Cardiovascular and Gas Exchange Effects of Individualized Positive End-Expiratory Pressures in Cats Anesthetized With Isoflurane.

Objectives: To 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 Design: Prospective, randomized, controlled trial. Animals: Six healthy male neutered purpose-bred cats. Methods: Anesthesia 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 < 0.05. Results: Mean 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. Conclusion: In 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.

Effect of fentanyl, with or without treatment of bradycardia, on the minimum alveolar concentration of isoflurane and cardiovascular function in dogs.

OBJECTIVE: To determine the effect of fentanyl on the minimum alveolar concentration of isoflurane (MACISO) and cardiovascular variables in dogs, and how the treatment of bradycardia affects them. STUDY DESIGN: Prospective, randomized crossover-controlled trial. ANIMALS: A total of six male Beagle dogs weighing 9.9 ± 0.7 kg (mean ± standard deviation) and aged 13 months. METHODS: To each dog, two treatments were assigned on different days: fentanyl (FENTA) or fentanyl plus glycopyrrolate (FENTAglyco) to maintain heart rate (HR) between 100 and 132 beats minute-1. Determinations of MACISO were performed with 10 plasma fentanyl target concentrations ([Fenta]Target (0, 0.16, 0.32, 0.64, 1.25, 2.5, 5.0, 10.0, 20.0 and 40.0 ng mL-1) for FENTA and 5 [Fenta]Target (0, 1.25, 2.5, 5.0, 10.0 ng mL-1)) for FENTAglyco. During each MACISO determination, cardiovascular variables [mean arterial pressure (MAP), HR and cardiac index (CI)] were measured, and systemic vascular resistance index (SVRI) calculated. Pharmacodynamic models were used to describe the plasma fentanyl concentration [Fenta]-response relationship for the effect on MACISO and cardiovascular variables. A mixed-model analysis of variance followed by Dunnett's or Tukey's test, and the Bonferroni adjustment were used for comparisons within and between each treatment, respectively. Significance was set as p < 0.05. RESULTS: Fentanyl decreased MACISO by a maximum of 84%. The [Fenta] producing 50% decrease in MAC, HR and CI were 2.64, 3.65 and 4.30 ng mL-1 (typical values of population model), respectively. The prevention of fentanyl-mediated bradycardia caused no significant effect on MACISO, but increased HR, MAP and CI, and decreased SVRI when compared with isoflurane alone. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl caused a plasma concentration-dependent decrease in MACISO, HR and CI and an increase in SVRI. Cardiovascular improvements associated with fentanyl in isoflurane-anesthetized dogs only occurred when the fentanyl-mediated bradycardia was prevented.

Pharmacokinetics of a high-concentration formulation of buprenorphine (Simbadol) in male dogs.

OBJECTIVE: To describe the pharmacokinetics of buprenorphine in dogs following administration of a high-concentration formulation of buprenorphine. STUDY DESIGN: Prospective, randomized, crossover study. ANIMALS: A total of six healthy male intact Beagle dogs, aged 9-13 months and weighing 10.3 ± 1.4 kg (mean ± standard deviation). METHODS: Dogs were randomized to be administered buprenorphine (0.12 mg kg-1; Simbadol, 1.8 mg mL-1) 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 chromatography-tandem 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-1. The metabolic and two distribution clearances were 25.7 (21), 107.5 (74) and 5.7 (61) mL minute-1 kg-1. The absorption half-life for the fast absorption phase was 8.9 minutes with a 0.7 (103) minute delay. The absorption half-life for the slow absorption phase was 347 minutes with a 226 (42) minute delay. Median (range) bioavailability calculated from noncompartmental analysis was 143 (80-239)%. Calculated terminal half-life was 963 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: The 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.

Cardiovascular function, pulmonary gas exchange and tissue oxygenation in isoflurane-anesthetized, mechanically ventilated Beagle dogs with four levels of positive end-expiratory pressure.

OBJECTIVES: To compare pulmonary gas exchange, tissue oxygenation and cardiovascular effects of four levels of end-expiratory pressure: no positive end-expiratory pressure (ZEEP), positive end-expiratory pressure (PEEP) of maximal respiratory system compliance (PEEPmaxCrs), PEEPmaxCrs + 2 cmH2O (PEEPmaxCrs+2), PEEPmaxCrs + 4 cmH2O (PEEPmaxCrs+4), in isoflurane-anesthetized dogs. STUDY DESIGN: Prospective randomized crossover study. ANIMALS: A total of seven healthy male Beagle dogs, aged 1 year and weighing 10.2 ± 0.7 kg (mean ± standard deviation). METHODS: The dogs were administered acepromazine and anesthesia was induced with propofol and maintained with isoflurane. Ventilation was controlled for 4 hours with ZEEP, PEEPmaxCrs, PEEPmaxCrs+2 or PEEPmaxCrs+4. Cardiovascular, pulmonary gas exchange and tissue oxygenation data were evaluated at 5, 60, 120, 180 and 240 minutes of ventilation and compared using a mixed-model anova followed by Bonferroni test. p < 0.05 was considered significant. RESULTS: Cardiac index (CI) and mean arterial pressure (MAP) were lower in all PEEP treatments at 5 minutes when compared with ZEEP. CI persisted lower throughout the 4 hours only in PEEPmaxCrs+4 with the lowest CI at 5 minutes (2.15 ± 0.70 versus 3.45 ± 0.94 L minute-1 m-2). At 180 and 240 minutes, MAP was lower in PEEPmaxCrs+4 than in PEEPmaxCrs, with the lowest value at 180 minutes (58 ± 7 versus 67 ± 7 mmHg). Oxygen delivery index (DO2I) was lower in PEEPmaxCrs+4 than in ZEEP at 5, 60, 120 and 180 minutes. Venous admixture was not different among treatments. CONCLUSION AND CLINICAL RELEVANCE: The use of PEEP caused a transient decrease in MAP and CI in lung-healthy dogs anesthetized with isoflurane, which improved after 60 minutes of ventilation in all levels of PEEP except PEEPmaxCrs+4. A clinically significant improvement in arterial oxygenation and DO2I was not observed with PEEPmaxCrs and PEEPmaxCrs+2 in comparison with ZEEP, whereas PEEPmaxCrs+4 decreased DO2I.

Effect of heart rate on the pharmacokinetics of fentanyl in dogs anesthetized with isoflurane and hydromorphone.

OBJECTIVE: To compare the pharmacokinetics of fentanyl at lower (LHR) or higher heart rate (HHR) in dogs anesthetized with isoflurane. STUDY DESIGN: Prospective, randomized, crossover controlled trial. ANIMALS: A group of six healthy 13-month-old male Beagle dogs weighing 9.9 ± 0.7 kg (mean ± standard deviation). METHODS: Dogs were allocated to two treatments: LHR (HR: 45-75 beats minute-1) and HHR (HR: 100-130 beats minute-1). Anesthesia was maintained with isoflurane and hydromorphone (0.1 mg kg-1 followed by 0.02-0.10 mg kg-1 hour-1) for both treatments. Glycopyrrolate was administered in HHR to maintain HR within the desired range. Afterwards, fentanyl (20 µg kg-1) was intravenously administered over 5 minutes. Arterial blood samples were collected for plasma fentanyl concentration measurement by liquid chromatography/mass spectrometry. The pharmacokinetics of fentanyl were compared between treatments and the differences were considered significant at p < 0.05. RESULTS: A three-compartment model best fitted the changes in plasma fentanyl concentration. Clearance (CL; mL minute-1 kg-1) was 33.2 (24.0-48.0) and 61.3 (44.5-72.7), maximum concentration (ng mL-1) 33.6 (23.4-36.6) and 20.0 (16.7-28.0), apparent volume of the rapid peripheral compartment (mL kg-1) 436 (352-723) and 925 (499-1887), apparent volume at steady state (mL kg-1) 4064 (3453-6546) and 7195 (5077-8601), cardiac index (CI; mL minute-1 m-2) 2.83 (1.98-3.67) and 4.91 (3.22-6.09) and HR (beats minute-1) 68 (49-72) and 120 (102-129) for LHR and HHR, respectively, with significant differences between treatments. Significant correlations (0.92 and 0.90) were found between CI and CL, and between HR and CL, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The increase in HR and the resultant improvement in cardiac output increased fentanyl CL and volume of distribution, which resulted in a decrease in plasma fentanyl concentration in isoflurane-anesthetized dogs.

Dose-finding study comparing three treatments of remifentanil in cats anesthetized with isoflurane undergoing ovariohysterectomy.

Objectives Three infusion rates of remifentanil were used in isoflurane-anesthetized cats undergoing ovariohysterectomy. The aim of this study was to identify a dosage regimen that would provide optimal anesthetic and surgical conditions, as well as to compare cardiovascular response to surgical stimulation, postoperative analgesia, anesthetic duration and quality of recovery among the tested remifentanil infusion rates. Methods Twenty-seven client-owned, mixed-breed adult healthy female cats were randomized to receive remifentanil 0.1 µg/kg/min (REMI01), remifentanil 0.2 µg/kg/min (REMI02) or remifentanil 0.4 µg/kg/min (REMI04). After premedication with acepromazine and induction of anesthesia with propofol, cats were mechanically ventilated and anesthesia was maintained at approximately 1.0 minimum alveolar concentration (MAC) of isoflurane (1.63% end-tidal isoflurane [ETISO]). Remifentanil infusion rate was increased or decreased by 20% if blood pressure had increased or decreased by 20% from previous values. Pulse rate (PR), systolic arterial pressure (SAP), esophageal temperature, pulse oximetry, end-tidal partial pressure of CO2 and ETISO were recorded at different time points during surgery. Meloxicam was administered before the end of surgery. Data within each treatment group were analyzed using a mixed-model ANOVA and Friedman's test followed by the Wilcoxon signed rank test. Bonferroni or Dunnett's post-hoc tests were used. The Kruskal-Wallis test followed by Dunn's post-hoc test were used to compare data between groups; significance was set at P <0.05. Results Time to sternal recumbency and time to standing were significantly longer in REMI04 than in the other groups. SAP was higher when compared with baseline in REMI01 and REMI02 groups than in REMI04. No significant difference in PR among groups was observed. One cat in REMI01 and another in REMI02 required postoperative rescue analgesia. Conclusion and relevance The dosage regimen of 0.4 µg/kg/min seemed to be the most appropriate to be used in cats undergoing ovariohysterectomy and anesthetized with 1.0 MAC of isoflurane.