoflurane despite severe induced hypotension (mean arterial pressure, 66 ± 8 mm Hg), suggesting that cardiac output was maintained or increased.

Administration of medetomidine IV causes an initial increase in arterial blood pressure owing to peripheral vasoconstriction, which wanes over time because of a central hypotensive effect.3 In dogs receiving medetomidine (40 μg/kg, IV), systolic blood pressure returned to baseline by 15 minutes after drug administration, and diastolic pressure returned to baseline by 30 minutes after administration.10 The doses used in the present study were lower, and medetomidine was administered IM. With IM administration of medetomidine, central hypotension has been reported to predominate, and values reportedly return to baseline sooner.26 Blood pressures in the present study were all recorded after the initial 15 minutes following drug administration and therefore should not have been distorted by any possible early hypertensive effects of medetomidine.

For all groups in the present study, adverse effects associated with administration of preanesthetic medications were mild and self-limiting. Opioids can cause nausea (manifested by vomiting and salivation). Acepromazine has antiemetic properties, but is clinically effective only if administered 15 minutes before opioid administration.27 The low incidence of salivation and the lack of vomiting in the acepromazine group was therefore likely attributable to buprenorphine being less likely to cause vomiting than other opioids. The greater incidence of vomiting in the medetomidine groups was considered to be more likely attributable to the medetomidine, rather than the buprenorphine, which is supported by reports5 that IM administration of medetomidine caused vomiting in 10% to 20% of dogs. Pain on injection may be caused by the pH, temperature, or volume of the injectate. Dogs in the acepromazine group received the largest volume of injectate (0.075 mL/kg [0.03 mL/lb]), but this was still considerably lower than the generally recommended maximum volume for IM injections in dogs (0.25 mL/kg [0.11 mL/lb]).28 Because injectate volumes for dogs in the medetomidine groups were even smaller, it was assumed that the medetomidine formulation caused some irritation, which was manifested more frequently in the higher-dose group.

Abbreviations

ASA

American Society of Anesthesiologists

IQR

Interquartile range

Petco2

End-tidal partial pressure of carbon dioxide

Spo2

Oxygen saturation as determined by pulse oximetry

a.

ACP Injection, Novartis Animal Health UK Ltd, Royston, Hertfordshire, England.

b.

Vetergesic, Alsto Ltd, Sheriff Hutton, North Yorkshire, England.

c.

Domitor, Sandwich, Kent, England.

d.

Propoflo, Abbott Laboratories Ltd, Queenborough, Kent, England.

e.

Terufusion Syringe Pump TE311, Terumo Medical Corp, Somerset, NJ.

f.

Isoflo, Abbott Laboratories Ltd, Queenborough, Kent, England.

g.

Aqupharm No. 11, Animalcare Ltd, York, England.

h.

Rimadyl Small Animal Injection, Pfizer Ltd, Sandwich, Kent, England.

i.

Tidal Wave Sp, Novametrix, Wallingford, Conn.

j.

Cardell 9401 BP Veterinary Monitor, Minrad International Inc, Orchard Park, NY.

k.

Antisedan, Pfizer Ltd, Sandwich, Kent, England.

l.

Atrocare Injection, Animalcare Ltd, York, England.

m.

Minitab, release 14, Minitab Ltd, Coventry, West Midlands, England.

n.

SPSS, version 15.0 for Windows, SPSS Inc, Chicago, Ill.

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  • 10 Kuusela ERaekallio MAnttila M, et al. Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs. J Vet Pharmacol Ther 2000; 23:1520

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11 Kojima KNishimura RMutoh T, et al. Effects of medetomidine-midazolam, acepromazine-butorphanol, and midazolam-butorphanol on induction dose of thiopental and propofol and on cardiopulmonary changes in dogs. Am J Vet Res 2002; 63:16711679

    • Search Google Scholar
    • Export Citation
  • 12 Hall LWLagerweij ENolan AM, et al. Effect of medetomidine on the pharmacokinetics of propofol in dogs. Am J Vet Res 1994; 55:116120

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13 Vainio O. Propofol infusion anaesthesia in dogs premedicated with medetomidine. J Vet Anaesth 1991; 18:3537

  • 14 Murison PJ. Effect of propofol at two injection rates or thiopentone on post-intubation apnoea in the dog. J Small Anim Pract 2001; 42:7174

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15 Hammond RAEngland GCW. The effect of medetomidine pre-medication upon propofol induction and infusion anaesthesia in the dog. J Vet Anaesth 1994; 21:2428

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16 Kuusela ERaekallio MVäisänen M, et al. Comparison of medetomidine and dexmedetomidine as premedicants in dogs undergoing propofol-isoflurane anesthesia. Am J Vet Res 2001; 62:10731080

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17 Geel JK. The effect of premedication on the induction dose of propofol in dogs and cats. J S Afr Vet Assoc 1991; 62:118123

  • 18 Morgan DWLegge K. Clinical evaluation of propofol as an intravenous anaesthetic agents in dogs and cats. Vet Rec 1989; 124:3133

  • 19 Robinson KJJones RSCripps PJ. Effects of medetomidine and buprenorphine administered for sedation in dogs. J Small Anim Pract 2001; 42:444447

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20 Slingsby LSTaylor PMWaterman-Pearson AE. Effects of two doses of buprenorphine four or six hours apart on nociceptive thresholds, pain and sedation in dog after castration. Vet Rec 2006; 159:705711

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21 Brodbelt DCTaylor PMStanway GW. A comparison of preoperative morphine and buprenorphine for post operative analgesia for arthrotomy in dogs. J Vet Pharmacol Ther 1997; 20:284289

    • Search Google Scholar
    • Export Citation
  • 22 Wouters PFVen de Velde MAMarcus MAE, et al. Hemodynamic changes during induction of anesthesia with eltanolone and propofol in dogs. Anesth Analg 1995; 81:125131

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23 Merin RGBernard J-MDoursout M-F, et al. Comparison of the effects of isoflurane and desflurane on cardiovascular dynamics and regional blood flow in the chronically instrumented dog. Anesthesiology 1991; 74:568574

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24 Bostrom INyman GKampa N, et al. Effects of acepromazine on renal function in anesthetized dogs. AmJ Vet Res 2003; 64:590598

  • 25 Stepien RLBonagura JDBednarski RM, et al. Cardiorespiratory effects of acepromazine maleate and buprenorphine hydrochlo-ride in clinically normal dogs. Am J Vet Res 1995; 56:7884

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26 Pypendop BHVerstegen JP. Haemodynamic effects of medetomidine in the dog, a dose titration study. Vet Surg 1998; 27:612622

  • 27 Valverde ACantwell SHernandez J, et al. Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs. Vet Anaesth Analg 2004; 31:4045

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28 Diehl KHHull RMorton D, et al. A good practice guide to the administration of substances and removal of blood, including routes and volumes. J Appl Toxicol 2001; 21:1523

    • Crossref
    • Search Google Scholar
    • Export Citation

Appendix

Composite simple descriptive sedation score system (adapted from Young et al9 and Kuusela et al10).

VariableScore
Spontaneous posture 
   Standing0
   Tired but standing1
   Lying but able to rise2
   Lying and difficulty rising3
   Unable to rise4
Palpebral reflex 
   Brisk0
   Slow but with full corneal sweep1
   Slow and with only partial corneal sweep2
   Absent3
Eye position 
   Central0
   Rotated forward or downward but not obscured by third eyelid1
   Rotated forward or downward and obscured by third eyelid2
Jaw and tongue relaxation 
   Normal jaw tone and strong gag reflex0
   Reduced jaw tone but moderate gag reflex1
   Much reduced jaw tone and slight gag reflex2
   No jaw tone or gag reflex3
Response to noise (handclap) 
   Normal startle reaction (head turns toward noise or dog cringes)0
   Reduced startle reaction (reduced head turn or minimal cringing)1
   Minimal startle reaction2
   Absent startle reaction3
Resistance when laid in lateral recumbency 
   Much struggling; will not allow being placed in this position0
   Some struggling, but will allow being placed in this position1
   Minimal struggling2
   No struggling3
General appearance and attitude 
   Excitable0
   Awake and normal1
   Tranquil2
   Stuporous3

Contributor Notes

Dr. Grint's present address is Animal Pain and Behavior Group, University of Bristol, Langford, Bristol, BS40 5DU, England.

Supported by Pfizer UK.

Presented as a poster at the Association of Veterinary Anaesthetist's Spring Meeting, Liverpool, England, April 2006.

The authors thank Liza Ebeck for assistance with medication administration.

Address correspondence to Dr. Dugdale (alexd@liv.ac.uk).
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  • 9 Young LEBrearley JCRichards DLS, et al. Medetomidine as a premedicant in dogs and its reversal by atipamezole. J Small Anim Pract 1990; 31:554559

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10 Kuusela ERaekallio MAnttila M, et al. Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs. J Vet Pharmacol Ther 2000; 23:1520

    • Search Google Scholar
    • Export Citation
  • 11 Kojima KNishimura RMutoh T, et al. Effects of medetomidine-midazolam, acepromazine-butorphanol, and midazolam-butorphanol on induction dose of thiopental and propofol and on cardiopulmonary changes in dogs. Am J Vet Res 2002; 63:16711679

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12 Hall LWLagerweij ENolan AM, et al. Effect of medetomidine on the pharmacokinetics of propofol in dogs. Am J Vet Res 1994; 55:116120

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13 Vainio O. Propofol infusion anaesthesia in dogs premedicated with medetomidine. J Vet Anaesth 1991; 18:3537

  • 14 Murison PJ. Effect of propofol at two injection rates or thiopentone on post-intubation apnoea in the dog. J Small Anim Pract 2001; 42:7174

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15 Hammond RAEngland GCW. The effect of medetomidine pre-medication upon propofol induction and infusion anaesthesia in the dog. J Vet Anaesth 1994; 21:2428

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16 Kuusela ERaekallio MVäisänen M, et al. Comparison of medetomidine and dexmedetomidine as premedicants in dogs undergoing propofol-isoflurane anesthesia. Am J Vet Res 2001; 62:10731080

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17 Geel JK. The effect of premedication on the induction dose of propofol in dogs and cats. J S Afr Vet Assoc 1991; 62:118123

  • 18 Morgan DWLegge K. Clinical evaluation of propofol as an intravenous anaesthetic agents in dogs and cats. Vet Rec 1989; 124:3133

  • 19 Robinson KJJones RSCripps PJ. Effects of medetomidine and buprenorphine administered for sedation in dogs. J Small Anim Pract 2001; 42:444447

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20 Slingsby LSTaylor PMWaterman-Pearson AE. Effects of two doses of buprenorphine four or six hours apart on nociceptive thresholds, pain and sedation in dog after castration. Vet Rec 2006; 159:705711

    • Search Google Scholar
    • Export Citation
  • 21 Brodbelt DCTaylor PMStanway GW. A comparison of preoperative morphine and buprenorphine for post operative analgesia for arthrotomy in dogs. J Vet Pharmacol Ther 1997; 20:284289

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22 Wouters PFVen de Velde MAMarcus MAE, et al. Hemodynamic changes during induction of anesthesia with eltanolone and propofol in dogs. Anesth Analg 1995; 81:125131

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23 Merin RGBernard J-MDoursout M-F, et al. Comparison of the effects of isoflurane and desflurane on cardiovascular dynamics and regional blood flow in the chronically instrumented dog. Anesthesiology 1991; 74:568574

    • Search Google Scholar
    • Export Citation
  • 24 Bostrom INyman GKampa N, et al. Effects of acepromazine on renal function in anesthetized dogs. AmJ Vet Res 2003; 64:590598

  • 25 Stepien RLBonagura JDBednarski RM, et al. Cardiorespiratory effects of acepromazine maleate and buprenorphine hydrochlo-ride in clinically normal dogs. Am J Vet Res 1995; 56:7884

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26 Pypendop BHVerstegen JP. Haemodynamic effects of medetomidine in the dog, a dose titration study. Vet Surg 1998; 27:612622

  • 27 Valverde ACantwell SHernandez J, et al. Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs. Vet Anaesth Analg 2004; 31:4045

    • Search Google Scholar
    • Export Citation
  • 28 Diehl KHHull RMorton D, et al. A good practice guide to the administration of substances and removal of blood, including routes and volumes. J Appl Toxicol 2001; 21:1523

    • Search Google Scholar
    • Export Citation

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