Cardiovascular effects of dobutamine, norepinephrine and phenylephrine in isoflurane-anaesthetized dogs administered dexmedetomidine-vatinoxan.

OBJECTIVE: To determine whether dobutamine, norepinephrine or phenylephrine infusions alleviate hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine with vatinoxan. STUDY DESIGN: Balanced, randomized crossover trial. ANIMALS: A total of eight healthy Beagle dogs. METHODS: Each 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. RESULTS: Most 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 RELEVANCE: Hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine and vatinoxan can be treated with either dobutamine or norepinephrine.

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

OBJECTIVE: To 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 ANIMALS: A total of 10 healthy red deer were included in a randomised, controlled, experimental, crossover study. METHODS: Deer 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 (fR), 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). RESULTS: Maximal (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, fR 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 RELEVANCE: Vatinoxan 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.

Plasma concentration and cardiovascular effects of intramuscular medetomidine combined with three doses of the peripheral alpha2-antagonist MK-467 in dogs.

OBJECTIVE: We investigated the plasma concentrations and cardiovascular effects of intramuscularly (IM) administered medetomidine, administered alone or with three different doses of MK-467. STUDY DESIGN: Prospective, randomized, open, crossover trial. ANIMALS: Eight purpose-bred healthy Beagle dogs. METHODS: Each dog was administered four treatments: medetomidine 20 µg kg-1 IM alone or mixed in the same syringe with MK-467 (200 µg kg-1, 400 µg kg-1 or 600 µg kg-1). Instrumentation was performed under standardized anaesthesia. The dogs were allowed to recover before measurement of baseline values. Composite sedation scores, cardiovascular variables, i.e., heart rate (HR), cardiac output (CO), mean arterial and central venous blood pressures (MAP and CVP) and arterial blood gases were recorded at baseline and for 60 minutes after treatment. Drug concentrations in venous plasma were analysed. Generalized linear mixed models for repeated measures with post hoc Bonferroni correction were used with statistical significance level set at α=0.05. RESULTS: All treatments initially demonstrated the effects of medetomidine: HR and CO decreased and CVP increased. MAP transiently increased and then significantly decreased from baseline with the two highest MK-467 doses. The cardiovascular effects of medetomidine disappeared more rapidly with MK-467 than with medetomidine alone. With medetomidine alone, sedation scores remained high until the end of the 60 minute follow-up. Maximum concentrations of medetomidine were more rapidly achieved and were higher with MK-467. CONCLUSIONS AND CLINICAL RELEVANCE: Initial haemodynamic effects of medetomidine were not prevented by MK-467, but these effects were attenuated and their duration shortened by MK-467, independently of dose. Absorption of medetomidine was accelerated by MK-467, when administered concomitantly IM, resulting in faster sedation; addition of MK-467 shortened the sedative effect of medetomidine.

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

OBJECTIVE: To compare the cardiopulmonary effects of intravenous (IV) and intramuscular (IM) medetomidine and butorphanol with or without MK-467. STUDY DESIGN: Prospective, randomized experimental cross-over. ANIMALS: Eight purpose-bred beagles (two females, six males), 3-4 years old and weighing 14.5 ±1.6 kg (mean ± SD). METHODS: All 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 (fR ), 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 (DO2 I) were calculated. After the follow-up period atipamezole 50 µg kg(-1) IM was given to reverse sedation. RESULTS: HR, CI and DO2 I 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 fR 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 RELEVANCE: MK-467 attenuated the cardiovascular effects of a medetomidine-butorphanol combination after IV and IM administration.

A comparison in dogs of medetomidine, with or without MK-467, and the combination acepromazine-butorphanol as premedication prior to anaesthesia induced by propofol and maintained with isoflurane.

OBJECTIVE: To compare the haemodynamic effects of three premedicant regimens during propofol-induced isoflurane anaesthesia. STUDY DESIGN: Prospective, randomized cross-over study. ANIMALS: Eight healthy purpose-bred beagles aged 4 years and weighing mean 13.6 ± SD 1.9 kg. METHODS: The dogs were instrumented whilst under isoflurane anaesthesia prior to each experiment, then allowed to recover for 60 minutes. Each dog was treated with three different premedications given intravenously (IV): medetomidine 10 µg kg⁻¹ (MED), medetomidine 10 µg kg⁻¹ with MK-467 250 µg kg⁻¹ (MMK), or acepromazine 0.01 mg kg⁻¹ with butorphanol 0.3 mg kg⁻¹ (AB). Anaesthesia was induced 20 minutes later with propofol and maintained with isoflurane in oxygen for 60 minutes. Heart rate (HR), cardiac output, arterial blood pressures (ABP), central venous pressure (CVP), respiratory rate, inspired oxygen fraction, rectal temperature (RT) and bispectral index (BIS) were measured and arterial and venous blood gases analyzed. Cardiac index (CI), systemic vascular resistance index (SVRI), oxygen delivery index (DO2 I), systemic oxygen consumption index (VO2 I) and oxygen extraction (EO2) were calculated. Times to extubation, righting, sternal recumbency and walking were recorded. The differences between treatment groups were evaluated with repeated measures analysis of covariance. RESULTS: HR, CI, DO2 I and BIS were significantly lower with MED than with MMK. ABP, CVP, SVRI, EO2, RT and arterial lactate were significantly higher with MED than with MMK and AB. HR and ABP were significantly higher with MMK than with AB. However, CVP, CI, SVRI, DO2 I, VO2 I, EO2, T, BIS and blood lactate did not differ significantly between MMK and AB. The times to extubation, righting, sternal recumbency and walking were significantly shorter with MMK than with MED and AB. CONCLUSIONS AND CLINICAL RELEVANCE: MK-467 attenuates certain cardiovascular effects of medetomidine in dogs anaesthetized with isoflurane. The cardiovascular effects of MMK are very similar to those of AB.

Thermographic imaging of superficial temperature in dogs sedated with medetomidine and butorphanol with and without MK-467 (L-659'066).

OBJECTIVE: To record, with a thermal camera, peripheral temperature changes during different sedation protocols and to relate the results to changes in the rectal temperature. STUDY DESIGN: Randomized crossover part-blinded experimental study. ANIMALS: Eight healthy purpose-bred neutered Beagles (two females and six males) weight 14.5 ± 1.6 kg (mean ± SD) and aged 3-4 years. METHODS: Each dog was sedated four times. Treatments were medetomidine 20 µg kg(-1) and butorphanol 0.1 mg kg(-1) (MB) with or without MK-467 500 µg kg(-1) (MK). Both drug combinations were administered IV and IM as separate treatments. A thermal camera (T425, FLIR) with a resolution of 320 by 240 was used for imaging. The dogs were placed in lateral recumbency on an insulated mattress. Digital (DFT) and metatarsal footpad temperatures (MFT) were measured with thermography. Thermograms and rectal temperature (RT) were taken before and at 3, 10, 20, 30, 45 and 60 minutes after treatment. RESULTS: At 60 minutes after drug administration, MFT was higher (p < 0.001) after MB+MK (34.5 ± 1.1 IV, 34.8 ± 0.5 IM) than MB (31.1 ± 2.9 IV, 30.5 ± 3.6 IM), DFT was higher (p < 0.001) after MB+MK (33.6 ± 1.4 IV, 34.0 ± 0.6 IM) than MB (26.7 ± 1.4 IV, 26.7 ± 2.5 IM), and RT was lower (p < 0.001) after MB+MK (36.7 ± 0.8 IV, 36.9 ± 0.3 IM) than MB (37.5 ± 0.3 IV, 37.4 ± 0.4 IM), with both routes. The change from baseline was greater with MB+MK than MB in all variables. CONCLUSIONS: Superficial temperature changes can be seen and detected with thermography. MK-467 used with MB resulted in increased superficial temperatures and a decline in rectal temperature compared to MB alone. CLINICAL RELEVANCE: The sedation protocol may influence core temperature loss, and may also have an effect on thermographic images.

Effect of MK-467 on organ blood flow parameters detected by contrast-enhanced ultrasound in dogs treated with dexmedetomidine.

OBJECTIVE: To evaluate the dexmedetomidine-induced reduction in organ blood flow with quantitative contrast-enhanced ultrasound (CEUS) method and to observe the influence of MK-467 on such reduction. STUDY DESIGN: Randomized cross-over study. ANIMALS: Six adult purpose-bred laboratory beagle dogs (mean body weight 15.3 ± 1.9 kg). METHODS: Contrast-enhanced ultrasound was performed on six conscious healthy laboratory beagles. The animals on separate occasions underwent three treatments: awake without any medication (CTRL), dexmedetomidine 10 µg kg(-1) (DEX) and DEX + MK-467 500 µg kg(-1) (DMK) intravenously (IV). The kidney (10-15 minutes post-treatment), spleen (25-30 minutes post-treatment), small intestine (40-45 minutes post-treatment) and liver (50-55 minutes post-treatment) were examined with CEUS. A time curve was generated and the following perfusion parameters were analysed: arrival time (AT), time to peak from injection (TTPinj), peak intensity (PI) and wash-in rate (Wi). In addition to CEUS, renal glomerular filtration rate was indirectly estimated by the rate of iohexol elimination. RESULTS: AT and TTPinj were significantly higher for DEX than for CTRL in all studied organs. The same parameters were significantly higher for DEX than for DMK in the kidney, spleen and small intestine. PI was significantly lower for DEX than for CTRL or DMK in the kidney. Wi was significantly lower for DEX than for CTRL or DMK in the kidney and significantly lower than for CTRL only in the small intestine. Plasma concentration of iohexol was significantly higher after DEX than CTRL administration. CONCLUSIONS: Contrast-enhanced ultrasound was effective in detecting DEX-induced changes in blood flow. MK-467 attenuated these changes. CLINICAL RELEVANCE: Clinicians should consider the effects of the sedation protocol when performing CEUS. Addition of MK-467 might beneficially impact the haemodynamic function of sedation with alpha-2 adrenoceptor agonists.

Anaesthetic management and complications of a Humboldt penguin (Spheniscus humboldti) undergoing diagnostic imaging.

BACKGROUND: The presence of a tracheal septum dividing the trachea into two makes intubation one of the main challenges of penguin anaesthesia. Differences in the length and location of the aforementioned tracheal septum have been described in some penguin species. However, to the best of the authors' knowledge, it has not been reported in Humboldt penguins (Spheniscus humboldti). Therefore, one of the aims of this publication is to report the septal position in this Humboldt penguin. Furthermore, this publication describes the anaesthetic protocol and complications encountered and discusses some of the more important features of penguin anaesthesia. It is anticipated that this case report will aid in future procedures requiring anaesthesia of this penguin species. CASE PRESENTATION: A 25-year-old female Humboldt penguin was anaesthetized at the University College Dublin Veterinary Hospital for radiographs and computed tomography (CT) following three weeks of inappetence. After assessing the health status of the penguin from the clinical history and performing a physical examination, an American Society of Anesthesiologists physical status score of II was assigned and a combination of butorphanol 1 mg/kg and midazolam 1 mg/kg was administered intramuscularly to sedate the penguin. Induction of anaesthesia was performed via a face mask using sevoflurane in oxygen. The airway was intubated with a 4.0 mm Cole tube and anaesthesia was maintained with sevoflurane in oxygen during the entire procedure. Anaesthetic monitoring consisted of an electrocardiogram, pulse oximetry, non-invasive blood pressure, capnography, and body temperature. CONCLUSIONS: Tracheal bifurcation was identified as the start of the tracheal septum 4.67 cm from the glottis using CT. Most of the anticipated complications of penguin anaesthesia, such as hyperthermia, hypothermia, regurgitation, hypoventilation, and difficulties in intubation were present in this case. However, no major sequalae occurred following the anaesthetic protocol described.

Validity and Repeatability Characteristics of a Non-Invasive, Infrared-Based Method Estimating Plasma Indocyanine Green Decay in Healthy Dogs.

Plasma clearance of indocyanine green (ICG-CL) is an invasive method to evaluate liver dysfunction. We aimed to investigate the practicality of a noninvasive, transcutaneous, infrared-based method estimating the disappearance rate of indocyanine green (ICG-PDR). In a randomized, cross-over study, both ICG-CL and ICG-PDR were determined in eight healthy dogs while conscious and when sedated with medetomidine and medetomidine-vatinoxan. ICG-PDR was further repeated in six of the dogs to assess its repeatability. Differences were tested with repeated-measures analysis of variance and post hoc t-tests with Bonferroni corrections, while associations were evaluated by both Spearman and Pearson correlation analyses. Furthermore, repeatability was assessed by examining calculated coefficients of variation (CV). A significant decrease in ICG-CL was observed in dogs sedated with medetomidine, while no difference between conscious and sedated states was detected with ICG-PDR. Overall, correlations between ICG-CL and ICG-PDR were poor, as was the intrasubject repeatability of ICG-PDR in conscious dogs with CV consistently above 20%. While some of the results may be explained by poor signal quality for the non-invasive method, we conclude that in healthy dogs ICG-PDR performed poorly.

Influence of MK-467, a peripherally acting α2-adrenoceptor antagonist on the disposition of intravenous dexmedetomidine in dogs.

Growing evidence supports the use of (2R-trans)-N-(2-(1,3,4,7,12b-hexahydro-2'-oxo-spiro(2H-benzofuro(2,3-a)quinolizine-2,4'-imidazolidin)-3'-yl)ethyl) methanesulfonamide (MK-467), a peripherally acting α(2)-adrenoceptor antagonist, in conjunction with the sedative-anesthetic agent dexmedetomidine in animals to avoid hemodynamic compromise. We evaluated the possible effects of different doses of MK-467 on the plasma concentrations of dexmedetomidine in eight beagle dogs. Both drugs were administered intravenously. Each dog received five treatments: dexmedetomidine alone (10 µg/kg), MK-467 alone (250 µg/kg), and dexmedetomidine (10 µg/kg) combined with different doses of MK-467 (250, 500, and 750 µg/kg) in a randomized, crossover fashion. Selected pharmacokinetic parameters were calculated. The area under the time-concentration curve of dexmedetomidine was significantly greater after dexmedetomidine alone (by 101 ± 20%, mean ± 95% confidence interval) compared with that after dexmedetomidine and 250 µg/kg MK-467. Increasing the dose of the antagonist had no further effect on the exposure to dexmedetomidine. The apparent volume of distribution of dexmedetomidine was significantly smaller after dexmedetomidine alone compared with that after all treatments that included MK-467. Dexmedetomidine (10 µg/kg) did not significantly influence the plasma concentrations of MK-467 (250 µg/kg). The results suggest that the peripherally acting α(2)-adrenoceptor antagonist MK-467 markedly influenced the early disposition of dexmedetomidine without obvious effects on the later plasma concentrations of the drug.

Effect of intraperitoneal or incisional bupivacaine on pain and the analgesic requirement after ovariohysterectomy in dogs.

OBJECTIVE: To compare the effect of intraperitoneal (IP) or incisional (INC) bupivacaine on pain and the analgesic requirement after ovariohysterectomy in dogs. STUDY DESIGN: Prospective, randomized clinical study. ANIMALS: Thirty female dogs undergoing ovariohysterectomy (OHE). METHODS: Dogs admitted for elective OHE were anesthetized with acepromazine, butorphanol, thiopental and halothane. Animals were randomly assigned to one of three groups (n = 10 per group). The treatments consisted of preincisional infiltration with saline solution (NaCl 0.9%) or bupivacaine with epinephrine and/or IP administration of the same solutions, as follows: INC and IP 0.9% NaCl (control group); INC 0.9% NaCl and IP bupivacaine (5 mg kg(-1), IP group); INC bupivacaine (1 mg kg(-1)) and IP 0.9% NaCl (INC group). Postoperative pain was evaluated by a blinded observer for 24 hours after extubation by means of a visual analog scale (VAS) and a numeric rating scale (NRS). Rescue analgesia (morphine, 0.5 mg kg(-1) , IM) was administered if the VAS was >5/10 or the NRS >10/29. RESULTS: At 1 hour after anesthesia, VAS pain scores were [medians (interquartile range)]: 6.4 (3.1-7.9), 0.3 (0.0-2.6) and 0.0 (0.0-7.0) in control, IP and INC groups, respectively. VAS pain scores were lower in the IP compared to the control group. Over the first 24 hours, rescue analgesia was administered to 7/10, 5/10 and 3/10 dogs of the control, INC and IP groups, respectively. Total number of dogs given rescue analgesia over the first 24 hours did not differ significantly among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Intraperitoneal bupivacaine resulted in lower pain scores during the first hour of the postoperative period and there was a trend towards a decreased need for rescue analgesia after OHE in dogs.

Effects of different doses of L-659'066 on the bispectral index and clinical sedation in dogs treated with dexmedetomidine.

OBJECTIVE: To evaluate the effects of three doses of L-659'066 (MK-467) on the bispectral index (BIS) and clinical sedation in dexmedetomidine-sedated Beagles. STUDY DESIGN: Randomized, experimental cross over study. ANIMALS: Eight purpose-bred healthy laboratory Beagles. METHODS: Dexmedetomidine (10 µg kg(-1) IV [DEX]) was administered alone or in combination with three doses of L-659'066 (250 µg kg(-1) [DL250]; 500 µg kg(-1) [DL500] and 750 µg kg(-1) [DL750] IV) in the same syringe in a randomized crossover manner. The bispectral index (BIS), electromyography (EMG) and sedation score were recorded at baseline and 5, 10, 20, 30, 45 and 60 minutes after treatment. RESULTS: When compared to DEX, BIS and EMG were significantly higher and the sedation score significantly lower with DL500 and DL750. With DEX, BIS was significantly decreased at times 20, 30 and 60 minutes whereas the sedation scores were significantly increased at all time points after drug administration in all groups. Bioequivalence for clinical sedation was detected between DEX and all doses of L-659'066, reaching European Medicines Agency (EMA) standards. CONCLUSIONS AND CLINICAL RELEVANCE: Although L-659'066 interfered with dexmedetomidine induced sedation, the degree of the reduction was not clinically relevant. Despite performing better when dexmedetomidine was used alone, BIS did not reflect the clinical sedative status when the antagonist was added.

Avian extremity reconstruction via osseointegrated leg-prosthesis for intuitive embodiment.

For large avians such as vultures, limb loss leads to loss of ambulation and eventually death from malnutrition. Prosthetic devices may replace the limb, however, conventional prosthetic sockets are not feasible in feathered limbs and the extreme stress and strain of unreflected daily use in animals. Osseointegration is a novel technique, where external prosthetic parts are connected directly to a bone anchor to provide a solid skeletal-attachment. This concept provides a high degree of embodiment since osseoperception will provide direct intuitive feedback allowing natural use of the limb in gait and feeding. Here we demonstrate for the first time an osseointegrated bionic reconstruction of a limb in a vulture after a tarsometatarsal amputation with a longterm follow-up.

Investigation of the effects of vatinoxan on somatic and visceral antinociceptive efficacy of medetomidine in dogs.

OBJECTIVE: To determine whether concurrent vatinoxan administration affects the antinociceptive efficacy of medetomidine in dogs at doses that provide circulating dexmedetomidine concentrations similar to those produced by medetomidine alone. ANIMALS: 8 healthy Beagles. PROCEDURES: Dogs received 3 IV treatments in a randomized crossover-design trial with a 2-week washout period between experiments (medetomidine [20 µg/kg], medetomidine [20 µg/kg] and vatinoxan [400 µg/kg], and medetomidine [40 µg/kg] and vatinoxan [800 µg/kg]; M20, M20V400, and M40V800, respectively). Sedation, visceral and somatic nociception, and plasma drug concentrations were assessed. Somatic and visceral nociception measurements and sedation scores were compared among treatments and over time. Sedation, visceral antinociception, and somatic antinociception effects of M20V400 and M40V800 were analyzed for noninferiority to effects of M20, and plasma drug concentration data were assessed for equivalence between treatments. RESULTS: Plasma dexmedetomidine concentrations after administration of M20 and M40V800 were equivalent. Sedation scores, visceral nociception measurements, and somatic nociception measurements did not differ significantly among treatments within time points. Overall sedative effects of M20V400 and M40V800 and visceral antinociceptive effects of M40V800 were noninferior to those produced by M20. Somatic antinociception effects of M20V400 at 10 minutes and M40V800 at 10 and 55 minutes after injection were noninferior to those produced by M20. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested coadministration with vatinoxan did not substantially diminish visceral antinociceptive effects of medetomidine when plasma dexmedetomidine concentrations were equivalent to those produced by medetomidine alone. For somatic antinociception, noninferiority of treatments was detected at some time points.

Cardiovascular and sedation reversal effects of intramuscular administration of atipamezole in dogs treated with medetomidine hydrochloride with or without the peripheral α2-adrenoceptor antagonist vatinoxan hydrochloride.

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