Objective: To evaluate the cardiopulmonary effects of IV fentanyl administration in dogs during isoflurane anesthesia and during anesthetic recovery with or without dexmedetomidine or acepromazine. Animals: 7 sexually intact male purpose-bred hound-type dogs aged 11 to 12 months. Procedures: Dogs received a loading dose of fentanyl (5 μg/kg, IV) followed by an IV infusion (5 μg/kg/h) for 120 minutes while anesthetized with isoflurane and for an additional 60 minutes after anesthesia was discontinued. Dogs were randomly assigned in a crossover design to receive dexmedetomidine (2.5 μg/kg), acepromazine (0.05 mg/kg), or saline (0.9% NaCl) solution (1 mL) IV after anesthesia ceased. Cardiopulmonary data were obtained during anesthesia and for 90 minutes after treatment administration during anesthetic recovery. Results: Concurrent administration of fentanyl and isoflurane resulted in significant decreases in mean arterial blood pressure, heart rate, and cardiac index and a significant increase in Paco2. All but Paco2 returned to pretreatment values before isoflurane anesthesia was discontinued. During recovery, dexmedetomidine administration resulted in significant decreases in heart rate, cardiac index, and mixed venous oxygen tension and a significant increase in arterial blood pressure, compared with values for saline solution and acepromazine treatments. Acepromazine administration resulted in significantly lower blood pressure and higher cardiac index and Po2 in mixed venous blood than did the other treatments. Dexmedetomidine treatment resulted in significantly lower values for Pao2 and arterial pH and higher Paco2 values than both other treatments. Conclusions and Clinical Relevance: Fentanyl resulted in transient pronounced cardiorespiratory effects when administered during isoflurane anesthesia. During anesthetic recovery, when administered concurrently with an IV fentanyl infusion, dexmedetomidine resulted in evidence of cardiopulmonary compromise and acepromazine transiently improved cardiopulmonary performance.

Objective—To determine the cardiopulmonary effects of 3 doses of isoflurane, with and without controlled mechanical ventilation and noxious stimulation, in healthy adult New Zealand white rabbits. Animals—6 adult female rabbits. Procedures—Each rabbit was administered isoflurane in oxygen at each of 3 anesthetic doses (1.0, 1.5, or 2.0 times the published minimum alveolar concentration of 2.07%). At each anesthetic dose, blood gas and cardiopulmonary measurements were obtained before and during application of a supramaximal noxious stimulus. Effects of spontaneous and mechanical ventilation were assessed during separate anesthetic episodes. Results—Mean ± SEM isoflurane concentrations used were 2.11 ± 0.04%, 3.14 ± 0.07%, and 4.15 ± 0.06%. During spontaneous ventilation, the rabbits’ Paco2 and mixed venous Pco2 significantly increased with concomitant reductions in both arterial and mixed venous pH as isoflurane concentration increased. Cardiac output and vascular resistance did not change significantly. Noxious stimulation minimally affected measured cardiopulmonary variables. During mechanical ventilation, significant reductions in arterial blood pressures and cardiac output occurred with increasing isoflurane dose. Systemic vascular resistance index at the highest anesthetic dose was significantly lower than the value at the lowest anesthetic dose. During noxious stimulation, systolic arterial blood pressure and cardiac output significantly increased at the 2 lower isoflurane concentrations, but not at the highest concentration. Conclusions and Clinical Relevance—In rabbits, isoflurane-induced dose-dependent cardiopulmonary depression was attributable to vasodilation and negative inotropy. At an isoflurane concentration of 4.15% with mechanical ventilation, cardiovascular depression was severe; use of unnecessarily high isoflurane concentrations in this species should be avoided.

Objective: To compare effects of isoflurane and sevoflurane on intracranial pressure and cardiovascular variables at 1.0, 1.5, and 2.0 times the minimum alveolar concentration (MAC) in mechanically ventilated normocapnic dogs. Animals: 6 healthy male Beagles. Procedures: The individual MAC was determined for each agent with an electrical stimulus. After a minimum of 1 week, anesthetic induction by use of a mask with one of the inhalation anesthetics selected randomly was followed by mechanical ventilation and instrumentation for measurement of intracranial pressure and cardiovascular variables. Heart rate; systolic, mean, and diastolic arterial blood pressures; central venous pressure; mean pulmonary arterial pressure; pulmonary artery occlusion pressure; cardiac output; intracranial pressure (ICP); core body temperature; end-tidal inhalation anesthetic and carbon dioxide concentration; and arterial blood gas values were measured after attaining equilibrium at 1.0, 1.5, and 2.0 MAC of each inhalation anesthetic. Cardiac index, systemic vascular resistance, pulmonary vascular resistance, and cerebral perfusion pressure (CPP) were calculated. Results: Mean ICP did not differ within and between anesthetics at any MAC. Compared with equipotent concentrations of isoflurane, the CPP and mean values for systolic, mean, and diastolic arterial blood pressures were increased at 2.0 MAC for sevoflurane, whereas mean values for mean and diastolic arterial blood pressures and systemic vascular resistance were increased at 1.5 MAC for sevoflurane. Conclusions and Clinical Relevance: Although ICP was similar in healthy normocapnic dogs, CPP was better maintained during 2.0 MAC for sevoflurane, compared with isoflurane.

Objective-To compare effects of anesthetic induction with midazolam-propofol or midazolam-etomidate on intraocular pressure (IOP), pupillary diameter (PD), pulse rate, blood pressure, and respiratory rate in clinically normal dogs. Animals-18 dogs. Procedures-Dogs undergoing ophthalmic surgery received midazolam (0.2 mg/kg, IV) and either propofol or etomidate (IV) until intubatable. For all dogs, results of physical examinations, ophthalmic examinations of the nonoperated eye, and preanesthetic blood analyses were normal. Intraocular pressure, PD, blood pressure, pulse rate, and respiratory rate were measured in the nonoperated eye at 5 time points: just prior to the anesthetic induction sequence, after 5 minutes of preanesthetic oxygenation via face mask, after IV administration of midazolam, after IV anesthetic induction, and after endotracheal intubation. Results-PD decreased significantly from baseline by 4.4 +/- 0.4 mm (mean +/- SD) after anesthetic induction and 5.3 +/- 0.4 mm after intubation in the etomidate group and by 1. 2 +/- 0.4 mm after intubation in the propofol group. Intraocular pressure was increased significantly from baseline by 3.2 +/- 1.0 mm Hg after anesthetic induction in the etomidate group and by 4.7 +/- 1.2 mm Hg after anesthetic induction and 4.5 +/- 1. 2 mm Hg after intubation in the propofol group. Pulse rate was significantly lower by 28.6 +/- 12.6 beats/min after anesthetic induction in the etomidate group, compared with the propofol group. Conclusions and Clinical Relevance-At the studied doses, midazolam-etomidate caused clinically important miosis and increased IOP. Midazolam-propofol caused an even greater increase in IOP but had minimal effects on PD.

Objective—To evaluate the effect of pneumoperitoneum on cardiorespiratory variables and working space during experimental induction of 3 intra-abdominal pressures (IAPs) in cats. Animals—6 healthy young adult neutered male domestic shorthair cats. Procedures—All cats were anesthetized through use of a standardized protocol. A catheter was placed in the right femoral artery for blood pressure and blood gas monitoring. A thermodilution catheter was placed in the right jugular vein via fluoroscopic guidance. Cardiopulmonary variables were measured before (baseline) and 2 and 30 minutes after initiation of pneumoperitoneum at IAPs of 4, 8, and 15 mm Hg; these were created through the use of a mechanical insufflator. At each IAP, abdominal dimensions (height, width, and circumference) were measured at a standardized location. Results—At 4 mm Hg and 8 mm Hg IAP, no clinically important changes were identified in cardiorespiratory values. Heart rate, cardiac index, and stroke volume index remained unchanged throughout the study at all IAPs. Mean arterial blood pressure began to increase at 8 mm Hg and was significantly higher, compared with baseline, at both time points at 15 mm Hg. At 15 mm Hg, Paco2 was significantly higher and cats were more acidotic than at baseline. Working space was subjectively greater at 8 mm Hg than at 4 mm Hg IAP; however, at 15 mm Hg, no clinically important enlargement of the working space was identified, compared with at 8 mm Hg. Conclusions and Clinical Relevance—Values of cardiopulmonary variables were largely unchanged by induction of pneumoperitoneum in healthy cats up to an IAP of 8 mm Hg, and no clinically important increases in working space were evident at an IAP of 15 versus 8 mm Hg. These findings provide little justification for use of IAPs > 8 mm Hg in healthy cats undergoing laparoscopic procedures; however, whether the situation is similar in diseased or elderly cats remains to be determined.

Objective—To determine the pharmacokinetics and hemodynamic effects of trazodone after IV and oral administration in dogs and bioavailability after oral administration. Animals—6 adult Beagles. Procedures—Dogs received trazodone HCl (8 mg/kg) orally and IV in a randomized controlled crossover design. Blood samples were collected at various times after administration. Heart rates and indirectly measured blood pressures of dogs and plasma concentrations and pharmacokinetics of trazodone were determined. Results—Following IV administration, the mean ± SD elimination half-life, apparent volume of distribution, and plasma total body clearance were 169 ± 53 minutes, 2.53 ± 0.47 L/kg, and 11.15 ± 3.56 mL/min/kg, respectively. Following oral administration, the mean ± SD elimination half-life and absolute bioavailability were 166 ± 47 minutes and 84.6 ± 13.2%, respectively. Maximum plasma concentration following oral administration was 1.3 ± 0.5 μ/mL, and time to maximum plasma concentration was 445 ± 271 minutes. After IV administration, all dogs immediately developed transient tachycardia (184.3 ± 8.0 beats/min), and 3 of 6 dogs developed aggression. Increase in heart rate was significantly associated with increase in plasma drug concentration following IV administration. Conclusions and Clinical Relevance—Results of this study indicated oral administration of trazodone resulted in acceptable absolute bioavailability, with substantial variability in time to maximum plasma concentration. Individualized approaches in dosing intervals may be necessary for dogs receiving oral trazodone. An orally administered dose of 8 mg/kg was well tolerated in dogs; IV administration of a dose of 8 mg/kg caused substantial adverse effects, including tachycardia and behavior disinhibition.

Objective: To evaluate the effects of dorsal versus lateral recumbency on the cardiopulmonary system during isoflurane anesthesia in red-tailed hawks (Buteo jamaicensis). Animals: 6 adult 1.1- to 1.6-kg red-tailed hawks. Procedures: A randomized, crossover study was used to evaluate changes in respiratory rate, tidal volume, minute ventilation, heart rate, mean arterial and indirect blood pressures, and end-tidal Pco2 measured every 5 minutes plus Paco2 and Pao2 and arterial pH measured every 15 minutes throughout a 75-minute study period. Results: Respiratory rate was higher, tidal volume lower, and minute ventilation not different in lateral versus dorsal recumbency. Position did not affect heart rate, mean arterial blood pressure, or indirect blood pressure, although heart rate decreased during the anesthetic period. Birds hypoventilated in both positions and Paco2 differed with time and position × time interaction. The Petco2 position × time interaction was significant and Petco2 was a mean of 7 Torr higher than Paco2. The Paco2 in dorsal recumbency was a mean of 32 Torr higher than in lateral recumbency. Birds in both positions developed respiratory acidosis. Conclusions and Clinical Relevance: Differences in tidal volume with similar minute ventilation suggested red-tailed hawks in dorsal recumbency might have lower dead space ventilation. Despite similar minute ventilation in both positions, birds in dorsal recumbency hypoventilated more yet maintained higher Pao2, suggesting parabronchial ventilatory or pulmonary blood flow distribution changes with position. The results refute the hypothesis that dorsal recumbency compromises ventilation and O2 transport more than lateral recumbency in red-tailed hawks.

Objective: To compare the effects of 2 fractions of inspired oxygen, 50% and > 95%, on ventilation, ventilatory rhythm, and gas exchange in isoflurane-anesthetized horses. Animals: 8 healthy adult horses. Procedures: In a crossover study design, horses were assigned to undergo each of 2 anesthetic sessions in random order, with 1 week separating the sessions. In each session, horses were sedated with xylazine hydrochloride (1.0 mg/kg, IV) and anesthesia was induced via IV administration of diazepam (0.05 mg/kg) and ketamine (2.2 mg/kg) Anesthesia was subsequently maintained with isoflurane in 50% or > 95% oxygen for 90 minutes. Measurements obtained during anesthesia included inspiratory and expiratory peak flow and duration, tidal volume, respiratory frequency, end-tidal CO2 concentration, mixed expired partial pressures of CO2 and O2, Pao2, Paco2, blood pH, arterial O2 saturation, heart rate, and arterial blood pressure. Calculated values included the alveolar partial pressure of oxygen, alveolar-to-arterial oxygen tension gradient (Pao2 − Pco2), rate of change of Pao2 − Pao2, and physiologic dead space ratio. Ventilatory rhythm, based on respiratory rate and duration of apnea, was continuously observed and recorded. Results: Use of the lower inspired oxygen fraction of 50% resulted in a lower arterial oxygen saturation and Pao2 than did use of the higher fraction. No significant difference in Paco2, rate of change of Pao2 − Pao2, ventilatory rhythm, or other measured variables was observed between the 2 sessions. Conclusion and Clinical Relevance: Use of 50% inspired oxygen did not improve the ventilatory rhythm or gas exchange and increased the risk of hypoxemia in spontaneously breathing horses during isoflurane anesthesia. Use of both inspired oxygen fractions requires adequate monitoring and the capacity for mechanical ventilation.

Objective-To determine whether tepoxalin alters kidney function in dogs with chronic kidney disease (CKD). Animals-16 dogs with CKD (International Renal Interest Society stage 2 or 3) and osteoarthritis. Procedures-Kidney function was assessed via serum biochemical analysis, urinalysis, urine protein-to-creatinine concentration ratio, urine γ-glutamyl transpeptidase-to-creatinine concentration ratio, iohexol plasma clearance, and indirect blood pressure measurement twice before treatment. Dogs received tepoxalin (10 mg/kg, PO, q 24 h) for 28 days (acute phase; n = 16) and an additional 6 months (chronic phase; 10). Recheck examinations were performed weekly (acute phase) and at 1, 3, and 6 months (chronic phase). Kidney function variables were analyzed via repeated-measures ANOVA. Results-There was no difference over time for any variables in dogs completing both phases of the study. Adverse drug events (ADEs) resulting in discontinuation of tepoxalin administration included increased serum creatinine concentration (1 dog; week 1), collapse (1 dog; week 1), increased liver enzyme activities (1 dog; week 4), vomiting and diarrhea (1 dog; week 8), hematochezia (1 dog; week 24), and gastrointestinal ulceration or perforation (1 dog; week 26). Preexisting medical conditions and concomitant drug use may have contributed to ADEs. Kidney function was not affected in the latter 5 dogs. Discontinuation of tepoxalin administration stabilized kidney function in the former dog and resolved the ADEs in 4 of the 5 latter dogs. Conclusions and Clinical Relevance-Tepoxalin may be used, with appropriate monitoring, in dogs with International Renal Interest Society stage 2 or 3 CKD and osteoarthritis.