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- Author or Editor: John A. E. Hubbell x
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Abstract
Objective—To compare systemic bioavailability and duration for therapeutic plasma concentrations and cardiovascular, respiratory, and analgesic effects of morphine administered per rectum, compared with IV and IM administration in dogs.
Animals—6 healthy Beagles.
Procedure—In a randomized study, each dog received the following: morphine IV (0.5 mg/kg of body weight), morphine per rectum (1, 2, and 5 mg/kg as a suppository and 2 mg/kg as a solution), and a control treatment. Intramuscular administration of morphine (1 mg/kg) was evaluated separately. Heart and respiratory rates, systolic, diastolic, and mean blood pressures, adverse effects, and plasma morphine concentrations were measured. Analgesia was defined as an increase in response threshold, compared with baseline values, to applications of noxious mechanical (pressure) and thermal (heat) stimuli. Data were evaluated, using Friedman repeated-measures ANOVA on ranks and Student-Newman-Keuls post-hoc t-tests.
Results—Significant differences were not found in cardiovascular, respiratory, or analgesia values between control and morphine groups. Overall systemic bioavailability of morphine administered per rectum was 19.6%. Plasma morphine concentration after administration of the highest dose (5 mg/kg) as a suppository was significantly higher than concentrations 60 and 360 minutes after IV and IM administration, respectively. A single route of administration did not consistently fulfill our criteria for providing analgesia.
Conclusions and Clinical Relevance—Rectal administration of morphine did not increase bioavailability above that reported for oral administration of morphine in dogs. Low bioavailability and plasma concentrations limit the clinical usefulness of morphine administered per rectum in dogs. (Am J Vet Res 2000;61:24–28)
Abstract
Objective—To determine the anesthetic, cardiorespiratory, and metabolic effects of 4 IV anesthetic regimens in Thoroughbred horses recuperating from a brief period of maximal exercise.
Animals—6 adult Thoroughbreds.
Procedure—Horses were preconditioned by exercising them on a treadmill. Each horse ran 4 simulated races, with a minimum of 14 days between races. Races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until fatigued or for a maximum of 2 minutes. Two minutes after exercise, horses received a combination of xylazine hydrochloride (2.2 mg/kg of body weight) and acepromazine maleate (0.04 mg/kg) IV. Five minutes after exercise, horses received 1 of the following 4 IV anesthetic regimens: ketamine hydrochloride (2.2 mg/kg); ketamine (2.2 mg/kg) and diazepam (0.1 mg/kg); tiletamine hydrochloride-zolazepam hydrochloride (1 mg/kg); and guaifenesin (50 mg/kg) and thiopental sodium (5 mg/kg). Treatments were randomized. Cardiopulmonary indices were measured, and samples of blood were collected before and at specific times for 90 minutes after each race.
Results—Each regimen induced lateral recumbency. The quality of induction and anesthesia after ketamine administration was significantly worse than after other regimens, and the duration of anesthesia was significantly shorter. Time to lateral recumbency was significantly longer after ketamine or guaifenesinthiopental administration than after ketaminediazepam or tiletamine-zolazepam administration. Arterial blood pressures after guaifenesin-thiopental administration were significantly lower than after the other regimens.
Conclusions and Clinical Relevance—Anesthesia can be safely induced in sedated horses immediately after maximal exercise. Ketamine-diazepam and tiletamine- zolazepam induced good quality anesthesia with acceptable perturbations in cardiopulmonary and metabolic indices. Ketamine alone and guaifenesinthiopental regimens are not recommended. (Am J Vet Res 2000;61:1545–1552)
Abstract
Objective
To determine effects of walking or standing on hepatic blood flow of horses after brief, intense exercise.
Animals
6 adult Thoroughbreds (4 mares, 2 geldings).
Procedure
Horses were preconditioned on a treadmill to establish uniform level of fitness. Once fit, treadmill speed causing each horse to exercise at 120% of maximal oxygen consumption was determined and used in simulated races at 14-day intervals. In a three-way crossover study, horses were exercised at a speed inducing 120% of maximal oxygen consumption until fatigued or for a maximum of 2 minutes. Three interventions were studied: resting on the treadmill (REST), exercised then standing on the treadmill for 30 minutes (MS), and exercised then walking at 2 m/s for 30 minutes (MW). At 60 seconds after completion of exercise, bromsulphalein (BSP) was infused IV, and blood samples were collected every 2 minutes for 30 minutes for analysis of BSP concentration. Hematocrit and plasma total solids concentration were measured. Pharmacokinetic parameters were derived, using nonlinear regression, and were compared, using Friedman’s repeated measures analysis on ranks.
Results
Plasma BSP concentration was higher after exercise. Median hepatic blood flow (BSP clearance) decreased significantly from 23.8 (REST) to 20.7 (MS) and 18.7 (MW) ml/min/kg. Median steady-state volume of distribution of BSP decreased from 47.6 (REST) to 42.7 (MW) and 40.2 (MS) ml/kg. Differences among trials were not significant when horses walked or stood after exercise.
Conclusions
Hepatic blood flow and pharmacokinetics of BSP are markedly altered immediately after exercise. Limiting movement of horses during this period did not affect hepatic blood flow. (Am J Vet Res 1998;59:1476–1480)
Abstract
Objective
To determine sedative, cardiorespiratory and metabolic effects of xylazine hydrochloride, detomidine hydrochloride, and a combination of xylazine and acepromazine administered IV at twice the standard doses in Thoroughbred horses recuperating from a brief period of maximal exercise.
Animals
6 adult Thoroughbreds,
Procedure
Horses were preconditioned by exercising them on a treadmill to establish a uniform level of fitness. Each horse ran 4 simulated races, with a minimum of 14 days between races. Simulated races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until they were fatigued or for a maximum of 2 minutes. One minute after the end of exercise, horses were treated IV with xylazine (2.2 mg/kg of body weight), detomidine (0.04 mg/kg), a combination of xylazine (2.2 mg/kg) and acepromazine (0.04 mg/kg), or saline (0.9% NaCl) solution. Treatments were randomized so that each horse received each treatment once, in random order. Cardiopulmonary indices were measured, and samples of arterial and venous blood were collected immediately before and at specific times for 90 minutes after the end of each race.
Results
All sedatives produced effective sedation. The cardiopulmonary depression that was induced was qualitatively similar to that induced by administration of these sedatives to resting horses and was not severe. Sedative administration after exercise prolonged the exercise-induced increase in body temperature.
Conclusions and Clinical Relevance
Administration of xylazine, detomidine, or a combination of xylazine-acepromazine at twice the standard doses produced safe and effective sedation in horses that had just undergone a brief, intense bout of exercise. (Am J Vet Res 1999;60:1271–1279)
Abstract
Objective—To determine the effect of IV administration of crystalloid (lactated Ringer's solution [LRS]) or colloid (hetastarch) fluid on isoflurane-induced hypotension in dogs.
Animals—6 healthy Beagles.
Procedures—On 3 occasions, each dog was anesthetized with propofol and isoflurane and instrumented with a thermodilution catheter (pulmonary artery). Following baseline assessments of hemodynamic variables, end-tidal isoflurane concentration was increased to achieve systolic arterial blood pressure (SABP) of 80 mm Hg. At that time (0 minutes), 1 of 3 IV treatments (no fluid, LRS [80 mL/kg/h], or hetastarch [80 mL/kg/h]) was initiated. Fluid administration continued until SABP was within 10% of baseline or to a maximum volume of 80 mL/kg (LRS) or 40 mL/kg (hetastarch). Hemodynamic variables were measured at intervals (0 through 120 minutes and additionally at 150 and 180 minutes in LRS- or hetastarch-treated dogs). Several clinicopathologic variables including total protein concentration, PCV, colloid osmotic pressure, and viscosity of blood were assessed at baseline and intervals thereafter (0 through 120 minutes).
Results—Administration of 80 mL of LRS/kg did not increase SABP in any dog, whereas administration of ≤ 40 mL of hetastarch/kg increased SABP in 4 of 6 dogs. Fluid administration increased cardiac index and decreased systemic vascular resistance. Compared with hetastarch treatment, administration of LRS decreased blood viscosity. Treatment with LRS decreased PCV and total protein concentration, whereas treatment with hetastarch increased colloid osmotic pressure.
Conclusions and Clinical Relevance—Results indicated that IV administration of hetastarch rather than LRS is recommended for the treatment of isoflurane-induced hypotension in dogs.
Abstract
OBJECTIVE To determine pharmacokinetics and pharmacodynamics of buprenorphine after IV and SC administration and of sustained-release (SR) buprenorphine after SC administration to adult alpacas.
ANIMALS 6 alpacas.
PROCEDURES Buprenorphine (0.02 mg/kg, IV and SC) and SR buprenorphine (0.12 mg/kg, SC) were administered to each alpaca, with a 14-day washout period between administrations. Twenty-one venous blood samples were collected over 96 hours and used to determine plasma concentrations of buprenorphine. Pharmacokinetic parameters were calculated by use of noncompartmental analysis. Pharmacodynamic parameters were assessed via sedation, heart and respiratory rates, and thermal and mechanical antinociception indices.
RESULTS Mean ± SD maximum concentration after IV and SC administration of buprenorphine were 11.60 ± 4.50 ng/mL and 1.95 ± 0.80 ng/mL, respectively. Mean clearance was 3.00 ± 0.33 L/h/kg, and steady-state volume of distribution after IV administration was 3.8 ± l.0 L/kg. Terminal elimination half-life was 1.0 ± 0.2 hours and 2.7 ± 2.8 hours after IV and SC administration, respectively. Mean residence time was 1.3 ± 0.3 hours and 3.6 ± 3.7 hours after IV and SC administration, respectively. Bioavailability was 64 ± 28%. Plasma concentrations after SC administration of SR buprenorphine were below the LLOQ in samples from 4 alpacas. There were no significant changes in pharmacodynamic parameters after buprenorphine administration. Alpacas exhibited mild behavioral changes after all treatments.
CONCLUSIONS AND CLINICAL RELEVANCE Buprenorphine administration to healthy alpacas resulted in moderate bioavailability, rapid clearance, and a short half-life. Plasma concentrations were detectable in only 2 alpacas after SC administration of SR buprenorphine.
Abstract
Objective—To determine pharmacokinetic and pharmacodynamic properties of midazolam after IV and IM administration in alpacas.
Animals—6 healthy alpacas.
Procedures—Midazolam (0.5 mg/kg) was administered IV or IM in a randomized crossover design. Twelve hours prior to administration, catheters were placed in 1 (IM trial) or both (IV trial) jugular veins for drug administration and blood sample collection for determination of serum midazolam concentrations. Blood samples were obtained at intervals up to 24 hours after IM and IV administration. Midazolam concentrations were determined by use of tandem liquid chromatography–mass spectrometry.
Results—Maximum concentrations after IV administration (median, 1,394 ng/mL [range, 1,150 to 1,503 ng/mL]) and IM administration (411 ng/mL [217 to 675 ng/mL]) were measured at 3 minutes and at 5 to 30 minutes, respectively. Distribution half-life was 18.7 minutes (13 to 47 minutes) after IV administration and 41 minutes (30 to 80 minutes) after IM administration. Elimination half-life was 98 minutes (67 to 373 minutes) and 234 minutes (103 to 320 minutes) after IV and IM administration, respectively. Total clearance after IV administration was 11.3 mL/min/kg (6.7 to 13.9 mL/min/kg), and steady-state volume of distribution was 525 mL/kg (446 to 798 mL/kg). Bioavailability of midazolam after IM administration was 92%. Peak onset of sedation occurred at 0.4 minutes (IV) and 15 minutes (IM). Sedation was significantly greater after IV administration.
Conclusions and Clinical Relevance—Midazolam was well absorbed after IM administration, had a short duration of action, and induced moderate levels of sedation in alpacas.
Abstract
Case Description—An 11-year-old 72-kg (158-lb) sexually intact female alpaca was examined for diagnosis and treatment of hematuria of 4 months' duration.
Clinical Findings—Pigmenturia was detected by the owner when the alpaca was 8 months pregnant. Radiographic, ultrasonographic, vaginal speculum, and cystoscopic evaluation of the urinary tract revealed normal vaginal and urethral epithelia and increased bladder vessel tortuosity, with pulses of hemorrhage from the left ureter. Regenerative anemia and mild leukopenia were detected and serum urea nitrogen and creatinine concentrations were within reference ranges.
Treatment and Outcome—Chronic hematuria resolved after unilateral nephrectomy of the left kidney, and no dysfunction was detected in the remaining kidney. Histologic evaluation of the kidney revealed a transitional cell tumor in the renal pelvis.
Clinical Relevance—Although anemia is common in South American camelids, hematuria is an uncommon sign of this condition. Chronic urinary tract infection, toxin ingestion, and neoplasia causing hematuria or hemoglobinuria should be considered in South American camelids with pigmenturia. Thorough and systematic evaluation of the urinary tract should be performed to locate the site of hemorrhage to treat hematuria appropriately.
