The effects of selected sedatives on basal and stimulated serum cortisol concentrations in healthy dogs.

Background: Hormone assessment is typically recommended for awake, unsedated dogs. However, one of the most commonly asked questions from veterinary practitioners to the endocrinology laboratory is how sedation impacts cortisol concentrations and the adrenocorticotropic hormone (ACTH) stimulation test. Butorphanol, dexmedetomidine, and trazodone are common sedatives for dogs, but their impact on the hypothalamic-pituitary-adrenal axis (HPA) is unknown. The objective of this study was to evaluate the effects of butorphanol, dexmedetomidine, and trazodone on serum cortisol concentrations. Methods: Twelve healthy beagles were included in a prospective, randomized, four-period crossover design study with a 7-day washout. ACTH stimulation test results were determined after saline (0.5 mL IV), butorphanol (0.3 mg/kg IV), dexmedetomidine (4 µg/kg IV), and trazodone (3-5 mg/kg PO) administration. Results: Compared to saline, butorphanol increased basal (median 11.75 µg/dL (range 2.50-23.00) (324.13 nmol/L; range 68.97-634.48) vs 1.27 µg/dL (0.74-2.10) (35.03 nmol/L; 20.41-57.93); P < 0.0001) and post-ACTH cortisol concentrations (17.05 µg/dL (12.40-26.00) (470.34 nmol/L; 342.07-717.24) vs 13.75 µg/dL (10.00-18.90) (379.31 nmol/L; 275.96-521.38); P ≤ 0.0001). Dexmedetomidine and trazodone did not significantly affect basal (1.55 µg/dL (range 0.75-1.55) (42.76 nmol/L; 20.69-42.76); P = 0.33 and 0.79 µg/dL (range 0.69-1.89) (21.79 nmol/L; 19.03-52.14); P = 0.13, respectively, vs saline 1.27 (0.74-2.10) (35.03 nmol/L; 20.41-57.93)) or post-ACTH cortisol concentrations (14.35 µg/dL (range 10.70-18.00) (395.86 nmol/L; 295.17-496.55); (P = 0.98 and 12.90 µg/dL (range 8.94-17.40) (355.86 nmol/L; 246.62-480); P = 0.65), respectively, vs saline 13.75 µg/dL (10.00-18.60) (379.31 nmol/L; 275.86-513.10). Conclusion: Butorphanol administration should be avoided prior to ACTH stimulation testing in dogs. Further evaluation of dexmedetomidine and trazodone's effects on adrenocortical hormone testing in dogs suspected of HPA derangements is warranted to confirm they do not impact clinical diagnosis.

Long-term deep sedation using Zoletil and haloperidol for the treatment of streptococcal pneumonia in an orangutan (Pongo pygmaeus).

A 13-year-old Bornean orangutan diagnosed with life threatening Streptococcus pyogenes broncho-pneumonia was kept in a state of deep sedation for 20 days via continuous intra-venous (IV) infusion of zolazepam -tiletamine and IV haloperidol to allow consistent IV administration of ceftazidime and gatifloxacine. The use of long-term deep sedation allowed carrying out a particularly demanding treatment not generally associated with zoological patients. The treatment was ultimately successful.

Sedative and cardiorespiratory effects of intramuscular administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs.

OBJECTIVE: To evaluate the sedative and cardiorespiratory effects of IM administration of alfaxalone and butorphanol combined with acepromazine, midazolam, or dexmedetomidine in dogs. ANIMALS: 6 young healthy mixed-breed hounds. PROCEDURES: Dogs received each of 3 treatments (alfaxalone [2 mg/kg] and butorphanol [0.4 mg/kg] combined with acepromazine [0.02 mg/kg; AB-ace], midazolam [0.2 mg/kg; AB-mid], or dexmedetomidine [0.005 mg/kg; AB-dex], IM) in a blinded, randomized crossover-design study with a 1-week washout period between treatments. Sedation scores and cardiorespiratory variables were recorded at predetermined time points. Data were analyzed by use of mixed-model ANOVA and linear generalized estimating equations with post hoc adjustments. RESULTS: All treatments resulted in moderate to deep sedation (median score, ≥ 15/21) ≤ 5 minutes after injection. Sedation scores did not differ among treatments until the 40-minute time point, when the score was higher for AB-dex than for other treatments. Administration of AB-dex resulted in median scores reflecting deep sedation until 130 minutes, versus 80 and 60 minutes for AB-ace and AB-mid, respectively, after injection. Heart rate, cardiac output, and oxygen delivery decreased significantly after AB-dex, but not AB-ace or AB-mid administration. Respiratory variables remained within clinically acceptable ranges after all treatments. Undesirable recovery characteristics were observed in 4 dogs after AB-mid treatment. Four dogs required atipamezole administration 180 minutes after AB-dex injection. CONCLUSIONS AND CLINICAL RELEVANCE: All protocols produced reliable sedation. The results indicated that in young, healthy dogs, AB-mid may produce undesirable recovery characteristics; AB-dex treatment caused cardiovascular depression and should be used with caution.

Evaluation of gastrointestinal activity in healthy rabbits by means of duplex Doppler ultrasonography.

OBJECTIVE: To use duplex Doppler ultrasonography to compare gastrointestinal activity in healthy sedated versus nonsedated rabbits and to evaluate agreement between B-mode and pulsed-wave Doppler (PWD) ultrasonographic measurements. ANIMALS: 10 healthy client-owned rabbits brought for routine physical examination and 11 brought for routine ovariohysterectomy or castration. PROCEDURES: Duplex Doppler ultrasonography of the gastrointestinal tract was performed once for the 10 rabbits that underwent physical examination and twice (before and after presurgical sedation) for the 11 rabbits that underwent routine ovariohysterectomy or castration. Mean number of peristaltic contractions during a 30-second period was determined for the stomach, duodenum, jejunum, cecum, and colon from B-mode and PWD ultrasonographic images that had been video recorded. Findings for the duodenum and jejunum were compared between B-mode and PWD ultrasonography and between sedated and nonsedated rabbits. RESULTS: Duodenal and jejunal segments had measurable peristaltic waves; however, the stomach, cecum, and colon had no consistent measurable activity. B-mode and PWD ultrasonographic measurements for the duodenum and jejunum had high agreement. No significant difference was identified between nonsedated and sedated rabbits in mean number of peristaltic contractions of the duodenum or jejunum. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that both B-mode and PWD ultrasonography of the duodenum and jejunum may be suitable for noninvasive evaluation of small intestinal motility in rabbits and that the sedation protocol used in this study had no impact on measured peristaltic values.

Cortical motor threshold determination in dogs.

In humans, determining the cortical motor threshold (CMT) is a critical step in successfully applying a transcranial magnetic stimulation (TMS) treatment. Stimulus intensity, safety and efficacy of a TMS treatment are dependent of the correct assessment of the CMT. Given that TMS in dogs could serve as a natural animal model, an accurate and reliable technique for the measurement of the CMT should be available for dogs. Using a visual descending staircase paradigm (Rossini paradigm), the CMT repeatability was assessed and compared to the electromyographic (EMG) variant. The influence of a HF-rTMS treatment on the CMT was examined. Subsequently, the CMT was measured under sedation and general anaesthesia. Finally, the coil-cortex distance was associated with the CMT, weight, age and gender. During one year the CMT was measured three times, during which it remained constant, although a higher CMT was measured (40% higher machine output) when using EMG (P-value < .001) and under general anaesthesia (P-value = .005). On average, a 40% and 12% higher machine output were registered. An aHF-rTMS protocol does not influence the CMT. Males have on average a 5.2 mm larger coil cortex distance and an 11.81% higher CMT. The CMT was positively linearly associated (P-value < .05) with the weight and age of the animals. Only within female subjects, a positive linear association was found between the CMT and the coil-cortex distance (P-value = .02). Using the visual Rossini paradigm, the CMT can be reliably used over time and during a TMS treatment. It has to be kept in mind that when using EMG or assessing the CMT under general anaesthesia, a higher CMT is to be expected. As in humans, every parameter that influences the coil-cortex distance may also influence the CMT.

Comparison of intraocular pressure and pupil diameter after sedation with either acepromazine or dexmedetomidine in healthy dogs.

OBJECTIVE: To compare intraocular pressure (IOP) and pupillary diameter (PD) following intravenous (IV) administration of dexmedetomidine and acepromazine in dogs. STUDY DESIGN: Prospective, randomized experimental trial. ANIMALS: A group of 16 healthy adult dogs aged (mean ± standard deviation) 4.9 ± 3.3 years and weighing 15.7 ± 9.6 kg, without pre-existing ophthalmic disease. METHODS: IV dexmedetomidine hydrochloride (0.002 mg kg-1; DEX) or acepromazine maleate (0.015 mg kg-1; ACE) was administered randomly to 16 dogs (eight per group). The IOP and PD, measured using applanation tonometry and Schirmer's strips mm scale, respectively, and the heart rate (HR), systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures and respiratory rate (fR) were recorded at baseline, at time of injection, and then 5, 10, 15, 20 and 25 minutes after injection. A single ophthalmologist, unaware of treatment, performed all measurements under consistent light conditions. Values were compared with baseline and among treatments using a multivariate mixed-effects model (p ≤ 0.05). RESULTS: The IOP was significantly lower in the DEX group compared with the ACE group at 10 (p < 0.01) and 15 minutes (p < 0.01) after drug injection. PD was significantly smaller compared to baseline for the entire duration of the study (p < 0.01) in both groups. Dogs in the DEX group had significant lower HR (p < 0.01) and fR (p < 0.01), higher SAP (p < 0.01) and DAP (p < 0.01) at all time points, and higher MAP (p < 0.01) during the first 15 minutes following drug injection in comparison with the ACE group. CONCLUSIONS AND CLINICAL RELEVANCE: Our results suggest that premedication with IV dexmedetomidine temporarily decreases IOP when compared with IV acepromazine. Both drugs cause miosis.

Comparison of sedation in dogs: methadone or butorphanol in combination with dexmedetomidine intravenously.

OBJECTIVE: Opioids can be combined with alpha-2-adrenoreceptor agonists to sedate dogs for radiography. The study investigated the sedative effects of methadone or butorphanol in combination with dexmedetomidine in dogs undergoing stifle radiography. STUDY DESIGN: Prospective, blinded, randomized, clinical trial. ANIMALS: A total of 52 healthy dogs requiring sedation for stifle radiography were enrolled. METHODS: Dogs were assessed for body condition [body condition score (BCS)], temperament and pain using the short-form composite measure pain scale (CMPS-SF). Dogs were randomized to be administered methadone 0.2 mg kg-1 (group M) or butorphanol 0.2 mg kg-1 (group B) in combination with dexmedetomidine 2 µg kg-1 intravenously (IV). Sedation was assessed using a numerical descriptive score, from 0 (no sedation) to 11 (greatest sedation), before administration and at 5, 10, 15 and 20 minutes by one blinded assessor. Onset signs of sedation, pulse rate and respiratory rates were recorded. Positioning for radiography was attempted at 5 minutes. If positioning was not possible at 10 minutes, dexmedetomidine 2 µg kg-1 was administered IV, with the dog recorded as failed sedation and withdrawn from further analysis. Following normality testing, data were assessed using Student t test, Mann-Whitney test, two-way analysis of variance and Fisher's exact test for failed sedations. Results are reported as mean ± standard deviation. Statistical significance was set at p < 0.05. RESULTS: Groups were similar for sex, age, weight, BCS, temperament and CMPS-SF. The onset of sedation was faster in group B than in group M (p = 0.048). Sedation scores were higher in group B at 10 minutes compared to group M (p = 0.003). Failed sedation occurred in 12 dogs in group M and two in group B (p = 0.002). Pulse rates were lower in group B at 5 and 10 minutes (p = 0.002). CONCLUSION AND CLINICAL RELEVANCE: IV butorphanol provides more effective sedation at 10 minutes than methadone, in combination with dexmedetomidine.

Peripheral α2-adrenoceptor antagonism affects the absorption of intramuscularly coadministered drugs.

OBJECTIVE: We determined the possible effects of a peripherally acting α2-adrenoceptor antagonist, MK-467, on the absorption of intramuscularly (IM) coadministered medetomidine, butorphanol and midazolam. STUDY DESIGN: Randomized, experimental, blinded crossover study. ANIMALS: Six healthy Beagle dogs. METHODS: Two IM treatments were administered: 1) medetomidine hydrochloride (20 µg kg-1) + butorphanol (100 µg kg-1) + midazolam (200 µg kg-1; MBM) and 2) MBM + MK-467 hydrochloride (500 µg kg-1; MBM-MK), mixed in a syringe. Heart rate was recorded at regular intervals. Sedation was assessed with visual analog scales (0-100 mm). Drug concentrations in plasma were analyzed with liquid chromatography-tandem mass spectrometry, with chiral separation of dex- and levomedetomidine. Maximum drug concentrations in plasma (Cmax) and time to Cmax (Tmax) were determined. Paired t-tests, with Bonferroni correction when appropriate, were used for comparisons between the treatments. RESULTS: Data from five dogs were analyzed. Heart rate was significantly higher from 20 to 90 minutes after MBM-MK. The Tmax values for midazolam and levomedetomidine (mean ± standard deviation) were approximately halved with coadministration of MK-467, from 23 ± 9 to 11 ± 6 minutes (p = 0.049) for midazolam and from 32 ± 15 to 18 ± 6 minutes for levomedetomidine (p = 0.036), respectively. CONCLUSIONS AND CLINICAL RELEVANCE: MK-467 accelerated the absorption of IM coadministered drugs. This is clinically relevant as it may hasten the onset of peak sedative effects.

Comparison of morphological changes and tactile sensitivity of the pharynx and larynx between four standing sedative and analgesic protocols in eight adult healthy horses.

OBJECTIVE: To compare the topographic modifications and tactile sensitivity of the pharynx and larynx after administration of four sedative and analgesic protocols in standing horses. STUDY DESIGN: Experimental, observer-blinded, crossover study. ANIMALS: Eight healthy mares. METHODS: Five protocols were evaluated: 1) xylazine and butorphanol administered intravenously (IV); 2) detomidine and butorphanol administered IV; 3) xylazine administered IV and lidocaine topically; 4) detomidine administered IV and lidocaine topically and 5) no analgesia or sedation (control). Quality of sedation, head height and sudden head movements were recorded. The degree of arytenoid cartilage displacement, the degree of pharyngeal collapse and the occurrence of soft palate displacement were scored using standardized scales. Tactile sensitivity was tested on 10 different pharyngeal and laryngeal regions using an atraumatic transendoscopic probe. Statistical analysis was performed using linear or generalized mixed-effects models. RESULTS: Head height was significantly decreased in protocols with xylazine (p = 0.002). Head movements were significantly increased in protocols with butorphanol (p = 0.0001). No changes in abduction grade or degree of soft palate displacement were observed between all sedative protocols and the control group. Pharyngeal collapse was significantly more frequent in protocols with lidocaine (p < 0.001) or xylazine (p = 0.017). For the pharyngeal regions, no tactile sensitivity difference was observed between the control and treatment protocols. All treatment protocols led to greater desensitization of all the laryngeal regions compared with the control protocol. CONCLUSION AND CLINICAL RELEVANCE: All the protocols provided adequate sedation and analgesia for the manipulation of the larynx and pharynx but significant differences were noted. Xylazine produces a more profound sedation compared with detomidine, but can induce dorsal pharyngeal collapse. Lidocaine caused pharyngeal collapse and its use should be limited to the target area. Butorphanol can be added to improve analgesia in the other regions but frequent head jerking can be expected.

Peri-anaesthetic mortality and nonfatal gastrointestinal complications in pet rabbits: a retrospective study on 210 cases.

OBJECTIVE: The aim of this study was to determine the incidence and the associated risk factors of peri-anaesthetic mortality and gastrointestinal complications in pet rabbits. STUDY DESIGN: Retrospective cohort study. ANIMALS: A total of 185 pet rabbits admitted to the Exotic Referal Service of Beaumont Sainsbury's Animal Hospital over the period 2009-2016. METHODS: The clinical records of the rabbits were obtained from the database. To evaluate the incidence of peri-anaesthetic mortality, three possible outcomes were considered: alive, dead or euthanized within the 72 hours following the anaesthetic event. Food intake and stool production during the first 72 hours following the anaesthetic event were evaluated to investigate the occurrence of gastrointestinal complications. Thereafter, various hypothesized risk factors, including administration of alpha-2 agonists, body weight, American Society of Anaesthesiologists classification and endotracheal intubation were tested against peri-anaesthetic mortality and gastrointestinal complications, with both univariate and multivariate binary logistic regression. RESULTS: Twenty-five out of 185 rabbits underwent two anaesthetic events; therefore, data from 210 cases were used. Of these 210 cases, six died during sedation or general anaesthesia and four (one of which euthanized) died during the first 72 postoperative hours, accounting for an actual mortality rate equal to 4.8% (95% confidence interval, 0.025-0.086). Peri-anaesthetic gastrointestinal complications developed in 77 (38%) out of the 204 anaesthetic events whose outcome was not intraoperative death (95% confidence interval, 0.314-0.446). Species-specific risk factors could not be identified for peri-anaesthetic mortality; however, the odds for post-anaesthetic gastrointestinal complications increased significantly with body weight (p = 0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Our findings confirm that rabbits continue to have a higher incidence of peri-anaesthetic mortality than dogs and cats, and highlight a high risk for nonfatal peri-anaesthetic gastrointestinal complications in this species.

Surgical Extraction of Viable Hen ( Gallus gallus domesticus) Follicles for In Vitro Fertilization.

Assisted reproduction techniques in birds have been developed for zootechnical purposes and have been adapted for use in conservation of wild bird species. To develop a technique for obtaining follicles in live hens, 5 Rhode Island red hens ( Gallus gallus domesticus) were anesthetized, and abdominal ultrasound was performed to confirm the presence of ovarian follicles. A left celiotomy then was performed to obtain follicles in different stages of maturation for in vitro fertilization. The follicles were located by digital exploration, then extracted by isolating each follicle with the index finger of each hand, holding it by the stigma, and then applying slight traction towards the exterior of the coelomic cavity until the follicle separated from the ovary. In total, 18 of 30 (60%) follicles obtained were suitable for in vitro fertilization, but only 3 (16%) were fertilized successfully. All birds recovered from the procedure and remained in good condition postoperatively. Perfecting assisted reproduction technique holds potential benefits for determining sex of embryos by blastomeres sexing, supporting the conservation efforts of avian species, and benefiting research areas, such as genetic and biopharmaceutical research.

Alfaxalone anaesthesia in Lemur catta following dexmedetomidine-butorphanol-midazolam sedation.

OBJECTIVE: To evaluate the clinical effects and quality of sedation, induction, maintenance and recovery in Lemur catta after dexmedetomidine-butorphanol-midazolam sedation and alfaxalone anaesthesia. STUDY DESIGN: Prospective, observational study. ANIMALS: Six male L. catta weighing 3.0 ± 0.6 kg undergoing surgical castration. METHODS: Lemurs were sedated with intramuscular dexmedetomidine (0.015 mg kg-1), butorphanol (0.2 mg kg-1) and midazolam (0.2 mg kg-1). Anaesthesia was induced with intravenous alfaxalone 0.5 mg kg-1 over 60 seconds; further boluses were administered until tracheal intubation was feasible and final dose recorded. Alfaxalone continuous infusion was used to maintain anaesthesia. Atipamezole (0.15 mg kg-1) was administered during recovery. The quality of sedation, induction, intubation, maintenance and recovery was assessed using a scoring system. Physiological parameters were recorded during sedation, maintenance and recovery. RESULTS: Sedation was achieved in 13.6 ± 5.6 minutes and no reactions were observed during handling or venepuncture. The mean dose of alfaxalone required for induction and maintenance was 2.09 ± 0.65 and 0.08 ± 0.02 mg kg-1 minute-1, respectively. Quality of induction, intubation and maintenance was good in almost all animals. Mild self-limiting muscle twitching was observed after alfaxalone administration in three animals. Cardiorespiratory function was stable in all animals but one. One lemur showed respiratory depression and required oxygen administration and manual ventilation. The mean maintenance time was 29.2 ± 7.4 minutes. The mean times from the end of alfaxalone administration to extubation, atipamezole administration and full recovery were: 15.3 ± 8.0, 22.2 ± 4.6 and 60.0 ± 8.4 minutes, respectively. Recovery was considered good in all animals. CONCLUSIONS AND CLINICAL RELEVANCE: Dexmedetomidine-butorphanol-midazolam combination provided reliable sedation and adequate muscle relaxation in L. catta. Alfaxalone proved to be a useful drug for induction and maintenance of anaesthesia and might be considered an option for injectable anaesthesia in lemurs.

Pharmacokinetics and pharmacodynamic effects in koi carp (Cyprinus carpio) following immersion in propofol.

OBJECTIVE: To test the hypothesis that plasma propofol concentration (PPC) is associated with anesthetic effect in koi carp administered propofol by immersion. STUDY DESIGN: Prospective study. ANIMALS: Twenty mature koi carp (mean ± standard deviation, 409.4 ± 83.7 g). METHODS: Fish were immersed in propofol (5 mg L-1). Physiological variables and induction and recovery times were recorded. In phase I, blood was sampled for PPC immediately following induction and at recovery. In phase II, following induction, fish were maintained with propofol (4 mg L-1) via a recirculating system for 20 minutes. Following established induction, blood was sampled at 1, 10 and 20 minutes. In phase III (n = 19), fish were anesthetized as in phase II with blood sampled nine times in a sparse sampling strategy. Simultaneously, a pharmacodynamics rubric was used to evaluate anesthetic depth. PPC was determined using high performance liquid chromatography with fluorescence detection. Following evaluation of normality, data were analyzed using paired t test or Spearman correlation test (significance was set at p < 0.05). RESULTS: In phase I, mean PPCs at induction (20.12 µg mL-1) and recovery (11.62 µg mL-1) were different (p < 0.001). In phase II, only mean PPCs at induction (17.92 µg mL-1) and 10 minutes (21.50 µg mL-1) were different (p = 0.013). In phase III, a correlation between PPCs and the pharmacodynamic rubric scores was found (p < 0.001, r = -0.93). There was no correlation between PPCs and recovery time (p = 0.057, r = 0.433). A two-compartment open model was chosen for the pharmacokinetic model. Absorption rate constant, elimination rate constant and intercompartmental rate constant were 0.48, 0.006 and 0.02 minute-1, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Measurable PPCs were achieved in koi carp anesthetized with propofol by immersion. Anesthetic depth of fish was negatively correlated with PPCs, but recovery time was not.

Evaluation of sedative and antinociceptive effects of dexmedetomidine, midazolam and dexmedetomidine-midazolam in tegus (Salvator merianae).

OBJECTIVE: To evaluate dexmedetomidine, midazolam and dexmedetomidine-midazolam for sedation and antinociception in tegus. STUDY DESIGN: Prospective, crossover, randomized, blinded study. ANIMALS: Six healthy tegus (Salvator merianae) weighing 1.6±0.3 kg. METHODS: Tegus were administered intramuscularly saline (0.5 mL; CON), dexmedetomidine (0.2 mg kg-1; DX), midazolam (1 mg kg-1; MZ) and dexmedetomidine-midazolam (same doses; DM). Heart rate (HR) and respiratory frequency (fR) were recorded before treatment (baseline) and 15, 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours after the treatments. Sedation scores were recorded according to resistance to manual restraint, posture and response to noxious stimulus, at baseline and 5, 10, 15, 30 minutes, 1, 2, 3, 4, 6, 8, 12 and 24 hours after the treatments. Antinociception was evaluated by measurement of latency of limb withdrawal reflex (LWR) to thermal stimulus, recorded at baseline and 15 minutes, 1, 2, 4, 8, 12 and 24 hours after the treatments. RESULTS: Lower HR (DX and DM) and fR (MZ, DX and DM) than CON were measured 15 minutes after the treatment and for up to 6 hours. Sedation was mild to moderate in MZ, deep in DM and absent in DX, although animals showed behavioral changes in DX, with increase in aggressiveness. Median (interquartile range) duration of sedation were 170 (50; 235) minutes in MZ and 230 (115; 235) minutes in DM. Recovery period was prolonged in both treatments, surpassing the duration of the experiment. Higher LWR than CON was detected from 15 minutes until 12 hours in DX and DM. CONCLUSIONS AND CLINICAL RELEVANCE: Midazolam provided sedation without antinociception, and dexmedetomidine provided antinociception without sedation. Drug combination increased the duration of sedation but not antinociception. Due to increased duration of sedation, reversal of effects with flumazenil and atipamezole should be considered after conclusion of clinical procedures.

Pharmacokinetics and effects of alfaxalone after intravenous and intramuscular administration to cats.

AIMS: To determine the pharmacokinetics, and anaesthetic and sedative effects of alfaxalone after I/V and I/M administration to cats. METHODS: Six European shorthair cats, three males and three females, with a mean weight of 4.21 (SD 0.53) kg and aged 3.8 (SD 0.9) years were enrolled in this crossover, two-treatment, two-period study. Alfaxalone at a dose of 5 mg/kg was administered either I/V or I/M. Blood samples were collected between 2-480 minutes after drug administration and analysed for concentrations of alfaxalone by HPLC. The plasma concentration-time curves were analysed by non-compartmental analysis. Sedation scores were evaluated between 5-120 minutes after drug administration using a numerical rating scale (from 0-18). Intervals from drug administration to sit, sternal and lateral recumbency during the induction phase, and to head-lift, sternal recumbency and standing position during recovery were recorded. RESULTS: The mean half-life and mean residence time of alfaxalone were longer after I/M (1.28 (SD 0.21) and 2.09 (SD 0.36) hours, respectively) than after I/V (0.49 (SD 0.07) and 0.66 (SD 0.16) hours, respectively) administration (p<0.05). Bioavailability after I/M injection of alfaxalone was 94.7 (SD 19.8)%. The mean intervals to sternal and lateral recumbency were longer in the I/M (3.73 (SD 1.99) and 6.12 (SD 0.90) minutes, respectively) compared to I/V (0 minutes for all animals) treated cats (p<0.01). Sedation scores indicative of general anaesthesia (scores >15) were recorded from 5-15 minutes after I/V administration and deep sedation (scores 11-15) at 20 and 30 minutes. Deep sedation was observed from 10-45 minutes after I/M administration. One cat from each group showed hyperkinesia during recovery, and the remainder had an uneventful recovery. CONCLUSIONS AND CLINICAL RELEVANCE: Alfaxalone administered I/V in cats provides rapid and smooth induction of anaesthesia. After I/M administration, a longer exposure to the drug and an extended half life were obtained compared to I/V administration. Therefore I/M administration of alfaxalone could be a reliable, suitable and easy route in cats, taking into account that alfaxalone has a slower onset of sedation than when given I/V and achieves deep sedation rather than general anaesthesia.

The effect of sedation with a combination of butorphanol and midazolam on quantitative contrast-enhanced ultrasonography of duodenum in healthy dogs.

Quantitative contrast-enhanced ultrasonography (CEUS) enables non-invasive and objective evaluation of intestinal perfusion by quantifying the intensity of enhancement on the intestine after microbubble contrast administration. During CEUS scanning, sedation is sometimes necessary to maintain animal cooperation. Nevertheless, the effect of sedative administration on the canine intestinal CEUS is unknown. This study aimed to investigate the effect of sedation with a combination of butorphanol and midazolam on the duodenal CEUS-derived perfusion parameters of healthy dogs. For this purpose, duodenum was imaged following contrast administration (Sonazoid®, 0.01 ml/kg) in six healthy beagles before and after intravenous injection of a combination of butorphanol (0.2 mg/kg) and midazolam (0.1 mg/kg). Furthermore, hemodynamic parameters including blood pressure and heart rate were recorded during the procedure. Five CEUS derived perfusion parameters including time-to-peak (TTP), peak intensity (PI), area under the curve (AUC), wash-in and wash-out rates (WiR and WoR, respectively) before and after sedation were statistically compared. The result showed that no significant change was detected in any of perfusion parameters. Systolic and mean arterial pressures significantly reduced after sedative administration, but diastolic arterial pressure and heart rate did not significantly change. Moreover, no significant partial correlation was observed between perfusion parameters and hemodynamic parameters. Thus, we concluded that the combination did not cause significant influence in duodenal CEUS perfusion parameters and could be a good option for sedation prior to duodenal CEUS in debilitated dogs.

Comparison of the sedative effects of nalbuphine and butorphanol, alone or in combination with acepromazine in dogs.

OBJECTIVE: To compare sedation and effects on heart rate (HR), mean arterial pressure (MAP) and respiratory rate (fR) of nalbuphine and butorphanol, alone or combined with acepromazine in dogs. STUDY DESIGN: Prospective, randomized experimental trial. ANIMALS: Eight healthy Beagle dogs, aged (mean ± standard deviation) 3.4 ± 0.5 years and weighing 11.0 ± 1.3 kg. METHODS: Each dog was treated four times: physiological saline (1 mL) combined with nalbuphine (0.5 mg kg-1; SAL-NAL) or butorphanol (0.15 mg kg-1; SAL-BUT), and acepromazine (0.05 mg kg-1) combined with nalbuphine (0.5 mg kg-1; ACP-NAL) or butorphanol (0.15 mg kg-1; ACP-BUT), intravenously (IV). The degree of sedation, assessed by a numeric descriptive scale (NDS) and simple numerical scale (SNS), HR, MAP, fR and rectal temperature (RT), were recorded before and 20 minutes after administration of saline or acepromazine, then 15, 30, 60, 90 and 120 minutes after nalbuphine or butorphanol. Values were compared with baseline and among treatments. RESULTS: Mild sedation was recorded for SAL-NAL and SAL-BUT, and moderate sedation for ACP-NAL and ACP-BUT. NDS and SNS scores were higher for SAL-BUT and ACP-BUT at some time points when compared with SAL-NAL and ACP-NAL, respectively (p < 0.001). HR was lower in ACP-NAL than in ACP-BUT at 120 minutes and fR was lower in SAL-BUT than in SAL-NAL at 30 and 120 minutes (p < 0.05). RT was lower in SAL-BUT (37.5 ± 0.5 °C) compared with SAL-NAL (38.0 ± 0.5 °C) at 60-120 minutes (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Butorphanol promoted a higher sedative effect than nalbuphine when alone and combined with acepromazine. IV administration of nalbuphine or butorphanol, with or without acepromazine, at the doses studied, resulted in minimal decreases in MAP, HR, fR and RT.

Effect of premedication with butorphanol or methadone on ease of endoscopic duodenal intubation in dogs.

OBJECTIVE: The effect of premedication with butorphanol or methadone on ease of endoscopic duodenal intubation. STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: A group of 20 client-owned dogs. METHODS: Dogs were assigned randomly to be administered intravenous (IV) premedication with either butorphanol (0.4 mg kg-1) or methadone (0.3 mg kg-1). General anaesthesia was induced with propofol to effect and maintained with isoflurane in 100% oxygen. Sedation score 20 minutes after premedication administration and induction dose of propofol were recorded. Heart rate, mean arterial pressure, haemoglobin oxygen saturation, respiratory rate and end-tidal isoflurane concentration were recorded every 5 minutes. Spontaneous lower oesophageal and pyloric sphincter opening, presence of gastro-oesophageal and duodeno-gastric reflux, antral peristaltic contractions and response to endoscopy were recorded as yes or no. Ease of duodenal intubation (EDI) was graded on a scale ranging from 1 (immediate entry with minimal manoeuvring required) to 4 (no entry after 2 minutes). Time (seconds) from the start of pyloric intubation to successfully entering the duodenum was recorded. RESULTS: Median EDI score [3 ± 1 (butorphanol), 4 ± 1 (methadone), p = 0.035], time [65 ± 36 seconds (butorphanol), 120 ± 38 seconds (methadone), p = 0.028] and number of dogs with spontaneous pyloric sphincter opening [7/10 (butorphanol), 2/10 (methadone), p = 0.035] differed between groups. No other significant differences were found. CONCLUSIONS AND CLINICAL RELEVANCE: In these clinical cases, duodenal intubation was performed with greater ease, shorter time and more frequent spontaneous opening of the pyloric sphincter after premedication with butorphanol in comparison to methadone. The use of butorphanol facilitated the passage of the endoscope and is therefore recommended for premedication prior to upper gastrointestinal tract endoscopy.

Hemodynamic effects of dexmedetomidine, with and without MK-467, following intramuscular administration in cats anesthetized with isoflurane.

OBJECTIVE: To characterize the hemodynamic effects of dexmedetomidine, with or without MK-467, following intramuscular (IM) administration in cats. STUDY DESIGN: Randomized, crossover, experimental study. ANIMALS: Six healthy adult male castrated purpose-bred cats. METHODS: Cats were anesthetized with isoflurane in oxygen and instrumented. Cats were administered dexmedetomidine (25 µg kg-1), with (DM) or without (D) MK-467 (600 µg kg-1), IM in the epaxial muscles. Cardiovascular variables, respiratory variables, temperature, and arterial and mixed-venous pH, blood gases and electrolytes were measured prior to drug administration and at various time points for 6 hours thereafter, during anesthesia with isoflurane. Additional variables were calculated from the measurements, using standard equations. Results were analyzed with a two-way repeated-measures analysis of variance, followed by Dunnett's and paired t tests where appropriate. RESULTS: Dexmedetomidine resulted in a significant decrease in cardiac index (CI) and significant increases in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI). The addition of MK-467 failed to prevent most of the early cardiovascular effects of dexmedetomidine, but the duration of systemic vasoconstriction was shorter and CI did not decrease. The lowest and highest post-treatment values in each treatment were 0.1 ± 0.03 and 0.13 ± 0.03 L minute-1 BW-0.67 (D) versus 0.14 ± 0.01 and 0.19 ± 0.03 L minute-1 BW-0.67 (DM) for CI, 87 ± 13 and 181 ± 21 mmHg (D) versus 70 ± 11 and 153 ± 18 mmHg (DM) for MAP and 58,948 ± 17,754 and 119,432 ± 40,423 dynes second cm-5 BW-0.67 (D) versus 25,870 ± 3782 and 76,498 ± 17,258 dynes second cm-5 BW-0.67 (DM) for SVRI, respectively. CONCLUSION AND CLINICAL RELEVANCE: IM coadministration of MK-467 and dexmedetomidine in isoflurane-anesthetized cats shortened dexmedetomidine-induced cardiovascular effects. This drug combination may be useful in cats in which longer-lasting hypertension and hemodynamic depression is of concern.

Chemical capture of impala (Aepyceros melampus): A review of factors contributing to morbidity and mortality.

OBJECTIVE: To review the factors that contribute to morbidity and mortality of impala undergoing chemical capture, and discuss how they are potentially mitigated. DATABASES USED: PubMed, Science Direct, Google Scholar and Onderstepoort Veterinary Academic Hospital records. CONCLUSIONS AND CLINICAL RELEVANCE: Impala are an important species of antelope in Africa and are often captured during management procedures, veterinary interventions and research projects. Chemical capture is a preferred technique over physical capture and restraint for veterinary interventions as it allows for easier handling and better clinical assessment and treatment. However, this capture technique results in high mortality (4%) and morbidity rates (23%), which translates into animal welfare and economic concerns. Investigation of environmental, drug and drug delivery, and animal factors to elucidate the origin of these high rates was reviewed. The greatest risks emanate from the drug and drug delivery factors where potent opioids (etorphine and thiafentanil) cause profound respiratory compromise, that if left untreated often translates into fatalities. Furthermore, the procedure of darting, an essential tool in game capture, can cause irreparable fractures and other fatal injuries mainly through accidental misplacement of the dart into a long bone, thoracic or peritoneal cavity. Impala are anxious and flighty, and this demeanour (animal related factor) can contribute towards mortality and morbidity rates. Impala that mount an inappropriate stress response to capture tend to die; therefore, procedures that induce an intense stress response (awake clinical examinations) should be avoided. Sequela of a heightened stress response include capture-induced hyperthermia, myopathies, fractures, maladaptation to confinement or new environments and death. Impala serve as a useful model for improving immobilizing and anaesthetic drug protocols, darting techniques or new methods of remote injection in wildlife. However, the risks associated with chemical capture in this species should be understood, and all efforts to mitigate these should be employed.