Objective: The purpose of this study was to compare the effects of pretreatment with medetomidine (Me), midazolam (Mi), and ketamine (Ke) on stress-related neurohormonal and metabolic responses in isoflurane-anesthetized cats undergoing ovariohysterectomy and castration. Materials and Methods: We prospectively recruited 112 client-owned healthy mixed-breed cats. In both surgeries, we divided the cats into seven groups (eight cats per group): non-treatment (control), Me (50 μg/kg), Mi (0.5 mg/kg), Ke (5 mg/kg), Me + Mi, Me + Ke and Me + Mi + Ke administered intramuscularly. After pretreatments, we maintained anesthesia with isoflurane and oxygen. Venous blood was taken before pretreatment, pre- and post-operatively during anesthesia, and at early- and complete-recovery. Results: Both plasma adrenaline and noradrenaline were reduced during anesthesia in all groups. Plasma cortisol increased during anesthesia and at early recovery in non-Me-treated groups, whereas it decreased in Me-treated groups in both surgeries. Plasma insulin and non-esterified fatty acid (NEFA) decreased, and glucose increased during anesthesia in all groups, but hyperglycemia and decrease in NEFA were greater in Me-treated groups. Conclusions: In isoflurane-anesthetized cats undergoing surgeries, premedication with Me alone and in combination is useful for reducing the perioperative stress-related increase in cortisol and catecholamines except for hyperglycemia. [J Adv Vet Anim Res 2021; 8(4.000): 563-575]

Objective: A randomized, blinded clinical study was conducted to evaluate ketofol (Ketamine + Propofol combination) anesthesia in 12 entire male mongrel dogs sedated with either aceproma¬zine (ACP) or medetomidine. Materials and Methods: Group A (6) dogs were pre-medicated with ACP and Group B (6) dogs with medetomidine. Anesthesia was induced and maintained using ketofol (ketamine and propo¬fol). Routine open pre-scrotal castration was performed. Sedation score and ease of arousal were assessed and recorded. Duration and depth of anesthesia were evaluated using apnea and the absence of palpebral and pedal reflexes, attempts to stand up, and muscle tremors and post-operative pain. Simple statistics were compared using Student t-test and MannWhitney test (p < 0.05). Results: Medetomidine-sedated dogs had higher sedation scores compared to ACP-sedated dogs. Medetomidine-ketofol produced significantly (p < 0.05) longer duration of anesthesia (24.5 ± 3.1 min) compared to ACP-ketofol (10.0 ± 4.4 min). Sixty-seven percent of dogs anesthetized with ACP-ketofol required top up with ketofol to complete the castration. However, none of the Med-ketofol anesthetized dogs required top up. Med-ketofol produced a more profound depth of anes¬thesia and smoother recovery from anesthesia compared to ACP-ketofol. Med-ketofol (median score 6) attained better overall post-operative analgesia compared to ACP-ketofol (median score 7), though not statistically significant (p = 0.25). Although both protocols provided adequate anes¬thesia for castration, top up was required to complete the operation in more than half of ACP-ketofol anesthetized dogs, making Med-ketofol a better protocol. Conclusion: The study recommends the use of Med-ketofol anesthesia for castration in a dog, and post-operative analgesia to be administered with either protocol, but more so in ACP-ketofol anesthetized dogs undergoing castration. [J Adv Vet Anim Res 2019; 6(2.000): 215-221]

OBJECTIVE To investigate use of the plethysmographic variability index (PVI) and perfusion index (PI) for evaluating changes in arterial blood pressure in anesthetized tigers (Panthera tigris). ANIMALS 8 adult tigers. PROCEDURES Each tiger was anesthetized once with a combination of ketamine, midazolam, medetomidine, and isoflurane. Anesthetic monitoring included assessment of PI, PVI, direct blood pressure measurements, anesthetic gas concentrations, esophageal temperature, and results of capnography and ECG. Mean arterial blood pressure (MAP) was maintained for at least 20 minutes at each of the following blood pressure conditions: hypotensive (MAP = 50 ± 5 mm Hg), normotensive (MAP = 70 ± 5 mm Hg), and hypertensive (MAP = 90 ± 5 mm Hg). Arterial blood gas analysis was performed at the beginning of anesthesia and at each blood pressure condition. RESULTS Mean ± SD PI values were 1.82 ± 2.38%, 1.17 ± 0.77%, and 1.71 ± 1.51% and mean PVI values were 16.00 ± 5.07%, 10.44 ± 3.55%, and 8.17 ± 3.49% for hypotensive, normotensive, and hypertensive conditions, respectively. The PI values did not differ significantly among blood pressure conditions. The PVI value for the hypotensive condition differed significantly from values for the normotensive and hypertensive conditions. The PVI values were significantly correlated with MAP (r = −0.657). The OR of hypotension to nonhypotension for PVI values ≥ 18% was 43.6. CONCLUSIONS AND CLINICAL RELEVANCE PVI was a clinically applicable variable determined by use of noninvasive methods in anesthetized tigers. Values of PVI ≥ 18% may indicate hypotension.

OBJECTIVE To evaluate the effects of a medetomidine-ketamine combination on tear production of clinically normal cats by use of the Schirmer tear test (STT) 1 before and during anesthesia and after reversal of medetomidine with atipamezole. ANIMALS 40 client-owned crossbred domestic shorthair cats (23 males and 17 females; age range, 6 to 24 months). PROCEDURES A complete physical examination, CBC, and ophthalmic examination were performed on each cat. Cats with no abnormalities on physical and ophthalmic examinations were included in the study. Cats were allocated into 2 groups: a control group (n = 10 cats) anesthetized by administration of a combination of medetomidine hydrochloride (80 μg/kg) and ketamine hydrochloride (5 mg/kg), and an experimental group (30) anesthetized with the medetomidine-ketamine combination and reversal by administration of atipamezole. Tear production of both eyes of each cat was measured by use of the STT I before anesthesia, 15 minutes after the beginning of anesthesia, and 15 minutes after administration of atipamezole. RESULTS Anesthesia with a medetomidine-ketamine combination of cats with no ophthalmic disease caused a significant decrease in tear production. The STT I values returned nearly to preanesthetic values within 15 minutes after reversal with atipamezole, whereas the STT I values for the control group were still low at that point. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that a tear substitute should be administered to eyes of cats anesthetized with a medetomidine-ketamine combination from the time of anesthetic administration until at least 15 minutes after administration of atipamezole.

OBJECTIVE To determine the temporal effects on tear flow measurements obtained by use of a Schirmer tear test (STT) I after IM administration of various doses of medetomidine or xylazine to healthy dogs. ANIMALS 5 healthy purpose-bred male Beagles. PROCEDURES Each dog received IM injections of 2.0 mL of physiologic saline (0.9% NaCl) solution (control treatment); 0.1% medetomidine hydrochloride (5, 10, 20, and 40 μg/kg), and 2.0% xylazine hydrochloride (0.5, 1.0, 2.0, and 4.0 mg/kg). Treatments were injected into the semimembranosus muscles; there was at least a 1-week interval between successive injections. Order of treatments was determined via a randomized Latin square crossover design. The STT I was performed on both eyes before (baseline) and 0.25, 0.50, 0.75, 1, 2, 3, 4, 5, 6, 7, 8, and 24 hours after each injection.RESULTS STT I values decreased significantly within 45 minutes after injection of medetomidine or xylazine, which was followed by gradual recovery. The lowest mean STT I value was < 10 mm/min for all sedation treatments, except when dogs received 5 μg of medetomidine/kg. Linear regression of the area under the curve for the 8 hours after administration yielded significant effects for all sedation treatments. CONCLUSIONS AND CLINICAL RELEVANCE IM administration of medetomidine or xylazine to dogs reduced tear flow in a dose-related manner. Artificial tear solution or ophthalmic ointment should be used to protect the ocular surface when these drugs are administered to dogs.

The effects of 2 different 8-hour continuous rate infusions (CRIs) of medetomidine on epinephrine, norepinephrine, cortisol, glucose, and insulin levels were investigated in 6 healthy dogs. Each dog received both treatments and a control as follows: MED1 = 2 μg/kg bodyweight (BW) loading dose followed by 1 μg/kg BW per hour CRI; MED2 = 4 μg/kg BW loading dose followed by 2 μg/kg BW per hour CRI; and CONTROL = saline bolus followed by a saline CRI. Both infusion rates of medetomidine decreased norepinephrine levels throughout the infusion compared to CONTROL. While norepinephrine levels tended to be lower with the MED2 treatment compared to the MED1, this difference was not significant. No differences in epinephrine, cortisol, glucose, or insulin were documented among any of the treatments at any time point. At the low doses used in this study, both CRIs of medetomidine decreased norepinephrine levels over the 8-hour infusion period, while no effects were observed on epinephrine, cortisol, glucose, and insulin.

Objective: To evaluate effects of racemic ketamine and S-ketamine in gazelles. Animals: 21 male gazelles (10 Rheem gazelles [Gazella subgutturosa marica] and 11 Subgutturosa gazelles [Gazella subgutturosa subgutturosa]), 6 to 67 months old and weighing (mean±SD) 19 ± 3 kg. Procedures: In a randomized, blinded crossover study, a combination of medetomidine (80 μg/kg) with racemic ketamine (5 mg/kg) or S-ketamine (3 mg/kg) was administered IM. Heart rate, blood pressure, respiratory rate, rectal temperature, and oxygen saturation (determined by means of pulse oximetry) were measured. An evaluator timed and scored induction of, maintenance of, and recovery from anesthesia. Medetomidine was reversed with atipamezole. The alternate combination was used after a 4-day interval. Comparisons between groups were performed with Wilcoxon signed rank and paired t tests. Results: Anesthesia induction was poor in 2 gazelles receiving S-ketamine, but other phases of anesthesia were uneventful. A dominant male required an additional dose of S-ketamine (0.75 mg/kg, IM). After administration of atipamezole, gazelles were uncoordinated for a significantly shorter period with S-ketamine than with racemic ketamine. Recovery quality was poor in 3 gazelles with racemic ketamine. No significant differences between treatments were found for any other variables. Time from drug administration to antagonism was similar between racemic ketamine (44.5 to 53.0 minutes) and S-ketamine (44.0 to 50.0 minutes). Conclusions and Clinical Relevance: Administration of S-ketamine at a dose 60% that of racemic ketamine resulted in poorer induction of anesthesia, an analogous degree of sedation, and better recovery from anesthesia in gazelles with unremarkable alterations in physiologic variables, compared with racemic ketamine.

Medetomidine, an investigational drug indicated for clinical use as a short-term chemical restraint in dogs, was evaluated for its cardiopulmonary effects, in 10 naturally heartworm-infected (HW+) and 10 noninfected (HW-) Beagles. The drug was randomly administered IV (30 microgram/kg of body weight) and IM (40 microgram/kg) in single injections to all dogs. Heart rate, respiratory rate, ECG, blood gas tensions, blood pH, central venous and arterial pressures were measured at 0, 15, 30, 60, 90, 120, and 180 minutes. Medetomidine induced an immediate significant (P less than or equal to 0.001) increase in mean arterial blood pressure followed by decreased blood pressure that remained below normal throughout the study in both groups, irrespective of route of administration. Medetomidine increased central venous pressure, over time, for both groups and both routes of administration. Heart and respiratory rates were significantly (P less than or equal 0.001) decreased after medetomidine administration and remained reduced for the duration of the study in all dogs. The ECG variables were not significantly different between groups or between routes of administration. The HW+ dogs tended to have higher mean PaO2 than did HW- dogs at several postinjection determination times, particularly when the drug was administered IM. The PaO2 decreased during the first 30 minutes in both groups and tended to increase gradually thereafter. The pH decreased over time for both groups and both routes. A significant (P less than or equal to 0.05) decrease in pH was seen in the HW- dogs, compared with HW+ dogs at each measuring time for both routes. The PaCO2 did not significantly change for groups or routes. In general, bradycardia was the predominant cardiovascular effect seen after medetomidine administration in all dogs, irrespective of route. Lowering of blood pressure and heart rate (after a transient blood pressure increase) was synchronized with sedation in these dogs. The overall clinical response with regard to cardiopulmonary effects in HW+ dogs was similar to that in HW- dogs.

Pharmacokinetic variables of propofol were investigated in 6 mixed-breed dogs, and the effect of medetomidine (10 microgram/kg of body weight) on these kinetics was investigated using a two-way crossover design. On 2 occasions, dogs received either a bolus dose of propofol sufficient to allow endotracheal intubation, followed by an infusion of propofol (0.4 mg/kg/min) for 120 minutes, or medetomidine (10 microgram/kg, IM), 15 minutes prior to induction of anesthesia as described, followed by infusion of propofol (0.2 mg/kg/min). Dogs given medetomidine received atipamezole (50 microgram/kg, IM) at the end of the 120-minute propofol infusion. Blood propofol concentration was measured, using high- performance liquid chromatography with fluorescence detection. Mean elimination half-life, blood clearance, mean residence time, and mean volume of distribution at steady state, were 486.2 minutes, 34.4 ml/kg/min, 301.8 minutes, and 6.04 L/kg, respectively, in the absence of medetomidine, and 136.9 minutes, 36.2 ml/kg/min, 215.1 minutes, and 3.38 L/kg, respectively, in the presence of medetomidine. Mean time to walking without ataxia was 174 minutes in the nonpremedicated dogs (with a median blood propofol concentration of 2.2 microgram/ml) and was 160 minutes in the premedicated dogs in which median blood propofol concentration was 1.03 microgram/ml.

OBJECTIVE To evaluate effects of the peripherally acting α2-adrenoceptor antagonist MK-467 on cardiopulmonary function in sheep sedated with medetomidine and ketamine. ANIMALS 9 healthy adult female sheep. PROCEDURES Each animal received an IM injection of a combination of medetomidine (30 μg/kg) and ketamine (1 mg/kg; Med-Ket) alone and Med-Ket and 3 doses of MK-467 (150, 300, and 600 μg/kg) in a randomized blinded 4-way crossover study. Atipamezole (150 μg/kg, IM) was administered 60 minutes later to reverse sedation. Cardiopulmonary variables and sedation scores were recorded, and drug concentrations in plasma were analyzed. Data were analyzed with a repeated-measures ANCOVA and 1-way ANOVA. Reference limits for the equivalence of sedation scores were set at 0.8 and 1.25. RESULTS Heart rate, cardiac output, and Pao2 decreased and mean arterial blood pressure, central venous pressure, and systemic vascular resistance increased after Med-Ket alone. Administration of MK-467 significantly alleviated these effects, except for the decrease in cardiac output. After sedation was reversed with atipamezole, no significant differences were detected in cardiopulmonary variables among the treatments. Administration of MK-467 did not significantly alter plasma concentrations of medetomidine, ketamine, norketamine, or atipamezole. Sedation as determined on the basis of overall sedation scores was similar among treatments. CONCLUSIONS AND CLINICAL RELEVANCE Concurrent administration of MK-467 alleviated cardiopulmonary effects in sheep sedated with Med-Ket without affecting sedation or reversal with atipamezole.