Effects of intramuscular vatinoxan (MK-467), co-administered with medetomidine and butorphanol,on cardiopulmonary and anaesthetic effects of intravenous ketamine in dogs

ObjectiveTo investigate the impact of intramuscular (IM) co-administration of the peripheral α₂-adrenoceptor agonist vatinoxan (MK-467) with medetomidine and butorphanol prior to intravenous (IV) ketamine on the cardiopulmonary and anaesthetic effects in dogs, followed by atipamezole reversal.Study designRandomized, masked crossover study.AnimalsA total of eight purpose-bred Beagle dogs aged 3 years.MethodsEach dog was instrumented and administered two treatments 2 weeks apart: medetomidine (20 μg kg^–1) and butorphanol (100 μg kg^–1) premedication with vatinoxan (500 μg kg^–1; treatment MVB) or without vatinoxan (treatment MB) IM 20 minutes before IV ketamine (4 mg kg^–1). Atipamezole (100 μg kg^–1) was administered IM 60 minutes after ketamine. Heart rate (HR), mean arterial (MAP) and central venous (CVP) pressures and cardiac output (CO) were measured; cardiac (CI) and systemic vascular resistance (SVRI) indices were calculated before and 10 minutes after MVB or MB, and 10, 25, 40, 55, 70 and 100 minutes after ketamine. Data were analysed with repeated measures analysis of covariance models. A p-value <0.05 was considered statistically significant. Sedation, induction, intubation and recovery scores were assessed.ResultsAt most time points, HR and CI were significantly higher, and SVRI and CVP significantly lower with MVB than with MB. With both treatments, SVRI and MAP decreased after ketamine, whereas HR and CI increased. MAP was significantly lower with MVB than with MB; mild hypotension (57–59 mmHg) was recorded in two dogs with MVB prior to atipamezole administration. Sedation, induction, intubation and recovery scores were not different between treatments, but intolerance to the endotracheal tube was observed earlier with MVB.Conclusions and clinical relevanceHaemodynamic performance was improved by vatinoxan co-administration with medetomidine–butorphanol, before and after ketamine administration. However, vatinoxan was associated with mild hypotension after ketamine with the dose used in this study. Vatinoxan shortened the duration of anaesthesia.     

A clinical study on the effect in horses during medetomidine-isoflurane anaesthesia, of butorphanol constant rate infusion on isoflurane requirements, on cardiopulmonary function and on recovery characteristics

ObjectiveTo test if the addition of butorphanol by constant rate infusion (CRI) to medetomidine–isoflurane anaesthesia reduced isoflurane requirements, and influenced cardiopulmonary function and/or recovery characteristics.Study designProspective blinded randomised clinical trial.Animals61 horses undergoing elective surgery.MethodsHorses were sedated with intravenous (IV) medetomidine (7 μg kg^?1); anaesthesia was induced with IV ketamine (2.2 mg kg^?1) and diazepam (0.02 mg kg^?1) and maintained with isoflurane and a CRI of medetomidine (3.5 μg kg^?1 hour^?1). Group MB (n = 31) received butorphanol CRI (25 μg kg^?1 IV bolus then 25 μg kg^?1 hour^?1); Group M (n = 30) an equal volume of saline. Artificial ventilation maintained end-tidal CO₂ in the normal range. Horses received lactated Ringer’s solution 5 mL kg^?1 hour^?1, dobutamine <1.25 μg kg^?1 minute^?1 and colloids if required. Inspired and exhaled gases, heart rate and mean arterial blood pressure (MAP) were monitored continuously; pH and arterial blood gases were measured every 30 minutes. Recovery was timed and scored. Data were analyzed using two way repeated measures anova, independent t-tests or Mann–Whitney Rank Sum test (p < 0.05).ResultsThere was no difference between groups with respect to anaesthesia duration, end-tidal isoflurane (MB: mean 1.06 ± SD 0.11, M: 1.05 ± 0.1%), MAP (MB: 88 ± 9, M: 87 ± 7 mmHg), heart rate (MB: 33 ± 6, M: 35 ± 8 beats minute^?1), pH, PaO₂ (MB: 19.2 ± 6.6, M: 18.2 ± 6.6 kPa) or PaCO_2. Recovery times and quality did not differ between groups, but the time to extubation was significantly longer in group MB (26.9 ± 10.9 minutes) than in group M (20.4 ± 9.4 minutes).Conclusion and clinical relevanceButorphanol CRI at the dose used does not decrease isoflurane requirements in horses anaesthetised with medetomidine–isoflurane and has no influence on cardiopulmonary function or recovery.     

The impact of vatinoxan on medetomidine–ketamine–midazolam immobilization in Patagonian maras (Dolichotis patagonum)

ObjectiveTo compare cardiovascular and ventilatory effects, immobilization quality and effects on tissue perfusion of a medetomidine–ketamine–midazolam combination with or without vatinoxan (MK-467), a peripherally acting α₂-adrenoceptor antagonist.Study designRandomized, blinded, crossover study.AnimalsA group of nine healthy Patagonian maras (Dolichotis patagonum).MethodsMaras were immobilized twice with: 1) medetomidine hydrochloride (0.1 mg kg^–1) + ketamine (5 mg kg^–1) + midazolam (0.1 mg kg^–1) (MKM) + saline or 2) MKM + vatinoxan hydrochloride (0.8 mg kg^–1), administered intramuscularly. Drugs were mixed in the same syringe. At 20, 30 and 40 minutes after injection, invasive blood pressure, heart rate, respiration rate, end-tidal CO₂, haemoglobin oxygen saturation, and muscle oxygenation were measured, arteriovenous oxygen content difference was calculated. Muscle tone, jaw tone, spontaneous blinking and palpebral reflex were evaluated. Times to initial effect, recumbency, initial arousal and control of the head were recorded. Paired t test, Wilcoxon matched-pairs signed rank test and analysis of variance were used to compare protocols; (p < 0.05).ResultsVatinoxan significantly reduced systolic (p = 0.0002), mean (MAP; p < 0.0001) and diastolic (p < 0.0001) arterial blood pressures between 20 and 40 minutes. MAPs at 30 minutes (mean ± standard deviation) with MKM and MKM + vatinoxan were 105 ± 12 and 71 ± 14 mmHg, respectively. Without vatinoxan, four animals were hypertensive (MAP > 120 mmHg), whereas with vatinoxan, four animals were hypotensive (MAP < 60 mmHg). Muscle and jaw tone were significantly more frequently present with MKM (both p = 0.039). Other measurements did not significantly differ between protocols.Conclusions and clinical relevanceIn Patagonian maras, vatinoxan attenuated the increase in blood pressure induced by medetomidine. Muscle and jaw tone were more frequently present with MKM, indicating that quality of immobilization with vatinoxan was more profound.     

Cardiovascular effects of intravenous vatinoxan (MK-467) in medetomidine–tiletamine–zolazepam anaesthetised red deer (Cervus elaphus)

ObjectiveTo determine the effect of intravenous vatinoxan administration on bradycardia, hypertension and level of anaesthesia induced by medetomidine–tiletamine–zolazepam in red deer (Cervus elaphus).Study design and animalsA total of 10 healthy red deer were included in a randomised, controlled, experimental, crossover study.MethodsDeer were administered a combination of 0.1 mg kg^–1 medetomidine hydrochloride and 2.5 mg kg^–1 tiletamine–zolazepam intramuscularly, followed by 0.1 mg kg^–1 vatinoxan hydrochloride or equivalent volume of saline intravenously (IV) 35 minutes after anaesthetic induction. Heart rate (HR), mean arterial blood pressure (MAP), respiration rate (f_R), end-tidal CO₂ (Pe′CO₂), arterial oxygen saturation (SpO₂), rectal temperature (RT) and level of anaesthesia were assessed before saline/vatinoxan administration (baseline) and at intervals for 25 minutes thereafter. Differences within treatments (change from baseline) and between treatments were analysed with linear mixed effect models (p < 0.05).ResultsMaximal (81 ± 10 beats minute^–1) HR occurred 90 seconds after vatinoxan injection and remained significantly above baseline (42 ± 4 beats minute^–1) for 15 minutes. MAP significantly decreased from baseline (122 ± 10 mmHg) to a minimum MAP of 83 ± 6 mmHg 60 seconds after vatinoxan and remained below baseline until end of anaesthesia. HR remained unchanged from baseline (43 ± 5 beats minute^–1) with the saline treatment, whereas MAP decreased significantly (112 ± 16 mmHg) from baseline after 20 minutes. Pe′CO₂, f_R and SpO₂ showed no significant differences between treatments, whereas RT decreased significantly 25 minutes after vatinoxan. Level of anaesthesia was not significantly influenced by vatinoxan.Conclusions and clinical relevanceVatinoxan reversed hypertension and bradycardia induced by medetomidine without causing hypotension or affecting the level of anaesthesia in red deer. However, the effect on HR subsided 15 minutes after vatinoxan IV administration. Vatinoxan has the potential to reduce anaesthetic side effects in non-domestic ruminants immobilised with medetomidine–tiletamine–zolazepam.     

The sedative effects of low-dose medetomidine and butorphanol alone and in combination intravenously in dogs

ObjectiveTo evaluate the sedative effects of intravenous (IV) medetomidine (1 μg kg^?1) and butorphanol (0.1 mg kg^?1) alone and in combination in dogs.Study designProspective, blinded, randomized clinical trial.AnimalsSixty healthy (American Society of Anesthesiologists I) dogs, aged 6.2 ± 3.2 years and body mass 26 ± 12.5 kg.MethodsDogs were assigned to four groups: Group S (sodium chloride 0.9% IV), Group B (butorphanol IV), Group M (medetomidine IV) and Group MB (medetomidine and butorphanol IV). The same clinician assessed sedation before and 12 minutes after administration using a numerical scoring system in which 19 represented maximum sedation. Heart rate (HR), respiratory rate, pulse quality, capillary refill time and rectal temperature were recorded after each sedation score assessment. Sedation scores, sedation score difference (score after minus score before administration) and patient variables were compared using one-way anova for normally distributed variables and Kruskal–Wallis test for variables with skewed distributions and/or unequal variances. Where significance was found, further evaluation used Bonferroni multiple comparisons for pair-wise testing.ResultsBreed, sex, neuter status, age and body mass did not differ between groups. Sedation scores before substance administration were similar between groups (p = 0.2). Sedation scores after sedation were significantly higher in Group MB (mean 9.5 ± SD 5.5) than in group S (2.5 ± 1.8) (p < 0.001), group M (3.1 ± 2.5) (p < 0.001) and group B (3.7 ± 2.0) (p = 0.003). Sedation score difference was significantly higher in Group MB [7 (0–13)] than in Group S [0 (?1 to 4)] (p < 0.001) and Group M [0 (0–6)] (p < 0.001). HR decreased significantly in Groups M and MB compared with Group S (p < 0.05).Conclusion and clinical relevanceLow-dose medetomidine 1 μg kg^?1 IV combined with butorphanol 0.1 mg kg^?1 IV produced more sedation than medetomidine or butorphanol alone. HR was significantly decreased in both medetomidine groups.     

Concentrations of medetomidine enantiomers and vatinoxan,an α2-adrenoceptor antagonist,in plasma and central nervous tissue after intravenous coadministration in dogs

ObjectiveTo quantify the peripheral selectivity of vatinoxan (L-659,066, MK-467) in dogs by comparing the concentrations of vatinoxan, dexmedetomidine and levomedetomidine in plasma and central nervous system (CNS) tissue after intravenous (IV) coadministration of vatinoxan and medetomidine.Study designExperimental, observational study.AnimalsA group of six healthy, purpose-bred Beagle dogs (four females and two males) aged 6.5 ± 0.1 years (mean ± standard deviation).MethodsAll dogs were administered a combination of medetomidine (40 μg kg⁻¹) and vatinoxan (800 μg kg⁻¹) as IV bolus. After 20 minutes, the dogs were euthanized with an IV overdose of pentobarbital (140 mg kg⁻¹) and both venous plasma and CNS tissues (brain, cervical and lumbar spinal cord) were harvested. Concentrations of dexmedetomidine, levomedetomidine and vatinoxan in all samples were quantified by liquid chromatography–tandem mass spectrometry and data were analyzed with nonparametric tests with post hoc corrections where appropriate.ResultsAll dogs became deeply sedated after the treatment. The CNS-to-plasma ratio of vatinoxan concentration was approximately 1:50, whereas the concentrations of dexmedetomidine and levomedetomidine in the CNS were three- to seven-fold of those in plasma.Conclusions and clinical relevanceWith the doses studied, these results confirm the peripheral selectivity of vatinoxan in dogs, when coadministered IV with medetomidine. Thus, it is likely that vatinoxan preferentially antagonizes α₂-adrenoceptors outside the CNS.     

Alfaxalone induction dose following administration of medetomidine and butorphanol in the dog

ObjectiveTo determine in dogs the effects of medetomidine and butorphanol, alone and in combination, on the induction dose of alfaxalone and to describe the induction and intubation conditions.Study designProspective, randomized, blinded clinical trial.AnimalsEighty-five client-owned dogs (ASA 1 or 2).MethodsSubjects were block randomized to treatment group according to temperament. The treatment groups were: medetomidine 4 μg kg^?1 (M), butorphanol 0.1 mg kg^?1 (B), or a combination of both (MB), all administered intramuscularly. After 30 minutes, a sedation score was assigned, and alfaxalone 0.5 mg kg^?1 was administered intravenously over 60 seconds by an observer who was unaware of treatment group. Tracheal intubation conditions were assessed and, if tracheal intubation was not possible after 20 seconds, further boluses of 0.2 mg kg^?1 were given every 20 seconds until intubation was achieved. Induction dose and adverse events (sneezing, twitching, paddling, excitement, apnoea and cyanosis) were recorded; induction quality and intubation conditions were scored and recorded.ResultsThe mean dose of alfaxalone required for induction was similar for groups M and B: 1.2 ± 0.4 mg kg^?1. The mean dose requirement for group MB (0.8 ± 0.3 mg kg^?1) was lower than groups M and B (p < 0.0001). Induction dose was not influenced by temperament or level of sedation. Induction and intubation scores did not differ between treatment groups. Adverse events were noted in 16 dogs; there was no association with treatment group, temperament or level of sedation.Conclusions and clinical relevanceMedetomidine and butorphanol administered in combination reduce the anaesthetic induction dose of alfaxalone compared to either agent alone. This difference should be taken into account when using this combination of drugs in a clinical setting.     

A comparison of the efficacy and cardiorespiratory effects of four medetomidine-based anaesthetic protocols in the red fox (Vulpes vulpes)

ObjectiveTo evaluate the anaesthetic and cardiorespiratory effects of four anaesthetic protocols in red foxes (Vulpes vulpes).Study designProspective, blinded and randomized complete block design.AnimalsTen adult captive red foxes.MethodsFoxes were anaesthetized by intramuscular (IM) injection using four protocols in random order: medetomidine 40 μg kg^?1, midazolam 0.3 mg kg^?1 and butorphanol 0.1 mg kg^?1 (MMiB), medetomidine 40 μg kg^?1 and ketamine 4 mg kg^?1 (MK40/4), medetomidine 60 μg kg^?1 and ketamine 4 mg kg^?1 (MK60/4), medetomidine 40 μg kg^?1 and tiletamine/zolazepam 2 mg kg^?1 (MTZ). Time to lateral recumbency, induction time and time to recovery following IM administration of atipamezole 0.2 mg kg^?1 were recorded. Heart rate (HR), respiratory rate (_fR) and rhythm, blood pressure, rectal temperature, end-tidal CO₂ tension (Pe′Co₂), functional oxygen saturation and presence/absence of interdigital, palpebral and ear reflexes were recorded every 10 minutes, and following administration of atipamezole. Data were analysed using two-way repeated-measures anova with Bonferroni post tests; p < 0.05 was considered significant.ResultsAll protocols produced profound sedation with good muscle relaxation. Only the MMiB protocol diverged significantly from the others. Induction of anaesthesia and recovery time following atipamezole were significantly longer, and f_R and initial HR significantly lower with MMiB than with the other protocols. With all protocols, mean arterial blood pressure (MAP) was initially relatively high (140–156 mmHg), and decreased significantly over time. With all protocols, the administration of atipamezole resulted in a rapid, significant decrease in MAP and an increase in HR.Conclusions and clinical relevanceAll four protocols provided anaesthetic conditions suitable for minor procedures and allowed endotracheal intubation. The cyclohexanone protocols provided quicker and more reliable inductions and recoveries than the MMiB protocol.     

Minimum infusion rate of alfaxalone for total intravenous anaesthesia after sedation with acepromazine or medetomidine in cats undergoing ovariohysterectomy

ObjectiveTo determine the induction doses, then minimum infusion rates of alfaxalone for total intravenous anaesthesia (TIVA), and subsequent, cardiopulmonary effects, recovery characteristics and alfaxalone plasma concentrations in cats undergoing ovariohysterectomy after premedication with butorphanol-acepromazine or butorphanol-medetomidine.Study designProspective randomized blinded clinical study.AnimalsTwenty-eight healthy cats.MethodsCats undergoing ovariohysterectomy were assigned into two groups: together with butorphanol [0.2 mg kg^?1 intramuscularly (IM)], group AA (n = 14) received acepromazine (0.1 mg kg^?1 IM) and group MA (n = 14) medetomidine (20 μg kg^?1 IM). Anaesthesia was induced with alfaxalone to effect [0.2 mg kg^?1 intravenously (IV) every 20 seconds], initially maintained with 8 mg kg^?1 hour^?1 alfaxalone IV and infusion adjusted (±0.5 mg kg^?1 hour^?1) every five minutes according to alterations in heart rate (HR), respiratory rate (f_R), Doppler blood pressure (DBP) and presence of palpebral reflex. Additional alfaxalone boli were administered IV if cats moved/swallowed (0.5 mg kg^?1) or if f_R >40 breaths minute^?1 (0.25 mg kg^?1). Venous blood samples were obtained to determine plasma alfaxalone concentrations. Meloxicam (0.2 mg kg^?1 IV) was administered postoperatively. Data were analysed using linear mixed models, Chi-squared, Fishers exact and t-tests.ResultsAlfaxalone anaesthesia induction dose (mean ± SD), was lower in group MA (1.87 ± 0.5; group AA: 2.57 ± 0.41 mg kg^?1). No cats became apnoeic. Intraoperative bolus requirements and TIVA rates (group AA: 11.62 ± 1.37, group MA: 10.76 ± 0.96 mg kg^?1 hour^?1) did not differ significantly between groups. Plasma concentrations ranged between 0.69 and 10.76 μg mL^?1. In group MA, f_R, end-tidal carbon dioxide, temperature and DBP were significantly higher and HR lower.Conclusion and clinical relevanceAlfaxalone TIVA in cats after medetomidine or acepromazine sedation provided suitable anaesthesia with no need for ventilatory support. After these premedications, the authors recommend initial alfaxalone TIVA rates of 10 mg kg^?1 hour^?1.     

Behavioural and cardiovascular effects of medetomidine constant rate infusion compared with detomidine for standing sedation in horses

ObjectiveTo compare the efficacy of a medetomidine constant rate infusion (CRI) with a detomidine CRI for standing sedation in horses undergoing high dose rate brachytherapy.Study designRandomized, controlled, crossover, blinded clinical trial.AnimalsA total of 50 horses with owner consent, excluding stallions.MethodsEach horse was sedated with intravenous acepromazine (0.02 mg kg^–1), followed by an α₂-adrenoceptor agonist 30 minutes later and then by butorphanol (0.1 mg kg^–1) 5 minutes later. A CRI of the same α₂-adrenoceptor agonist was started 10 minutes after butorphanol administration and maintained for the treatment duration. Treatments were given 1 week apart. Each horse was sedated with detomidine (bolus dose, 10 μg kg^–1; CRI, 6 μg kg^–1 hour^–1) or medetomidine (bolus dose, 5 μg kg^–1; CRI, 3.5 μg kg^–1 hour^–1). If sedation was inadequate, a quarter of the initial bolus of the α₂-adrenoceptor agonist was administered. Heart rate (HR) was measured via electrocardiography, and sedation and behaviour evaluated using a previously published scale. Between treatments, behaviour scores were compared using a Wilcoxon signed-rank test, frequencies of arrhythmias with chi-square tests, and HR with two-tailed paired t tests. A p value <0.05 indicated statistical significance.ResultsTotal treatment time for medetomidine was longer than that for detomidine (p = 0.04), and ear movements during medetomidine sedation were more numerous than those during detomidine sedation (p = 0.03), suggesting there may be a subtle difference in the depth of sedation. No significant differences in HR were found between treatments (p ≥ 0.09). Several horses had arrhythmias, with no difference in their frequency between the two infusions.Conclusions and clinical relevanceMedetomidine at this dose rate may produce less sedation than detomidine. Further studies are required to evaluate any clinical advantages to either drug, or whether a different CRI may be more appropriate.     

Medetomidine continuous rate intravenous infusion in horses in which surgical anaesthesia is maintained with isoflurane and intravenous infusions of lidocaine and ketamine

ObjectiveTo evaluate medetomidine as a continuous rate infusion (CRI) in horses in which anaesthesia is maintained with isoflurane and CRIs of ketamine and lidocaine.Study designProspective, randomized, blinded clinical trial.AnimalsForty horses undergoing elective surgery.MethodsAfter sedation and induction, anaesthesia was maintained with isoflurane. Mechanical ventilation was employed. All horses received lidocaine (1.5 mg kg^?1 initially, then 2 mg kg^?1 hour^?1) and ketamine (2 mg kg^?1 hour^?1), both CRIs reducing to 1.5 mg kg^?1 hour^?1 after 50 minutes. Horses in group MILK received a medetomidine CRI of 3.6 μg kg^?1 hour^?1, reducing after 50 minutes to 2.75 μg kg^?1 hour^?1, and horses in group ILK an equal volume of saline. Mean arterial pressure (MAP) was maintained above 70 mmHg using dobutamine. End-tidal concentration of isoflurane (FE′ISO) was adjusted as necessary to maintain surgical anaesthesia. Group ILK received medetomidine (3 μg kg^?1) at the end of the procedure. Recovery was evaluated. Differences between groups were analysed using Mann-Whitney, Chi-Square and anova tests as relevant. Significance was taken as p < 0.05.ResultsFE′ISO required to maintain surgical anaesthesia in group MILK decreased with time, becoming significantly less than that in group ILK by 45 minutes. After 60 minutes, median (IQR) FE′ISO in MILK was 0.65 (0.4–1.0) %, and in ILK was 1 (0.62–1.2) %. Physiological parameters did not differ between groups, but group MILK required less dobutamine to support MAP. Total recovery times were similar and recovery quality good in both groups.Conclusion and clinical relevanceA CRI of medetomidine given to horses which were also receiving CRIs of lidocaine and ketamine reduced the concentration of isoflurane necessary to maintain satisfactory anaesthesia for surgery, and reduced the dobutamine required to maintain MAP. No further sedation was required to provide a calm recovery.     

Comparative cardiovascular, analgesic, and sedative effects of medetomidine, medetomidine–hydromorphone, and medetomidine–butorphanol in dogs

The purpose of this study was to determine the cardiovascular, analgesic, and sedative effects of IV medetomidine (M, 20 µg kg^?1), medetomidine–hydromorphone (MH, 20 µg kg^?1 ? 0.1 mg kg^?1), and medetomidine–butorphanol (MB, 20 µg kg^?1 ? 0.2 mg kg^?1) in dogs. Using a randomized cross‐over design and allowing 1 week between treatments, six healthy, mixed‐breed dogs (five males and one female) weighing 20 ± 3 kg, were induced to anesthesia by face‐mask administration of 2.9% ET sevoflurane to facilitate instrumentation prior to administration of the treatment combinations. Dogs were intubated and instrumented to enable measurement of heart rate (HR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), mean pulmonary arterial pressure (PAP), pulmonary arterial occlusion pressure (PAOP), central venous pressure (CVP), pulmonary arterial temperature (TEMP), and cardiac output via thermodilution using 5 mL of 5% dextrose, and recording the average of the three replicate measurements. Cardiac index (CI) and systemic (SVR) and pulmonary vascular resistances were calculated. After instrumentation was completed, administration of sevoflurane was discontinued, and the dogs were allowed to recover for 30 minutes prior to administration of the treatment drugs. After collection of the baseline samples for blood gas analysis and recording the baseline cardiovascular variables, the test agents were administered IV over 10 seconds and the CV variables recorded at 5, 10, 15, 30, 45, and 60 minutes post‐injection. In addition, arterial blood was sampled for blood gas analysis at 15 and 45 minutes following injection. Intensity and duration of analgesia (assessed by toe‐pinch response using a hemostat) and level of sedation were evaluated at the above time points and at 75 and 90 minutes post‐injection. Data were analyzed using anova for repeated measures with posthoc differences between means identified using Bonferroni's method (p < 0.05). Administration of M, MH, or MB was associated with increases in SAP, MAP, DAP, PAP, PAOP, CVP, SVR, and TEMP and with decreases in HR and CI. No differences in CV variables between treatment groups were identified at any time. PaO₂ increased over time in all groups and was significantly higher when MH was compared with M. At 45 minutes, PaO₂ tended to decrease over time and was significantly lower when MH and MB were compared with M at 15 minutes. Analgesia scores for MH and MB were significantly higher compared with M through 45 minutes, while analgesia scores for MH were significantly higher compared with M through 90 minutes. Sedation scores were higher for MH and MB compared with M throughout 90 minutes. Durations of lateral recumbency were 108 ± 10.8, 172 ± 15.5, and 145 ± 9.9 minutes for M, MH, and MB, respectively. We conclude that MH and MB are associated with improved analgesia and sedation and have similar CV effects when compared with M.     

Immobilization,cardiopulmonary and blood gas effects of ketamine–butorphanol–medetomidine versus butorphanol–midazolam–medetomidine in free-ranging serval (Leptailurus serval)

ObjectiveTo compare ketamine–butorphanol–medetomidine (KBM) with butorphanol–midazolam–medetomidine (BMM) immobilization of serval.Study designBlinded, randomized trial.AnimalsA total of 23 captures [KBM: five females, six males; 10.7 kg (mean); BMM: 10 females, two males; 9.6 kg].MethodsServal were cage trapped and immobilized using the assigned drug combination delivered via a blow dart into gluteal muscles. Prior to darting, a stress score was assigned (0: calm; to 3: markedly stressed). Drug combinations were dosed based on estimated body weights: 8.0, 0.4 and 0.08 mg kg^–1 for KBM and 0.4, 0.3 and 0.08 mg kg^–1 for BMM, respectively. Time to first handling, duration of anaesthesia and recovery times were recorded. Physiological variables including blood glucose and body temperature were recorded at 5 minute intervals. Atipamezole (5 mg mg^–1 medetomidine) and naltrexone (2 mg mg^–1 butorphanol) were administered intramuscularly prior to recovery. Data, presented as mean values, were analysed using general linear mixed model and Spearman’s correlation (stress score, glucose, temperature); significance was p < 0.05.ResultsDoses based on actual body weights were 8.7, 0.4 and 0.09 mg kg^–1 for KBM and 0.5, 0.4 and 0.09 mg kg^–1 for BMM, respectively. Time to first handling was 10.2 and 13.3 minutes for KBM and BMM, respectively (p = 0.033). Both combinations provided cardiovascular stability during anaesthesia that lasted a minimum of 35 minutes. Recovery was rapid and calm overall, but ataxia was noted in KBM. Stress score was strongly correlated to blood glucose (r² = 0.788; p = 0.001) and temperature (r² = 0.634; p = 0.015).Conclusions and clinical relevanceBoth combinations produced similar effective immobilization that was cardiovascularly stable in serval. Overall, BMM is recommended because it is fully antagonizable. A calm, quiet environment before drug administration is essential to avoid capture-induced hyperglycaemia and hyperthermia.     

The cardiopulmonary effects of a peripheral alpha‐2‐adrenoceptor antagonist,MK‐467, in dogs sedated with a combination of medetomidine and butorphanol

ObjectiveTo compare the cardiopulmonary effects of intravenous (IV) and intramuscular (IM) medetomidine and butorphanol with or without MK-467.Study designProspective, randomized experimental cross-over.AnimalsEight purpose–bred beagles (two females, six males), 3–4 years old and weighing 14.5 ±1.6 kg (mean ± SD).MethodsAll dogs received four different treatments as follows: medetomidine 20 μg kg^?1 and butorphanol tartrate 0.1 mg kg^?1 IV and IM (MB), and MB combined with MK-467,500 μg kg^?1 (MBMK) IV and IM. Heart rate (HR), arterial blood pressures (SAP, MAP, DAP), central venous pressure (CVP), cardiac output, respiratory rate (f_R), rectal temperature (RT) were measured and arterial blood samples were obtained for gas analysis at baseline and at 3, 10, 20, 30, 45 and 60 minutes after drug administration. The cardiac index (CI), systemic vascular resistance index (SVRI) and oxygen delivery index (DO₂I) were calculated. After the follow-up period atipamezole 50 μg kg^?1 IM was given to reverse sedation.ResultsHR, CI and DO₂I were significantly higher with MBMK after both IV and IM administration. Similarly, SAP, MAP, DAP, CVP, SVRI and RT were significantly lower after MBMK than with MB. There were no differences in f_R between treatments, but arterial partial pressure of oxygen decreased transiently after all treatments. Recoveries were uneventful following atipamezole administration after all treatments.Conclusions and clinical relevanceMK-467 attenuated the cardiovascular effects of a medetomidine-butorphanol combination after IV and IM administration.     

Sedative, cardiovascular, haematologic and biochemical effects of four different drug combinations administered intramuscularly in cats

ObjectiveTo compare effects of four drug combinations on sedation, echocardiographic, haematologic and biochemical variables and recovery in cats.Study designExperimental randomized ‘blinded’ cross-over study.AnimalsSix healthy cats.Materials and MethodsTreatments were administered intramuscularly: midazolam 0.4 mg kg^?1 and butorphanol 0.4 mg kg^?1 (MB); midazolam 0.4 mg kg^?1, butorphanol 0.4 mg kg^?1 and ketamine 3 mg kg^?1 (MBK); midazolam 0.4 mg kg^?1, butorphanol 0.4 mg kg^?1 and dexmedetomidine 5 μg kg^?1 (MBD); ketamine 3 mg kg^?1 and dexmedetomidine 5 μg kg^?1(KD). Sedation was evaluated at time-points over 10 minutes post injection. Echocardiography, systolic arterial blood pressure (SAP) measurement and blood sampling were performed at baseline and from 10 minutes after treatment. Quality of recovery was scored. Data were analysed by anova for repeated measures. p < 0.05 was considered significant.ResultsThe lowest sedation score was obtained by MB, (median 10.5 [7; 20]), highest by KD (36.5 [32; 38]). Quality of recovery was best with KD (0.5 [0; 2]), and worst with MB (7.5 [4; 11]). Relative to baseline measurements, treatments decreased SAP by 17%, 25%, 13%, 5% in MB, MBK, MBD and KD, respectively. Heart rate decreased (p < 0.05) after MBD (44%) and KD (34%). All treatments decreased stroke volume by 24%, 21%, 24%, 36%, and cardiac output by 23%, 34%, 54%, 53% in MB, MBK, MBD and KD, respectively. Packed cell volume was decreased (p < 0.05) by 20%, 31%, 29% in MBK, MBD and KD, respectively. Plasma glucose was increased after MBD (31%) and KD (52%) and lactate concentration was decreased (p < 0.05) after MBK (58%), MBD (72%) and KD (65%).Conclusions and clinical relevanceThe MB combination did not produce sedation in healthy cats. Treatment MBK led to acceptable sedation and minimal cardiovascular changes. Both treatments with dexmedetomidine produced excellent sedation and recovery but induced more cardiovascular depression and haematologic changes.     

Cardiopulmonary effects of butorphanol in sevoflurane‐anesthetized guineafowl (Numida meleagris)

ObjectiveTo evaluate the cardiopulmonary changes induced by intravenous butorphanol administration in guineafowl anesthetized with sevoflurane.Study designProspective experimental trial.AnimalsEight adult guineafowl (Numida meleagris) weighing 1.61 ± 0.49 kg were used for the study.MethodsBirds were anesthetized with sevoflurane and allowed to breathe spontaneously. After endotracheal intubation, end-tidal sevoflurane was adjusted to 1.0 individual sevoflurane MAC that was previously determined in triplicate using a standard bracketing technique. The brachial artery was catheterized for direct pressure measurement and blood sampling. Heart rate and rhythm were monitored by electrocardiography and respiratory rate was recorded. Baseline data were recorded 30 minutes after induction. Then, end-tidal sevoflurane was adjusted to 0.8 individual MAC and after 15 minutes physiologic variables were measured again. Subsequently, butorphanol (4 mg kg^?1) was administered intravenously over 10 seconds and physiologic responses were recorded at 1, 5, 10, 15, 20, 30 and 45 minutes after administration.ResultsButorphanol administration was associated with arrhythmias in all birds, including second-degree atrioventricular block, sinus arrest, ventricular and supraventricular tachycardia and ventricular premature complexes. Heart rate and arterial blood pressures decreased significantly 1 minute after butorphanol administration. Two birds developed severe hypotension, apnea and ventricular fibrillation 5 minutes after administration, and one died.Conclusions and clinical relevanceThe butorphanol dose (4 mg kg^?1) that produces clinically relevant sevoflurane MAC reduction in guineafowl caused severe adverse cardiopulmonary effects in two birds and was considered unsafe under the conditions used in this study.     

Effects of a medetomidine-midazolam-butorphanol combination on renal cortical, intestinal and muscle microvascular blood flow in isoflurane anaesthetized dogs: a laser Doppler study

Objective To obtain renal cortical, ileal, colonic and skeletal muscle microvascular blood flow measurements in dogs using the laser Doppler technique and to characterize the effects of medetomidine‐midazolam‐butorphanol combination on these flows. Study Design Prospective randomized experimental study. Animals Fourteen clinically normal beagles (two groups of seven), aged 1–4 years and weighing 13.2 ± 1.8 kg. Methods All dogs were anaesthetized with 1.7% end‐tidal isoflurane in oxygen. In the treatment group, after instrumentation and when anaesthesia was considered stable, medetomidine (1 mg m^?2 body surface area (BSA)) was administered intramuscularly (time 0). Midazolam (1 mg kg^?1) and butorphanol (0.1 mg kg^?1) were administered intravenously 20 minutes later. Atipamezole (2.5 mg m^?2 BSA) was administered intramuscularly 60 minutes after medetomidine. In the control group, saline (0.5, 2.5 and 0.25 mL) was administered at the corresponding times. Heart rate, systolic, diastolic and mean arterial pressures, body temperature, renal cortical, ileal, colonic and skeletal muscle microvascular blood flows were measured before time 0, and 5, 15, 25, 40, 60, 65, 70 and 90 minutes thereafter. Results Heart rate, ileal and skeletal muscle blood flows decreased in the treatment group, while no changes were observed in the control group. Conclusions Laser Doppler flowmetry allowed the measurement of microvascular blood flow in different organs. The medetomidine‐midazolam‐butorphanol combination decreases intestinal and skeletal muscle microvascular blood flows, while renal cortical blood flow is maintained. Clinical relevance Medetomidine‐midazolam‐butorphanol combination can be used to induce a short duration anaesthesia in dogs, but it will induce cardiovascular depression. This depression appears to be accompanied by a redistribution of blood flow.