Comparison of Plasma Fentanyl Concentrations by Using Three Transdermal Fentanyl Patch Sizes in Dogs

Objective—To compare plasma fentanyl concentrations attained after the application of three transdermal fentanyl patch sizes (50, 75, and 100 μg/hour) in dogs. Design—Repeated Latin square controlled study. Animals—Six intact, mixed-breed adult dogs (2 males, 4 females) weighing 19.9 ± 3.4 kg. Methods—Each dog was randomly assigned to receive each of three treatments: 50 (P50), 75 (P75), or 100 (P100) μg/hour transdermal patches. Patches were left in place for 72 hours. Jugular venous blood was collected at 1,2, 4, 8, 12, 24, 36, 48, 60, and 72 hours after patch application and for 1, 2, 4, 8, and 12 hours after patch removal. Plasma fentanyl concentrations were measured using a radioimmunoassay technique. After a 96-hour washout period, each dog was moved to another treatment group and received a different patch size. Results—The following results were obtained (mean ± SD): average plasma fentanyl concentration from 24 to 72 hours, 0.7 ± 0.2 ng/mL (P50), 1.4 ± 0.5 ng/mL (P75), 1.2 ± 0.5 ng/mL (P100); the total area under the concentration versus time curve (0 hours to infinity), 46 ± 12.2 ng/h/mL (P50), 101.2 ± 41.4 ng/h/mL (P75), 80.4 ± 38.3 ng/h/mL (P100); and the apparent elimination half-life, 3.6 ± 1.2 hours (P50), 3.4 ± 2.7 hours (P75), and 2.5 ± 2.0 hours (P100). There was a high degree of variability in plasma fentanyl concentrations achieved. Plasma fentanyl concentrations declined rapidly after patch removal. Conclusions—The attainment of steady-state plasma concentrations takes up to 24 hours, and there is a great deal of variability in the final concentrations reached in different individuals. In this study, the 100 μg/hour patches did not provide statistically increased plasma concentrations when compared with the 50 μg/hour patches. Clinical Relevance—Because of the interindividual and intraindividual variation in plasma fentanyl concentrations, patches should be applied 24 hours before the anticipated time that analgesia will be required. Adequacy of analgesia and potentially deleterious side effects, such as sedation and respiratory depression, should be monitored while the patches are in place. Skin reactions may occur, and the patches should be removed if such skin irritation is seen. After the patch is removed, it is expected that analgesia will wane rapidly because of the brief elimination half-life.     

Determinants and Utility of the Anion Gap in Predicting Hyperlactatemia in Cattle

The objectives of this study were to investigate the determinants of the anion gap (AG) in cattle and to evaluate the utility of AG in detecting hyperlactatemia in sick neonatal calves and adult cattle. The AG was calculated as AG = ([Na+] + [K+]) - ([Cl^-] + [HCO₃]), with all values in mEq/L. The AG of healthy neonatal calves (n = 16) was 29.6 ± 6.2 mEq/L (mean ± SD), and the blood L-lactate concentration ranged from 0.5 to 1.2 mM/L. The AG was significantly (P > .05) correlated with serum phosphate (r = .66) and creatinine (r = .51) concentrations. The AG of neonatal calves with experimentally induced diarrhea (n = 16) was 28.6 ± 5.6 mEq/L, and the blood L-lactate concentration ranged from 1.1 to 2.9 mM/L. The AG was significantly correlated with blood L-lactate concentration (r = .67), serum phosphate concentration (r = .63), creatinine concentration (r = .76), and blood pH (r = -.61). The AG of adult cattle with abomasal volvulus (n = 41) was 20.5 ± 7.8 mEq/L, and the blood L-lactate concentration ranged from 0.6 to 15.6 mM/L. The AG was significantly correlated with blood L-lactate concentration (r = .60), serum phosphate concentration (r = .71), creatinine concentration (r = .65), albumin concentration (r = .47), total protein concentration (r = .54), blood pyruvate concentration (r = .67), and blood pH (r = -.41) but not plasma β-OH butyrate concentration. The results indicate that the AG in cattle is only moderately correlated with blood L-lactate concentration and is similarly correlated with serum phosphate and creatinine concentrations in neonatal calves and adult cattle, as well as with serum albumin and total protein concentrations in adult cattle. Anion gap determination is of limited usefulness in predicting blood L-lactate concentration in sick cattle, whereas the correlation between AG and serum creatinine concentration in sick cattle suggests that an increased AG should alert the clinician to the potential presence of uremic anions.     

Hyperthermia and Delayed-Onset Myopathy after Recovery from Anesthesia in a Horse

A 13-year old Thoroughbred cross gelding (528 kg) underwent lameness investigation. Because of his temperament, general anesthesia was required to facilitate ultrasound of the left fore fetlock and intra-articular medication of three joints. Anesthesia was induced with ketamine/diazepam after acepromazine/detomidine premedication. Anesthesia was maintained for 40 minutes with a guaifenesin/detomidine/ketamine intravenous infusion. Recovery from anesthesia was initially uneventful, although of a moderate duration (70 minutes). Once standing, the horse proceeded to box walk in an agitated state and became recumbent on two occasions. The horse was manually restrained, at which time its rectal temperature was 41.8°C. Cooling measures were employed (fans, ice-water enemas, wet rugs, intravenous fluid therapy (IVFT), and topical application of surgical spirit) until rectal temperature reached 38.7°C. IVFT was continued for a further 16 hours. Four days after recovery from anesthesia, bilateral triceps, deltoideus, trapezius, and rhomboideus muscle swelling was observed. Blood creatinine kinase was elevated (24,898 IU/L). Treatment for postanesthetic myopathy was initiated (hot packing of the muscle groups, topical dimethylsulfoxide [DMSO] cream application, and oral phenylbutazone). Myoglobinuria was not observed at any time. Muscle swelling decreased over the following 3 days. The horse was discharged on day 11 and has since returned to work.     

Relative Flow-Time Relationships in Single Breaths Recorded After Treadmill Exercise in Thoroughbred Horses

Analysis of individual breaths after exercise has potential for pulmonary function testing. The aims of this study were to investigate the dependence of measurements of pulmonary function in single breaths on time postexercise and tidal volume (V_T) after treadmill exercise. Five Thoroughbred horses without evidence of airway disease were used. Horses had been previously acclimated to treadmill exercise and to wearing a face mask. A Quadflow spirometer recorded airflow rates continuously during 90 seconds after intense treadmill exercise to fatigue. Indices of function were based on ratios of times within each breath and analyses of the shape of relative flow–time curves within inspiration and expiration. Restricted maximum likelihood, general linear regression, repeated-measures one-way analysis of variance (ANOVA), and two sample t-tests were used, with statistical significance at P < .05. Time postexercise had no effect on several ratios based on time for inspiration (T_I) and expiration (T_E), and times to peak flows (T_I/T_T, T_E/T_T, T_E/T_I, Tpef [peak expiratory flow]/T_E, and Tpif [peak inspiratory flow]/T_I). Many variables were significantly dependent on V_T. Occasional big respiratory cycles with V_T more than 10% greater than in the previous breath had significantly different means for relative flow (Rf)/(T_E/T_I), epz_50% (50% of the time from Tpef to end of expiration), epz_75% (75% of the time from Tpef to end of expiration), and ipz_75% (75% of the time from Tpif to end of inspiration). Predicted means for these variables differed by 10–20%. This study establishes guidelines for the selection of breaths after exercise, and describes a new approach to measurement of relative flow and time relationships. It was concluded that several time-based ratios have potential for measuring pulmonary function. However, care is needed when selecting breaths for calculation of most of the new relative flow–time variables.     

DETECTION OF PORTAL BLOOD FLOW USING PER-RECTAL 99mTc-PERTECHNETATE SCINTIGRAPHY IN NORMAL CATS

This study reports data obtained from per-rectal ^99mTc-pertechnetate portal scintigraphy in normal cats. It examines the effects of chemical restraint and the methods employed in defining regions of interest (ROIs) on the shunt index derived from this data. Six normal cats were used for the study; all six were chemically restrained for imaging using propofol and later four of them were manually restrained for comparison. Portal blood flow was studied and the mean shunt index was found to be 5.9%± 3.9 when ROIs were operator defined and 9.2%± 4.4 when ROIs were defined using an isocontour program. In cats that were restrained using propofol and operator defined ROIs, the mean value for the time between detection of radioactivity in the liver and in the heart was 14 ± 1 seconds.     

Effects of α-tocopherol and Ascorbic Acid on Equine Semen Quality after Cryopreservation

This study investigated the effects of ascorbic acid and α-tocopherol supplementation on semen quality parameters of equine thawed-frozen semen. Semen was divided in seven different treatments in a final concentration of 100 × 10⁶ sperm/mL by using Gent extender containing no supplements (control) and the following supplements with three different concentrations: α-tocopherol (0.5, 1, and 2 mM) and ascorbic acid (0.45, 0.9, and 1.8 g/L). After thawing, all samples were maintained at 37°C, while analyses were performed at 0, 60, and 120 minutes. Evaluation of viability and acrosome status (using Pisum sativum agglutinin conjugated to fluorescein isothiocyanate and propidium iodide), mitochondrial membrane potential (5,5′,6,6′-tetrachloro-1,1′,3,3′tetraethylbenzimidazolyl carbocyanine iodine [JC-1]), membrane lipid peroxidation (LPO; C₁₁-BODIPY^581/591), and stability of the plasmatic membrane (merocyanine 540 and Yo-Pro-1) of each sample was determined by flow cytometry. Relative to the control group, supplementation with α-tocopherol improved (P ≤ .05) postthaw membrane LPO, yet the higher concentrations of ascorbic acid (0.9 and 1.8 g/L, respectively) showed a negative effect on membrane LPO. Neither antioxidant significantly increased (P > .05) the acrosome integrity and mitochondrial membrane potential of frozen-thawed spermatozoa, although supplementation with α-tocopherol and ascorbic acid (0.9 and 1.8 g/L, respectively) had a positive effect on membrane integrity and stability (P ≤ .05). For all semen parameters, the lower concentration of ascorbic acid (0.45 g/L) did not show significant differences (P > .05) compared with the control. In conclusion, α-tocopherol seems to be an efficient antioxidant for reducing the oxidative stress provoked by cryopreservation, decreasing lipid peroxidation on equine spermatozoa.     

A Necropsy Survey of Neurologic Diseases in 4,319 Horses Examined in Normandy (France) from 1986 to 2006

The frequencies of neurologic diseases and various corresponding causes were analyzed in 4,319 Norman horses examined by autopsy between 1986 and 2006. Five hundred forty-three cases of nervous system disorders were detected, or a total prevalence of 12.6%. One hundred eighty-seven of the 543 horses (34.4%) exhibited lesions of a traumatic origin affecting the skull or the vertebral column at different levels. Their frequency was less in foals younger than 1 month of age and higher in horses aged 6 months to 2 years. Eighty-three cases of cervical vertebral compressive myelopathy (CVCM) (15.3%) were identified. Males and geldings were more often affected than females. CVCM was diagnosed mostly in animals aged 6 months to 2 years. Horses affected with lesions in the mid-cervical region (region C3–C5) were significantly younger than those exhibiting more caudal lesions (region C5–C7). Neonatal maladjustment syndrome was diagnosed in 62 foals younger than 3.5 days (4.8% of the causes of death between birth and 1 month) by using clinical or lesional criteria. The prevalence was higher in Thoroughbreds as well as in the miscellaneous breed category and less in French Standardbreds. Bacterial meningoencephalomyelitis and meningitis represented 9.6% of nervous system disorders (52 cases) and most often affected foals aged 1 to 6 months. The main bacteria identified were beta-hemolytic Streptococci , Escherichia coli, Listeria monocytogenes, Staphylococcus aureus, and Actinobacillus sp. The other causes diagnosed were, in decreasing order of frequency: grass sickness or equine dysautonomia (6.3% of neurologic diseases), hepatic encephalopathy syndrome (5.2%), septic vertebral arthritis or osteitis mainly caused by Rhodococcus equi (2.6%), congenital defects of the nervous system (2.4%), equine herpesvirus 1 myeloencephalopathy (2.2%), botulism (2.2%), malformations of the vertebral column other than CVCM (2%), and neighboring polyneuritis associated with guttural pouch mycosis (1.5%).