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.     

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.     

Effects of vatinoxan in dogs premedicated with medetomidine and butorphanol followed by sevoflurane anaesthesia: a randomized clinical study

ObjectiveTo investigate effects of vatinoxan in dogs, when administered as intravenous (IV) premedication with medetomidine and butorphanol before anaesthesia for surgical castration.Study designA randomized, controlled, blinded, clinical trial.AnimalsA total of 28 client-owned dogs.MethodsDogs were premedicated with medetomidine (0.125 mg m^?2) and butorphanol (0.2 mg kg^?1) (group MB; n = 14), or medetomidine (0.25 mg m^?2), butorphanol (0.2 mg kg^?1) and vatinoxan (5 mg m^?2) (group MB-VATI; n = 14). Anaesthesia was induced 15 minutes later with propofol and maintained with sevoflurane in oxygen (targeting 1.3%). Before surgical incision, lidocaine (2 mg kg^?1) was injected intratesticularly. At the end of the procedure, meloxicam (0.2 mg kg^?1) was administered IV. The level of sedation, the qualities of induction, intubation and recovery, and Glasgow Composite Pain Scale short form (GCPS-SF) were assessed. Heart rate (HR), respiratory rate (f_R), mean arterial pressure (MAP), end-tidal concentration of sevoflurane (Fe′Sevo) and carbon dioxide (Pe′CO₂) were recorded. Blood samples were collected at 10 and 30 minutes after premedication for plasma medetomidine and butorphanol concentrations.ResultsAt the beginning of surgery, HR was 61 ± 16 and 93 ± 23 beats minute^?1 (p = 0.001), and MAP was 78 ± 7 and 56 ± 7 mmHg (p = 0.001) in MB and MB-VATI groups, respectively. No differences were detected in f_R, Pe′CO₂, Fe′Sevo, the level of sedation, the qualities of induction, intubation and recovery, or in GCPS-SF. Plasma medetomidine concentrations were higher in group MB-VATI than in MB at 10 minutes (p = 0.002) and 30 minutes (p = 0.0001). Plasma butorphanol concentrations were not different between groups.Conclusions and clinical relevanceIn group MB, HR was significantly lower than in group MB-VATI. Hypotension detected in group MB-VATI during sevoflurane anaesthesia was clinically the most significant difference between groups.     

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.     

Comparison of the effects of butorphanol–midazolam–medetomidine and butorphanol–azaperone–medetomidine in wild common palm civets (Paradoxurus musangus)

ObjectiveTo assess the efficacy of butorphanol–azaperone–medetomidine (BAM) and butorphanol–midazolam–medetomidine (BMM) protocols for immobilization of wild common palm civets (Paradoxurus musangus) with subsequent antagonization with atipamezole.Study designProspective, randomized, blinded clinical trial.AnimalsA total of 40 adult wild common palm civets, 24 female and 16 male, weighing 1.5–3.4 kg.MethodsThe civets were randomly assigned for anesthesia with butorphanol, azaperone and medetomidine (0.6, 0.6 and 0.2 mg kg^–1, respectively; group BAM) or with butorphanol, midazolam and medetomidine (0.3, 0.4 and 0.1 mg kg^–1, respectively; group BMM) intramuscularly (IM) in a squeeze cage. When adequately relaxed, the trachea was intubated for oxygen administration. Physiological variables were recorded every 5 minutes after intubation. Following morphometric measurements, sampling, microchipping and parasite treatment, medetomidine was reversed with atipamezole at 1.0 or 0.5 mg kg^–1 IM to groups BAM and BMM, respectively. Physiological variables and times to reach the different stages of anesthesia were compared between groups.ResultsOnset time of sedation and recumbency was similar in both groups; time to achieve complete relaxation and tracheal intubation was longer in group BAM. Supplementation with isoflurane was required to enable intubation in five civets in group BAM and one civet in group BMM. All civets in group BAM required topical lidocaine to facilitate intubation. End-tidal carbon dioxide partial pressure was lower in group BAM, but heart rate, respiratory rate, rectal temperature, peripheral hemoglobin oxygen saturation and mean arterial blood pressure were not different. All civets in both groups recovered well following administration of atipamezole.Conclusions and clinical relevanceBoth BAM and BMM combinations were effective for immobilizing wild common palm civets. The BMM combination had the advantage of producing complete relaxation that allowed intubation more rapidly.     

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 dobutamine,norepinephrine and phenylephrine in isoflurane-anaesthetized dogs administered dexmedetomidine–vatinoxan

ObjectiveTo determine whether dobutamine, norepinephrine or phenylephrine infusions alleviate hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine with vatinoxan.Study designBalanced, randomized crossover trial.AnimalsA total of eight healthy Beagle dogs.MethodsEach dog was anaesthetized with isoflurane (end-tidal isoflurane 1.3%) and five treatments: dexmedetomidine hydrochloride (2.5 μg kg^–1) bolus followed by 0.9% saline infusion (DEX-S); dexmedetomidine and vatinoxan hydrochloride (100 μg kg^–1) bolus followed by an infusion of 0.9% saline (DEX-VAT-S), dobutamine (DEX-VAT-D), norepinephrine (DEX-VAT-N) or phenylephrine (DEX-VAT-P). The dexmedetomidine and vatinoxan boluses were administered at baseline (T0) and the treatment infusion was started after 15 minutes (T15) if mean arterial pressure (MAP) was < 90 mmHg. The treatment infusion rate was adjusted every 5 minutes as required. Systemic haemodynamics were recorded at T0 and 10 (T10) and 45 (T45) minutes. A repeated measures analysis of covariance model was used.ResultsMost dogs had a MAP < 70 mmHg at T0 before treatment. Treatments DEX-S and DEX-VAT all significantly increased MAP at T10, but systemic vascular resistance index (SVRI) was significantly higher and cardiac index (CI) lower after DEX-S than after DEX-VAT. CI did not significantly differ between DEX-S and DEX-VAT-S at T45, while SVRI remained higher with DEX-S. Normotension was achieved by all vasoactive infusions in every dog, whereas MAP was below baseline with DEX-VAT-S, and higher than baseline with DEX-S at T45. Median infusion rates were 3.75, 0.25 and 0.5 μg kg^–1 minute^–1 for dobutamine, norepinephrine and phenylephrine, respectively. Dobutamine and norepinephrine increased CI (mean ± standard deviation, 3.35 ± 0.70 and 3.97 ± 1.24 L minute^–1 m^–2, respectively) and decreased SVRI, whereas phenylephrine had the opposite effect (CI 2.13 ± 0.45 L minute^–1 m^–2).Conclusions and clinical relevanceHypotension in isoflurane-anaesthetized dogs administered dexmedetomidine and vatinoxan can be treated with either dobutamine or norepinephrine.     

Medetomidine/midazolam/ketamine anaesthesia in ferrets: effects on cardiorespiratory parameters and evaluation of plasma drug concentrations

ObjectiveTo evaluate the cardiorespiratory effects and plasma concentrations of medetomidine-midazolam-ketamine (MMK) combinations administered by intramuscular (IM) or subcutaneous (SC) injection in sable ferrets (Mustela putorius furo).Study designProspective randomized experimental study.AnimalsEighteen adult ferrets: weight median 1.19 (range 0.81–1.60) kg.MethodsAnimals were allocated to one of three groups: group IM07 received 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 7 mg kg^?1 ketamine IM; group IM10 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 10 mg kg^?1 ketamine IM; and group SC10 20 μg kg^?1 medetomidine, 0.5 mg kg^?1 midazolam and 10 mg kg^?1 ketamine SC. Following instrumentation, cardiorespiratory parameters and plasma drug concentrations were measured every 5 minutes (T5–T30) for 30 minutes Ferrets were then euthanased. Data were analysed using anova for repeated measures. p < 0.05 was considered significant.ResultsResults are mean ± SD. Induction of anaesthesia (minutes) in IM07 and IM10 [2 (1)] was significantly faster than in SC10 [5 (2)]. All groups demonstrated the following: results given as groups IM07, IM10 and SC10 respectively. Mean arterial blood pressures (mmHg) were initially high [186 (13); 174 (33) and 174 (9) at T5] but decreased steadily. Pulse rates were initially 202 (20), 213 (17) and 207 (33) beats minute^?1, decreasing with time. PaO₂ (mmHg) was low [54.0 (8), 47.7 (10) and 38.5 (1)] at T5, although in groups IM07 and IM10 it increased over time. Plasma concentrations of all drugs were highest at T5 (36, 794 and 8264 nmol L^?1 for medetomidine, midazolam and ketamine, respectively) and decreased thereafter: for both midazolam and ketamine, concentrations in IM07 and IM10 were higher than SC10.Conclusions and clinical relevanceMMK combinations containing either 7 or 10 mg kg^?1 ketamine and given IM are suitable combinations for anaesthetising ferrets, although the observed degree of hypoxaemia indicates that oxygen administration is vital.     

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.     

Evaluation of the perioperative stress response from dexmedetomidine infusion alone,with butorphanol bolus or remifentanil infusion compared with ketamine and morphine infusions in isoflurane-anesthetized horses

ObjectiveTo evaluate perioperative stress-related hormones in isoflurane-anesthetized horses administered infusions of dexmedetomidine alone or with butorphanol or remifentanil, compared with ketamine–morphine.Study designRandomized, prospective, nonblinded clinical study.AnimalsA total of 51 horses undergoing elective surgical procedures.MethodsHorses were premedicated with xylazine, anesthesia induced with ketamine–diazepam and maintained with isoflurane and one of four intravenous infusions. Partial intravenous anesthesia (PIVA) was achieved with dexmedetomidine (1.0 μg kg^–1 hour^–1; group D; 12 horses); dexmedetomidine (1.0 μg kg^–1 hour^–1) and butorphanol bolus (0.05 mg kg^–1; group DB; 13 horses); dexmedetomidine (1.0 μg kg^–1 hour^–1) and remifentanil (3.0 μg kg^–1 hour^–1; group DR; 13 horses); or ketamine (0.6 mg kg^–1 hour^–1) and morphine (0.15 mg kg^–1, 0.1 mg kg^–1 hour^–1; group KM; 13 horses). Infusions were started postinduction; butorphanol bolus was administered 10 minutes before starting surgery. Blood was collected before drugs were administered (baseline), 10 minutes after ketamine–diazepam, every 30 minutes during surgery and 1 hour after standing. Mean arterial pressure (MAP), pulse rate, end-tidal isoflurane concentration, cortisol, nonesterified fatty acids (NEFA), glucose and insulin concentrations were compared using linear mixed models. Significance was assumed when p < 0.05.ResultsWithin D, cortisol was lower at 120–180 minutes from starting surgery compared with baseline. Cortisol was higher in KM than in D at 60 minutes from starting surgery. Within all groups, glucose was higher postinduction (except DR) and 60 minutes from starting surgery, and insulin was lower during anesthesia and higher after standing compared with baseline. After standing, NEFA were higher in KM than in DB. In KM, MAP increased at 40–60 minutes from starting surgery compared with 30 minutes postinduction.Conclusions and clinical relevanceDexmedetomidine suppressed cortisol release more than dexmedetomidine–opioid and ketamine–morphine infusions. Ketamine–morphine PIVA might increase catecholamine activity.     

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.     

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.     

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.     

Anaesthesia with medetomidine,midazolam and ketamine in six gorillas after premedication with oral zuclopenthixol dihydrochloride

ObjectiveTo evaluate the effects of medetomidine, midazolam and ketamine (MMK) in captive gorillas after premedication with oral zuclopenthixol.Study designCase series.AnimalsSix gorillas, two males and four females, aged 9–52 years and weighing 63–155 kg.MethodsThe gorillas were given zuclopenthixol dihydrochloride 0.2 ± 0.05 mg kg^?1 per os twice daily for 3 days for premedication. On the day of anaesthesia the dose of zuclopenthixol was increased to 0.27 mg kg^?1 and given once early in the morning. Anaesthesia was induced with medetomidine 0.04 ± 0.004 mg kg^?1, midazolam 0.048 ± 0.003 mg kg^?1 and ketamine 4.9 ± 0.4 mg kg^?1 intramuscularly (IM). Upon recumbency, the trachea was intubated and anaesthesia was maintained on 1–2% isoflurane in oxygen. Physiological parameters were monitored every 10 minutes and arterial blood gas analysis was performed once 30–50 minutes after initial darting. At the end of the procedure, 42–115 minutes after initial darting, immobilisation was antagonized with atipamezole 0.21 ± 0.03 mg kg^?1 and sarmazenil 5 ± 0.4 μg kg^?1 IM.ResultsRecumbency was reached within 10 minutes in five out of six animals. One animal required two additional darts before intubation was feasible. Heart rate ranged from 60 to 85 beats minute^?1, respiratory rate from 17 to 46 breaths minute^?1 and temperature from 36.9 to 38.3 °C. No spontaneous recoveries were observed and anaesthetic level was stable. Blood gas analyses revealed mild respiratory acidosis, and mean PaO₂ was 24.87 ± 17.16 kPa (187 ± 129 mmHg) with all values being above 13.4 kPa (101 mmHg). Recovery was smooth and gorillas were sitting within 25 minutes.Conclusion and clinical relevanceThe drug combination proved to be effective in anaesthetizing captive gorillas of various ages and both sexes, with minimal cardio-respiratory changes.     

Short term pharmacological immobilization in macaque monkeys

ObjectiveTo develop a safe and effective immobilization protocol in rhesus monkeys, which is not based on dissociative anaesthetic agent.Study designProspective, randomised, experimental trial.AnimalsTwenty rhesus monkeys, weighing 2.6–8.0 kg, 1–3 years of age, of both sexes.MethodsThe monkeys received 50 μg kg^?1 medetomidine, 0.25 mg kg^?1 midazolam and 5 μg kg^?1 fentanyl with 150 IU hyaluronidase intramuscularly (IM). The animals were closely observed for behavioural changes and reaction to sound stimulus. Pulse rate and oxygen saturation of haemoglobin (SpO₂) were monitored every 5 minutes, for 20 minutes. After this period, 250 μg kg^?1 atipamezole or a placebo was administered IM and behavioural changes were closely observed.ResultsFull immobilization was observed after mean 269 ± SD 116 seconds. Ten minutes after injection mean arterial oxygen saturation of haemoglobin was 94 ± 4%, but did not fall significantly further. The median pulse rate was 116 beats minute^?1 5 minutes after the administration of the drug. This level further decreased to a median level of 108 beats minute^?1 20 minutes after the drug's administration. The median time to recover from immobilization was significantly shorter after atipamezole administration when compared to placebo (2.7 versus 55 minutes). All animals awoke smoothly and no side effects such as vomiting or agitation were observed.ConclusionsShort term and reversible pharmacological immobilization was achieved using combination of midazolam, medetomidine, and fentanyl.Clinical relevanceThe present study demonstrates that 20-minute pharmacological immobilization with a combination of midazolam, medetomidine, and fentanyl is feasible in rhesus monkeys with minimal effect on heart rate.     

Chemical immobilization of chimpanzees (Pan troglodytes) using a combination of detomidine and ketamine

Objective To determine if a combination of detomidine and ketamine can be used for effective chemical immobilization of chimpanzees. Study design Observational study. Animals Twenty‐one adult captive chimpanzees (12 males, nine females), age 8–46 years, weighing 40.4–68.4 kg. Methods The chimpanzees were immobilized with intramuscular (IM) detomidine and ketamine by a darting system. Based on estimated weights, doses administered were 50 μg kg^?1 detomidine and 4 mg kg^?1 ketamine in groups 1 and 2, and 60 μg kg^?1 and 5 mg kg^?1 respectively in group 3. Eight minutes in group 1 and 15 minutes in groups 2 and 3 were allowed from the time of apparent immobilization before removing the animals from their enclosures. Body temperature, arterial haemoglobin saturation and pulse rate were measured. The time from injection to induction (recumbency and absence of voluntary movement), total anaesthetic and recovery times (with or without atipamezole) were recorded. Results Immobilization occurred within 5 minutes after darting in most animals. Early handling of the chimpanzees often resulted in arousal and required further doses of ketamine IM. Most animals were hypoxaemic and hypothermic. Occasionally, bradycardia was observed. Atipamezole resulted in an acceptable quality of recovery 10 minutes after IM injection. The duration of immobilization varied widely when no antagonist was administered. Conclusions and clinical relevance The combination detomidine (60 μg kg^?1) and ketamine (5–6 mg kg^?1) can be used for the immobilization of chimpanzees for non‐ to minimally invasive procedures. A period of 15 minutes should be allowed before handling to avoid unwanted arousal. Oxygen administration is recommended to reduce hypoxaemia. Administration of atipamezole is justified to hasten recovery.