Evaluation of Nasal Oxygen Administration at Various Flow Rates and Concentrations in Conscious, Standing Adult Horses.

This study evaluated the effects of various flow rates and fractions of oxygen on arterial blood gas parameters and on the fraction of inspired oxygen (FIO2) delivered to the distal trachea. Oxygen was administered to 6 healthy, conscious, standing, adult horses via single nasal cannula positioned within the nasopharynx. Three flow rates (5, 15, 30 L/min) and fractions of oxygen (21, 50, 100%) were delivered for 15 minutes, each in a randomized order. FIO2 was measured at the level of the nares and distal trachea. Adverse reactions were not observed with any flow rate. FIO2 (nares and trachea) and PaO2 increased with increasing flow rate and fraction of oxygen (P < .0001). FIO2 (trachea) was significantly less than FIO2 (nares) at 50% and 100% oxygen at all flow rates (P < .0001). Differences in PaO2 were not observed between 100% oxygen-5L/min and 50% oxygen-15L/min and or between 100% oxygen-15L/min and 50% oxygen-30L/min. Tracheal FIO2 for 100% oxygen-15L/min was increased compared to 50% oxygen-30L/min (P < .0001). Respiratory rate, ETCO2, PaCO2, and pH did not differ between treatments. Administration of 50% oxygen via nasal cannula at 15 and 30 L/min effectively increased in PaO2 and was well tolerated in conscious, standing, healthy horses. While these results can be used guide therapy in hypoxemic horses, evaluation of the administration of 50% oxygen to horses with respiratory disease is warranted.

Effects of a single dose of orally and rectally administered misoprostol in an in vivo endotoxemia model in healthy adult horses.

OBJECTIVE: To describe misoprostol pharmacokinetics and anti-inflammatory efficacy when administered orally or per rectum in endotoxin-challenged horses. ANIMALS: 6 healthy geldings. PROCEDURES: A randomized 3-treatment crossover design was performed with a minimum washout period of 28 days between treatment arms. Prior to endotoxin challenge (lipopolysaccharide, 30 ng/kg IV over 30 minutes), horses received misoprostol (5 µg/kg once) per os (M-PO) or per rectum (M-PR) or water as control (CON). Clinical parameters were evaluated and blood samples obtained to measure plasma misoprostol free acid concentration, leukocyte counts, and tumor necrosis factor-α (TNFα) and interleukin 6 (IL-6) leukocyte gene expression and serum concentrations. RESULTS: In the M-PO treatment arm, maximum plasma concentration and area under the concentration-versus-time curve (mean ± SD) were higher (5,209 ± 3,487 pg/mL and 17,998,254 ± 13,194,420 h·pg/mL, respectively) and median (interquartile range) time to maximum concentration (25 min [18 to 34 min]) was longer than in the M-PR treatment arm (854 ± 855 pg/mL; 644,960 ± 558,866 h·pg/mL; 3 min [3 to 3.5 min]). Significant differences in clinical parameters, leukocyte counts, and TNFα or IL-6 gene expression or serum protein concentration were not detected. Downregulation of relative gene expression was appreciated for individual horses in the M-PO and M-PR treatment arms at select time points. CLINICAL RELEVANCE: Considerable variability in measured parameters was detected among horses within and between treatment arms. Misoprostol absorption and systemic exposure after PO administration differed from previous reports in horses not administered LPS. Investigation of multidose administration of misoprostol is warranted to better evaluate efficacy as an anti-inflammatory therapeutic.

The Effect of Inhaled Albuterol on PaO2 in Anesthetized Horses Receiving a FiO2 of 0.5 or >0.95.

Impairment of oxygen uptake can occur during general anesthesia in horses resulting in hypoxemia. Multiple treatments have been investigated for correction of hypoxemia with varying levels of success. In clinical trials, albuterol, a short-acting ß2 adrenergic agonist, improved arterial oxygen partial pressure (PaO2) in anesthetized horses unresponsive to adjustments in mechanical ventilation and administration of positive inotropic drugs. However, controlled studies comparing the magnitude of change and duration of effect of albuterol on PaO2 in healthy, nonhypoxemic anesthetized horses are lacking. In a prospective study, 14 horses were anesthetized and received a FiO2 of 0.5 (n = 7) or > 0.95 (n = 7). Horses were maintained on isoflurane and mechanically ventilated. After 15 minutes, baseline PaO2 was determined. Within each FiO2 group, five horses were administered inhaled albuterol (2 µg/kg) and two horses received no treatment. At 10, 20, 30, and 40 minutes after baseline, PaO2 was measured. Data for horses that received albuterol were analyzed with repeated measures analysis of variance with significance at P < .05. Horses that received albuterol had an increase in PaO2 for at least 40 minutes after baseline. Albuterol administered via inhalation, was associated with an increased PaO2 of at least 40 minutes compared to baseline in healthy, nonhypoxemic horses undergoing anesthesia at similar depth, using a FiO2 of 0.5 and > 0.95. Side effects were mild and consisted of increased heart rate and sweating. Albuterol administered at 2 µg/kg via inhalation may be useful for increasing PaO2 in anesthetized horses.

Quantitative assessment of left ventricular volume and function by transthoracic and transesophageal echocardiography, ultrasound velocity dilution, and gated magnetic resonance imaging in healthy foals.

OBJECTIVE: To compare measurements of left ventricular volume and function derived from 2-D transthoracic echocardiography (2DE), transesophageal echocardiography (TEE), and the ultrasound velocity dilution cardiac output method (UDCO) with those derived from cardiac MRI (cMRI) in healthy neonatal foals. ANIMALS: 6 healthy 1-week-old Standardbred foals. PROCEDURES: Foals were anesthetized and underwent 2DE, TEE, and cMRI; UDCO was performed simultaneously with 2DE. Images acquired by 2DE included the right parasternal 4-chamber (R4CH), left apical 4- and 2-chamber (biplane), and right parasternal short-axis M-mode (M-mode) views. The longitudinal 4-chamber view was obtained by TEE. Measurements assessed included left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), ejection fraction, stroke volume (LVSV), cardiac output (CO), and cardiac index (CI). Bland-Altman analyses were used to compare measurements derived from biplane, R4CH, and M-mode images and UDCO with cMRI-derived measurements. Repeatability of measurements calculated by 3 independent reviewers was assessed by the intraclass correlation coefficient. RESULTS: Compared with cMRI, all 2DE and TEE modalities underestimated LVEDV and LVESV and overestimated ejection fraction, CO, and CI. The LVSV was underestimated by the biplane, R4CH, and TEE modalities and overestimated by UDCO and M-mode methods. However, the R4CH-derived LVSV, CO, and CI were clinically comparable to cMRI-derived measures. Repeatability was good to excellent for measures derived from the biplane, R4CH, M-mode, UDCO, and cMRI methods and poor for TEE-derived measures. CONCLUSIONS AND CLINICAL RELEVANCE: All assessed modalities yielded clinically acceptable measurements of LVEDV, LVESV, and function, but those measurements should not be used interchangeably when monitoring patient progress.

Clinical Feasibility and Airway Deposition of Nebulized Voriconazole in Healthy Horses.

Voriconazole (VRC) is a potential treatment for pneumomycosis in horses. The objectives of this study were to determine if the delivery of Vfend using a Flexineb nebulizer produced clinically significant [VRC] in lower airways. The hypothesis was that [VRC] after delivery by nebulization would be greater in the pulmonary epithelial lining fluid than plasma. A secondary objective was to determine [VRC] in upper airways through the collection of nasopharyngeal wash (NPW) samples. Voriconazole solution [Vfend-6.25 mg/mL, 100 (n = 2), 200 (n = 3), 500 (n = 1) mg] was nebulized once in 6 healthy geldings. Clinical responses, duration of nebulization, and [VRC] at various time points (up to 8 hours) in plasma, bronchoalveolar lavage fluid (BALF) supernatant and cell pellet, and NPW samples were recorded. Voriconazole (Vfend-6.25 mg/mL, 200 mg) was nebulized in 5 additional, healthy geldings, and [VRC] was measured in NPW samples pre- and postnebulization at time points up to 8 hours. The antifungal activity of BALF and NPW samples was determined using agar disk diffusion. Concentrations of voriconazole were below detection in plasma, BALF supernatant, and cell pellets for all time points and doses except the BALF cell pellet (0.4 µg/g) immediately after nebulization of 500 mg. For 5 horses, administered 200 mg of Vfend, mean [VCR] in NPW at the end of nebulization and 1, 6, and 8 hours postnebulization were: 30.8 ± 29, 1.0 ± 0.84, 0.2 ± 0.19, and 0.34 ± 0.67 µg/mL, respectively. Only NPW samples obtained immediately postnebulization showed antifungal activity. A nebulized Vfend solution is not recommended for the treatment of pneumomycosis in horses.

Tensile strength and early healing of self-locking and surgeon's knots.

OBJECTIVE: To compare the biomechanical properties and healing of ventral midline celiotomies (VMC) closed with a self-locking knot combination and forwarder start and Aberdeen end (F-A) vs a traditional knot combination and surgeon's start and end (S-S). STUDY DESIGN: In vivo, experimental. ANIMALS: Twenty-one horses. METHODS: Fourteen horses underwent VMC, which was closed with either an F-A (n = 7) or an S-S (n = 7) knot combination. Incisions were subjectively graded by masked evaluators for dehiscence, edema, and drainage. Biomechanical testing was performed on three abdominal segments, and histology was performed on one segment from each animal after humane euthanasia 10 days post-VMC. The abdominal wall of control horses (n = 7, no celiotomy) was collected for biomechanical testing. RESULTS: Forwarder start and Aberdeen end and S-S horses had less tensile strength compared with control horses (P ≤ .001). No differences were detected between treatment groups for any variable evaluated, including tensile strength (P = .975), location of failure (P = .240), and histologic healing at the knot (P = .600). CONCLUSION: Closure of VMC with self-locking knots resulted in biomechanical and healing features similar to those with a traditional closure technique, with neither restoring the tensile strength of the linea alba. CLINICAL SIGNIFICANCE: Results of this study provide evidence to support a clinical trial to evaluate long-term performance of the F-A self-locking knot closure in horses.

Pharmacokinetics and pharmacodynamics of hydromorphone hydrochloride in healthy horses.

OBJECTIVES: To determine the physiologic and behavioral effects and pharmacokinetic profile of hydromorphone administered intravenously (IV) to horses. STUDY DESIGN: Prospective, randomized, crossover study. ANIMALS: A group of six adult healthy horses weighing 585.2 ± 58.7 kg. METHODS: Each horse was administered IV hydromorphone (0.025 mg kg-1; treatment H0.025), hydromorphone (0.05 mg kg-1; treatment H0.05) or 0.9% saline in random order with a 7 day washout period. For each treatment, physiologic, hematologic, abdominal borborygmi scores and behavioral data were recorded over 5 hours and fecal output was totaled over 24 hours. Data were analyzed using repeated measures anova with significance at p < 0.05. Blood samples were collected in treatment H0.05 for quantification of plasma hydromorphone and hydromorphone-3-glucuronide and subsequent pharmacokinetic parameter calculation. RESULTS: Hydromorphone administration resulted in a dose-dependent increase in heart rate (HR) and systolic arterial pressure (SAP). HR and SAP were 59 ± 17 beats minute-1 and 230 ± 27 mmHg, respectively, in treatment H0.05 at 5 minutes after administration. No clinically relevant changes in respiratory rate, arterial gases or temperature were observed. The borborygmi scores in both hydromorphone treatments were lower than baseline values for 2 hours. Fecal output did not differ among treatments and no evidence of abdominal discomfort was observed. Recorded behaviors did not differ among treatments. For hydromorphone, mean ± standard deviation for volume of distribution at steady state, total systemic clearance and area under the curve until the last measured concentration were 1.00 ± 0.29 L kg-1, 106 ± 21 mL minute-1 kg-1 and 8.0 ± 1.5 ng hour mL-1, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Hydromorphone administered IV to healthy horses increased HR and SAP, decreased abdominal borborygmi and did not affect fecal output.

Cardiopulmonary effects and recovery characteristics of horses anesthetized with xylazine-ketamine with midazolam or propofol.

OBJECTIVE: To evaluate cardiopulmonary and recovery characteristics of horses administered total intravenous anesthesia (TIVA) with xylazine and ketamine combined with midazolam or propofol. STUDY DESIGN: Randomized crossover study. ANIMALS: A group of eight adult horses, aged 7-22 years, weighing 493-740 kg. METHODS: Horses were administered xylazine (1 mg kg-1) intravenously (IV), and anesthesia was induced with ketamine (2.2 mg kg-1) IV. Anesthesia was maintained for 45 minutes via IV infusion of xylazine (0.016 mg kg-1 minute-1) and ketamine (0.03 mg kg-1 minute-1) combined with midazolam at 0.002 mg kg-1 minute-1 (MKX), propofol at 0.05 mg kg-1 minute-1 (PKXlow) or propofol at 0.1 mg kg-1 minute-1 (PKXhigh). Additional ketamine was administered if a horse moved spontaneously. Cardiopulmonary variables, blood gases, lactate concentration, packed cell volume and total solids were recorded before sedation (baseline), at 10, 20, 30 and 45 minutes during TIVA and 10 minutes after standing. Recovery variables and quantitative recovery scores were compared. Significance was set at p < 0.05. RESULTS: Additional ketamine was required for 50% of MKX horses. Systolic arterial pressure was elevated in MKX at 20 minutes compared with baseline (p = 0.043), at 10 and 20 minutes compared with PKXhigh (p = 0.007, p = 0.024) and at 20 and 30 minutes compared with PKXlow (p = 0.009, p = 0.02). MKX horses (5/8) were hypertensive compared with PKXlow (1/8; p = 0.017). All horses became hypoxemic (PaO2 ≤80 mmHg; 10.7 kPa) during TIVA. Recovery variables did not differ among treatments. CONCLUSIONS AND CLINICAL RELEVANCE: PKXlow and PKXhigh had similar cardiopulmonary and recovery performance compared with MKX. PKX combinations provided superior quality of anesthesia to that of MKX. A combination of propofol, ketamine and xylazine administered as TIVA can be used in horses to provide anesthesia for short procedures. Supplemental oxygen is recommended.

Pulmonary disposition and pharmacokinetics of minocycline in adult horses.

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.

Assessment of agreement among diplomates of the American College of Veterinary Anesthesia and Analgesia for scoring the recovery of horses from anesthesia by use of subjective grading scales and development of a system for evaluation of the recovery of horses from anesthesia by use of accelerometry.

OBJECTIVE To evaluate agreement among diplomates of the American College of Veterinary Anesthesia and Analgesia for scores determined by use of a simple descriptive scale (SDS) or a composite grading scale (CGS) for quality of recovery of horses from anesthesia and to investigate use of 3-axis accelerometry (3AA) for objective evaluation of recovery. ANIMALS 12 healthy adult horses. PROCEDURES Horses were fitted with a 3AA device and then were anesthetized. Eight diplomates evaluated recovery by use of an SDS, and 7 other diplomates evaluated recovery by use of a CGS. Agreement was tested with κ and AC1 statistics for the SDS and an ANOVA for the CGS. A library of mathematical models was used to map 3AA data against CGS scores. RESULTS Agreement among diplomates using the SDS was slight (κ = 0.19; AC1 = 0.22). The CGS scores differed significantly among diplomates. Best fit of 3AA data against CGS scores yielded the following equation: RS = 9.998 × SG0.633 × ∑UG0.174, where RS is a horse's recovery score determined with 3AA, SG is acceleration of the successful attempt to stand, and ∑UG is the sum of accelerations of unsuccessful attempts to stand. CONCLUSIONS AND CLINICAL RELEVANCE Subjective scoring of recovery of horses from anesthesia resulted in poor agreement among diplomates. Subjective scoring may lead to differences in conclusions about recovery quality; thus, there is a need for an objective scoring method. The 3AA system removed subjective bias in evaluations of recovery of horses and warrants further study.