Topical ropivacaine hydrochloride 0.5% and lidocaine hydrochloride 2% significantly reduce corneal sensitivity without short-term negative side effects in horses.

OBJECTIVE: To evaluate corneal sensitivity and acute side effects following application of ropivacaine hydrochloride 0.5% and lidocaine hydrochloride 2% on the healthy equine cornea. ANIMALS STUDIED: Eight healthy adult horses. PROCEDURE: A randomized, masked, crossover study design was utilized. Baseline Semiquantitative Preclinical Ocular Toxicology (SPOT) scores and corneal touch thresholds (CTT) using a Cochet-Bonnet esthesiometer were recorded and measured, respectively, for eight healthy adult horses before medication application. Commercially available eyewash was used as a negative control. Ropivacaine hydrochloride 0.5% or lidocaine hydrochloride 2% solution was sprayed on a randomly selected eye, and the contralateral eye received eyewash. CTT was measured in both eyes at 1, 5, 15, 25, 35, 45, 55, 65, and 75 min post-application. Post-application SPOT scores were recorded immediately following the trial. Linear mixed model statistical analyses (mean ± standard error) were performed (p < .05). RESULTS: Mean eyewash CTT (3.41 cm ± 0.464) was significantly different from ropivacaine-treated (1.44 cm ± 0.562) (p = .008) and lidocaine-treated eyes (1.75 cm ± 0.562) (p = .024); CTT was not significantly different between drug groups (p = .88). Time to maximum anesthesia was not significantly different between ropivacaine (13.25 min ± 3.353) and lidocaine (16.25 min ± 3.353) (p = .40). No side effects were appreciated as confirmed by SPOT. CONCLUSIONS: Ropivacaine and lidocaine similarly decreased corneal sensitivity when applied topically without clinically evident short-term ocular side effects. Lidocaine may be preferable in clinical settings due to its large, multi-use vials and similar effects to ropivacaine.

Effects of subconjunctival ropivacaine, liposomal bupivacaine, and mepivacaine on corneal sensitivity in healthy horses.

OBJECTIVE: To evaluate corneal sensitivity and adverse events following subconjunctival administration of three local anesthetics in horses. STUDY DESIGN: Randomized, masked, crossover study. ANIMALS: Twelve healthy adult mares. METHODS: The subconjunctival space of the treated eye was injected with 0.2 mL of liposomal bupivacaine (1.3%), ropivacaine (0.5%), or mepivacaine (2%). All horses received each medication once and the contralateral eye received saline (control). Corneal touch threshold (CTT) was measured using a Cochet-Bonnet esthesiometer before sedation, after sedation, and at specified intervals until it returned to baseline. Ocular examinations were performed at 24-, 72, and 168 h post-injection to monitor for adverse effects. RESULTS: The mean total time of anesthesia (TTA) was 168.3 min for ropivacaine, 169.2 min for liposomal bupivacaine, 103.3 min for mepivacaine and 30.7 min for the control. TTA for liposomal bupivacaine (p < .001) and ropivacaine (p = .001) was longer than the control. TTA for mepivacaine was not different from the control (p = .138), liposomal bupivacaine (p = .075) or ropivacaine (p = .150). Injection site hemorrhage reduced TTA regardless of treatments (p = .047). No adverse effects attributed to injections were noted. CONCLUSION: All three medications were well tolerated. Subconjunctival administration of ropivacaine and liposomal bupivacaine resulted in longer TTAs compared to the control; however, their TTAs were not different from that of mepivacaine. CLINICAL SIGNIFICANCE: Subconjunctivally administered liposomal bupivacaine and ropivacaine are viable options to provide prolonged corneal analgesia in horses. Future studies are needed to assess the efficacy in diseased eyes.

In vitro antibacterial efficacy of autologous conditioned plasma and amniotic membrane eye drops.

OBJECTIVE: To determine the in vitro antibacterial efficacy of equine and canine autologous conditioned plasma (ACP) and amniotic membrane extract eye drops (AMEED) against aerobic bacteria common to the corneal surface. PROCEDURES: Canine (n = 4) and equine (n = 4) anticoagulated whole blood samples were sterilely collected, pooled for each species, and processed using the Arthrex ACP® Double-Syringe System. Platelet counts were performed on ACP and pooled blood. AMEED were obtained from a commercial source. An electronic medical records search (2013-2022) identified aerobic bacteria cultured from canine and equine corneal ulcers at Mississippi State University College of Veterinary Medicine (MSU-CVM). Ten commonly isolated bacteria for each species were collected from cultures submitted to the MSU-CVM Microbiology Diagnostic Service and frozen at -80°C. The Kirby-Bauer disk diffusion method was used to determine the sensitivities of these isolates to ACP and AMEED. Bacterial isolates were plated onto Mueller-Hinton +5% sheep blood agar and blank sterile discs saturated with 20 µL of ACP or AMEED were tested in duplicate. Imipenem discs served as positive controls and blank discs as negative controls. Zones of inhibition were measured at 18 h. RESULTS: ACP platelet counts were 1.06 and 1.65 times higher than blood for equine and canine samples, respectively. Growth of a multi-drug resistant Enterococcus faecalis was partially inhibited by canine and equine ACP. AMEED did not inhibit growth of any examined bacteria. CONCLUSIONS: Canine and equine ACP partially inhibited E. faecalis growth in vitro. Further studies using varying concentrations of ACP against bacterial isolates from corneal ulcers are warranted.

Subconjunctival enucleation with orbital implant placement in standing horses: 20 cases (2014-2017).

OBJECTIVE: To develop a protocol for subconjunctival enucleation and orbital implant placement in standing horses and to document short- and long-term complications, cosmesis, and client satisfaction. ANIMALS: 20 horses with nonneoplastic ocular disease requiring enucleation. PROCEDURES: A standardized protocol of surgical suite cleaning, patient preparation, sedation, local nerve blocks, surgical procedure, and postoperative care was performed. Owners were required to provide follow-up information at 1 year after surgery during a phone questionnaire. Additionally, some owners provided follow-up information at 1.8 to 4 years postoperatively. RESULTS: 11 mares, 6 geldings, and 3 stallions with a mean age of 9 years (range, 0.5 to 25 years) were included in this study. Reasons for enucleation included corneal lacerations (n = 3), perforated ulcers (4), end-stage uveitis (7), fungal keratitis (3), endophthalmitis (1), glaucoma (1), and stromal abscess (1). The mean surgery time was 64 minutes (range, 50 to 83 minutes). The most common implant size used was 45-mm diameter (range, 43- to 47-mm diameter). Complications included mild postoperative colic (n = 4), incisional swelling (1), and drainage from the surgical site (1) that resolved without implant removal. One-year follow-up information was available for 19 of 20 horses. Fourteen owners were very satisfied and 5 owners were satisfied with the cosmetic appearance. One horse was lost to follow-up. CONCLUSIONS AND CLINICAL RELEVANCE: Subconjunctival enucleation and orbital implant placement in standing horses was a safe and efficient alternative to general anesthesia when a standardized perioperative protocol was used. No horse developed clinically relevant complications, and owner satisfaction and cosmesis were good.

Pharmacokinetics and pharmacodynamics of intravenous continuous rate infusion and repeated intramuscular administration of dexmedetomidine in standing horses.

An ideal dexmedetomidine protocol has yet to be determined for standing sedation in horses. It was hypothesized that an IV bolus followed by CRI dexmedetomidine would have a quicker increase in plasma concentrations compared with repeated IM injections. In a crossover design, eight adult, female horses were randomly placed into two groups: the CRI group (IV bolus dexmedetomidine at 0.005 mg/kg followed by a CRI at 0.01 mg/kg/h for 15 min then 0.005 mg/kg/h for 60 min) and the IM group (dexmedetomidine at 0.01 mg/kg, followed by 0.005 mg/kg in 30-min intervals for 60 min). Clearance and elimination half-life were 134 ± 67.4 ml/kg/min and 44.3 ± 26.3 min, respectively, in the CRI group, and apparent clearance and half-life were 412 ± 306 ml/kg/min (Cl/F) and 38.9 ± 18.6 min, respectively, in the IM group. Analgesia was evaluated using mechanical pressure threshold. Intravenous dexmedetomidine produced faster onset of sedation and increased pressure threshold compared with IM administration. Individual horses had a large variability in dexmedetomidine plasma concentrations between CRI and IM administration. The odds of a decreased GI motility following IV administration was 12.34 times greater compared with IM administration.

Retrospective Evaluation of Fluoxetine Hydrochloride Use in Horses: 95 Cases (2010-2019).

This study aimed to describe the clinical use of oral fluoxetine hydrochloride administration in horses using a retrospective medical records analysis and to determine owner perception of efficacy via a standardized questionnaire. The records of ninety-five horses for which fluoxetine had been prescribed by the equine service of a veterinary teaching hospital from November 2010 and February 2019 were identified, and data were collected from the medical records. A standardized questionnaire was used to obtain data from owners regarding length of administration, ease of administration, adverse effects, and whether the owner noted improvement in the horse's behavior. Ninety-five horses received fluoxetine during the study period. Fluoxetine was prescribed to facilitate stall rest in 68 horses (Group A) and for behavior-related problems in 27 horses (Group B). The mean dosage was 0.25 mg/kg (range 0.15-0.54). Forty-seven of the 66 owners (71%) that completed the follow-up questionnaire reported a perceived improvement in the animal's behavior (29/41 in Group A and 18/25 in Group B). Fifty-eight owners (88%) reported that they felt the medication was easy to administer. When used to facilitate extended stall confinement, fluoxetine appears to be perceived as efficacious by most owners. Although the number of behavioral cases was low, the results indicate that the drug may also be useful for some problem behaviors. Further controlled behavioral studies are needed to investigate the use of fluoxetine for equine behavioral problems.

Synovial butorphanol concentrations and mechanical nociceptive thresholds after intravenous regional limb perfusion in standing sedated horses.

OBJECTIVE: To determine synovial butorphanol concentrations and mechanical nociceptive threshold (MNT) changes after butorphanol intravenous regional limb perfusion (IVRLP). STUDY DESIGN: Experimental ANIMALS: Six adult horses. METHODS: Cephalic IVRLP was performed with 10 mg butorphanol in sedated horses with a wide rubber tourniquet and a total volume of 30 mL. Radiocarpal synovial fluid and serum concentrations along with MNT were evaluated prior to and 0.5, 1, 2, 4, and 6 hours after IVRLP. Butorphanol concentrations were determined with liquid chromatography coupled to tandem mass spectrometry positive electrospray ionization. RESULTS: Butorphanol concentrations reached mean (SD) peak concentrations of 9.47 ng/mL (±12.00) in synovial fluid and 3.89 ng/mL (3.29) in serum 30 minutes after IVRLP. Concentrations remained above baseline for 4 hours in synovial fluid (P ≤ .017) and for 2 hours in serum (P ≤ .016). The only difference in MNT was detected 1 hour after IVRLP, when MNT were higher in controls than in treated horses (P = .047). CONCLUSION: Butorphanol IVRLP seemed well tolerated and resulted in measurable levels of butorphanol in the radiocarpal synovial fluid of five of six horses. CLINICAL SIGNIFICANCE: Intravenous regional limb perfusion appears to be a viable alternative to administer butorphanol, but additional investigation is required to evaluate the dose and local concentrations required for analgesia.

Plasma and synovial fluid pharmacokinetics of a single intravenous dose of meropenem in adult horses.

The objective of this study was to determine the pharmacokinetics of meropenem in horses after intravenous (IV) administration. A single IV dose of meropenem was administered to six adult horses at 10 mg/kg. Plasma and synovial fluid samples were collected for 6 hr following administration. Meropenem concentrations were determined by bioassay. Plasma and synovial fluid data were analyzed by compartmental and noncompartmental pharmacokinetic methods. Mean ± SD values for elimination half-life, volume of distribution at steady-state, and clearance after IV administration for plasma samples were 0.78 ± 0.176 hr, 136.1 ± 19.69 ml/kg, and 165.2 ± 29.72 ml hr-1  kg-1 , respectively. Meropenem in synovial fluid had a slower elimination than plasma with a terminal half-life of 2.4 ± 1.16 hr. Plasma protein binding was estimated at 11%. Based on a 3-compartment open pharmacokinetic model of simultaneously fit plasma and synovial fluid, dosage simulations were performed. An intermittent dosage of meropenem at 5 mg/kg IV every 8 hr or a constant rate IV infusion at 0.5 mg/kg per hour should maintain adequate time above the MIC target of 1 µg/ml. Carbapenems are antibiotics of last resort in humans and should only be used in horses when no other antimicrobial would likely be effective.

Meropenem synovial fluid concentrations after intravenous regional limb perfusion in standing horses.

OBJECTIVE: To determine meropenem concentrations in radiocarpal (RC) joint fluid and plasma after intravenous regional limb perfusion (IVRLP). STUDY DESIGN: In vivo experimental study. ANIMALS: Nine healthy adult mares. METHODS: Meropenem (500 mg) was injected in the forelimb of standing sedated horses via IVRLP with a pneumatic tourniquet inflated to 400 mmHg. Synovial fluid was collected from RC joints at 0, 0.5, 1, 2, 4, 6, 8, 12, and 18 hours after meropenem injection. Blood samples were collected from the jugular vein at the same time points and at 5 and 15 minutes following injection. Meropenem concentrations were determined by using a microbiological bioassay. RESULTS: Median synovial fluid concentrations reached a time of maximum synovial fluid concentration 0.5 hours after IVRLP. Synovial fluid concentrations varied greatly, with a mean maximum synovial fluid concentration of 25.6 µg/mL (range, below limit of quantitation to 75.5). Concentrations remained above the breakpoint for susceptibility (1 µg/mL) for 3 hours (last nonzero concentration measured, median) and 4.1 hours (predicted, mean). Concentrations >6 µg/mL were measured for 2 hours (observed, median) and 1.7 hours (predicted, mean). Six horses had mild swelling at the injection site. CONCLUSION: Administration of 500 mg meropenem resulted in highly variable concentrations between horses and achieved levels above clinically relevant minimum inhibitory concentration for a minor portion of a once-daily dosing interval. CLINICAL SIGNIFICANCE: If time-dependent pharmacodynamics apply, IVRLP with 500 mg of meropenem may be ineffective and would likely promote resistance.

The effects of subconjunctival bupivacaine, lidocaine, and mepivacaine on corneal sensitivity in healthy horses.

OBJECTIVE: To compare the efficacy and duration of effect of three local anesthetics on corneal sensitivity when administered subconjunctivally in horses. ANIMALS STUDIED: Eight healthy adult horses. PROCEDURE: A randomized, masked, crossover study design was used, with a two-week washout period between trials. The subconjunctival space of the randomly selected eye was injected with 0.2 mLs of bupivacaine (0.5%), lidocaine (2%), mepivacaine (2%), or saline. All horses received each medication once. The contralateral eye served as a control. The corneal touch threshold (CTT) was measured in both eyes with a Cochet-Bonnet esthesiometer prior to sedation with xylazine, after sedation, and at 10-min intervals after subconjunctival injection until corneal sensitivity returned to baseline. The total time of decreased CTT and the maximum decrease in CTT were compared for each medication using a general linear mixed model (P < 0.05). RESULTS: Total time of decreased CTT was 105.0 min for bupivacaine, 103.8 min for lidocaine, 138.8 min for mepivacaine, and 7.5 min for saline. All local anesthetics decreased CTT longer than saline (P < 0.001) and mepivacaine decreased CTT longer than lidocaine (P = 0.04). The mean minimum CTT was 1.67 cm for bupivacaine, 1.42 cm for lidocaine, and 0.73 cm for mepivacaine, which were all significantly less (P < 0.001) than saline (4.73 cm). No evidence of corneal toxicity was noted with any treatment. CONCLUSION: Subconjunctival injections of lidocaine, bupivacaine, and mepivacaine effectively and safely reduce corneal sensitivity in eyes of healthy horses for 1.5-2 h, and may be useful for providing perioperative analgesia for equine corneal procedures.

Effects of Firocoxib, Flunixin Meglumine, and Phenylbutazone on Platelet Function and Thromboxane Synthesis in Healthy Horses.

OBJECTIVE: Determine the effects of nonsteroidal anti-inflammatory drugs (NSAID) on platelet function and thromboxane synthesis immediately after drug administration and following 5 days of NSAID administration in healthy horses. STUDY DESIGN: Randomized cross-over study. ANIMALS: Healthy adult horses (n=9; 6 geldings and 3 mares). METHODS: Horses received either flunixin meglumine (1.1 mg/kg IV every 12 hours), phenylbutazone (2.2 mg/kg IV every 12 hours), or firocoxib (loading dose of 0.27 mg/kg IV on day 1, then 0.09 mg/kg IV every 24 hours for 4 days) for a total of 5 days. Blood samples were collected prior to drug administration (day 0), 1 hour after initial NSAID administration (day 1), and then 1 hour post-NSAID administration on day 5. Platelet function was assessed using turbidimetric aggregometry and a platelet function analyzer. Serum thromboxane B2 concentrations were determined by commercial ELISA kit. A minimum 14 day washout period occurred between trials. RESULTS: At 1 hour and 5 days postadministration of firocoxib, flunixin meglumine, or phenylbutazone, there was no significant effect on platelet aggregation or function using turbidimetric aggregometry or a platelet function analyzer. There was, however, a significant decrease in thromboxane synthesis at 1 hour and 5 days postadministration of flunixin meglumine and phenylbutazone that was not seen with firocoxib. CONCLUSION: Preoperative administration of flunixin meglumine, phenylbutazone, or firocoxib should not inhibit platelet function based on our model. The clinical implications of decreased thromboxane B2 synthesis following flunixin meglumine and phenylbutazone administration are undetermined.

Simple tube centrifugation for processing platelet-rich plasma in the horse.

This study evaluated the quality and bacteriologic safety of platelet-rich plasma (PRP) produced by 3 simple, inexpensive tube centrifugation methods and a commercial system. Citrated equine blood collected from 26 normal horses was processed by 4 methods: blood collection tubes centrifuged at 1200 and 2000 × g, 50-mL conical tube, and a commercial system. White blood cell (WBC), red blood cell (RBC), and platelet counts and mean platelet volume (MPV) were determined for whole blood and PRP, and aerobic and anaerobic cultures were performed. Mean platelet concentrations ranged from 1.55- to 2.58-fold. The conical method yielded the most samples with platelet concentrations greater than 2.5-fold and within the clinically acceptable range of > 250,000 platelets/µL. White blood cell counts were lowest with the commercial system and unacceptably high with the blood collection tubes. The conical tube method may offer an economically feasible and comparatively safe alternative to commercial PRP production systems.

Centrifugation en tube pour le traitement du plasma riche en plaquettes chez le cheval. Cette étude a évalué la qualité et l'innocuité bactériologique du plasma riche en plaquettes (PRP) produit par 3 méthodes simples et économiques de centrifugation en tube et un système commercial. Du sang équin citraté prélevé de 26 chevaux normaux a été traité à l'aide de 4 méthodes : des tubes de prélèvement du sang centrifugés à 1200 et à 2000 × g, un tube conique de 50 ml et un système commercial. La numération des globules blancs, des globules rouges et des plaquettes ainsi que le volume moyen des plaquettes ont été déterminés pour le sang total et le PRP et des cultures bactériennes en aérobiose et en anaérobiose ont été réalisées. Les concentrations moyennes des plaquettes s'échelonnaient d'un ordre de grandeur variant de 1,55 à 2,58. La méthode conique a donné le plus d'échantillons avec des concentrations de plaquettes supérieures à un ordre de 2,5 et dans la fourchette cliniquement acceptable de > 250 000 plaquettes/µL. La numération des globules blancs était la plus basse avec le système commercial et était trop élevée par la méthode avec les tubes de prélèvement du sang. La méthode du tube conique peut offrir une méthode de remplacement abordable et d'innocuité comparable aux systèmes de production commerciaux de PRP.(Traduit par Isabelle Vallières).