Effects of alfaxalone, propofol and isoflurane on cerebral blood flow and cerebrovascular reactivity to carbon dioxide in dogs: A pilot study.

Propofol total intravenous anesthesia is a common choice to anesthetize patients with increased intracranial pressure, reducing cerebral blood flow while maintaining cerebrovascular reactivity to CO2. Propofol and alfaxalone are commonly used for total intravenous anesthesia in dogs, but the effects of alfaxalone on cerebral blood flow and cerebrovascular reactivity to CO2 are unknown. Our hypothesis was that alfaxalone would not be significantly different to propofol, while isoflurane would increase cerebral blood flow and decrease cerebrovascular reactivity to CO2. Six healthy hound dogs were evaluated in this randomized crossover trial. Dogs were anesthetized with 7.5 mg/kg propofol, 3 mg/kg alfaxalone or 8 % sevoflurane, mechanically ventilated and maintained with propofol (400 µg/kg/min), alfaxalone (150 µg/kg/min) or 1.7 % end-tidal isoflurane, respectively, with one week washout between treatments. Cerebral blood flow and cerebrovascular reactivity to CO2 during hypercapnic and hypocapnic challenges were measured using arterial spin labelling and blood oxygen level-dependent magnetic resonance imaging sequences, respectively. Median (interquartile range, IQR) normocapnic cerebral blood flow was significantly lower (P = 0.016) with alfaxalone compared to isoflurane, in the whole brain 15.39 mL/min/100 g (14.90-19.90 mL/min/100 g) vs. 34.10 mL/min/100 g (33.35-43.17 mL/min/100 g), the grey matter 14.57 mL/min/100 g (13.66-18.72 mL/min/100 g) vs. 32.37 mL/min/100 g (31.03-42.99 mL/min/100 g), the caudal brain 15.47 mL/min/100 g (13.37-21.45 mL/min/100 g) vs. 36.85 mL/min/100 g (32.50-47.18 mL/min/100 g) and the temporal lobe grey matter 18.80 mL/min/100 g (15.89-20.84 mL/min/100 g) vs. 43.32 (36.07-43.58 mL/min/100 g). Median (IQR) hypocapnic cerebrovascular reactivity to CO2 was significantly higher (P = 0.016) for alfaxalone compared to isoflurane 8.85 %S/mm Hg (6.92-10.44 %S/mm Hg) vs. 3.90 %S/mm Hg (3.80-4.33 %S/mm Hg). Alfaxalone maintained lower cerebral blood flow and higher hypocapnic cerebrovascular reactivity to CO2 than isoflurane.

Pharmacokinetics and pharmacodynamics comparison between subcutaneous and intravenous butorphanol administration in horses.

The study objective was to compare butorphanol pharmacokinetics and physiologic effects following intravenous and subcutaneous administration in horses. Ten adult horses received 0.1 mg/kg butorphanol by either intravenous or subcutaneous injections, in a randomized crossover design. Plasma concentrations of butorphanol were measured at predetermined time points using highly sensitive liquid chromatography-tandem mass spectrometry assay (LC-MS/MS). Demeanor and physiologic variables were recorded. Data were analyzed with multivariate mixed-effect model on ranks (P ≤ 0.05). For subcutaneous injection, absorption half-life and peak plasma concentration of butorphanol were 0.10 ± 0.07 h and 88 ± 37.4 ng/mL (mean ± SD), respectively. Bioavailability was 87%. After intravenous injection, mean ± SD butorphanol steady-state volume of distribution and clearance was 1.2 ± 0.96 L/kg and 0.65 ± 0.20 L/kg/h, respectively. Terminal half-lives for butorphanol were 2.31 ± 1.74 h and 5.29 ± 1.72 h after intravenous and subcutaneous administrations. Subcutaneous butorphanol reached and maintained target plasma concentrations >10 ng/mL for 2 ± 0.87 h (Mean ± SD), with less marked physiologic and behavioral effects compared to intravenous injection. Subcutaneous butorphanol administration is an acceptable alternative to the intravenous route in adult horses.

Effects of maropitant citrate or acepromazine on the incidence of adverse events associated with hydromorphone premedication in dogs.

BACKGROUND: Vomiting is a common complication associated with the use of hydromorphine for pre-emptive analgesia in dogs. The ideal anti-emetic protocol for prevention of this complication has not been established. HYPOTHESIS: Maropitant administered concurrently or before hydromorphone would reduce the incidence of vomiting, signs of nausea, ptyalism, and increased panting compared to administration of acepromazine or a 0.9% saline control. ANIMALS: Sixty mixed-breed female dogs scheduled for ovariohysterectomy. METHODS: Randomized, blinded, placebo-controlled experimental study. Dogs were assigned to 4 experimental groups with 15 dogs per group. All groups received 0.2 mg/kg of hydromorphone IM. Group "Control" received 0.1 mL/kg saline SC 30-45 minutes before hydromorphone, group "Marop1" received 1 mg/kg maropitant SC 30-45 minutes before hydromorphone, group "Ace" received 0.02 mg/kg IM acepromazine 30-45 minutes before hydromorphone, and group "Marop2" received 1 mg/kg SC maropitant concurrently with hydromorphone. A trained and blinded observer documented adverse events from the time hydromorphone was administered until the time dogs were induced for surgery. RESULTS: Marop1 had significantly less vomiting (0%) compared to Control (87%; P < .01) and Ace (53%; P < .01). Marop2 had significantly less vomiting (27%) compared to Control (P < .01). Marop1 had significantly greater incidence of ptyalism (73%) compared to Ace (P < .01; 20%). Ace showed significantly less panting (33%) compared to Marop2 (93%; P < .01). CONCLUSIONS AND CLINICAL IMPORTANCE: In healthy dogs, maropitant citrate administered before hydromorphone significantly decreases the incidence of vomiting in dogs but does not improve signs of nausea, ptyalism, or increased panting.

Clinical features and prognostic variables in 109 horses with esophageal obstruction (1992-2009).

BACKGROUND: Esophageal obstruction is common in horses and can result in life-threatening complications. Previous studies have described clinical findings in horses with esophageal obstruction, but there are no reports that attempt to make correlations of clinical findings with outcome. HYPOTHESIS: Specific clinical features of horses with esophageal obstruction are associated with increased likelihood of complications. ANIMALS: One hundred and nine horses with esophageal obstruction. METHODS: Retrospective cross-sectional study. All clinical records of horses admitted between April 1992 and February 2009 for esophageal obstruction were reviewed. The association among 24 clinical, hematological, biochemical, therapeutic variables and the likelihood of complications was investigated by a univariable logistic regression model, followed by multivariable analysis. RESULTS: Multiple logistic regression analysis revealed that intact males (P= .02), age >15 years (P < .01), and a need for general anesthesia (P < .01) were associated with the development of complications after an episode of esophageal obstruction. Increased respiratory rate (>22 breaths/min) and moderate or severe tracheal contamination, although not associated with complications as a whole, significantly increased the risk of developing aspiration pneumonia (P≤ .01). CONCLUSIONS AND CLINICAL IMPORTANCE: Signalment, clinical variables, and endoscopic findings were confirmed as important tools in assessing the severity of the esophageal lesion and pulmonary involvement. Knowledge of risk factors for the development of complications will aid in making informed decisions to optimize treatment and assist in the assessment of prognosis.

In vivo administration of acepromazine or promethazine to horse decreases the reactive oxygen species production response of subsequently isolated neutrophils to stimulation with phorbol myristate acetate.

The previous experiments have shown that some phenothiazines have antioxidant and anti-inflammatory properties in vitro. In this study the inhibition of the production of reactive oxygen species (ROS) by neutrophils was studied in two groups of horses, which received a dose of 0.1 mg/kg of either acepromazine or promethazine intravenously. Blood samples were collected before (T0) and 0.5, 1, 3 and 5 h after drug administration. The chemiluminescence (CML) response of neutrophils was measured ex vivo in the presence of luminol for a period of 10 min and the maximum CML value (peak value) recorded. There was a significant inhibition of the ROS production in the acepromazine treated group (49% inhibition) at 5 h after administration and in the promethazine group (24% inhibition) at 3 h after administration (P < 0.05 vs. T0). These findings are of therapeutic relevance in the use of phenothiazines in equine patients with inflammatory diseases where neutrophil activation and ROS production are implicated.