Acepromazine and dexmedetomidine are likely the most commonly used agents for preanesthetic sedation in healthy dogs. While both agents are used for a common purpose, they are chemically unrelated and can produce substantially different undesired effects. Acepromazine is a phenothiazine agent that, in addition to its sedative and anesthetic-sparing effects, produces α1adrenergic receptor blockade resulting in vasodilation and arterial hypotension; the latter effect might be magnified by the vasodilatory effects of inhalational anesthetic agents.1–3 Dexmedetomidine is an α2-adrenergic receptor agonist; stimulation of presynaptic α2-adrenergic receptors produces sedation, analgesia, and anesthetic-sparing effects. Stimulation of peripheral α2-adrenergic receptors results in vasoconstriction and arterial hypertension. Bradycardia occurs through 2 mechanisms: a reflexive response to arterial hypertension and a central effect.3–5
The undesired hemodynamic effects of these agents are almost in direct opposition, and therefore, incidences of arterial hypotension and bradycardia under general anesthesia are likely to differ in dogs that received either agent as a preanesthetic sedative. Arterial hypotension and excessive bradycardia during general anesthesia could contribute to insufficient perfusion of tissues. For example, renal blood flow decreases as the MAP falls below the lower limits of autoregulation, and even if MAP is not low, decreased cardiac output can occur in the presence of bradycardia and hypertension resulting from administration of dexmedetomidine and can result in insufficient organ perfusion.6 Information is available on the hemodynamic effects of acepromazine and dexmedetomidine used alone as preanesthetic agents,3 but to our knowledge, a systematic investigation of these agents and complications associated with their use during anesthesia in a clinical setting has not been performed. The purpose of the study reported here was to evaluate potential associations between preanesthetic administration of acepromazine or dexmedetomidine and development of arterial hypotension or bradycardia in isoflurane-anesthetized dogs undergoing ovariohysterectomy. In addition, we aimed to evaluate associations of other putative risk factors (selected signalment and anesthesia variables) with the outcomes of interest in the same dogs. We hypothesized that acepromazine would be associated with increased odds of hypotension and that dexmedetomidine would be associated with increased odds of bradycardia in this population of dogs.
Materials and Methods
Case selection criteria
Electronic medical records of the Cornell University Companion Animal Hospital were searched to identify dogs that underwent ovariohysterectomy between January 1, 2009, and December 31, 2010, and received hydromorphone hydrochloridea and acepromazine maleateb or dexmedetomidine hydrochloridec as preanesthetic agents. Electronic search terms included dog and ovariohysterectomy. To be included in the study, dogs had to be assigned an American Society of Anesthesiologists status of I or II on the basis of clinical examination findings, pertinent history, and results of hematologic analysis (measurement of Hct and BUN, blood glucose, and plasma protein concentrations). Dogs that received other preoperative medications, those assigned an American Society of Anesthesiologists status ≥ III, and those that had regional anesthesia in the perioperative period or received additional analgesics during surgery were excluded.
Anesthesia and surgical procedures
All dogs in the study underwent ovariohysterectomy by laparotomy with a ventral midline approach. The surgeries were performed by veterinary students under the supervision of a faculty member. For all patients, acepromazine or dexmedetomidine was combined with hydromorphone in 1 syringe and administered IM. Anesthesia was induced by IV administration of propofol, thiopental, or a combination of ketamine and a benzodiazepine (diazepam or midazolam). Endotracheal intubation was accomplished with a suitably sized, cuffed endotracheal tube, and anesthesia was maintained with isoflurane in oxygen delivered through a circular breathing system. The vaporizer setting was recorded every 5 minutes, and the mean was calculated over the duration of isoflurane administration. The MAP and heart rate were monitored by means of oscillometryd and by ECGd (confirmed by auscultation or evaluation of pulses by palpation or pulse oximetryd), respectively, throughout anesthesia and were recorded every 5 minutes. The blood pressure cuff was placed in the midregion of an antebrachium or closely proximal or distal to a tarsal (hock) joint. A cuff with a width of approximately 40% of the circumference of the limb was selected in each case. Drug doses, selection of induction agents, the use of PPV, and administration of fluids and drugs to support blood pressure or treat bradycardia were at the discretion of the attending anesthesiologist.
Data collection
For each dog, age, body weight, and BCS (scale, 1 to 97) at the time of surgery; heart rate immediately prior to administration of premedicants; sedative agent (acepromazine or dexmedetomidine); premedicant doses; anesthetic induction agent or agents; duration of general anesthesia (measured from the time of induction to the time of extubation); use of PPV (yes or no); and the mean vaporizer setting were obtained from the anesthesia record. The MAP and heart rate data for each patient were reviewed to identify occurrence of arterial hypotension or bradycardia.
Arterial hypotension was defined as a MAP < 60 mm Hg; presence (yes vs no) of hypotension and the timing and duration relative to the general anesthesia episode, if applicable, were recorded. Bradycardia was defined as a heart rate < 50% of the presedation value (an arbitrary selection) and recorded as present or absent. Lastly, supportive pharmacological treatments (dopamine, atropine, or glycopyrrolate) were recorded as administered or not administered for each dog during general anesthesia, and the treatment given was annotated if applicable.
Statistical analysis
A commercial software packagee was used for all analyses. Dogs were grouped according to the sedative administered (acepromazine or dexmedetomidine). Initial descriptive statistics were calculated, and plots of the data were used to assess normality of distribution. Patient age, body weight, BCS, dose of hydromorphone, mean vaporizer setting, duration of anesthesia, and use of PPV were compared between groups with unpaired Wilcoxon tests. The doses of each sedative were summarized with descriptive statistics. The frequencies of administration for each anesthetic induction agent and the use of PPV were compared between groups with χ2 tests.
Logistic regression with backward elimination was used to evaluate potential associations between each of the putative risk factors and arterial hypotension or bradycardia. The list of the putative risk factors included sedative agent, induction agent, duration of anesthesia, mean vaporizer setting, use of PPV, and patient age, body weight, and BCS. Association between the event of interest and each of the putative factors while controlling for other factors was evaluated with the respective regression coefficient and quantified by the magnitude of the respective OR (calculated with 95% CI). For interval putative risk factors (mentioned above), we computed the probability of the event of interest given a certain value of the factor as follows:
Where the event is hypotension or bradycardia, α is the constant of the logistic regression equation, βi is the effect of the respective putative factor (Xi) on the probability of the respective event, and exp is the exponential function.
The incidence of arterial hypotension or bradycardia was calculated for each group and compared between the 2 treatment groups with a χ2 test. In addition, the frequency of administration of dopamine, atropine, or glycopyrrolate was compared between treatment groups with χ2 tests. For dogs with hypotension, the time to the first hypotensive event and the duration of hypotension (relative to total anesthesia duration) were compared between groups with unpaired Wilcoxon tests.
Results were summarized as mean ± SD and as median and range for parametric and nonparametric data, respectively. Values of P < 0.05 were considered significant.
Results
Three hundred forty-one dogs were included in the analysis; 149 (44%) dogs received acepromazine (median dose, 0.02 mg/kg [0.009 mg/lb]; range, 0.01 to 0.02 mg/kg [0.005 to 0.009 mg/lb]) and 192 (56%) received dexmedetomidine (median dose, 3 μg/kg [1.4 μg/lb]; range, 2 to 20 μg/kg [0.9 to 9.1 μg/lb]) prior to anesthesia. Induction agents and the mean ± SD doses used for general anesthesia were as follows. Propofol was administered IV at 3.5 ± 1.4 mg/kg (1.6 ± 0.6 mg/lb) and 3.2 ± 1.3 mg/kg (1.5 ± 0.6 mg/lb) to dogs of the acepromazine (n = 64) and dexmedetomidine (142) groups, respectively. Thiopental was administered IV at 8.8 ± 3.5 mg/kg (4.0 ± 1.6 mg/lb) and 7.3 ± 3.3 mg/kg (3.3 ± 1.5 mg/lb) to dogs of the acepromazine (n = 49) and dexmedetomidine (38) groups, respectively. The ketamine-benzodiazepine (diazepam or midazolam) combination was mixed in 1 syringe and administered IV at 3.9 ± 2.3 mg of ketamine/kg (1.8 ± 1.0 mg/lb) plus 0.2 ± 0.1 mg of benzodiazepine/kg (0.09 ± 0.05 mg/lb) to dogs of the acepromazine group (n = 36) and 3.8 ± 2.2 mg of ketamine/kg (1.7 ± 1.0 mg/lb) plus 0.2 ± 0.1 mg of benzodiazepine/kg to dogs of the dexmedetomidine group (12). Demographic data, the preanesthetic dose of hydromorphone, and anesthesia variables were compared between groups (Table 1).
Comparison of demographic data, preanesthetic doses of hydromorphone, and anesthesia variables in a retrospective study to evaluate potential associations between preanesthetic administration of acepromazine or dexmedetomidine and development of arterial hypotension or bradycardia during ovariohysterectomy in isoflurane-anesthetized dogs (n = 341).
| Variable | Acepromazine (n = 149) | Dexmedetomidine (n = 192) | P value |
|---|---|---|---|
| Age (y) | 1.0 (0.08–11) | 1.0 (0.17–11) | 0.8 |
| Body weight (kg) | 19 (1.8–67) | 16.6 (1.6–61.5) | 0.09 |
| BCS* | 5 (2–8) | 5 (2–8) | 0.9 |
| Hydromorphone (mg/kg) | 0.1 (0.05–0.1) | 0.1 (0.05–0.1) | 0.8 |
| Anesthetic induction agent | < 0.001 | ||
| Thiopental | 49 (33) | 38 (20) | — |
| Propofol | 64 (43) | 142 (74) | — |
| Ketamine-benzodiazepine | 36 (24) | 12 (6) | — |
| Mean vaporizer setting (%) | 1.14 (0.6–1.9) | 1.24 (0.4–1.8) | 0.01 |
| Duration of anesthesia (min) | 200 (110–383) | 200 (85–363) | 0.1 |
| PPV | 0.1 | ||
| Yes | 85 (57) | 134 (70) | — |
| No | 64 (43) | 58 (30) | — |
Data are shown as median (range) or number (%) of dogs in the specified group. Hydromorphone was combined with acepromazine (median dose, 0.02 mg/kg [0.009 mg/lb]) or dexmedetomidine (median dose, 3 μg/kg [1.4 μg/lb]) in 1 syringe, and the solution was administered IM. Anesthetic induction agents were administered IV; median doses of propofol were 3.5 and 3.2 mg/kg (1.6 and 1.5 mg/lb) and median doses of thiopental were 8.8 and 7.3 mg/kg (4.0 and 3.3 mg/lb) for the acepromazine and dexmedetomidine groups, respectively. Ketamine was combined with diazepam or midazolam in 1 syringe; median dose for the acepromazine group was 3.9 mg of ketamine/kg (1.8 mg/lb) plus 0.2 mg of benzodiazepine/kg (0.09 mg/lb), and that for the dexmedetomidine group was 3.8 mg of ketamine/kg (1.7 mg/lb) plus 0.2 mg of benzodiazepine/kg. Values of P < 0.05 were considered significant.
The BCS was assessed on a scale of 1 to 9 as previously described.7
— = Not applicable.
The prevalence of arterial hypotension was 110 of 149 (74%) and 106 of 192 (55%) for dogs that received acepromazine and dexmedetomidine, respectively (P < 0.001). Body weight was significantly (P < 0.001) and negatively correlated with the probability of hypotension (R2 = 0.99; Figure 1). The odds of hypotension were significantly (P < 0.001) greater for dogs sedated with acepromazine (OR, 2.61; 95% CI, 1.61 to 4.23) than for dogs sedated with dexmedetomidine. No significant association was found between any other evaluated factor and development of hypotension.
Results of logistic regression analysis for association between body weight and the probability of arterial hypotension (MAP < 60 mm Hg) in 341 dogs that received acepromazine (n = 149) or dexmedetomidine (192) prior to anesthetic induction with propofol, thiopental, or a ketamine-benzodiazepine combination and maintenance with isoflurane for ovariohysterectomy. The coefficient of determination (R2) was 0.99. See Table 1 for premedicant dosages and induction and maintenance agent information.
Citation: Journal of the American Veterinary Medical Association 255, 2; 10.2460/javma.255.2.193
Results of logistic regression analysis for association between body weight and the probability of arterial hypotension (MAP < 60 mm Hg) in 341 dogs that received acepromazine (n = 149) or dexmedetomidine (192) prior to anesthetic induction with propofol, thiopental, or a ketamine-benzodiazepine combination and maintenance with isoflurane for ovariohysterectomy. The coefficient of determination (R2) was 0.99. See Table 1 for premedicant dosages and induction and maintenance agent information.
Citation: Journal of the American Veterinary Medical Association 255, 2; 10.2460/javma.255.2.193
Results of logistic regression analysis for association between body weight and the probability of arterial hypotension (MAP < 60 mm Hg) in 341 dogs that received acepromazine (n = 149) or dexmedetomidine (192) prior to anesthetic induction with propofol, thiopental, or a ketamine-benzodiazepine combination and maintenance with isoflurane for ovariohysterectomy. The coefficient of determination (R2) was 0.99. See Table 1 for premedicant dosages and induction and maintenance agent information.
Citation: Journal of the American Veterinary Medical Association 255, 2; 10.2460/javma.255.2.193
The incidence of bradycardia was 86 of 149 (58%) for dogs sedated with acepromazine and 154 of 192 (80%) for those sedated with dexmedetomidine (P < 0.001). The odds of bradycardia were significantly (P = 0.002) greater for dogs that received dexmedetomidine (OR, 2.45; 95% CI, 1.4 to 4.27) than for dogs that received acepromazine. The odds of bradycardia were significantly greater for dogs that received propofol (OR, 8.3; 95% CI, 4.64 to 14.8; P < 0.001) or ketamine-benzodiazepine (OR, 9.79; 95% CI, 4.05 to 23.6; P < 0.001) than for dogs that received thiopental, but these odds did not differ significantly (P = 0.7) for dogs that received ketamine, compared with those that received propofol (OR, 1.17; 95% CI, 0.5 to 2.75). No other variables tested were significantly associated with development of bradycardia.
Dopamine, but not atropine or glycopyrrolate, was administered more frequently to dogs that received acepromazine than to those that received dexmedetomidine (Table 2). Arterial hypotension also occurred earlier and lasted longer relative to the total duration of anesthesia in dogs of the former group, compared with the latter.
Frequency of dopamine and anticholinergic agent administration, time to first occurrence of hypotension (MAP < 60 mm Hg), and duration of hypotension for the same 341 dogs as in Table 1.
| Variable | Acepromazine (n = 149) | Dexmedetomidine (n = 192) | P value |
|---|---|---|---|
| Dopamine administration | < 0.001 | ||
| Yes | 70 (47) | 56 (29) | — |
| No | 79 (53) | 136 (71) | — |
| Atropine administration | 0.8 | ||
| Yes | 2 (1) | 3 (2) | — |
| No | 147 (99) | 189 (98) | — |
| Glycopyrrolate administration | 0.1 | ||
| Yes | 42 (28) | 67 (35) | — |
| No | 107 (72) | 125 (65) | — |
| Time of first hypotensive event (min) | 15 (0–95) | 20 (0–195) | 0.02 |
| Duration of hypotension (% of anesthesia time) | 25 (5–100) | 17 (4–85) | 0.04 |
Anesthesia time was measured from induction to extubation; hypotensive event timing is reported relative to anesthesia time.
See Table 1 for remainder of key.
Discussion
In this retrospective analysis of anesthetized dogs undergoing ovariohysterectomy at a veterinary teaching hospital, the odds of arterial hypotension for dogs premedicated with acepromazine were > 2 times those for those dogs premedicated with dexmedetomidine. Moreover, hypotension occurred sooner and lasted for a longer percentage of the total anesthesia time for dogs of the former group, compared with the latter. However, the odds of developing bradycardia for dogs that received dexmedetomidine were > 2 times those of dogs that received acepromazine. These results were not surprising, considering the effects of these agents on vascular α-adrenoceptors; however, other results deserve closer observation.
In our population of dogs, the incidence of arterial hypotension was noteworthy regardless of the sedative agent used; despite the significant difference between groups, the incidence of hypotension in dogs that received dexmedetomidine was 106 of 192 (55%), which was not a negligible finding for a complication that could contribute to hypoperfusion of vital organs. Dogs that received acepromazine were treated with dopamine more often than those that received dexmedetomidine, and thus even though more dogs received pharmacological treatment to revert hypotension, this complication was encountered at a higher rate and for longer periods than found for dogs of the dexmedetomidine group. For this study, we defined hypotension as MAP < 60 mm Hg. It is also possible that many dogs received dopamine as treatment for decreasing MAP before this value was < 60 mm Hg; in that situation, the true incidence of hypotension could have been underreported.
Lower body weight was also associated with increased odds of arterial hypotension in these dogs. The reason for this was unclear, but it should be noticed that we did not find an association between hypotension and BCS. Low body weight has been previously identified as a risk factor for anesthetic-associated death of dogs8,9; it was previously postulated that small size may predispose patients to inadvertent drug overdose or hypothermia.8 It is also possible that intraoperative hemorrhage is greater relative to body weight in small animals than in large ones, and that this may also contribute to hypotension. This factor could be especially important in teaching facilities, where surgery might be performed by inexperienced personnel, and hemorrhage may occur more frequently or be more severe than when experienced veterinarians perform the surgery. Age, BCS, choice of induction agent, mean vaporizer setting for isoflurane administration, duration of anesthesia, and use of PPV were not associated with hypotension in the present study. Because dogs in the present study were undergoing ovariohysterectomy, most of them were young animals, and we cannot speculate whether an association between age and hypotension (or bradycardia) would exist for dogs with a wider range of more evenly distributed ages. The mean vaporizer setting was not associated with hypotension, despite the well-known dose-dependent vasodilatory effects of isoflurane.10 We surmised 2 possible explanations for this observation: first, the range of vaporizer settings was very narrow in our sample, which made determining associations with this variable more difficult. Second, it was likely that as MAP decreased, the vaporizer setting was decreased in an attempt to limit the development of hypotension. Similarly, duration of anesthesia was not associated with hypotension. The procedures were fairly lengthy for this population of dogs, and we could not evaluate whether shorter anesthesia times might result in a lower incidence of hypotension. However, hypotension occurred at a median of 15 and 20 minutes after induction of anesthesia for the acepromazine and dexmedetomidine groups, respectively, so it should be expected that hypotension might occur even during short procedures. Moreover, the minimum time for first appearance of hypotension was 0 minutes for both groups (ie, the first MAP measured after anesthetic induction and tracheal intubation was < 60 mm Hg in some dogs).
We investigated potential associations between mechanical PPV and arterial hypotension because of a possibility that PPV can be associated with reductions in preload. The lack of detectable association between these variables in the present study was in agreement with previous experiments in healthy dogs, which demonstrated that hemodynamic function is not substantially affected by PPV.11,12 In our facility at the time of the study, PPV was typically performed with a peak inspiratory pressure of 10 cm H2O and positive end-expiratory pressure of 0; it is possible that the impact of this technique was such that the effects on MAP were limited. Moreover, data were collected in healthy, presumably euvolemic dogs. Considering these aspects and that PPV might have a greater hemodynamic impact in hypovolemic animals, our results should not be extrapolated to dogs ventilated with greater pressures or volumes or to hypovolemic dogs. Because we defined hypotension as a MAP < 60 mm Hg, it was possible that an association between PPV and lower MAP existed but at values that did not conform to our definition of hypotension. It is also possible that the overall incidence of hypotension was high enough that it did not permit discrimination between dogs that underwent PPV and those allowed to breathe spontaneously.
For study purposes, we defined bradycardia as a heart rate < 50% of the presedation value. This definition was arbitrary, and it is possible that many anesthetists would consider bradycardia to be present when heart rate decreases by a smaller fraction or falls outside of a predetermined range. Because all study dogs received an opioid, we expected that some degree of a reduction in heart rate would be observed in most of them. In addition, the clinical setting was that of a busy, noisy teaching hospital, and multiple veterinarians and students could have examined a given dog, so we anticipated that the resting heart rates of the dogs might have been increased by stress associated with the unfamiliar setting and unfamiliar people. For these reasons, we selected a threshold of 50% in an attempt to identify dogs in which the decrease in heart rate was more substantial than might typically occur after sedation and anesthesia in this setting. Under these conditions, administration of dexmedetomidine was associated with greater odds of bradycardia, compared with acepromazine administration. However, similar to the findings related to arterial hypotension, the incidence of bradycardia in both groups was high (154/192 [80%] for the dexmedetomidine group and 86/149 [58%] for the acepromazine group).
Although the choice of induction agent was not associated with arterial hypotension in our study, it was associated with bradycardia; dogs that received propofol or the ketamine-benzodiazepine combination had greater odds of bradycardia than did those that received thiopental, with no detectable difference in this variable between dogs that received propofol or ketamine-benzodiazepine. Whereas ketamine is typically associated with increased heart rate,13 induction with that agent did not result in a lower rate of bradycardia in the present study. It was possible that the combination of premedicants and the benzodiazepines used with ketamine (diazepam or midazolam) contributed to blunting the indirect sympathomimetic effects of ketamine that are ordinarily responsible for an increased heart rate. It was also possible that the definition of bradycardia used prevented detection of smaller differences in heart rate between induction agents. Thiopental increases heart rate in dogs sedated with medetomidine and hydromorphone,14 an effect that might have influenced the observations in the present study. Unfortunately, we did not have data between administration of the sedatives and anesthetic induction to assess whether heart rate was increased after thiopental administration in these dogs.
Despite the higher incidence of bradycardia in dogs that received dexmedetomidine, anticholinergic agents were not administered more frequently to dogs of this group. This observation reflected particular practices of our service; anticholinergic agents were not commonly administered to dogs that were bradycardic but not hypotensive (a scenario commonly encountered with dexmedetomidine treatment). This decision was made on the basis of several experimental research projects that demonstrated a lack of benefit in treating α-adrenoceptor agonist-induced bradycardia with anticholinergic drugs.15–17
The present study had several limitations, in part because of its retrospective nature. Intravenous fluid therapy was not evaluated in the study. Our practice was to administer crystalloid solutions to all animals undergoing general anesthesia; however, the volume infused could vary substantially depending on patient status and attending anesthesiologists’ preferences. Because of this, we considered that the volumes of crystalloid solutions administered would not reliably reflect treatment of arterial hypotension in this population of dogs. In addition, because our primary goal was to detect associations between the 2 sedative agents and development of hypotension or bradycardia, we collected data from a fairly homogenous subpopulation of dogs, in which other factors that could affect MAP and heart rate did not vary substantially. This was done so that changes in the incidence of these complications could be more directly associated to the sedatives. The unfortunate but unavoidable result was that those other factors (eg, vaporizer setting or duration of anesthesia) remained within a narrow range. This likely limited our ability to detect associations between these factors and development of hypotension or bradycardia. It should also be noted that arterial blood pressure was measured with oscillometric monitors. These monitors may introduce MAP measurement errors of various magnitudes, depending on where the cuff is placed18; such errors could have impacted the results pertaining to hypotension. Lastly, temperature data were not collected because temperature varied throughout the procedures and were not recorded in a systematic way in all dogs (eg, continuous esophageal temperature or intermittent rectal temperature could have been measured).
Acknowledgments
No external funding was received in connection with the study. The authors declare that there were no conflicts of interest.
Drs. Mostowy and Pittman were 4th-year veterinary students at the time of the study.
ABBREVIATIONS
| BCS | Body condition score |
| CI | Confidence interval |
| MAP | Mean arterial blood pressure |
| PPV | Positive-pressure ventilation |
Footnotes
West-Ward, Eatontown, NJ.
Aceproject, Henry Schein Animal Health, Columbus, Ohio.
Dexdomitor, Zoetis, Kalamazoo, Mich.
Cardell Touch veterinary monitor, Midmark Corp, Rononkoma, NY.
JMP Pro, version 12, SAS Institute Inc, Cary, NC.
References
1. Heard DJ, Webb AI, Daniels RT. Effect of acepromazine on the anesthetic requirement of halothane in the dog. Am J Vet Res 1986;47:2113–2115.
2. Popovic NA, Mullane JF, Yhap EO. Effects of acetylpromazine maleate on certain cardiorespiratory responses in dogs. Am J Vet Res 1972;33:1819–1824.
3. Grasso SC, Ko JC, Weil AB, et al. Hemodynamic influence of acepromazine or dexmedetomidine premedication in isoflurane-anesthetized dogs. J Am Vet Med Assoc 2015;246:754–764.
4. Bloor BC, Frankland M, Alper G, et al. Hemodynamic and sedative effects of dexmedetomidine in dog. J Pharmacol Exp Ther 1992;263:690–697.
5. Kuusela E, Raekallio M, Väisänen M, et al. Comparison of medetomidine and dexmedetomidine as premedicants in dogs undergoing propofol-isoflurane anesthesia. Am J Vet Res 2001;62:1073–1080.
6. Lote CJ, Harper L, Savage CO. Mechanisms of acute renal failure. Br J Anaesth 1996;77:82–89.
7. Laflamme D. Development and validation of a body condition score system for dogs. Canine Pract 1997;22:10–15.
8. Brodbelt DC, Pfeiffer DU, Young LE, et al. Results of the confidential enquiry into perioperative small animal fatalities regarding risk factors for anesthetic-related death in dogs. J Am Vet Med Assoc 2008;233:1096–1104.
9. Gil L, Redondo JI. Canine anaesthetic death in Spain: a multicentre prospective cohort study of 2012 cases. Vet Anaesth Analg 2013;40:e57–e67.
10. Brahim JS, Thut PD. Hemodynamic changes during isoflurane anesthesia. Anesth Prog 1984;31:207–212.
11. Venus B, Jacobs HK, Mathru M. Hemodynamic responses to different modes of mechanical ventilation in dogs with normal and acid aspirated lungs. Crit Care Med 1980;8:620–627.
12. Polis I, Gasthuys F, Laevens H, et al. The influence of ventilation mode (spontaneous ventilation, IPPV and PEEP) on cardiopulmonary parameters in sevoflurane anaesthetized dogs. J Vet Med A Physiol Pathol Clin Med 2001;48:619–630.
13. Henao-Guerrero N, Riccó CH. Comparison of the cardiorespiratory effects of a combination of ketamine and propofol, propofol alone, or a combination of ketamine and diazepam before and after induction of anesthesia in dogs sedated with acepromazine and oxymorphone. Am J Vet Res 2014;75:231–239.
14. Enouri SS, Kerr CL, McDonell WN, et al. Cardiopulmonary effects of anesthetic induction with thiopental, propofol, or a combination of ketamine hydrochloride and diazepam in dogs sedated with a combination of medetomidine and hydromorphone. Am J Vet Res 2008;69:586–595.
15. Alibhai HI, Clarke KW, Lee YH, et al. Cardiopulmonary effects of combinations of medetomidine hydrochloride and atropine sulphate in dogs. Vet Rec 1996;138:11–13.
16. Sinclair MD, O'Grady MR, Kerr CL, et al. The echocardiographic effects of romifidine in dogs with and without prior or concurrent administration of glycopyrrolate. Vet Anaesth Analg 2003;30:211–219.
17. Ko JC, Fox SM, Mandsager RE. Effects of preemptive atropine administration on incidence of medetomidine-induced bradycardia in dogs. J Am Vet Med Assoc 2001;218:52–58.
18. Sawyer DC, Guikema AH, Siegel EM. Evaluation of a new oscillometric blood pressure monitor in isoflurane-anesthetized dogs. Vet Anaesth Analg 2004;31:27–39.
