Influence of fentanyl, medetomidine-fentanyl or acepromazine-fentanyl premedication on oesophageal and rectal temperature in dogs under anaesthesia.

OBJECTIVE: To compare changes in oesophageal (T-Oeso) and rectal (T-Rec) temperature in dogs during general anaesthesia and premedicated with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl. STUDY DESIGN: Prospective, randomized, blind clinical study. ANIMALS: A total of 120 healthy dogs, aged 2-10 years and weighing 5-20 kg. METHODS: Dogs were randomly allocated to one of three groups. Animals of F group were premedicated with fentanyl (0.01 mg kg-1), MF group with medetomidine (0.005 mg kg-1) and fentanyl (0.01 mg kg-1) and AF group with acepromazine (0.01 mg kg-1) and fentanyl (0.01 mg kg-1). Anaesthesia was induced with propofol and maintained with isoflurane in oxygen-air mixture. Fentanyl was administered continuously (0.01 mg kg-1 hour-1). The T-Oeso, T-Rec and ambient temperatures were recorded after induction (T0) and subsequently at 10 minute intervals for 60 minutes (T10-T60). Data were analysed using anova or their non-parametric equivalents (p < 0.05). RESULTS: Median T-Oeso was significantly higher in MF group between T0-T20 compared with other groups. Median T-Oeso significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T30), 37.1 °C (T40), 36.9 °C (T50) and 36.6 °C (T60), in MF group from 38.3 °C (T0) to 37.7 °C (T30), 37.5 °C (T40), 37.2 °C (T50) and 37.1 °C (T60) and in AF group from 37.7 °C (T0) to 37.3 °C (T40), 37.2 °C (T50) and 37.1 °C (T60). The T-Rec significantly decreased in F group from 38.0 °C (T0) to 37.4 °C (T40), 37.2 °C (T50) and 36.9 °C (T60), in MF group from 38.3 °C (T0) to 37.5 °C (T50) and 37.4 °C (T60) and in AF group from 38.2 °C (T0) to 37.6 °C (T40), 37.5 °C (T50) and 37.4 °C (T60). CONCLUSIONS AND CLINICAL RELEVANCE: Premedication with fentanyl, medetomidine-fentanyl or acepromazine-fentanyl in the doses used decreased the T-Oeso and T-Rec. The T-Oeso at the beginning of anaesthesia was higher after premedication with medetomidine-fentanyl. However, this difference was not clinically significant.

TILETAMINE-ZOLAZEPAM-XYLAZINE ANESTHESIA IN EX SITU BLACK-HANDED SPIDER MONKEYS (ATELES GEOFFROYI SSP.).

Black-handed spider monkeys (Ateles geoffroyi ssp.) are endangered in Mexico. Safe anesthetic protocols are important for in situ and ex situ conservation problems. Such protocols are scarce in the literature; nor have safety and physiologic responses been reported. High doses and volume are a counter side for field immobilizations. We tested an anesthetic protocol with a combination of tiletamine-zolazepam (5 mg/kg) plus xylazine (1 mg/kg) in 14 black-handed spider monkeys under human care from two facilities in Mexico. Physiological parameters such as HR, RR, T, SPO2, systolic arterial pressure (), diastolic arterial pressure (DAP), and median arterial pressure (MAP) were obtained. HR and RR decreased over time, but T increased significantly during the anesthetic time for the whole group; RR and T decreased for juveniles only. Variation between individuals was observed for HR, RR, and DAP. Volume reduction of drugs was achieved compared to previously reported anesthesia protocols. Induction time was fast (6.2 ± 10.4 min) and no tail prehension was seen. Recovery was prolonged (mean and SD). Physiologic parameters remained stable throughout. The protocol proved to be safe for the chemical immobilization of black-handed spider monkeys.

Effects of isoflurane and sevoflurane alone and in combination with butorphanol or medetomidine on the bispectral index in chickens.

BACKGROUND: The bispectral index (BIS) is an anaesthesia monitoring technique able to assess the level of central nervous system depression in humans and various animal species. In birds, it has been validated in chickens undergoing isoflurane anaesthesia. The aim of this study was to evaluate in an avian species the influence of isoflurane and sevoflurane on BIS, each at different minimum anaesthetic concentrations (MAC) multiples, alone or combined with butorphanol or medetomidine. Ten chickens (5 males and 5 females) underwent general anaesthesia with isoflurane or sevoflurane alone, and combined with either intramuscular administration of butorphanol (1 mg/kg) or medetomidine (0.1 mg/kg), in a prospective and cross-over study (i.e., 6 treatments per animal). BIS measurements were compared to heart rate (HR), non-invasive blood pressure (NIBP) and to a visual analogue scale (VAS) of anaesthesia depth. RESULTS: HR was significantly increased, and both NIBP and VAS were significantly reduced, with higher gas concentrations. NIBP (but not HR or VAS) was additionally affected by the type of gas, being lower at higher concentrations of sevoflurane. Butorphanol had no additional effect, but medetomidine led to differences in HR, NIBP, and in particular a reduction in VAS. With respect to deeper level of hypnosis at higher concentrations and the absence of difference between gases, BIS measurements correlated with all other measures (except with HR, where no significant relationship was found) The difference in BIS before (BISpre) and after stimulation (BISpost) did not remain constant, but increased with increasing MAC multiples, indicating that the BISpost is not suppressed proportionately to the suppression of the BISpre values due to gas concentration. Furthermore, neither butorphanol nor medetomidine affected the BIS. CONCLUSIONS: The difference of degree of central nervous system depression monitored by BIS compared with neuromuscular reflexes monitored by VAS, indicate that BIS records a level of anaesthetic depth different from the one deducted from VAS monitoring alone. BIS provided complementary information such as that medetomidine suppressed spinal reflexes without deepening the hypnotic state. As a consequence, it is concluded that BIS improves the assessment of the level of hypnosis in chickens, improving anaesthesia monitoring and anaesthesia quality in this species.

Comparison of anesthetic effects of tiletamine-zolazepam-medetomidine or ketamine-medetomidine in captive Amur leopard cats (Prionailurus bengalensis euptailurus).

OBJECTIVE: To evaluate the effects and utility of tiletamine-zolazepam-medetomidine (TZM) and ketamine-medetomidine (KM) for anesthesia of Amur leopard cats (Prionailurus bengalensis euptailurus). STUDY DESIGN: Prospective, randomized experimental trial. ANIMALS: A total of six female (3.70 ± 0.49 kg) and six male (5.03 ± 0.44 kg; mean ± standard deviation) Amur leopard cats aged 2-6 years. METHODS: Each animal was administered four protocols separated by ≥3 weeks. Each protocol included medetomidine (0.05 mg kg-1) combined with tiletamine-zolazepam (1 mg kg-1; protocol MTZLO); tiletamine-zolazepam (2 mg kg-1; protocol MTZHI); ketamine (2 mg kg-1; protocol MKLO); or ketamine (4 mg kg-1; MKHI) administered intramuscularly. At time 0 (onset of lateral recumbency) and 30 minutes, heart rate (HR), respiratory rate (fR), rectal temperature, noninvasive mean arterial pressure (MAP) and hemoglobin oxygen saturation (SpO2) were recorded. Times to onset of lateral recumbency, duration of anesthesia and time to standing were recorded. RESULTS: Overall, animals were anesthetized with all protocols within 10 minutes, anesthesia was maintained ≥57 minutes, and recovery (time from the first head lift to standing) was completed within 5 minutes. During anesthesia with all protocols, HR, fR, rectal temperature, SpO2 and MAP were 99-125 beats minute-1, 33-44 breaths minute-1, 37.6-39.4 °C, 90-95% and 152-177 mmHg, respectively. No adverse event was observed. CONCLUSIONS AND CLINICAL RELEVANCE: TZM and KM at various dosages resulted in rapid onset of anesthesia, duration of >57 minutes and rapid recovery without administration of an antagonist. Accordingly, all these combinations are useful for anesthetizing Amur leopard cats and for performing simple procedures. However, the low doses of the anesthetic agents are recommended because there was no difference in duration of anesthesia between the dose rates studied.

Effects of constant rate infusions of dexmedetomidine, remifentanil and their combination on minimum alveolar concentration of sevoflurane in dogs.

OBJECTIVE: To evaluate the effects of constant rate infusions (CRIs) of dexmedetomidine and remifentanil alone and their combination on minimum alveolar concentration (MAC) of sevoflurane in dogs. STUDY DESIGN: Randomized crossover experimental study. ANIMALS: A total of six (three males, three females) healthy, adult neutered Beagle dogs weighing 12.6 ± 1.4 kg. METHODS: Anesthesia was induced with sevoflurane in oxygen until endotracheal intubation was possible and anesthesia maintained with sevoflurane using positive-pressure ventilation. Each dog was anesthetized five times and was administered each of the following treatments: saline (1 mL kg-1 hour-1) or dexmedetomidine at 0.1, 0.5, 1.0 or 5.0 µg kg-1 loading dose intravenously over 10 minutes followed by CRI at 0.1, 0.5, 1.0 or 5.0 µg kg-1 hour-1, respectively. Following 60 minutes of CRI, sevoflurane MAC was determined in duplicate using an electrical stimulus (50 V, 50 Hz, 10 ms). Then, CRI of successively increasing doses of remifentanil (0.15, 0.60 and 2.40 µg kg-1 minute-1) was added to each treatment. MAC was also determined after 30 minutes equilibration at each remifentanil dose. Isobolographic analysis determined interaction from the predicted doses required for a 50% MAC reduction (ED50) with remifentanil, dexmedetomidine and remifentanil combined with dexmedetomidine, with the exception of dexmedetomidine 5.0 µg kg-1 hour-1, obtained using log-linear regression analysis. RESULTS: The sevoflurane MAC decreased dose-dependently with increasing infusion rates of dexmedetomidine and remifentanil. Remifentanil ED50 values were lower when combined with dexmedetomidine than those obtained during saline-remifentanil. Synergistic interactions between dexmedetomidine and remifentanil for MAC reduction occurred with dexmedetomidine at 0.5 and 1.0 µg kg-1 hour-1. CONCLUSIONS AND CLINICAL RELEVANCE: Combined CRIs of dexmedetomidine and remifentanil synergistically resulted in sevoflurane MAC reduction. The combination of dexmedetomidine and remifentanil effectively reduced the requirement of sevoflurane during anesthesia in dogs.

Effects of intracoelomic alfaxalone-dexmedetomidine on righting reflex in common garter snakes (Thamnophis sirtalis): preliminary data.

OBJECTIVE: To evaluate the effect of dexmedetomidine on alfaxalone immobilization in snakes. STUDY DESIGN: Nonblinded, crossover study. ANIMALS: A total of eight mature common garter snakes (Thamnophis sirtalis). METHODS: Snakes were administered each of three treatments intracoelomically: alfaxalone (30 mg kg-1; treatment A), alfaxalone (30 mg kg-1) combined with dexmedetomidine (0.05 mg kg-1; treatment AD0.05); and alfaxalone (30 mg kg-1) combined with dexmedetomidine (0.10 mg kg-1; treatment AD0.10). A minimum of 10 days elapsed between experimental trials. Times to loss of righting reflex (LRR) and return of righting reflex (RRR) were recorded. Heart rate (HR) was recorded every 5 minutes throughout the period of LRR and averaged for each snake. Times to LRR and RRR, and mean HR in snakes that achieved LRR were reported. RESULTS: LRR occurred in eight (100%), five (63%) and three (38%) snakes in treatments A, AD0.05 and AD0.10, respectively. For all treatments, time to LRR ranged 3-20 minutes. Median (range) times to RRR were 39 (30-46), 89 (62-128) and 77 (30-185) minutes for treatments A, AD0.05 and AD0.10, respectively. In animals where righting reflex was lost, mean HR was lower in all dexmedetomidine treatments compared with treatment A. CONCLUSIONS AND CLINICAL RELEVANCE: In this pilot study, alfaxalone resulted in reliable immobilization, whereas dexmedetomidine and alfaxalone combinations resulted in highly variable durations of immobilization with low HR in immobilized animals. For snakes that achieved LRR, the addition of dexmedetomidine (0.05 mg kg-1) to alfaxalone appeared to extend the period of immobilization compared with alfaxalone alone.

Comparison of the effects of methadone and butorphanol combined with acepromazine for canine gastroduodenoscopy.

OBJECTIVE: To evaluate the feasibility of gastroduodenoscopy in dogs premedicated with acepromazine in combination with butorphanol or methadone. STUDY DESIGN: Prospective, randomized, double-blinded clinical trial. ANIMALS: A group of 40 client-owned dogs. METHODS: Dogs were randomly allocated to one of two groups and give intramuscular acepromazine 0.02 mg kg-1 combined with either butorphanol 0.3 mg kg-1 (group ACEBUT) or methadone 0.2 mg kg-1 (group ACEMET). General anaesthesia was induced with propofol and ketamine and maintained with sevoflurane (2.3%) in oxygen. Cardiopulmonary variables were recorded at 5 minute intervals during anaesthesia. Feasibility of the entire gastroduodenoscopy was evaluated with a visual analogue scale (VAS) from 0 (best) to 100 (worst) (primary outcome of the study). Lower oesophageal sphincter dilatation and duodenal intubation were scored. Pylorus diameter was measured with standard endoscopic inflatable balloons. Overall cardiovascular stability was assessed during anaesthesia, using a VAS (0-100), as was the presence of fluid in the oesophagus, regurgitation, need for mechanical ventilation, and intraoperative and postoperative rescue analgesia (secondary outcomes of the study). Differences between treatments were analysed with Mann-Whitney U, Student t test, Fisher exact test or mixed model analysis of variance as appropriate. Subsequently, feasibility VAS of the gastroduodenoscopy was assessed for noninferiority between groups. The noninferiority margin was set as -10. RESULTS: All gastroduodenoscopies were successfully completed in both groups using an endoscope tip diameter of 12.8 mm in all but one dog. Feasibility of gastroduodenoscopy was evaluated as 2.9 ± 5.6 in group ACEBUT and 5.1 ± 5.8 in group ACEMET. No significant differences between groups were detected in any measured or assessed variables, and noninferiority was confirmed. CONCLUSION AND CLINICAL RELEVANCE: In our study population, the effects of methadone and butorphanol when combined with acepromazine were comparable.

Sedative effects of two doses of alfaxalone in combination with methadone and a low dose of dexmedetomidine in healthy Beagles.

OBJECTIVE: To evaluate the sedative effects of two doses of alfaxalone when added to a combination of dexmedetomidine and methadone injected intramuscularly (IM) in healthy Beagles. STUDY DESIGN: Randomized, blinded, crossover, experimental study. ANIMALS: A group of six adult Beagles. METHODS: Dogs were sedated on three different occasions with IM dexmedetomidine (3 µg kg-1) and methadone (0.3 mg kg-1) combined with two doses of alfaxalone (0.5 and 1 mg kg-1; A0.5 and A1, respectively) or saline (A0). Quality of sedation, response to tail clamping and rectal temperature were recorded at baseline, 5, 15, 25, 35 and 45 minutes. Pulse and respiratory rates, oxygen saturation of haemoglobin (SpO2) and noninvasive blood pressure (NIBP) were recorded every 5 minutes. Onset of sedation and duration of recumbency, response to venous catheterization and recovery quality were assessed. Physiological variables (analysis of variance) were analysed between treatments and within treatments compared with baseline (Student t test). Nonparametric data were analysed using Friedman and Cochran's Q tests. Significance was p < 0.05. RESULTS: Sedation scores were significantly higher when alfaxalone was co-administered (area under the curve; p = 0.024, A0.5; p = 0.019, A1), with no differences between doses. Onset of sedation was similar, but duration of recumbency was longer in A0.5 than in A0 [median (minimum-maximum), 43 (35-54) versus 30 (20-47) minutes, p = 0.018], but not in A1. Response to venous catheterization and tail clamping, and quality of recovery (acceptable) presented no differences between treatments. A decrease in all physiological variables (compared with baseline) was observed, except for NIBP, with no differences between treatments. All dogs required oxygen supplementation due to reduced SpO2. CONCLUSIONS AND CLINICAL RELEVANCE: Adding alfaxalone to methadone and dexmedetomidine enhanced sedation and duration of recumbency. Although cardiopulmonary depression was limited, oxygen supplementation is advisable.

The effect of intramuscular dexmedetomidine-butorphanol combination on tear production in dogs.

This study assessed the effects of a combination of dexmedetomidine and butorphanol on the Schirmer tear test I (STT I) values in dogs. Ninety-eight dogs were sedated with an intramuscular injection of a combination of dexmedetomidine, 5 µg/kg body weight (BW), and butorphanol, 0.2 mg/kg BW. The effects of dexmedetomidine were reversed by administering atipamezole at the end of the procedure. The combination of dexmedetomidine and butorphanol significantly decreased tear production 15 minutes after sedation. The STT I values 15 minutes after reversal of dexmedetomidine with atipamezole were significantly higher than the STT I values 15 minutes after sedation but were significantly lower than the STT I values before sedation. Gender, weight, duration of sedation, right or left eye did not affect STT I values after sedation. It is recommended that dogs sedated with a combination of dexmedetomidine and butorphanol be treated with a tear substitute to combat decreased tear production.

Effet de l'association dexmédétomidin-butorphanol intramusculaire sur la production lacrymale chez le chien. L'étude vise à déterminer les effets de l'association dexmédétomidine-butorphanol sur les résultats du test de Schirmer I (STT I) chez le chien. Quatre-vingt-dix-huit chiens ont été sédatés avec l'association dexmédétomidine (5 µg/kg) butorphanol (0,2 mg/kg) intramusculaire. La dexmédétomidine a été antagonisée avec de l'atipamezole en fin de procédure. L'association dexmédétomidine-butorphanol diminue significativement la production lacrimale 15 minutes post-sédation. Les valeurs de STT I 15 minutes post-antagonisation de la dexmédétomidine étaient significativement plus élevées que celles de STT I 15 minutes post-sédation, mais significativement inférieures aux STT I pré-sédation. Les variables genre, poids, durée de la sédation, oeil droit/gauche, n'ont pas significativement influencé les valeurs de STT I post-sédation. L'association dexmédétomidine-butorphanol diminuant significativement leur production lacrimale il est recommandable de traiter les chiens avec des substituts lacrimaux pour éviter la sécheresse oculaire.(Traduit par les auteurs).

A clinical study to evaluate the cardiopulmonary characteristics of two different anaesthetic protocols for immobilization of healthy chimpanzees (Pan troglodytes).

OBJECTIVE: To characterize the cardiopulmonary characteristics of two different anaesthetic protocols (tiletamine/zolazepam ± medetomidine) and their suitability for the immobilization of healthy chimpanzees undergoing cardiac assessment. STUDY DESIGN: Prospective, clinical, longitudinal study. ANIMALS: Six chimpanzees (Pan troglodytes) aged 4-16 years weighing 19.5-78.5 kg were anaesthetized on two occasions. METHODS: Anaesthesia was induced with tiletamine/zolazepam (TZ) (3-4 mg kg-1) or tiletamine/zolazepam (2 mg kg-1) and medetomidine (0.02 mg kg-1) (TZM) via blow dart [intramuscular (IM)] and maintained with intermittent boluses of ketamine (IV) or zolazepam/tiletamine (IM) as required. The overall quality of the anaesthesia was quantified based on scores given for: quality of induction, degree of muscle relaxation and ease of intubation. The time to achieve a light plane of anaesthesia, number of supplemental boluses needed and recovery characteristics were also recorded. Chimpanzees were continuously monitored and heart rate (HR), pulse rate (PR), respiratory rate (fR) oxygen saturation of haemoglobin (SpO2), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP), rectal temperature, mucous membrane colour and capillary refill time recorded. During the first procedure (TZ) animals underwent a 12-channel electrocardiogram (ECG), haematology, biochemistry and cardiac biomarker assessment to rule out the presence of pre-existing cardiovascular disease. A detailed echocardiographic examination was carried out by the same blinded observer during both procedures. Data were compared using Student's paired t-test or Wilcoxon rank tests as appropriate. RESULTS: There was a significant difference for the area under the curves between anaesthetic protocols for HR, SAP, MAP and fR. No significant differences in the echocardiographic measurements were evident. Quality of anaesthesia was significantly better with TZM and no additional boluses were required. The TZ protocol required multiple supplemental boluses. CONCLUSIONS AND CLINICAL RELEVANCE: Both combinations are suitable for immobilization and cardiovascular evaluation of healthy chimpanzees. Further work is required to evaluate the effect of medetomidine in cardiovascular disease.

Effects of transdermal lidocaine or lidocaine with prilocaine or tetracaine on mechanical superficial sensation and nociceptive thermal thresholds in horses.

OBJECTIVE: To evaluate the transdermal local anaesthetic effect of lidocaine or lidocaine combined with prilocaine or tetracaine in horses. STUDY DESIGN: Experimental, randomized study. ANIMALS: A total of five healthy adult warmblood horses. METHODS: Horses were clipped bilaterally at the withers, cranial saddle area and caudal saddle area. Baseline measurements for mechanical superficial sensation via von Frey filaments and nociceptive thermal thresholds were performed. A 5% lidocaine patch (12 hour exposure, treatment L), a lidocaine/prilocaine cream (each 2.5%, treatment LP) and a lidocaine/tetracaine cream (each 7%, treatment LT) were applied (both 2 hour exposure). The same product was applied at the same location bilaterally, but on the right side an epidermal micro-perforation (dermaroller, 1200 needles) was performed prior to application. A total of five more measurements were performed at each location, immediately at the end of exposure time followed by hourly measurements. Thermal thresholds normalized to thermal excursion were analysed. One- or two-way anova and the Wilcoxon signed-rank test were used for statistical analysis with p<0.05 considered significant. RESULTS: Epidermal micro-perforation had no enhancing effect. Treatments L, LP, and LT resulted in increased thermal excursion (%) immediately (84.7±12.9; 100.0±0.0; 100.0±0.0) and 1 hour (81.7±66; 86.0±17.7; 87.7±14.4) after the removal of the respective product compared to baseline (66.1±9.3; 69.9±8.3; 76.5±7.8). Superficial mechanical sensation was decreased by the lidocaine-and-tetracaine cream at all time points, and by the lidocaine patch and lidocaine-and-prilocaine cream for three measurements. CONCLUSIONS AND CLINICAL RELEVANCE: Eutectic mixtures of lidocaine with either prilocaine or tetracaine led to a reduction in thermal nociception and mechanical sensation for up to 2 hours.

Comparison of the effects of alfaxalone and propofol with acepromazine, butorphanol and/or doxapram on laryngeal motion and quality of examination in dogs.

OBJECTIVE: To compare the effects of alfaxalone and propofol, with and without acepromazine and butorphanol followed by doxapram, on laryngeal motion and quality of laryngeal examination in dogs. STUDY DESIGN: Randomized, crossover, blinded study. ANIMALS: Ten female Beagle dogs, aged 11-13 months and weighing 7.2-8.6 kg. METHODS: The dogs were administered four intravenous (IV) treatments: alfaxalone (ALF), alfaxalone+acepromazine and butorphanol (ALF-AB), propofol (PRO) and propofol+AB (PRO-AB). AB doses were standardized. Dogs were anesthetized 5 minutes later by administration of alfaxalone or propofol IV to effect. Arytenoid motion during maximal inspiration and expiration was captured on video before and after IV doxapram (0.25 mg kg-1). The change in rima glottidis surface area (RGSA) was calculated to measure arytenoid motion. An investigator blinded to the treatment scored laryngeal examination quality. RESULTS: A 20% increase in RGSA was the minimal arytenoid motion that was detectable. RGSA was significantly less in ALF before doxapram compared with all other treatments. A <20% increase in RGSA was measured in eight of 10 dogs in PRO and in all dogs in ALF before doxapram. After doxapram, RGSA was significantly increased for PRO and ALF; however, 20% of dogs in PRO and 50% of dogs in ALF still had <20% increase in RGSA. A <20% increase in RGSA was measured in five of 10 dogs in PRO-AB and ALF-AB before doxapram. All dogs in PRO-AB and ALF-AB with <20% increase in RGSA before doxapram had ≥20% increase in RGSA after doxapram. Examination quality was significantly better in PRO-AB and ALF-AB. CONCLUSIONS AND CLINICAL RELEVANCE: The use of acepromazine and butorphanol improved the quality of laryngeal examination. Any negative impact on arytenoid motion caused by these premedications was overcome with doxapram. Using either propofol or alfaxalone alone is not recommended for the evaluation of arytenoid motion.

A combination of alfaxalone, medetomidine and midazolam for the chemical immobilization of Rhesus macaque (Macaca mulatta): Preliminary results.

BACKGROUND: Chemical immobilization of non-human primates can be required to perform scientific or veterinary procedure with different invasiveness degrees. This preliminary study was undertaken to assess the clinical effects of a combination of alfaxalone, medetomidine and midazolam (AMM). METHODS: Seven rhesus macaques were chemically immobilized, for invasive veterinary procedures, with alfaxan 2 mg kg-1 , medetomidine 20 µg kg-1 and midazolam 0.3 mg kg-1 injected subcutaneously. RESULTS: The alfaxalone combination induced surgical anaesthesia, with a complete absence of response to noxious stimuli, for at least 20 minutes. The total duration of anaesthesia was 56 ± 7 minutes, and the administration of atipamezole, to partially reverse the combination effects, did not appear to alter the depth of anaesthesia. CONCLUSION: In conclusion, the AMM combination produced rapid onset general anaesthesia, following subcutaneous administration of a relatively low volume (0.28 mL/kg) of injectate.

Isoflurane and ketamine:xylazine differentially affect intraocular pressure-associated scotopic threshold responses in Sprague-Dawley rats.

PURPOSE: Amplitudes of electroretinograms (ERG) are enhanced during acute, moderate elevation of intraocular pressure (IOP) in rats anaesthetised with isoflurane. As anaesthetics alone are known to affect ERG amplitudes, the present study compares the effects of inhalant isoflurane and injected ketamine:xylazine on the scotopic threshold response (STR) in rats with moderate IOP elevation. METHODS: Isoflurane-anaesthetised (n = 9) and ketamine:xylazine-anaesthetised (n = 6) rats underwent acute unilateral IOP elevation using a vascular loop anterior to the equator of the right eye. STRs to a luminance series (subthreshold to -3.04 log scotopic cd s/m2) were recorded from each eye of Sprague-Dawley rats before, during, and after IOP elevation. RESULTS: Positive STR (pSTR) amplitudes for all conditions were significantly smaller (p = 0.0001) for isoflurane- than for ketamine:xylazine-anaesthetised rats. In addition, ketamine:xylazine was associated with a progressive increase in pSTR amplitudes over time (p = 0.0028). IOP elevation was associated with an increase in pSTR amplitude (both anaesthetics p < 0.0001). The absolute interocular differences in IOP-associated enhancement of pSTR amplitudes for ketamine:xylazine and isoflurane were similar (66.3 ± 35.5 vs. 54.2 ± 24.1 µV, respectively). However, the fold increase in amplitude during IOP elevation was significantly higher in the isoflurane- than in the ketamine:xylazine-anaesthetised rats (16.8 ± 29.7x vs. 2.1 ± 2.7x, respectively, p = 0.0004). CONCLUSIONS: The anaesthetics differentially affect the STRs in the rat model with markedly reduced amplitudes with isoflurane compared to ketamine:xylazine. However, the IOP-associated enhancement is of similar absolute magnitude for the two anaesthetics, suggesting that IOP stress and anaesthetic effects operate on separate retinal mechanisms.

Blood acid-base status in impala (Aepyceros melampus) immobilised and maintained under total intravenous anaesthesia using two different drug protocols.

BACKGROUND: In mammals, homeostasis and survival are dependent on effective trans-membrane movement of ions and enzyme function, which are labile to extreme acid-base changes, but operate efficiently within a narrow regulated pH range. Research in patients demonstrating a pH shifts outside the narrow regulated range decreased the cardiac output and systemic vascular resistance and altered the oxygen binding to haemoglobin. These cardiopulmonary observations may be applicable to the risks associated with anaesthesia and performance of wildlife ungulates on game farms. The aim of this study was to compare blood pH changes over time in impala immobilised and anaesthetised with two different drug protocols (P-TMP - immobilisation: thiafentanil-medetomidine; maintenance: propofol-ketamine-medetomidine; P-EME - immobilisation: etorphine-medetomidine; maintenance: etorphine-ketamine-medetomidine). Additionally, we discuss the resultant blood pH using both the Henderson-Hasselbalch and the Stewart approaches. Two data collection time points were defined, Time1 before maintenance of general anaesthesia and Time 2 at end of maintenance of general anaesthesia. We hypothesise that blood pH would not be different between drug protocols and would not change over time. RESULTS: Significant differences were detected over time but not between the two drug protocols. Overall, the blood pH decreased over time from 7.37 ± 0.04 to 7.31 ± 0.05 (p = 0.001). Overall, over time arterial partial pressure of carbon dioxide changed from 51.3 ± 7.5 mmHg to 72.6 ± 12.4 mmHg (p < 0.001); strong ion difference from 44.6 ± 2.4 mEq/L to 46.9 ± 3.1 mEq/L (p < 0.001); anion gap from 15.0 ± 3.1 mEq/L to 10.9 ± 2.2 mEq/L (p < 0.001); and total weak acids from 16.1 ± 1.2 mmol/L to 14.0 ± 1.1 mmol/L (p < 0.001). The bicarbonate changed from 29.6 ± 2.7 mEq/L to 36.0 ± 4.1 mEq/L (p < 0.001); and lactate changed from 2.9 ± 1.5 mEq/L to 0.3 ± 0.03 mEq/L (p < 0.001) over time. CONCLUSIONS: The profound increase in the partial pressure of carbon dioxide that worsened during the total intravenous anaesthesia in both protocols initiated a substantial metabolic compensatory response to prevent severe acidaemia. This compensation resulted in a clinically acceptable mild acidaemic state, which worsened over time but not between the protocols, in healthy impala. However, these important compensatory mechanisms require normal physiological function and therefore when immobilising ill or anorexic wild ungulates their acid-base status should be carefully assessed.

Pharmacokinetics of dexmedetomidine in isoflurane-anesthetized New Zealand White rabbits.

OBJECTIVE: To characterize the pharmacokinetics of dexmedetomidine when administered as a short intravenous (IV) infusion to isoflurane-anesthetized rabbits. STUDY DESIGN: Experimental study. ANIMALS: A total of six healthy adult female New Zealand White rabbits. METHODS: Rabbits were anesthetized with isoflurane in oxygen. Following determination of isoflurane minimum alveolar concentration (MAC), the anesthetic dose was reduced to 0.7 × MAC, and dexmedetomidine hydrochloride (20 µg kg-1) was infused IV over 5 minutes. Arterial blood samples were obtained immediately before and at 1, 2, 5, 6, 7, 10, 15, 30, 60, 90, 120, 240 and 360 minutes following termination of the infusion. Samples were transferred into tubes containing ethylenediaminetetraacetic acid and centrifuged immediately. The plasma was harvested and stored at -80 °C until analyzed. Concentrations of dexmedetomidine in plasma were determined by liquid chromatography mass spectrometry. Compartment models were fitted to the time and concentration data using nonlinear regression. RESULTS: A three-compartment model best fit the data set. Median volume of distribution at steady state and terminal half-life were 3169 mL kg-1 (range, 2182-3859 mL kg-1) and 80 minutes (range, 72-88 minutes), respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The pharmacokinetics of dexmedetomidine in isoflurane-anesthetized, healthy, New Zealand White rabbits were characterized in this study. Data from this study can be used to determine dosing regimens for dexmedetomidine in isoflurane-anesthetized rabbits.

Effects of constant rate infusions of dexmedetomidine or MK-467 on the minimum alveolar concentration of sevoflurane in dogs.

OBJECTIVE: To determine the effects of low and high dose infusions of dexmedetomidine and a peripheral α2-adrenoceptor antagonist, MK-467, on sevoflurane minimum alveolar concentration (MAC) in dogs. STUDY DESIGN: Crossover experimental study. ANIMALS: Six healthy, adult Beagle dogs weighing 12.6±0.9 kg (mean±standard deviation). METHODS: Dogs were anesthetized with sevoflurane in oxygen. After a 60-minute instrumentation and equilibration period, the MAC of sevoflurane was determined in triplicate using the tail clamp technique. PaCO2 and temperature were maintained at 40±5 mmHg (5.3±0.7 kPa) and 38±0.5 ºC, respectively. After baseline MAC determination, dogs were administered two incremental loading and infusion doses of either dexmedetomidine (1.5 µg kg-1 then 1.5 µg kg-1 hour-1 and 4.5 µg kg-1 then 4.5 µg kg-1 hour-1) or MK-467 (90 µg kg-1 then 90 µg kg-1 hour-1 and 180 µg kg-1 then 180 µg kg-1 hour-1); loading doses were administered over 10 minutes. MAC was redetermined in duplicate starting 30 minutes after the start of drug administration at each dose. End-tidal sevoflurane concentrations were corrected for calibration and adjusted to sea level. A repeated-measures analysis was performed and comparisons between doses were conducted using Tukey's method. Statistical significance was considered at p<0.05. RESULTS: Sevoflurane MAC decreased significantly from 1.86±0.3% to 1.04±0.1% and 0.57±0.1% with incremental doses of dexmedetomidine. Sevoflurane MAC significantly increased with high dose MK-467, from 1.93±0.3% to 2.29±0.5%. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine caused a dose-dependent decrease in sevoflurane MAC, whereas MK-467 caused an increase in MAC at the higher infusion dose. Further studies evaluating the combined effects of dexmedetomidine and MK-467 on MAC and cardiovascular function may elucidate potential benefits of the addition of a peripheral α2-adrenergic antagonist to inhalation anesthesia in dogs.

Effect of fentanyl on the induction dose and minimum infusion rate of propofol preventing movement in dogs.

OBJECTIVE: To determine the effect of fentanyl on the induction dose of propofol and minimum infusion rate required to prevent movement in response to noxious stimulation (MIRNM) in dogs. STUDY DESIGN: Crossover experimental design. ANIMALS: Six healthy, adult intact male Beagle dogs, mean±standard deviation 12.6±0.4 kg. METHODS: Dogs were administered 0.9% saline (treatment P), fentanyl (5 µg kg-1) (treatment PLDF) or fentanyl (10 µg kg-1) (treatment PHDF) intravenously over 5 minutes. Five minutes later, anesthesia was induced with propofol (2 mg kg-1, followed by 1 mg kg-1 every 15 seconds to achieve intubation) and maintained for 90 minutes by constant rate infusions (CRIs) of propofol alone or with fentanyl: P, propofol (0.5 mg kg-1 minute-1); PLDF, propofol (0.35 mg kg-1 minute-1) and fentanyl (0.1 µg kg-1 minute-1); PHDF, propofol (0.3 mg kg-1 minute-1) and fentanyl (0.2 µg kg-1 minute-1). Propofol CRI was increased or decreased based on the response to stimulation (50 V, 50 Hz, 10 mA), with 20 minutes between adjustments. Data were analyzed using a mixed-model anova and presented as mean±standard error. RESULTS: ropofol induction doses were 6.16±0.31, 3.67±0.21 and 3.33±0.42 mg kg-1 for P, PLDF and PHDF, respectively. Doses for PLDF and PHDF were significantly decreased from P (p<0.05) but not different between treatments. Propofol MIRNM was 0.60±0.04, 0.29±0.02 and 0.22±0.02 mg kg-1 minute-1 for P, PLDF and PHDF, respectively. MIRNM in PLDF and PHDF was significantly decreased from P. MIRNM in PLDF and PHDF were not different, but their respective percent decreases of 51±3 and 63±2% differed (p=0.035). CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl, at the doses studied, caused statistically significant and clinically important decreases in the propofol induction dose and MIRNM.

Pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular administration in male cats.

OBJECTIVE: To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats. STUDY DESIGN: Prospective randomized crossover experimental study. ANIMALS: A total of eight healthy adult male castrated cats aged 1-2 years. METHODS: Cats were administered dexmedetomidine (25 µg kg-1) IM (treatment D25IM) or intravenously (IV; treatment D25IV); MK-467 (600 µg kg-1) IM (treatment MK600IM) or IV (treatment MK600IV); or dexmedetomidine (25 µg kg-1) IM with 300, 600 or 1200 µg kg-1 MK-467 IM (treatments D25MK300IM, D25MK600IM and D25MK1200IM). D25MK600IM was the only combination treatment analyzed. Blood samples were obtained prior to drug administration and at various times for 5 hours (D25IV) or 8 hours (all other treatments) thereafter. Plasma dexmedetomidine and MK-467 concentrations were measured using liquid chromatography/mass spectrometry. Compartment models were fitted to the time-concentration data. RESULTS: A one-compartment model best fitted the time-plasma dexmedetomidine concentration data in cats administered D25IM, and the time-plasma MK-467 concentration data in cats administered MK600IM and D25MK600IM. A two-compartment model best fitted the time-plasma dexmedetomidine concentration data in cats administered D25IV and D25MK600IM, and the time-plasma MK-467 concentration data in cats administered MK600IV. Median (range) area under the time-concentration curve, absorption rate half-life, maximum concentration, time to maximum concentration and terminal half-life for dexmedetomidine in D25IM and D25MK600IM were 1129 (792-1890) and 924 (596-1649) ng minute mL-1, 4.4 (0.4-15.7) and 2.3 (0.2-8.0) minutes, 10.2 (4.8-16.9) and 17.8 (15.8-73.5) ng mL-1, 17.8 (2.6-44.9) and 5.2 (1.2-15.1) minutes and 62 (52-139) and 50 (31-125) minutes, respectively. Rate of absorption but not systemic exposure was significantly influenced by treatment. No significant differences were observed in MK-467 pharmacokinetic parameters in MK600IM and D25MK600IM. CONCLUSIONS AND CLINICAL RELEVANCE: MK-467 significantly influenced the disposition of dexmedetomidine, whereas dexmedetomidine did not significantly affect the disposition of MK-467 when the drugs were coadministered IM.

Isoflurane minimum alveolar concentration sparing effects of fentanyl in the dog.

OBJECTIVE: To characterize the isoflurane-sparing effects of a high and a low dose of fentanyl in dogs, and its effects on mean arterial pressure (MAP) and heart rate (HR). STUDY DESIGN: Prospective, randomized crossover trial. ANIMALS: Eight healthy male Beagle dogs weighing 12.1 ± 1.6 kg [mean ± standard deviation (SD)] and approximate age 1 year. METHODS: Dogs were anesthetized using isoflurane and minimum alveolar concentration (MAC) was determined in duplicate by the bracketing method using an electrical stimulus on the tarsus. Animals were administered fentanyl: low dose (33 µg kg-1 loading dose, 0.2 µg kg-1 minute-1) or high dose (102 µg kg-1 loading dose, 0.8 µg kg-1 minute-1) and MAC was re-determined (MACISO-F). Blood was collected for analysis of plasma fentanyl concentrations before administration and after MACISO-F determination. All values are presented as mean ± SD. RESULTS: Isoflurane MAC (MACISO) was 1.30 ± 0.23% in the low dose treatment, which significantly decreased to 0.75 ± 0.22% (average MAC reduction 42.3 ± 9.4%). MACISO was 1.30 ± 0.18% in the high dose treatment, which significantly decreased to 0.30 ± 0.11% (average MAC reduction 76.9 ± 7.4%). Mean fentanyl plasma concentrations were 6.2 and 29.5 ng mL-1 for low and high dose treatments, respectively. MAP increased significantly only in the high dose treatment (from 81 ± 8 to 92 ± 9 mmHg). HR decreased significantly in both treatments from 108 ± 25 to 61 ± 14 beats minute-1 with the low dose and from 95 ± 14 to 42 ± 4 beats minute-1 with the high dose. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl administration resulted in a dose-dependent isoflurane MAC-sparing effect with bradycardia at both doses and an increase in MAP only at high dose. Further evaluation is needed to determine the effects of fentanyl on the overall cardiovascular function.