OBJECTIVE To determine the effects of acepromazine maleate premedication on cardiovascular function before and after infusion of dobutamine hydrochloride for 30 minutes in isoflurane-anesthetized horses. ANIMALS 6 healthy adult horses. PROCEDURES Each horse was anesthetized once following premedication with acepromazine (0.02 mg/kg, IV) administered 30 minutes prior to anesthetic induction (ACP+ treatment) and once without premedication (ACP– treatment). Anesthesia was induced with IV administration of xylazine hydrochloride (0.8 mg/kg), ketamine hydrochloride (2.2 mg/kg), and diazepam (0.08 mg/kg). Horses were positioned in right lateral recumbency, and anesthesia was maintained via inhalation of isoflurane delivered in oxygen. End-tidal isoflurane concentration was adjusted to achieve a target mean arterial blood pressure of 60 mm Hg (interquartile range [25th to 75th percentile], 57 to 63 mm Hg) for at least 15 minutes. Cardiac index, oxygen delivery index, and femoral arterial blood flow indices were determined 60 minutes after anesthetic induction (baseline). Dobutamine was then infused to achieve a target mean arterial blood pressure of 80 mm Hg (interquartile range, 76 to 80 mm Hg). Data collection was repeated 30 minutes after the start of dobutamine infusion for comparison with baseline values. RESULTS Complete data sets were available from 5 of the 6 horses. Dobutamine administration resulted in significant increases in oxygen delivery and femoral arterial blood flow indices but no significant change in cardiac index for each treatment. However, at baseline or 30 minutes after the start of dobutamine infusion, findings for the ACP+ and ACP– treatments did not differ. CONCLUSIONS AND CLINICAL RELEVANCE In isoflurane-anesthetized horses, dobutamine administration increased oxygen delivery and femoral arterial blood flow indices, but these changes were unaffected by premedication with acepromazine.

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.

The study aimed to evaluate the combination of Magnesium sulfate (Mg), ketorolac (Kr), Propofol (P), Ketamine (K), and Xylazine(X) anesthetic protocol in anesthesia and analgesia of rabbits. Twenty healthy male rabbits, weighing (1.300 0.200 kg) were used in the study. All rabbits were randomly assigned to four groups of five rabbits injected with the different protocols (G1(p10k50mg50 ), G2(p10k50kr10 ), G3(p10 k50 kr10mg50 ), and G4(p10 k50 kr10mg50x5)) of anesthesia intravenously in the marginal ear vein. The heart rate (HR), respiratory rate (RR), rectal temperature (RT) were taken before giving the drugs (Time 0 (control reading)), and then after 5,10,15,20,30,45,60,and 75 minutes of giving anesthesia. The induction time, duration of anesthesia, degree of analgesia, muscle relaxation and recovery time were recorded also. The anesthetic protocol in G3 (p10 k50 kr10mg50) is seen suitable for short operations (gives 24.2 minutes of surgical anesthesia), and the anesthetic protocol in G4 (p10 k50 kr10mg50x5) is seen suitable for long operations (gives 43.5 minutes of surgical anesthesia), and no signs of pain with the intravenously injection of propofol.

Objective: To compare the effects of 2 fractions of inspired oxygen, 50% and > 95%, on ventilation, ventilatory rhythm, and gas exchange in isoflurane-anesthetized horses. Animals: 8 healthy adult horses. Procedures: In a crossover study design, horses were assigned to undergo each of 2 anesthetic sessions in random order, with 1 week separating the sessions. In each session, horses were sedated with xylazine hydrochloride (1.0 mg/kg, IV) and anesthesia was induced via IV administration of diazepam (0.05 mg/kg) and ketamine (2.2 mg/kg) Anesthesia was subsequently maintained with isoflurane in 50% or > 95% oxygen for 90 minutes. Measurements obtained during anesthesia included inspiratory and expiratory peak flow and duration, tidal volume, respiratory frequency, end-tidal CO2 concentration, mixed expired partial pressures of CO2 and O2, Pao2, Paco2, blood pH, arterial O2 saturation, heart rate, and arterial blood pressure. Calculated values included the alveolar partial pressure of oxygen, alveolar-to-arterial oxygen tension gradient (Pao2 − Pco2), rate of change of Pao2 − Pao2, and physiologic dead space ratio. Ventilatory rhythm, based on respiratory rate and duration of apnea, was continuously observed and recorded. Results: Use of the lower inspired oxygen fraction of 50% resulted in a lower arterial oxygen saturation and Pao2 than did use of the higher fraction. No significant difference in Paco2, rate of change of Pao2 − Pao2, ventilatory rhythm, or other measured variables was observed between the 2 sessions. Conclusion and Clinical Relevance: Use of 50% inspired oxygen did not improve the ventilatory rhythm or gas exchange and increased the risk of hypoxemia in spontaneously breathing horses during isoflurane anesthesia. Use of both inspired oxygen fractions requires adequate monitoring and the capacity for mechanical ventilation.

Objective-To determine the effect of dexmedetomidine, morphine-lidocaine-ketamine (MLK), and dexmedetomidine-morphine-lidocaine-ketamine (DMLK) constant rate infusions on the minimum alveolar concentration (MAC) of isoflurane and bispectral index (BIS) in dogs. Animals-6 healthy adult dogs. Procedures-Each dog was anesthetized 4 times with a 7-day washout period between anesthetic episodes. During the first anesthetic episode, the MAC of isoflurane (baseline) was established. During the 3 subsequent anesthetic episodes, the MAC of isoflurane was determined following constant rate infusion of dexmedetomidine (0.5 μg/kg/h), MLK (morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine, 0.6 mg/kg/h), or DMLK (dexmedetomidine, 0.5 μg/kg/h; morphine, 0.2 mg/kg/h; lidocaine, 3 mg/kg/h; and ketamine 0.6 mg/kg/h). Among treatments, MAC of isoflurane was compared by means of a Friedman test with Conover posttest comparisons, and heart rate, direct arterial pressures, cardiac output, body temperature, inspired and expired gas concentrations, arterial blood gas values, and BIS were compared with repeated-measures ANOVA and a Dunn test for multiple comparisons. Results-Infusion of dexmedetomidine, MLK, and DMLK decreased the MAC of isoflurane from baseline by 30%, 55%, and 90%, respectively. Mean heart rates during dexmedetomidine and DMLK treatments was lower than that during MLK treatment. Compared with baseline values, mean heart rate decreased for all treatments, arterial pressure increased for the DMLK treatment, cardiac output decreased for the dexmedetomidine treatment, and BIS increased for the MLK and DMLK treatments. Time to extubation and sternal recumbency did not differ among treatments. Conclusions and Clinical Relevance-Infusion of dexmedetomidine, MLK, or DMLK reduced the MAC of isoflurane in dogs.

Objective: To compare the ability of 2 partial IV anesthesia (PIVA) techniques to maintain anesthesia, compared with isoflurane alone, in horses. Animals: 45 horses. Procedures: Client-owned horses requiring general anesthesia for a variety of procedures of at least 1 hour's duration were randomly allocated to 3 groups (n = 15/group) that differed for the maintenance protocol. Anesthesia was maintained with isoflurane with a starting end-tidal isoflurane concentration of 1.3% (isoflurane group) or a concentration of 1% supplemented with an adjustable continuous infusion of guaifenesin-ketamine (IGK group) or romifidine-ketamine (IRK group). A predefined scoring system was used to assess anesthetic depth and to adjust anesthetic delivery. The need for rescue anesthetics and recovery quality were compared. Results: A mean ± SD end-tidal isoflurane concentration of 1.36 ± 0.16% was necessary to maintain a surgical plane of anesthesia in the isoflurane group. Mean infusion rates of 5.0 ± 1.3 μL/kg/min and 5.1 ± 0.8 μL/kg/min were necessary to maintain a surgical plane of anesthesia in the IRK and IGK groups, respectively. A lower need for ketamine as a rescue anesthetic was observed in the IGK group, compared with the isoflurane group. Higher blood pressure and lower heart rates were found at selected time points for the IRK group, compared with the IGK and isoflurane groups. Conclusions and Clinical Relevance: Both PIVA protocols were satisfactory to maintain smooth and stable surgical anesthesia in horses. The present study supports previous findings in which PIVA has isoflurane-sparing effects. Furthermore, PIVA did not impair recovery quality.

Objective—To identify and characterize cytochrome P450 enzymes (CYPs) responsible for the metabolism of racemic ketamine in 3 mammalian species in vitro by use of chemical inhibitors and antibodies. Sample—Human, canine, and equine liver microsomes and human single CYP3A4 and CYP2C9 and their canine orthologs. Procedures—Chemical inhibitors selective for human CYP enzymes and anti-CYP antibodies were incubated with racemic ketamine and liver microsomes or specific CYPs. Ketamine N-demethylation to norketamine was determined via enantioselective capillary electrophoresis. Results—The general CYP inhibitor 1-aminobenzotriazole almost completely blocked ketamine metabolism in human and canine liver microsomes but not in equine microsomes. Chemical inhibition of norketamine formation was dependent on inhibitor concentration in most circumstances. For all 3 species, inhibitors of CYP3A4, CYP2A6, CYP2C19, CYP2B6, and CYP2C9 diminished N-demethylation of ketamine. Anti-CYP3A4, anti-CYP2C9, and anti-CYP2B6 antibodies also inhibited ketamine N-demethylation. Chemical inhibition was strongest with inhibitors of CYP2A6 and CYP2C19 in canine and equine microsomes and with the CYP3A4 inhibitor in human microsomes. No significant contribution of CYP2D6 to ketamine biotransformation was observed. Although the human CYP2C9 inhibitor blocked ketamine N-demethylation completely in the canine ortholog CYP2C21, a strong inhibition was also obtained by the chemical inhibitors of CYP2C19 and CYP2B6. Ketamine N-demethylation was stereoselective in single human CYP3A4 and canine CYP2C21 enzymes. Conclusions and Clinical Relevance—Human-specific inhibitors of CYP2A6, CYP2C19, CYP3A4, CYP2B6, and CYP2C9 diminished ketamine N-demethylation in dogs and horses. To address drug-drug interactions in these animal species, investigations with single CYPs are needed.

Objective-To determine the effects of ketamine hydrochloride, xylazine hydrochloride, and lidocaine hydrochloride after subarachnoid administration in goats. Animals-6 healthy goats. Procedure-In each goat, ketamine (3 mg/kg), xylazine (0.1 mg/kg), lidocaine (2.5 mg/kg), and saline (0.9% NaCl) solution were injected into the subarachnoid space between the last lumbar vertebra and first sacral vertebra (time 0). Analgesic, ataxic, sedative, cardiovascular, and respiratory effects and rectal temperature were evaluated before (baseline) and 2, 5, 10, 15, and 30 minutes after administration and at 30-minute intervals thereafter as needed. Results-Administration of anesthetics induced varying degrees of analgesia. Onset of the analgesic effect was more delayed for xylazine (mean +/- SD, 9.5 +/- 2.6 minutes) than for ketamine (6.7 +/- 2.6 minutes) or lidocaine (3.5 +/- 1.2 minutes). Duration of analgesia induced by xylazine (88.3 ± 15 minutes) was twice as long as the duration of analgesia induced by ketamine (48.8 ± 13.5 minutes) but similar to that induced by lidocaine (66.5 ± 31 minutes). Xylazine induced bradycardia, whereas ketamine caused a nonsignificant increase in heart rate. Xylazine induced a reduction in arterial pressure, whereas ketamine or lidocaine did not affect arterial pressure. Conclusion and Clinical Relevance-Subarachnoid administration of xylazine in goats resulted in longer duration of analgesia of the tail, perineum, hind limbs, flanks, and caudodorsal rib areas than administration of ketamine or lidocaine. However, xylazine caused bradycardia and respiratory depression. Additional studies are needed to determine whether the analgesia would be sufficient to allow clinicians to perform surgical procedures.

Objective-To compare cardiopulmonary responses during anesthesia maintained with halothane and responses during anesthesia maintained by use of a total intravenous anesthetic (TIVA) regimen in horses. Animals-7 healthy adult horses (1 female, 6 geldings). Procedure-Each horse was anesthetized twice. Romifidine was administered IV, and anesthesia was induced by IV administration of ketamine. Anesthesia was maintained for 75 minutes by administration of halothane (HA) or IV infusion of romifidine, guaifenesin, and ketamine (TIVA). The order for TIVA or HA was randomized. Cardiopulmonary variables were measured 40, 60, and 75 minutes after the start of HA or TIVA. Results-Systolic, diastolic, and mean carotid arterial pressures, velocity time integral, and peak acceleration of aortic blood flow were greater, and systolic, diastolic, and mean pulmonary arterial pressure were lower at all time points for TIVA than for HA. Pre-ejection period was shorter and ejection time was longer for TIVA than for HA. Heart rate was greater for HA at 60 minutes. Minute ventilation and alveolar ventilation were greater and inspiratory time was longer for TIVA than for HA at 75 minutes. The PaCO2 was higher at 60 and 75 minutes for HA than for TIVA. Conclusions and Clinical relevance-Horses receiving a constant-rate infusion of romifidine, guaifenesin, and ketamine maintained higher arterial blood pressures than when they were administered HA. There was some indication that left ventricular function may be better during TIVA, but influences of preload and afterload on measured variables could account for some of these differences.

We compared the anesthetic combination of detomidine, ketamine, and halothane in control horses not undergoing apparently painful procedures with that in horses during arthroscopic surgery. The effectiveness of this regimen in suppressing neurologic response to surgery was, thus, evaluated. In this study, significant differences were not observed in electroencephalographic total amplitude, spectral edge, or beta-to-delta frequency ratio between surgically treated and nonsurgically treated (control) horses. On the basis of its attenuation of encephalographic responses, we conclude that detomidine (20 microgram/kg of body weight, IV) and ketamine (2.2 mg/kg, IV) induction of anesthesia followed by maintenance with halothane is an effective regimen for control of pain in horses during arthroscopic surgery. The insignificant frequency changes observed without any other signs of inadequate anesthesia or pain may indicate a surgical stress response. We hypothesize that brain activity monitoring may give an earlier index to initiation of surgically induced stress than do hormonal responses, because endocrine alterations are not as rapidly perceived as is the electroencephalogram. Analysis of spectral edge frequency changes could be used to evaluate anesthetic regimens to find those that cause the least stress to the CNS during surgery in horses. Differences in species responses to an anesthetic agent or the regimen's effectiveness in prevention of pain during surgery may be identified by adoption of the study model. Evaluation of cardiopulmonary variables during anesthesia, with and without surgery, did not reveal any alterations that would be relevant to CNS responses. Blood pressure, heart rate, PAO2, PACO2 and pH were stabilized by use of intermittent positive-pressure ventilation in all horses, and dobutamine was administered as needed, to avoid bias of electroencephalogram data.