OBJECTIVE To determine effects of anesthesia on plasma concentrations and pulsatility of ACTH in samples obtained from the cavernous sinus and jugular vein of horses. ANIMALS 6 clinically normal adult horses. PROCEDURES Catheters were placed in a jugular vein and into the cavernous sinus via a superficial facial vein. The following morning (day 1), cavernous sinus blood samples were collected every 5 minutes for 1 hour (collection of first sample = time 0) and jugular venous blood samples were collected at 0, 30, and 60 minutes. On day 2, horses were sedated with xylazine hydrochloride and anesthesia was induced with propofol mixed with ketamine hydrochloride. Horses were positioned in dorsal recumbency. Anesthesia was maintained with isoflurane in oxygen and a continuous rate infusion of butorphanol tartrate. One hour after anesthesia was induced, the blood sample protocol was repeated. Plasma ACTH concentrations were quantified by use of a commercially available sandwich assay. Generalized estimating equations that controlled for horse and an expressly automated deconvolution algorithm were used to determine effects of anesthesia on plasma ACTH concentrations and pulsatility, respectively. RESULTS Anesthesia significantly reduced the plasma ACTH concentration in blood samples collected from the cavernous sinus. CONCLUSIONS AND CLINICAL RELEVANCE Mean plasma ACTH concentrations in samples collected from the cavernous sinus of anesthetized horses were reduced. Determining the success of partial ablation of the pituitary gland in situ for treatment of pituitary pars intermedia dysfunction may require that effects of anesthesia be included in interpretation of plasma ACTH concentrations in cavernous sinus blood.

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 objective of this study was to determine if prior measurement of the minimum alveolar concentration (MAC) of isoflurane influences the effect of ketamine on the MAC of isoflurane in dogs. Eight mixed-breed dogs were studied on 2 occasions. Anesthesia was induced and maintained using isoflurane. In group 1 the effect of ketamine on isoflurane MAC was determined after initially finding the baseline isoflurane MAC. In group 2, the effect of ketamine on isoflurane MAC was determined without previous measure of the baseline isoflurane MAC. In both groups, MAC was determined again 30 min after stopping the CRI of ketamine. Plasma ketamine concentrations were measured during MAC determinations. In group 1, baseline MAC (mean ± SD: 1.18 ± 0.14%) was decreased by ketamine (0.88 ± 0.14%; P < 0.05). The MAC after stopping ketamine was similar (1.09 ± 0.16%) to baseline MAC and higher than with ketamine (P < 0.05). In group 2, the MAC with ketamine (0.79 ± 0.11%) was also increased after stopping ketamine (1.10 ± 0.17%; P < 0.05). The MAC values with ketamine were different between groups (P < 0.05). Ketamine plasma concentrations were similar between groups during the events of MAC determination. The MAC of isoflurane during the CRI of ketamine yielded different results when methods of same day (group-1) versus separate days (group-2) are used, despite similar plasma ketamine concentrations with both methods. However, because the magnitude of this difference was less than 10%, either method of determining MAC is deemed acceptable for research purposes.

Objective: To evaluate the use of midazolam, ketamine, and xylazine for total IV anesthesia (TIVA) in horses. Animals: 6 healthy Thoroughbred mares. Procedures: Horses were sedated with xylazine (1.0 mg/kg, IV). Anesthesia was induced with midazolam (0.1 mg/kg, IV) followed by ketamine (2.2 mg/kg, IV) and was maintained with an IV infusion of midazolam (0.002 mg/kg/min), ketamine (0.03 mg/kg/min), and xylazine (0.016 mg/kg/min). Horses underwent surgical manipulation and injection of the palmar digital nerves; duration of the infusion was 60 minutes. Additional ketamine (0.2 to 0.4 mg/kg, IV) was administered if a horse moved its head or limbs during procedures. Cardiopulmonary and arterial blood variables were measured prior to anesthesia; at 10, 20, 30, 45, and 60 minutes during infusion; and 10 minutes after horses stood during recovery. Recovery quality was assessed by use of a numeric (1 to 10) scale with 1 as an optimal score. Results: Anesthesia was produced for 70 minutes after induction; supplemental ketamine administration was required in 4 horses. Heart rate, respiratory rate, arterial blood pressures, and cardiac output remained similar to preanesthetic values throughout TIVA. Arterial partial pressure of oxygen and oxygen saturation of arterial hemoglobin were significantly decreased from preanesthetic values throughout anesthesia; oxygen delivery was significantly decreased at 10- to 30-minute time points. Each horse stood on its first attempt, and median recovery score was 2. Conclusions and Clinical Relevance: Midazolam, ketamine, and xylazine in combination produced TIVA in horses. Further studies to investigate various dosages for midazolam and ketamine or the substitution of other α2-adrenoceptor for xylazine are warranted.

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 effects of a continuous rate infusion of lidocaine on the minimum alveolar concentration (MAC) of sevoflurane in horses. Animals—8 healthy adult horses. Procedures—Horses were anesthetized via IV administration of xylazine, ketamine, and diazepam; anesthesia was maintained with sevoflurane in oxygen. Approximately 1 hour after induction, sevoflurane MAC determination was initiated via standard techniques. Following sevoflurane MAC determination, lidocaine was administered as a bolus (1.3 mg/kg, IV, over 15 minutes), followed by constant rate infusion at 50 μg/kg/min. Determination of MAC for the lidocaine-sevoflurane combination was started 30 minutes after lidocaine infusion was initiated. Arterial blood samples were collected after the lidocaine bolus, at 30-minute intervals, and at the end of the infusion for measurement of plasma lidocaine concentrations. Results—IV administration of lidocaine decreased mean ± SD sevoflurane MAC from 2.42 ± 0.24% to 1.78 ± 0.38% (mean MAC reduction, 26.7 ± 12%). Plasma lidocaine concentrations were 2,589 ± 811 ng/mL at the end of the bolus; 2,065 ± 441 ng/mL, 2,243 ± 699 ng/mL, 2,168 ± 339 ng/mL, and 2,254 ± 215 ng/mL at 30, 60, 90, and 120 minutes of infusion, respectively; and 2,206 ± 329 ng/mL at the end of the infusion. Plasma concentrations did not differ significantly among time points. Conclusions and Clinical Relevance—Lidocaine could be useful for providing a more balanced anesthetic technique in horses. A detailed cardiovascular study on the effects of IV infusion of lidocaine during anesthesia with sevoflurane is required before this combination can be recommended.

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.

Anesthesia was induced and maintained in 6 Suffolk wethers by continuous IV infusion of guaifenesin (50 mg/ml), ketamine (1 mg/ml), and xylazine (0.1 mg/ml) in 5% dextrose in water (triple drip) to assess the anesthetic and cardiopulmonary effects. All sheep were positioned in right lateral recumbency. Dosages of triple drip used for induction and maintenance of anesthesia were 1.2 +/- 0.02 ml/kg and 2.6 ml/kg/h, respectively. Lack of gross purposeful movement of sheep to electrical stimulation indicated that analgesia and muscular relaxation induced by triple trip were adequate for surgical procedures. Heart rates and arterial blood pressure remained unchanged from baseline values during a 1-hour period of anesthesia. Arterial blood pressures were measured indirectly, using an inflation cuff placed over the metatarsal artery at the heart level. Significant decrease in arterial partial pressure of O2 (PaO2), coupled with an increase in arterial partial pressure of CO2 (PaCO2), from baseline values was observed throughout the course of the study. Decrease in PaO2 was observed concomitantly with significant (P < 0.05) increase in respiration rate. Changes in arterial blood gas tensions observed in this study were attributed to respiratory depressant effect induced by anesthetic drugs and right-to-left shunting, perfusion/ventilation mismatch, or both caused by right lateral recumbency. Administration of 100% O2 via the endotracheal tube reduced the magnitude of the decrease in PaO2. All sheep recovered smoothly and stood within 96.3 +/- 48.9 minutes after termination of triple drip administration.

Few safe and effective anesthesia regimens have been described for use in rabbits, partially because of the susceptibility of this species to sometimes fatal respiratory depression. Although inhalant anesthetics are generally safer than injectable anesthetics, their use may be limited by lack of equipment or facilities. This study was conducted to compare effects of several injectable anesthetics in rabbits on response to noxious stimuli, heart rate, respiratory rate, and rectal temperature. Six injectable anesthetic combinations were administered to rabbits: xylazine-ethyl-(l-methyl-propyl) malonyl-thio-urea salt (EMTU), ketamine-EMTU, xylazine-pentobarbital, xylazine-acepromazine-ketamine (XAK), ketamine-chloral hydrate, and ketamine-xylazine. All combinations induced a depression of respiratory rate. Although rectal temperature values were reduced to some degree in each group, the most profound hypothermia was induced by XAK. The combination that induced the longest duration of anesthesia was XAK. It was concluded that XAK was preferable for longer periods of anesthesia (60 to 120 minutes), although it induces severe hypothermia. For short periods of anesthesia, xylazine-pentobarbital, xylazine-EMTU, or ketamine-xylazine were deemed adequate; however, xylazine-EMTU induced the best survivability and consistency.

Dynamic baroreflex sensitivity for increasing arterial pressure (DBSI) was used to quantitatively assess the effects of anesthesia on the heart rate/arterial pressure relationship during rapid (less than or equal to 2 minutes) pressure changes in the horse. Anesthesia was induced with IV administration of xylazine and ketamine and maintained with halothane at a constant end-tidal concentration of 1.1 to 1.2% (1.25 to 1.3 minimal alveolar concentration). Systolic arterial pressure (SAP) was increased a minimum of 30 mm of Hg in response to an IV bolus injection of phenylephrine HCl. Linear regression was used to determine the slope of the R-R interval/SAP relationship. During dynamic increases in SAP, a significant correlation between R-R interval and SAP was observed in 8 of 8 halothane-anesthetized horses. Correlation coefficients between R-R interval and sap were > 0.80 in 5 of 8 horses. Mean (+/- SD) DBSI was 4.8 +/- 3.4 ms/mm of Hg in anesthetized horses. A significant correlation between R-R interval and SAP was observed in only 3 of 6 awake horses during dynamic increases in SAP. Lack of correlation between R-R interval and SAP in 3 of 6 awake horses indicated that rapidly increasing SAP with an IV phenylephrine bolus is a poor method to evaluate baroreceptor-mediated heart rate changes in awake horses. Reflex slowing of heart rate in response to a rising arterial pressure appeared to have been overridden by the effects of excitement. Mean (+/- SD) DBSI (3 horses) was 7.3 +/- 3.3 ms/mm of Hg in awake horses.