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.

Efficacy of lumbosacral and sacrococcygeal epidural ropivacaine in dogs undergoing surgery for perineal hernia.

Epidural anesthesia is commonly administered as part of balanced anesthesia for perioperative analgesia. The main goal of this randomized clinical trial was to compare the efficacy of two epidural approaches in dogs undergoing surgery for a perineal hernia. A secondary aim was to compare motor blockade. Intact ASA 1 and 2 male dogs, weighing ≤25 kg with no previous surgery for perineal hernia were enrolled. After premedication with IM acepromazine 0.02 mg/kg and butorphanol 0.3 mg/kg, general anesthesia was induced with propofol and maintained with sevoflurane in oxygen. Dogs were randomly allocated to receive either a lumbosacral (LS, n = 30) or a sacrococcygeal (SC, n = 26) epidural injection with ropivacaine 1% (0.2 mL/kg) under computed tomography guidance. Successful analgesia was defined as no need of intraoperative rescue analgesia (fentanyl 3 µg/kg IV). Clinical failure was defined as the need of more than two boluses of fentanyl/h each dog received meloxicam 0.2 mg/kg IV at the end of the surgery. The Glasgow Composite Pain Scale short form (GCPS-SF), tactile sensitivity, pressure pain thresholds and motor blockade were assessed at 4, 6, 8, and 24 h after the epidural injection. Methadone (0.2 mg/kg, IV) was administered if the GCPS-SF was ≥6/24 points. Differences between groups were analyzed with the Mann-Whitney U test, Student's t-test or Fisher's Exact test, as appropriate. Success rate was assessed for non-inferiority between groups. The non-inferiority margin was set at -10%. Epidural analgesia was successful in 24 dogs in group LS and 17 dogs in group SC (p = 0.243), resulting in success rates of 80 and 65% in LS and SC groups, respectively. The non-inferiority of group SC versus group LS was confirmed. Clinical failure was recorded in two dogs in group LS and one dog in group SC. No significant differences between groups were detected in the GCPS-SF score, tactile sensitivity, pressure pain thresholds, need of post-operative methadone, or motor blockade. Both epidural techniques are valuable analgesic options for perineal hernia repair in dogs.

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

OBJECTIVE: To investigate effects of vatinoxan in dogs, when administered as intravenous (IV) premedication with medetomidine and butorphanol before anaesthesia for surgical castration. STUDY DESIGN: A randomized, controlled, blinded, clinical trial. ANIMALS: A total of 28 client-owned dogs. METHODS: Dogs 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 (fR), 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. RESULTS: At 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 fR, 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 RELEVANCE: In 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.

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

OBJECTIVE: To 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 DESIGN: Experimental, observational study. ANIMALS: A group of six healthy, purpose-bred Beagle dogs (four females and two males) aged 6.5 ± 0.1 years (mean ± standard deviation). METHODS: All 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. RESULTS: All 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 RELEVANCE: With 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.

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.

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

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