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 evaluate the pharmacokinetics and pharmacodynamics of naloxone hydrochloride in dogs following intranasal (IN) and IV administration. ANIMALS 6 healthy adult mixed-breed dogs. PROCEDURES In a blinded crossover design involving 2 experimental periods separated by a washout period (minimum of 7 days), dogs were randomly assigned to receive naloxone IN (4 mg via a commercially available fixed-dose naloxone atomizer; mean ± SD dose, 0.17 ± 0.02 mg/kg) or IV (0.04 mg/kg) in the first period and then the opposite treatment in the second period. Plasma naloxone concentrations, dog behavior, heart rate, and respiratory rate were evaluated for 24 hours/period. RESULTS Naloxone administered IN was well absorbed after a short lag time (mean ± SD, 2.3 ± 1.4 minutes). Mean maximum plasma concentration following IN and IV administration was 9.3 ± 2.5 ng/mL and 18.8 ± 3.9 ng/mL, respectively. Mean time to maximum concentration following IN administration was 22.5 ± 8.2 minutes. Mean terminal half-life after IN and IV administration was 47.4 ± 6.7 minutes and 37.0 ± 6.7 minutes, respectively. Mean bioavailability of naloxone administered IN was 32 ± 13%. There were no notable changes in dog behavior, heart rate, or respiratory rate following naloxone administration by either route. CONCLUSIONS AND CLINICAL RELEVANCE Use of a naloxone atomizer for IN naloxone administration in dogs may represent an effective alternative to IV administration in emergency situations involving opioid exposure. Future studies are needed to evaluate the efficacy of IN naloxone administration in dogs with opioid intoxication, including a determination of effective doses.

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 evaluate the effects of providing 100% O2, compared with provision of room air, in sedated spontaneously breathing inland bearded dragons (Pogona vitticeps). ANIMALS 8 adult bearded dragons. PROCEDURES Animals were sedated with alfaxalone (20 mg/kg, SC) and received 21% O2 (equivalent to room air) or 100% O2 via face mask (flow rate, 1 L/min) in a randomized, blinded, complete crossover study (2-week interval between treatments). Sedation variables, cardiopulmonary variables, venous blood gas values, and postsedation food intake were evaluated. RESULTS Respiratory rate, heart rate, oxygen saturation, and sedation quality were comparable between treatments. Venous blood gas analysis revealed a higher total Pco2 and HCO3− concentration for the 21% O2 treatment. Postsedation food intake was not affected by the inspired oxygen fraction provided during sedation. CONCLUSIONS AND CLINICAL RELEVANCE The fraction of inspired oxygen did not appear to have clinically relevant effects on physiologic variables of bearded dragons during and after sedation. Therefore, provision of 100% O2 can be considered for use in sedated bearded dragons without the risk of inducing hypoventilation. Similarly, failure to provide 100% O2 would be unlikely to result in clinically relevant consequences in healthy sedated bearded dragons.

OBJECTIVE To compare IV doses of alfaxalone and ketamine needed to facilitate orotracheal intubation and assess effects of each treatment on selected physiologic variables in goats undergoing orthopedic surgery with isoflurane anesthesia. ANIMALS 18 healthy adult goats. PROCEDURES Behavior was assessed before and after sedation with midazolam (0.1 mg/kg, IV) for IV catheter placement. Anesthesia was induced with additional midazolam (0.1 mg/kg, IV) and alfaxalone (n = 9) or ketamine (9) at 2 mg/kg, IV, over 30 seconds. An additional dose of alfaxalone or ketamine (1 mg/kg) was given IV if needed for intubation; anesthesia was maintained with isoflurane in oxygen and IV fluids with ketamine (0.5 to 1 mg/kg/h). Direct systolic (SAP), diastolic (DAP), and mean (MAP) arterial blood pressures; heart rate; and respiratory rate were recorded before induction, immediately after intubation, and during surgery. Qualitative anesthetic induction and recovery characteristics were assessed. Variables were compared within and between groups by statistical methods. RESULTS No preinduction variables differed significantly between groups. Postintubation and 30-minute intraoperative SAP, DAP, and MAP were higher for the ketamine group than for the alfaxalone group; within the alfaxalone group, postintubation SAP, MAP, and respiratory rate prior to mechanical ventilation were lower than respective preinduction values. All alfaxalone-group goats were intubated after 1 dose of the induction agent; 5 of 9 ketamine-group goats required an additional (1-mg/kg) dose. Postoperative recovery was good to excellent for all animals. CONCLUSIONS AND CLINICAL RELEVANCE Both drugs were suitable for induction of anesthesia after sedation with midazolam, but most goats required higher doses of ketamine to allow intubation. For situations in which alfaxalone administration is appropriate, the potential for decreased arterial blood pressures and respiratory rate should be considered.

OBJECTIVE To assess effects of nitrogen and helium on efficacy of an alveolar recruitment maneuver (ARM) for improving pulmonary mechanics and oxygen exchange in anesthetized horses. ANIMALS 6 healthy adult horses. PROCEDURES Horses were anesthetized twice in a randomized crossover study. Isoflurane-anesthetized horses in dorsal recumbency were ventilated with 30% oxygen and 70% nitrogen (treatment N) or heliox (30% oxygen and 70% helium; treatment H) as carrier gas. After 60 minutes, an ARM was performed. Optimal positive end-expiratory pressure was identified and maintained for 120 minutes. Throughout the experiment, arterial blood pressures, heart rate, peak inspiratory pressure, dynamic compliance (C(dyn)), and Pao(2) were measured. Variables were compared with baseline values and between treatments by use of an ANOVA. RESULTS The ARM resulted in significant increases in Pao(2) and C(dyn) and decreases in the alveolar-arterial gradient in the partial pressure of oxygen in all horses. After the ARM and during the subsequent 120-minute phase, mean values were significantly lower for treatment N than treatment H for Pao2 and C(dyn). Optimal positive end-expiratory pressure was consistently 15 cm H(2)O for treatment N, but it was 10 cm H(2)O (4 horses) and 15 cm H(2)O (2 horses) for treatment H.

OBJECTIVE To compare effects of tiletamine-zolazepam, alfaxalone, ketamine-diazepam, and propofol for anesthetic induction on cardiorespiratory and acid-base variables before and during isoflurane-maintained anesthesia in healthy dogs. ANIMALS 6 dogs. PROCEDURES Dogs were anesthetized with sevoflurane and instrumented. After dogs recovered from anesthesia, baseline values for cardiorespiratory variables and cardiac output were determined, and arterial and mixed-venous blood samples were obtained. Tiletamine-zolazepam (5 mg/kg), alfaxalone (4 mg/kg), propofol (6 mg/kg), or ketamine-diazepam (7 and 0.3 mg/kg) was administered IV in 25% increments to enable intubation. After induction (M0) and at 10, 20, 40, and 60 minutes of a light anesthetic plane maintained with isoflurane, measurements and sample collections were repeated. Cardiorespiratory and acid-base variables were compared with a repeated-measures ANOVA and post hoc t test and between time points with a pairwise Tukey test. RESULTS Mean ± SD intubation doses were 3.8 ± 0.8 mg/kg for tiletamine-zolazepam, 2.8 ± 0.3 mg/kg for alfaxalone, 6.1 ± 0.9 mg/kg and 0.26 ± 0.04 mg/kg for ketamine-diazepam, and 5.4 ± 1.1 mg/kg for propofol. Anesthetic depth was similar among regimens. At M0, heart rate increased by 94.9%, 74.7%, and 54.3% for tiletamine-zolazepam, ketamine-diazepam, and alfaxalone, respectively. Tiletamine-zolazepam caused higher oxygen delivery than propofol. Postinduction apnea occurred in 3 dogs when receiving alfaxalone. Acid-base variables remained within reference limits. CONCLUSIONS AND CLINICAL RELEVANCE In healthy dogs in which a light plane of anesthesia was maintained with isoflurane, cardiovascular and metabolic effects after induction with tiletamine-zolazepam were comparable to those after induction with alfaxalone and ketamine-diazepam.

OBJECTIVE To investigate the cardiovascular and sedation reversal effects of IM administration of atipamezole (AA) in dogs treated with medetomidine hydrochloride (MED) or MED and vatinoxan (MK-467). ANIMALS 8 purpose-bred, 2-year-old Beagles. PROCEDURES A randomized, blinded, crossover study was performed in which each dog received 2 IM treatments at a ≥ 2-week interval as follows: injection of MED (20 μg/kg) or MED mixed with 400 μg of vatinoxan/kg (MEDVAT) 30 minutes before AA (100 μg/kg). Sedation score, heart rate, mean arterial and central venous blood pressures, and cardiac output were recorded before and at various time points (up to 90 minutes) after AA. Cardiac and systemic vascular resistance indices were calculated. Venous blood samples were collected at intervals until 210 minutes after AA for drug concentration analysis. RESULTS Heart rate following MED administration was lower, compared with findings after MEDVAT administration, prior to and at ≥ 10 minutes after AA. Mean arterial blood pressure was lower with MEDVAT than with MED at 5 minutes after AA, when its nadir was detected. Overall, cardiac index was higher and systemic vascular resistance index lower, indicating better cardiovascular function, in MEDVAT-atipamezole–treated dogs. Plasma dexmedetomidine concentrations were lower and recoveries from sedation were faster and more complete after MEDVAT treatment with AA than after MED treatment with AA. CONCLUSIONS AND CLINICAL RELEVANCE Atipamezole failed to restore heart rate and cardiac index in medetomidine-sedated dogs, and relapses into sedation were observed. Coadministration of vatinoxan with MED helped to maintain hemodynamic function and hastened the recovery from sedation after AA in dogs.

OBJECTIVE To compare anesthetic effects of alfaxalone-ketamine-dexmedetomidine (AKD) and alfaxalone-butorphanol-midazolam (ABM) in naked mole-rats (Heterocephalus glaber). ANIMALS 20 naked mole-rats. PROCEDURES Naked mole-rats received AKD (alfaxalone, 2 mg/kg; ketamine, 20 mg/kg; and dexmedetomidine, 0.02 mg/kg; n = 10) or ABM (alfaxalone, 2 mg/kg; butorphanol, 2 mg/kg; and midazolam, 1 mg/kg; 9) IM; 1 animal was removed from the study. Atipamezole (I mg/kg) and flumazenil (0.1 mg/kg) were administered 40 minutes after anesthetic induction (defined as loss of the righting reflex) with AKD and ABM, respectively. Heart rate, respiratory rate, oxygen saturation, and reflexes were recorded every 5 minutes. RESULTS The ABM group had significantly longer median times for induction and recovery than the AKD group. Administration of ABM resulted in significantly lower respiratory rates than administration of AKD from time of anesthetic induction to 10 minutes after induction. Respiratory rate significantly decreased in the AKD group from I0 minutes after induction through the end of the anesthetic period but did not change over time in the ABM group. Males had higher respiratory rates in both groups. Loss of the righting reflex was still evident 40 minutes after induction in both groups. In the AKD group, all tested reflexes were absent from I0 to 40 minutes after induction; the ABM group had variable reflexes that recovered within individual animals over time. CONCLUSIONS AND CLINICAL RELEVANCE Both AKD and ABM provided effective immobilization in naked mole-rats, but AKD appeared to provide more consistent and deeper anesthesia, compared with administration of ABM.

OBJECTIVE To evaluate the cardiovascular effects of atipamezole administered at half the volume or the same volume as dexmedetomidine to isoflurane-anesthetized cats. ANIMALS 6 adult (1 to 2 years old) domestic shorthair cats (body weight, 3 to 6 kg). PROCEDURES Each cat was anesthetized with isoflurane and rocuronium 3 times; there was a 1-week washout period between successive anesthetic procedures. For each anesthetic procedure, dexmedetomidine (5 μg/kg) was administered IV. Five minutes after dexmedetomidine was administered, atipamezole (25 or 50 μg/kg) or saline (0.9% NaCl) solution was administered IM. Pulse rate, mean arterial blood pressure (MAP), cardiac output (CO), and systemic vascular resistance (SVR) were measured during anesthesia before dexmedetomidine administration (baseline), after dexmedetomidine administration, and 15, 30, 60, and 120 minutes after administration of atipamezole or saline solution. Pulse rate and MAP were also recorded when MAP was at its lowest value. Hemodynamic variables were compared among treatments at baseline, after dexmedetomidine administration, and after administration of atipamezole or saline solution. Effects of treatment and time on all variables were assessed with mixed-effects models. RESULTS Both doses of atipamezole resulted in a significantly lower MAP than did saline solution. Pulse rate, CO, and SVR were not significantly different among treatments after atipamezole or saline solution were administered. CONCLUSIONS AND CLINICAL RELEVANCE Atipamezole administered IM at half the volume or the same volume as dexmedetomidine was ineffective at increasing pulse rate or CO in anesthetized cats that received dexmedetomidine. However, atipamezole caused short-lasting but severe arterial hypotension.