Objective—To determine and compare the effects of caffeine and doxapram on cardiorespiratory variables in foals during isoflurane-induced respiratory acidosis.
Animals—6 clinically normal foals (1 to 3 days old).
Procedures—At intervals of ≥ 24 hours, foals received each of 3 IV treatments while in a steady state of hypercapnia induced by isoflurane anesthesia (mean ± SD, 1.4 ± 0.3% endtidal isoflurane concentration). After assessment of baseline cardiorespiratory variables, a low dose of the treatment was administered and variables were reassessed; a high dose was then administered, and variables were again assessed. Sequential low- and high-dose treatments included doxapram (loading dose of 0.5 mg/kg, followed by a 20-minute infusion at 0.03 mg/kg/min and then 0.08 mg/kg/min), caffeine (5 mg/kg and 10 mg/kg), and saline (0.9% NaCl) solution (equivalent volumes).
Results—Administration of doxapram at both infusion rates resulted in a significant increase in respiratory rate, minute ventilation, arterial blood pH, PaO2, and arterial blood pressure. These variables were also significantly higher during doxapram administration than during caffeine or saline solution administration. There was a significant dose-dependent decrease in PaCO2 and arterial bicarbonate concentration during doxapram treatment. In contrast, PaCO2 increased from baseline values after administration of saline solution or caffeine. The PaCO2 value was significantly lower during doxapram treatment than it was during caffeine or saline solution treatment.
Conclusions and Clinical Relevance—Results indicated that doxapram restored ventilation in a dose-dependent manner in neonatal foals with isoflurane-induced hypercapnia. The effects of caffeine on respiratory function were indistinguishable from those of saline solution.
Objective—To determine the pharmacokinetics of
azithromycin and its concentration in body fluids and
bronchoalveolar lavage cells in foals.
Animals—6 healthy 6- to 10-week-old foals.
Procedure—Azithromycin (10 mg/kg of body weight)
was administered to each foal via IV and intragastric
(IG) routes in a crossover design. After the first IG
dose, 4 additional IG doses were administered at 24-hour intervals. A microbiologic assay was used to
measure azithromycin concentrations in serum, peritoneal
fluid, synovial fluid, pulmonary epithelial lining
fluid (PELF), and bronchoalveolar (BAL) cells.
Results—Azithromycin elimination half-life was 20.3
hours, body clearance was 10.4 ml/min·kg, and apparent
volume of distribution at steady state was 18.6
L/kg. After IG administration, time to peak serum concentration
was 1.8 hours and bioavailability was 56%.
After repeated IG administration, peak serum concentration
was 0.63 ± 0.10 µg/ml. Peritoneal and synovial
fluid concentrations were similar to serum concentrations.
Bronchoalveolar cell and PELF concentrations
were 15- to 170-fold and 1- to 16-fold higher than concurrent
serum concentrations, respectively. No
adverse reactions were detected after repeated IG
Conclusions and Clinical Relevance—On the basis
of pharmacokinetic values, minimum inhibitory concentrations
of Rhodococcus equi isolates, and drug
concentrations in PELF and bronchoalveolar cells, a
single daily oral dose of 10 mg/kg may be appropriate
for treatment of R equi infections in foals. Persistence
of high azithromycin concentrations in PELF and bronchoalveolar
cells 48 hours after discontinuation of
administration suggests that after 5 daily doses, oral
administration at 48-hour intervals may be adequate.
(Am J Vet Res 2001;62:1870–1875)
Objective—To evaluate WBC concentration, plasma
fibrinogen concentration, and an agar gel immunodiffusion
(AGID) test for early identification of Rhodococcus
Animals—162 foals from a farm with enzootic R equi
Procedure—Blood samples were obtained from
each foal at 4-week intervals for measurement of
WBC and plasma fibrinogen concentrations and at
2-week intervals for detection of anti-R equi antibody
by an AGID assay. Diagnostic performance of
WBC and fibrinogen concentrations was assessed
by use of receiver operating characteristic curve
analysis. For each assay, sensitivity, specificity, and
predictive values were calculated at various cutoff
points; bacteriologic culture of R equi from a tracheobronchial
aspirate was used as the reference
Results—Diagnostic performance of WBC concentration
was significantly higher than that of fibrinogen
concentration. Sensitivity and specificity of measurement
of WBC concentration at a cutoff of 13,000
cells/µL were 95.2 and 61.2%, respectively; at a cutoff
of 15,000 cells/µL, sensitivity was 78.6% and
specificity was 90.8%. When a positive test result
was used as the cutoff, sensitivity of the AGID assay
was 62.5% and specificity was 53.8%.
Conclusion and Clinical Relevance—Monitoring WBC
concentration is a useful approach for early detection of
infected foals on farms with a high prevalence of R equi
pneumonia. In contrast, serologic surveillance by use of
an AGID assay is of little benefit for that purpose. (J Am
Vet Med Assoc 2003;222:775–781)
Objective—To determine the disposition of gamithromycin in plasma, pulmonary epithelial lining fluid (PELF), bronchoalveolar lavage (BAL) cells, and lung tissue homogenate in cattle.
Animals—33 healthy Angus calves approximately 7 to 8 months of age.
Procedures—Calves were randomly assigned to 1 of 11 groups consisting of 3 calves each, which differed with respect to sample collection times. In 10 groups, 1 dose of gamithromycin (6 mg/kg) was administered SC in the neck of each calf (0 hours). The remaining 3 calves were not treated. Gamithromycin concentrations in plasma, PELF, lung tissue homogenate, and BAL cells (matrix) were measured at various points by means of high-performance liquid chromatography with tandem mass spectrometry.
Results—Time to maximum gamithromycin concentration was achieved at 1 hour for plasma, 12 hours for lung tissue, and 24 hours for PELF and BAL cells. Maximum gamithromycin concentration was 27.8 μg/g, 17.8 μg/mL, 4.61 μg/mL, and 0.433 μg/mL in lung tissue, BAL cells, PELF, and plasma, respectively. Terminal half-life was longer in BAL cells (125.0 hours) than in lung tissue (93.0 hours), plasma (62.0 hours), and PELF (50.6 hours). The ratio of matrix to plasma concentrations ranged between 4.7 and 127 for PELF, 16 and 650 for lung tissue, and 3.2 and 2,135 for BAL cells.
Conclusions and Clinical Relevance—Gamithromycin was rapidly absorbed after SC administration. Potentially therapeutic concentrations were achieved in PELF, BAL cells, and lung tissue within 30 minutes after administration and persisted for 7 (PELF) to > 15 (BAL cells and lung tissue) days after administration of a single dose.
Objective—To compare cardiac output (CO) measured by lithium arterial pressure waveform analysis (PULSECO) and CO measured by transpulmonary pulse contour analysis (PICCO) in anesthetized foals, with CO measured by use of lithium dilution (LIDCO) considered the criterion-referenced standard.
Sample Population—6 neonatal (1- to 4-day-old) foals that weighed 38 to 45 kg.
Procedures—Foals were anesthetized and instrumented to measure direct blood pressure, heart rate, arterial blood gases, and CO. The CO was measured by use of PULSECO, PICCO, and LIDCO techniques. Measurements were converted to specific CO (sCO) values for statistical analysis. Measurements were obtained during low, intermediate, and high CO states.
Results—sCO ranged from 75.5 to 310 mL/kg/min. Mean ± SD PICCO bias varied significantly among CO states and was −51.9 ± 23.1 mL/kg/min, 20.0 ± 19.5 mL/kg/min, and 87.2 ± 19.5 mL/kg/min at low, intermediate, and high CO states, respectively. Mean PULSECO bias (11.0 ± 37.5 mL/kg/min) was significantly lower than that of PICCO and did not vary among CO states. Concordance correlation coefficient between LIDCO and PULSECO was significantly greater than that between LIDCO and PICCO. The proportion of observations with a relative bias < ± 30% was significantly lower with the PULSECO method than with the PICCO method.
Conclusions and Clinical Relevance—Values for the PULSECO method were more reproducible and agreed better with values for the LIDCO method than did values for the PICCO method and were able to more accurately monitor changes in CO in anesthetized newborn foals.
Case Description—5 aged (≥ 17 years old) horses developed life-threatening Internal hemorrhage following IV administration of phenylephrine at 3 hospitals.
Clinical Findings—All 5 horses developed severe hemothorax, hemoabdomen, or both within minutes to hours following administration of phenylephrine.
Treatment and Outcome—Four of 5 horses died of hemorrhagic shock, and 1 horse survived with a blood transfusion. The exact source of hemorrhage was Identified In only 1 horse. Medical records of all horses with nephrosplenic entrapment of the large colon and treated with phenylephrine at the University of Florida Veterinary Medical Center between 2000 and 2008 (n = 74) were reviewed. Three of these 74 (4%) horses developed fatal hemorrhage (horses 1 through 3 of this report). The risk of developing phenylephrine-associated hemorrhage was 64 times as high (95% confidence interval, 3.7 to 1,116) in horses ≥ 15 years old than in horses < 15 years old.
Clinical Relevance—The potential risks versus benefits of phenylephrine administration should be evaluated carefully, especially In old horses. (J Am Vet Med Assoc 2010;237:830–834)
OBJECTIVE To determine pharmacokinetics and pulmonary disposition of minocycline in horses after IV and intragastric administration.
ANIMALS 7 healthy adult horses.
PROCEDURES For experiment 1 of the study, minocycline was administered IV (2.2 mg/kg) or intragastrically (4 mg/kg) to 6 horses by use of a randomized crossover design. Plasma samples were obtained before and 16 times within 36 hours after minocycline administration. Bronchoalveolar lavage (BAL) was performed 4 times within 24 hours after minocycline administration for collection of pulmonary epithelial lining fluid (PELF) and BAL cells. For experiment 2, minocycline was administered intragastrically (4 mg/kg, q 12 h, for 5 doses) to 6 horses. Plasma samples were obtained before and 20 times within 96 hours after minocycline administration. A BAL was performed 6 times within 72 hours after minocycline administration for collection of PELF samples and BAL cells.
RESULTS Mean bioavailability of minocycline was 48% (range, 35% to 75%). At steady state, mean ± SD maximum concentration (Cmax) of minocycline in plasma was 2.3 ± 1.3 μg/mL, and terminal half-life was 11.8 ± 0.5 hours. Median time to Cmax (Tmax) was 1.3 hours (interquartile range [IQR], 1.0 to 1.5 hours). The Cmax and Tmax of minocycline in the PELF were 10.5 ± 12.8 μg/mL and 9.0 hours (IQR, 5.5 to 12.0 hours), respectively. The Cmax and Tmax for BAL cells were 0.24 ± 0.1 μg/mL and 6.0 hours (IQR, 0 to 6.0 hours), respectively.
CONCLUSIONS AND CLINICAL RELEVANCE Minocycline was distributed into the PELF and BAL cells of adult horses.
OBJECTIVE To determine the effects of oral omeprazole administration on the fecal and gastric microbiota of healthy adult horses.
ANIMALS 12 healthy adult research horses.
PROCEDURES Horses were randomly assigned to receive omeprazole paste (4 mg/kg, PO, q 24 h) or a sham (control) treatment (tap water [20 mL, PO, q 24 h]) for 28 days. Fecal and gastric fluid samples were collected prior to the first treatment (day 0), and on days 7, 28, 35, and 56. Sample DNA was extracted, and bacterial 16S rRNA gene sequences were amplified and sequenced to characterize α and β diversity and differential expression of the fecal and gastric microbiota. Data were analyzed by visual examination and by statistical methods.
RESULTS Composition and diversity of the fecal microbiota did not differ significantly between treatment groups or over time. Substantial variation in gastric fluid results within groups and over time precluded meaningful interpretation of the microbiota in those samples.
CONCLUSIONS AND CLINICAL RELEVANCE Results supported that omeprazole administration had no effect on fecal microbiota composition and diversity in this group of healthy adult horses. Small sample size limited power to detect a difference if one existed; however, qualitative graphic examination supported that any difference would likely have been small and of limited clinical importance. Adequate data to evaluate potential effects on the gastric microbiota were not obtained. Investigations are needed to determine the effects of omeprazole in horses with systemic disease or horses receiving other medical treatments.
Case Description—A 4-year-old Thoroughbred mare was evaluated because of placental abnormalities and a retained placental remnant.
Clinical Findings—Microbial culture of the placenta yielded pure growth of Amycolatopsis spp. Histologic examination of the placenta revealed a focally expanding chorionitis with intralesional gram-positive filamentous bacilli and multifocal allantoic adenomatous hyperplasia on the apposing allantoic surface.
Treatment and Outcome—Treatment with lavage and oxytocin resulted in expulsion of the placental remnant within hours of parturition. The mare did not become pregnant again despite multiple breedings. The foal appeared healthy but died of complications during an elective surgical procedure at 7 weeks of age.
Conclusions and Clinical Relevance—To the author's knowledge, all previously confirmed cases of nocardioform placentitis have been in mares bred in the central Kentucky region. Indications that the pathogen in the mare reported here is a different species than that isolated in Kentucky suggest that this is an emerging disease. Mares with nocardioform placentitis usually do not have the same clinical signs as mares with placentitis resulting from an ascending pathogen.
To compare soil concentrations of macrolide- and rifampicin-resistant Rhodococcus equi strains (MRRE) on horse-breeding farms that used thoracic ultrasonographic screening (TUS) to identify foals with subclinical pneumonia combined with subsequent administration of macrolides and rifampin to affected foals (TUS farms) versus soil concentrations on farms that did not (non-TUS farms), determine whether the combined use of TUS and antimicrobial treatment of subclinically affected foals was associated with soil concentration of MRRE, and assess whether there were temporal effects on soil concentrations of MRRE during the foaling season.
720 soil samples and 20 completed questionnaires from 20 horse-breeding farms (10 TUS farms and 10 non-TUS farms) in central Kentucky.
A questionnaire was used to gather information from participating farms about their 2019 foaling season. Soil samples were collected during January, March, May, and July 2019 for bacterial culture and antimicrobial susceptibility testing to identify any isolates of MRRE. Results were compared for TUS farms versus non-TUS farms. Linear mixed-effects modeling was used to evaluate for potential associations between the soil concentration of MRRE and the use of TUS.
Overall, the sum of the mean soil concentrations of MRRE was significantly higher for TUS farms (8.85 log10-transformed CFUs/g) versus non-TUS farms (7.37 log10-transformed CFUs/g).
CONCLUSIONS AND CLINICAL RELEVANCE
Our findings indicated that farms that use TUS to identify foals with subclinical pneumonia for antimicrobial treatment select for antimicrobial-resistant R equi strains. Because prognosis is worse for foals infected with resistant versus nonresistant strains of R equi, prudent use of antimicrobials to treat foals with subclinical pulmonary lesions attributed to R equi is recommended.