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).
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.
| Variable | Group 1 (n = 28) | Group 2 (n = 30) | Group 3 (n = 30) | P value |
|---|---|---|---|---|
| Sex | 0.5 | |||
| Sexually intact female | 6 | 5 | 6 | |
| Spayed female | 4 | 11 | 8 | |
| Sexually intact male | 9 | 9 | 11 | |
| Castrated male | 9 | 5 | 5 | |
| 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 | |||
| 1 | 17 | 15 | 15 | |
| 2 | 11 | 15 | 15 | |
| 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.
Distribution of breeds and procedures for dogs in Table 1.
| Variable | Group 1 (n = 28) | Group 2 (n = 30) | Group 3 (n = 30) |
|---|---|---|---|
| Breed | |||
| Mixed | 4 | 1 | 6 |
| Retriever | 3 | 5 | 5 |
| Spaniel | 5 | 2 | 4 |
| German Shepherd Dog | 1 | 3 | 1 |
| Collie | 1 | 6 | 3 |
| Terrier | 3 | 5 | 4 |
| Others | 11 | 8 | 7 |
| Procedures | |||
| Neutering | 6 | 8 | 4 |
| Arthroscopy* | 4 | 2 | 5 |
| Endoscopy† | 4 | 6 | 7 |
| Other orthopedic | 2 | 2 | 3 |
| Other soft tissue | 3 | 0 | 3 |
| Radiography and minor procedures | 9 | 12 | 8 |
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).
Cardiopulmonary data for dogs in Table 1.
| Variable | Group 1 (n = 28) | Group 2 (n = 30) | Group 3 (n = 30) | P value |
|---|---|---|---|---|
| Systolic blood pressure (mm Hg)* | 106 ± 14 | 113 ± 16 | 116 ± 19 | 0.1 |
| Mean blood pressure (mm Hg)* | 76 ± 12 | 83 ± 15 | 87 ± 17 | 0.03 |
| Diastolic blood pressure (mm Hg)* | 52 ± 12 | 67 ± 15 | 68 ± 17 | < 0.001 |
| Heart rate (beats/min)* | 88 ± 15 | 72 ± 20 | 75 ± 20 | 0.004 |
| Lowest heart rate recorded (beats/min) | 69 ± 16 | 55 ± 16 | 53 ± 19 | 0.002 |
| Petco2 (mm Hg)* | 39 ± 6 | 42 ± 6 | 43 ± 7 | 0.03 |
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 |
ACP Injection, Novartis Animal Health UK Ltd, Royston, Hertfordshire, England.
Vetergesic, Alsto Ltd, Sheriff Hutton, North Yorkshire, England.
Domitor, Sandwich, Kent, England.
Propoflo, Abbott Laboratories Ltd, Queenborough, Kent, England.
Terufusion Syringe Pump TE311, Terumo Medical Corp, Somerset, NJ.
Isoflo, Abbott Laboratories Ltd, Queenborough, Kent, England.
Aqupharm No. 11, Animalcare Ltd, York, England.
Rimadyl Small Animal Injection, Pfizer Ltd, Sandwich, Kent, England.
Tidal Wave Sp, Novametrix, Wallingford, Conn.
Cardell 9401 BP Veterinary Monitor, Minrad International Inc, Orchard Park, NY.
Antisedan, Pfizer Ltd, Sandwich, Kent, England.
Atrocare Injection, Animalcare Ltd, York, England.
Minitab, release 14, Minitab Ltd, Coventry, West Midlands, England.
SPSS, version 15.0 for Windows, SPSS Inc, Chicago, Ill.
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Appendix
Composite simple descriptive sedation score system (adapted from Young et al9 and Kuusela et al10).
| Variable | Score |
|---|---|
| Spontaneous posture | |
| Standing | 0 |
| Tired but standing | 1 |
| Lying but able to rise | 2 |
| Lying and difficulty rising | 3 |
| Unable to rise | 4 |
| Palpebral reflex | |
| Brisk | 0 |
| Slow but with full corneal sweep | 1 |
| Slow and with only partial corneal sweep | 2 |
| Absent | 3 |
| Eye position | |
| Central | 0 |
| Rotated forward or downward but not obscured by third eyelid | 1 |
| Rotated forward or downward and obscured by third eyelid | 2 |
| Jaw and tongue relaxation | |
| Normal jaw tone and strong gag reflex | 0 |
| Reduced jaw tone but moderate gag reflex | 1 |
| Much reduced jaw tone and slight gag reflex | 2 |
| No jaw tone or gag reflex | 3 |
| 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 reaction | 2 |
| Absent startle reaction | 3 |
| Resistance when laid in lateral recumbency | |
| Much struggling; will not allow being placed in this position | 0 |
| Some struggling, but will allow being placed in this position | 1 |
| Minimal struggling | 2 |
| No struggling | 3 |
| General appearance and attitude | |
| Excitable | 0 |
| Awake and normal | 1 |
| Tranquil | 2 |
| Stuporous | 3 |
