Introduction: Clinical doses of anaesthetic agents were administered to rabbits and effects on the brain, heart, and liver were investigated biochemically and histopathologically. Material and Methods: The rabbits were randomly divided into three main groups (16 rabbits each) and each group into study (n = 8) and control (n = 8) groups. All study group rabbits received 3 mg/kg of midazolam (M) intramuscularly. Group 1.1 (M) received nothing further, group 2.1 (MK) also received 25 mg/kg of ketamine, and group 3.1 (MKI) besides ketamine was also given 2% isoflurane to induce anaesthesia for 30 min. NaCl solution in the same volume as midazolam and ketamine was injected into the controls. Results: In clinical evaluation significant differences were detected in respiratory and heart rates. In blood gas analysis the PO2 and PCO2 values showed statistical differences in anaesthesia intervals. Significant biochemical value changes were recorded in creatine kinase-Mb, glucose, and total protein. Histopathological liver examinations revealed higher total apoptotic and normal cell numbers in the MK than in the M and MKI groups. Apoptotic cell numbers were statistically significant in M and MK groups. Conclusion: Anaesthetic agents may increase programmed apoptosis. The MKI anaesthetics combination was found to cause less cell destruction in general than the other study groups. It was indicated that MKI was the safer anaesthetic combination in rabbits.

OBJECTIVE: To assess the analgesic efficacy of an IV constant rate infusion (CRI) of a morphine-lidocaine-ketamine (MLK) combination in calves undergoing umbilical herniorrhaphy. ANIMALS: 20 weaned Holstein calves with umbilical hernias. PROCEDURES: Calves were randomly assigned to receive a CRI of an MLK solution (0.11 mL/kg/h; morphine, 4.8 μg/kg/h; lidocaine, 2.1 mg/kg/h; and ketamine, 0.42 mg/kg/h) for 24 hours (MLK group) or 2 doses of flunixin meglumine (1.1 mg/kg, IV, q 24 h) and a CRI of saline (0.9% NaCl) solution (0.11 mL/kg/h) for 24 hours (control group). The assigned CRI was begun after anesthesia induction. A pain-scoring system and incisional algometry were used to assess pain, and blood samples were obtained to measure serum cortisol concentration at predetermined times for 120 hours after CRI initiation. RESULTS: Mean pain scores did not differ significantly between the MLK and control groups at any time. Mean algometry score for the MLK group was significantly greater (calves were less responsive to pressure) than that for the control group at 4 hours after CRI initiation. Mean cortisol concentration decreased over time for both groups and was significantly greater for the MLK group than the control group at 1, 4, and 18 hours after CRI initiation. CONCLUSIONS AND CLINICAL RELEVANCE: A CRI of MLK provided adequate postoperative analgesia to calves that underwent umbilical herniorrhaphy. However, the technical support required for CRI administration limits its use to hospital settings. Kinetic analyses of MLK infusions in cattle are necessary to establish optimal dosing protocols and withdrawal intervals.

OBJECTIVE To evaluate the effects of injectable dexmedetomidine-ketamine-midazolam (DKM) and isoflurane inhalation (ISO) anesthetic protocols on selected ocular variables in captive black-tailed prairie dogs (Cynomys ludovicianus; BTPDs). ANIMALS 9 zoo-kept BTPDs. PROCEDURES The BTPDs received dexmedetomidine hydrochloride (0.25 mg/kg, IM), ketamine hydrochloride (40 mg/kg, IM), and midazolam hydrochloride (1.5 mg/kg, IM) or inhalation of isoflurane and oxygen in a randomized complete crossover design (2-day interval between anesthetic episodes). Pupil size, globe position, tear production, and intraocular pressure measurements were recorded at 5, 30, and 45 minutes after induction of anesthesia. For each BTPD, a phenol red thread test was performed in one randomly selected eye and a modified Schirmer tear test I was performed in the other eye. Intraocular pressure was measured by rebound tonometry. RESULTS Compared with findings for the DKM protocol, pupil size was smaller at all time points when the BTPDs underwent the ISO protocol. Globe position remained central during anesthesia with the DKM protocol, whereas it varied among central, ventromedial, and ventrolateral positions during anesthesia with the ISO protocol. Tear production and intraocular pressure decreased significantly over time when the BTPDs underwent either protocol. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that ophthalmic examination findings for anesthetized BTPDs can be influenced by the anesthetic protocol used. The DKM protocol may result in more consistent pupil size and globe position, compared with that achieved by use of the ISO protocol. Tear production and intraocular pressure measurements should be conducted promptly after induction of anesthesia to avoid the effect of anesthetic episode duration on these variables.

OBJECTIVE To evaluate efficacy and safety of anesthesia with dexmedetomidine-ketamine-midazolam (DKM) in five-striped palm squirrels (Funambulus pennantii). ANIMALS 8 male squirrels. PROCEDURES Squirrels were anesthetized with DKM (dexmedetomidine, 0.1 mg/kg; ketamine hydrochloride, 30 mg/kg; and midazolam, 0.75 mg/kg) administered IM. Atipamezole (0.15 mg/kg) and flumazenil (0.1 mg/kg) were administered IM 40 minutes after induction of anesthesia. Vital signs and responses were recorded every 5 minutes during anesthesia. RESULTS Anesthetic induction and recovery from anesthesia were rapid and without complications in all squirrels. Median anesthetic induction time was 67.5 seconds (interquartile [25th to 75th percentile] range, 5.5 seconds), and mean ± SD recovery time after drug reversal was 147 ± 79 seconds. Heart rate, respiratory rate, and rectal temperature significantly decreased during the anesthetic period. All squirrels became hypothermic by 40 minutes after induction. The righting reflex was absent during the 40-minute anesthetic period in all squirrels, with variable responses for the palpebral reflex, jaw tone, forelimb withdrawal reflex, and hind limb withdrawal reflex. Only 2 of 8 squirrels had loss of the limb withdrawal reflex in both the forelimbs and hind limbs from anesthetic induction to 25 minutes after induction. CONCLUSIONS AND CLINICAL RELEVANCE DKM appeared to provide safe and effective anesthesia in five-striped palm squirrels, but oxygen and thermal support were indicated. At the doses administered, deep surgical anesthesia was not consistently achieved, and anesthetic depth of individual squirrels must be determined before surgical procedures are performed in palm squirrels anesthetized with this drug combination.

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.

The objective of this study was to evaluate the stability of 3 distinct preparations of ketamine and xylazine, with or without acepromazine, stored at room temperature or at 4°C for 1, 2, and 3 mo. Drug concentrations were compared to fresh solutions, using a high performance liquid chromatography-mass spectrometry/selected-ion monitoring (HPLC-MS/SIM) assay. The concentrations of ketamine and xylazine, diluted in physiological saline, did not change over time at room temperature or at 4°C. However, acepromazine concentrations decreased over time when stored at room temperature. In contrast, undiluted ketamine-xylazine preparations gradually decreased in concentration when stored at room temperature. All of the drug concentrations remained above 90% of their original concentration when stored at 4°C. In conclusion, when diluted in physiological saline, ketamine-xylazine cocktails can be stored for 3 mo, whereas undiluted cocktails can lose efficacy over 3 mo at room temperature. Storage at 4°C could preserve drug stability.

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.