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The purpose of this study was to compare cardiovascular and respiratory effects of two volumes of bupivacaine 0.25% (0.2 mL kg-1—treatment BUP02—and 0.4 mL kg-1 –treatment BUP04) administered epidurally at the lumbosacral intervertebral space in dogs anesthetized with isoflurane. This experimental prospective randomized crossover design trial used six mixed breed adult dogs, four neutered males and two spayed females. Each dog was anesthetized on three different occasions: the first for isoflurane minimum alveolar concentration (MAC) measurement, and the following two assigned treatments (BUP02 or BUP04). On the two treatment days, anesthesia was induced and maintained with isoflurane at 1.3 MAC during the experiments. Cardiovascular and respiratory measurements were recorded before (T0) and 5, 15, 30, 60 and 90 minutes after the epidural administration of bupivacaine. Comparisons between and within groups were performed by a mixed-model ANOVA and Friedman’s test when appropriate followed by Bonferroni post-hoc test or Dunnet’s test to compare time points within each treatment with T0 (p < 0.05). Mean arterial pressure decreased significantly from 15 to 90 minutes after the administration of BUP02 and from 5 to 60 minutes in BUP04, with lower values in BUP04 than in BUP02 lasting up to 30 minutes after bupivacaine administration. No significant changes in cardiac output and systemic vascular resistance were observed in either treatment. Hypoventilation was only detected in BUP04. Hemoglobin concentration and arterial oxygen content decreased after both treatment of bupivacaine with no significant decrease in oxygen delivery. Two dogs in BUP04 developed Horner’s syndrome. The epidural administration of 0.4 mL.kg-1 of bupivacaine to dogs in sternal recumbency anesthetized with isoflurane 1.3 MAC caused more cardiovascular and respiratory depression than 0.2 mL.kg-1.

ObjectivesTo compare the effects of four levels of end-expiratory pressure [zero (ZEEP) and three levels of positive end-expiratory pressure (PEEP)] on the cardiovascular system and gas exchange of cats anesthetized with isoflurane and mechanically ventilated for 3 h with a tidal volume of 10 ml/kg.Study DesignProspective, randomized, controlled trial.AnimalsSix healthy male neutered purpose-bred cats.MethodsAnesthesia was induced with isoflurane and maintained at 1.3 minimum alveolar concentration. PEEP of maximal respiratory compliance (PEEPmaxCrs) was identified in a decremental PEEP titration, and cats were randomly ventilated for 3 h with one of the following end-expiratory pressures: ZEEP, PEEPmaxCrs minus 2 cmH2O (PEEPmaxCrs−2), PEEPmaxCrs, and PEEPmaxCrs plus 2 cmH2O (PEEPmaxCrs+2). Cardiovascular and gas exchange variables were recorded at 5, 30, 60, 120, and 180 min (T5 to T180, respectively) of ventilation and compared between and within ventilation treatments with mixed-model ANOVA followed by Dunnet's and Tukey's tests (normal distribution) or Friedman test followed by the Dunn's test (non-normal distribution). Significance to reject the null hypothesis was considered p &lt; 0.05.ResultsMean arterial pressure (MAP—mmHg) was lower in PEEPmaxCrs+2 [63 (49–69); median (range)] when compared to ZEEP [71 (67–113)] at T5 and stroke index (ml/beat/kg) was lower in PEEPmaxCrs+2 (0.70 ± 0.20; mean ± SD) than in ZEEP (0.90 ± 0.20) at T60. Cardiac index, oxygen delivery index (DO2I), systemic vascular resistance index, and shunt fraction were not significantly different between treatments. The ratio between arterial partial pressure and inspired concentration of oxygen (PaO2/FIO2) was lower in ZEEP than in the PEEP treatments at various time points. At T180, DO2I was higher when compared to T5 in PEEPmaxCrs. Dopamine was required to maintain MAP higher than 60 mmHg in one cat during PEEPmaxCrs and in three cats during PEEPmaxCrs+2.ConclusionIn cats anesthetized with isoflurane and mechanically ventilated for 3 h, all levels of PEEP mildly improved gas exchange with no significant difference in DO2I when compared to ZEEP. The PEEP levels higher than PEEPmaxCrs−2 caused more cardiovascular depression, and dopamine was an effective treatment. A temporal increase in DO2I was observed in the cats ventilated with PEEPmaxCrs. The effects of these levels of PEEP on respiratory mechanics, ventilation-induced lung injury, as well as in obese and critically ill cats deserve future investigation for a better understanding of the clinical use of PEEP in this species.

Objective To describe the pharmacokinetics of buprenorphine in dogs following administration of a highconcentration formulation of buprenorphine.Study design Prospective, randomized, crossover study.Animals A total of six healthy male intact Beagle dogs, aged 9e13 months and weighing 10.3 ± 1.4 kg (mean ± standard deviation).Methods Dogs were randomized to be administered buprenorphine (0.12 mg kg e1 ; Simbadol, 1.8 mg mL e1 ) via the intravenous (lateral saphenous) or subcutaneous (dorsal interscapular) route followed by the alternative route of administration after a 14 day interval. Blood was sampled before administration and at set times up to 72 hours after injection. Plasma buprenorphine concentration was measured using liquid chromatographyetandem mass spectrometry.Results A three-compartment model with zero or biphasic rapid and slow first-order input in (intravenous or subcutaneous data, respectively) and first-order elimination from the central compartment best fitted the data. The rapid first-order input accounted for 63% of the dosage absorption. Typical values (% interindividual variability) for the three compartment volumes were 900 (33), 2425 (not estimated) and 6360 (28) mL kg e1 . The metabolic and two distribution clearances were 25.7 (21), 107.5 (74) and 5.7 (61) mL minute e1 kg e1 . The absorption half-life for the fast absorption phase was 8.9 minutes with a 0.7 (103) minute delay. The absorption halflife for the slow absorption phase was 347 minutes with a 226 (42) minute delay. Median (range) bioavailability calculated from noncompartmental analysis was 143 (80e239)%. Calculated terminal half-life was 963 minutes. Conclusions and clinical relevanceThe high-concentration formulation of buprenorphine administered subcutaneously had a large volume of distribution and a rapid absorption phase followed by slower, delayed absorption. The high estimate of bioavailability should be interpreted with caution as values above 100% are most commonly related to experimental issues.