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Objective—To compare 3 dose levels of medetomidine and dexmedetomidine for use as premedicants in dogs undergoing propofol-isoflurane anesthesia.
Animals—6 healthy Beagles.
Procedure—Dogs received medetomidine or dexmedetomidine intravenously at the following dose levels: 0.4 µg of medetomidine or 0.2 µg of dexmedetomidine/kg of body weight (M0.4/D0.2), 4.0 µg of medetomidine or 2.0 µg of dexmedetomidine/ kg (M4/D2), and 40 µg of medetomidine or 20 µg of dexmedetomidine/kg (M40/D20). Sedation and analgesia were scored before induction. Anesthesia was induced with propofol and maintained with isoflurane. End-tidal isoflurane concentration, heart rate, and arterial blood pressures and gases were measured.
Results—Degrees of sedation and analgesia were significantly affected by dose level but not drug. Combined mean end-tidal isoflurane concentration for all dose levels was higher in dogs that received medetomidine, compared with dexmedetomidine. Recovery time was significantly prolonged in dogs treated at the M40/D20 dose level, compared with the other dose levels. After induction, blood pressure decreased below reference range and heart rate increased in dogs treated at the M0.4/D0.2 dose level, whereas blood pressure was preserved in dogs treated at the M40/D20 dose level. However, dogs in these latter groups developed profound bradycardia and mild metabolic acidosis during anesthesia. Treatment at the M4/D2 dose level resulted in more stable cardiovascular effects, compared with the other dose levels. In addition, PaCO2 was similar among dose levels.
Conclusions and Clinical Relevance—Dexmedetomidine is at least as safe and effective as medetomidine for use as a premedicant in dogs undergoing propofol-isoflurane anesthesia. (Am J Vet Res 2001;62:1073–1080)
Objective—To determine whether a high dose of levomedetomidine had any pharmacologic activity or would antagonize the sedative and analgesic effects of dexmedetomidine in dogs.
Animals—6 healthy Beagles.
Procedure—Each dog received the following treatments on separate days: a low dose of levomedetomidine (10 µg/kg), IV, as a bolus, followed by continuous infusion at a dose of 25 µg/kg/h; a high dose of levomedetomidine (80 µg/kg), IV, as a bolus, followed by continuous infusion at a dose of 200 µg/kg/h; and a dose of isotonic saline (0.9% NaCl) solution, IV, as a bolus, followed by continuous infusion (control). For all 3 treatments, the infusion was continued for 120 minutes. After 60 minutes, a single dose of dexmedetomidine (10 µg/kg) was administered IV. Sedation and analgesia were scored subjectively, and heart rate, blood pressure, respiratory rate, arterial blood gas partial pressures, and rectal temperatures were monitored.
Results—Administration of levomedetomidine did not cause any behavioral changes. However, administration of the higher dose of levomedetomidine enhanced the bradycardia and reduced the sedative and analgesic effects associated with administration of dexmedetomidine.
Conclusion and Clinical Relevance—Results suggest that administration of dexmedetomidine alone may have some cardiovascular benefits over administration of medetomidine, which contains both dexmedetomidine and levomedetomidine. Further studies are needed to confirm the clinical importance of the effects of levomedetomidine in dogs. (Am J Vet Res 2001;62:616–621)
Objective—To identify behavioral alterations in client-owned cats recovering at home following elective ovariohysterectomy or castration and determine owner perceptions regarding severity of postoperative pain.
Animals—145 cats undergoing elective ovariohysterectomy (n = 80) or castration (65) at 4 veterinary clinics in Finland.
Procedures—Owners were asked to complete a questionnaire on their cats' behavior during the 3 days after surgery. Owners were also asked to indicate their perceptions of the severity of postoperative pain during these days by use of a 100-mm visual analog scale.
Results—Owners consistently indicated that there were changes in their cats' behavior, with the most commonly reported alterations being a decrease in overall activity level, an increase in the amount of time spent sleeping, a decrease in playfulness, and altered way of movement. Changes (ie, either an increase or decrease) in aggressive behavior were rare. Median pain score the day of surgery was 15.0 mm for male cats and 25.0 mm for female cats. Behavior score was significantly associated with day of observation, type of surgery (ovariohysterectomy vs castration), owner-assigned pain score, and veterinary clinic.
Conclusions and Clinical Relevance—Results suggested that behavioral alterations can be detected for several days after surgery in cats recovering at home following ovariohysterectomy or castration and emphasized owner concerns about the existence of postoperative pain.
Objective—To compare the perioperative stress response in dogs administered medetomidine or acepromazine as part of the preanesthetic medication.
Animals—42 client-owned dogs that underwent elective ovariohysterectomy.
Procedure—Each dog was randomly allocated to receive medetomidine and butorphanol tartrate (20 µg/kg and 0.2 mg/kg, respectively, IM) or acepromazine maleate and butorphanol (0.05 and 0.2 mg/kg, respectively, IM) for preanesthetic medication. Approximately 80 minutes later, anesthesia was induced by administration of propofol and maintained by use of isoflurane in oxygen. Each dog was also given carprofen before surgery and buprenorphine after surgery. Plasma concentrations of epinephrine, norepinephrine, cortisol, and β-endorphin were measured at various stages during the perioperative period. In addition, cardiovascular and clinical variables were monitored.
Results—Concentrations of epinephrine, norepinephrine, and cortisol were significantly lower for dogs administered medetomidine. Concentrations of β-endorphin did not differ between the 2 groups. Heart rate was significantly lower and mean arterial blood pressure significantly higher in dogs administered medetomidine, compared with values for dogs administered acepromazine.
Conclusions and Clinical Relevance—Results indicate that for preanesthetic medications, medetomidine may offer some advantages over acepromazine with respect to the ability to decrease perioperative concentrations of stress-related hormones. In particular, the ability to provide stable plasma catecholamine concentrations may help to attenuate perioperative activation of the sympathetic nervous system. (Am J Vet Res 2002;63:969–975)
OBJECTIVE To assess the possible impact of medetomidine on concentrations of alfaxalone in plasma, when coadministered as a constant rate infusion (CRI) to dogs, and to determine the possible impact of medetomidine on the cardiopulmonary effects of alfaxalone during CRI.
ANIMALS 8 healthy adult Beagles.
PROCEDURES 3 treatments were administered in a randomized crossover design as follows: 1 = saline (0.9% NaCl) solution injection, followed in 10 minutes by induction of anesthesia with alfaxalone (loading dose, 2.4 mg/kg; CRI, 3.6 mg/kg/h, for 60 minutes); 2 = medetomidine premedication (loading dose, 4.0 μg/kg; CRI, 4.0 μg/kg/h), followed by alfaxalone (as in treatment 1); and, 3 = medetomidine (as in treatment 2) and MK-467 (loading dose, 150 μg/kg; CRI, 120 μg/kg/h), followed by alfaxalone (as in treatment 1). The peripherally acting α2-adrenoceptor antagonist MK-467 was used to distinguish between the peripheral and central effects of medetomidine. Drugs were administered IV via cephalic catheters, and there was a minimum of 14 days between treatments. Cardiopulmonary parameters were measured for 70 minutes, and jugular venous blood samples were collected until 130 minutes after premedication. Drug concentrations in plasma were analyzed with liquid chromatography–tandem mass spectrometry.
RESULTS The characteristic cardiovascular effects of medetomidine, such as bradycardia, hypertension, and reduction in cardiac index, were obtunded by MK-467. The concentrations of alfaxalone in plasma were significantly increased in the presence of medetomidine, indicative of impaired drug distribution and clearance. This was counteracted by MK-467.
CONCLUSIONS AND CLINICAL RELEVANCE The alteration in alfaxalone clearance when coadministered with medetomidine may be attributed to the systemic vasoconstrictive and bradycardic effects of the α2-adrenoceptor agonist. This could be clinically important because the use of α2-adrenoceptor agonists may increase the risk of adverse effects if standard doses of alfaxalone are used.
Objective—To investigate heart rate characteristics in dogs undergoing ovariohysterectomy following premedication with medetomidine or acepromazine.
Animals—43 client-owned dogs.
Procedure—24-hour ambulatory electrocardiography was performed beginning approximately 1 hour prior to administration of premedications. Dogs were premedicated with medetomidine and butorphanol (n = 21) or acepromazine and butorphanol (22) and, approximately 85 minutes later, were anesthetized with propofol and isoflurane. Electrocardiographic recordings were examined to determine heart rate, cardiac conduction disturbances (ventricular premature complexes and atrioventricular block), and indices of heart rate variability (HRV).
Results—Minimum heart rate during the 24-hour recording period was significantly lower among dogs given medetomidine than among dogs given acepromazine, but during the postoperative period, heart rate increased in all dogs as they became physically active. Intraoperative time domain HRV indices were lower and the low frequency-to-high frequency ratio was higher among dogs given acepromazine than among dogs given medetomidine; however, significant differences between groups were no longer seen by 6 hours after surgery. There was no significant difference between groups with regard to the number of ventricular premature complexes or to values of scaling exponent α2 (a nonlinear measure of HRV).
Conclusions and Clinical Relevance—Results suggest that there are greater enhancements in vagally related heart rate indices in medetomidine-treated dogs that may persist until 6 hours after surgery. Despite the low heart rates, dogs given medetomidine showed expected responses to surgery and positional stimuli, and the 2 preanesthetic protocols may not result in different prevalences of ventricular premature complexes. (J Am Vet Med Assoc 2005;226:738–745)
Objective—To assess bioequivalence after oral, IM, and IV administration of racemic ketoprofen in pigs and to investigate the bioavailability after oral and IM administration.
Animals—8 crossbred pigs.
Procedures—Each pig received 4 treatments in a randomized crossover design, with a 6-day washout period. Ketoprofen was administered at 3 and 6 mg/kg, PO; 3 mg/kg, IM; and 3 mg/kg, IV. Plasma ketoprofen concentrations were measured by use of high-performance liquid chromatography for up to 48 hours. To assess bioequivalence, a 90% confidence interval was calculated for the area under the time-concentration curve (AUC) and maximum plasma concentration (Cmax).
Results—Equivalence was not detected in the AUCs among the various routes of administration nor in Cmax between oral and IM administration of 3 mg/kg. The bioavailability of ketoprofen was almost complete after each oral or IM administration. Mean ± SD Cmax was 5.09 ± 1.41 μg/mL and 7.62 ± 1.22 μg/mL after oral and IM doses of 3 mg/kg, respectively. Mean elimination half-life varied from 3.52 ± 0.90 hours after oral administration of 3 mg/kg to 2.66 ± 0.50 hours after IV administration. Time to peak Cmax after administration of all treatments was approximately 1 hour. Increases in AUC and Cmax were proportional when the orally administered dose was increased from 3 to 6 mg/kg.
Conclusions and Clinical Relevance—Orally administered ketoprofen was absorbed well in pigs, although bioequivalence with IM administration of ketoprofen was not detected. Orally administered ketoprofen may have potential for use in treating pigs.
Objective—To evaluate perfusion of abdominal organs in healthy cats by use of contrastenhanced ultrasonography.
Animals—10 young healthy anesthetized cats.
Procedures—Contrast-enhanced ultrasonography of the liver, left kidney, pancreas, small intestine, and mesenteric lymph nodes was performed on anesthetized cats.
Results—Typical perfusion patterns were found for each of the studied organs. Differences in perfusion among organs were associated with specific physiologic features. The liver was enhanced gradually and had a more heterogeneous perfusion pattern because of its dual blood supply and close proximity to the diaphragm, compared with other organs. An obvious and significant difference in perfusion was detected between the renal cortex and medulla. No significant differences in perfusion were detected among the pancreas, small intestine, and mesenteric lymph nodes.
Conclusions and Clinical Relevance—Results indicated that contrast-enhanced ultrasonography can be used in cats to estimate organ perfusion as in other species. Observed differences in perfusion variables can be mostly explained by physiologic differences in vascularity. (Am J Vet Res 2010;71:1305–1311)
OBJECTIVE To compare cardiovascular effects of premedication with medetomidine alone and with each of 3 doses of MK-467 or after glycopyrrolate in dogs subsequently anesthetized with isoflurane.
ANIMALS 8 healthy purpose-bred 5-year-old Beagles.
PROCEDURES In a randomized crossover study, each dog received 5 premedication protocols (medetomidine [10 μg/kg, IV] alone [MED] and in combination with MK-467 at doses of 50 [MMK50], 100 [MMK100], and 150 [MMK150] μg/kg and 15 minutes after glycopyrrolate [10 μg/kg, SC; MGP]), with at least 14 days between treatments. Twenty minutes after medetomidine administration, anesthesia was induced with ketamine (0.5 mg/kg, IV) and midazolam (0.1 mg/kg, IV) increments given to effect and maintained with isoflurane (1.2%) for 50 minutes. Cardiovascular variables were recorded, and blood samples for determination of plasma dexmedetomidine, levomedetomidine, and MK-467 concentrations were collected at predetermined times. Variables were compared among the 5 treatments.
RESULTS The mean arterial pressure and systemic vascular resistance index increased following the MED treatment, and those increases were augmented and obtunded following the MGP and MMK150 treatments, respectively. Mean cardiac index for the MMK100 and MMK150 treatments was significantly greater than that for the MGP treatment. The area under the time-concentration curve to the last sampling point for dexmedetomidine for the MMK150 treatment was significantly lower than that for the MED treatment.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated concurrent administration of MK-467 with medetomidine alleviated medetomidine-induced hemodynamic changes in a dose-dependent manner prior to isoflurane anesthesia. Following MK-467 administration to healthy dogs, mean arterial pressure was sustained at acceptable levels during isoflurane anesthesia.
OBJECTIVE To compare the effects of MK-467 and hyoscine butylbromide on detomidine hydrochloride–induced cardiorespiratory and gastrointestinal changes in horses.
ANIMALS 6 healthy adult horses.
PROCEDURES Horses received detomidine hydrochloride (20 μg/kg, IV), followed 10 minutes later by MK-467 hydrochloride (150 μg/kg; DET-MK), hyoscine butylbromide (0.2 mg/kg; DET-HYO), or saline (0.9% NaCl) solution (DET-S), IV, in a Latin square design. Heart rate, respiratory rate, rectal temperature, arterial and venous blood pressures, and cardiac output were measured; blood gases and arterial plasma drug concentrations were analyzed; selected cardiopulmonary variables were calculated; and sedation and gastrointestinal borborygmi were scored at predetermined time points. Differences among treatments or within treatments over time were analyzed statistically.
RESULTS With DET-MK, detomidine-induced hypertension and bradycardia were reversed shortly after MK-467 injection. Marked tachycardia and hypertension were observed with DET-HYO. Mean heart rate and mean arterial blood pressure differed significantly among all treatments from 15 to 35 and 15 to 40 minutes after detomidine injection, respectively. Cardiac output was greater with DET-MK and DET-HYO than with DET-S 15 minutes after detomidine injection, but left ventricular workload was significantly higher with DET-HYO. Borborygmus score, reduced with all treatments, was most rapidly restored with DET-MK. Sedation scores and pharmacokinetic parameters of detomidine did not differ between DET-S and DET-MK.
CONCLUSIONS AND CLINICAL RELEVANCE MK-467 reversed or attenuated cardiovascular and gastrointestinal effects of detomidine without notable adverse effects or alterations in detomidine-induced sedation in horses. Further research is needed to determine whether these advantages are found in clinical patients and to assess whether the drug influences analgesic effects of detomidine.