The effect of systemic acetazolamide administration on intraocular pressure in healthy horses-A preliminary study.

OBJECTIVES: In equine glaucoma, topical treatment with carbonic anhydrase inhibitors (CAIs) is recommended. Oral acetazolamide, a systemic CAI, is used in horses with hyperkalemic periodic paralysis. Information regarding its effect on equine intraocular pressure (IOP) is scarce. The aim of the study was to determine the effect of oral acetazolamide treatment on IOP in horses, in a case-control study. ANIMALS: Ten healthy horses. PROCEDURES: Horses were treated with oral acetazolamide (4.4 mg/kg) BID for 1 week. Serum acetazolamide concentrations were determined by liquid chromatography/tandem mass spectrometry, and IOP were measured before treatment, daily during treatment, and at 48 and 72 h after treatment. RESULTS: Acetazolamide serum levels reached steady state at 72 h after the first oral dose. In a mixed effect model logistic regression, there was a significant decrease in IOP on the third treatment day, of 2.4 mmHg (p = .012) and 2.7 mmHg (p = .006) in the left (OS) and right eye (OD), respectively. On the seventh day, there was a decrease in 2.5 mmHg (p = .008) and 2.7 mmHg (p = .007) OS and OD, respectively. A significant increase occurred 48 h following treatment discontinuation (3.6 mmHg, p < .001 and 3.5 mmHg, p < .001 OS and OD, respectively). The area under the concentration versus time curve (AUC(0-10h)) was 1.1 ± 0.5 µg/mL*h, mean residence time 6.7 ± 4.3 h, peak plasma concentration (Cmax) 0.4 ± 0.4 µg/mL and time to reach Cmax 1.8 h. There was a significant increase in serum concentrations 1, 2, 48, 72, and 156 h following the first drug administration (p < .05). CONCLUSIONS: Further studies are required to determine whether acetazolamide is a potential treatment for equine glaucoma.

Trimethoprim-sulfonamide: a valid antimicrobial treatment in foals?

Trimethoprim-sulfonamide (TMPS) combinations are widely used to treat a range of infectious diseases in horses, but some equine practitioners are reluctant to use them for treatment of both neonatal and older foals. Considering the emergence of increased antimicrobial resistance, the use of protected antimicrobials commonly prescribed to foals should be avoided and alternative first-line therapy considered, where appropriate. This review examines the characteristics and pharmacokinetics of TMPS and its suitability for treatment of foals. Data regarding dosage and route of administration are reported on the basis of recent publications in foals. The review intends to share significant information about the common infections that are most likely responsive to TMPS treatment in foals and, as such, where TMPS might be considered a suitable first-line therapeutic option.

Concentration of amikacin sulphate in synovial fluid when given in combination with dexamethasone phosphate in intravenous regional limb perfusion in standing horses.

Eight horses underwent IVRLP at two occasions through a 23-gauge 2 cm long butterfly catheter. Regional anaesthesia of the ulnar, median and medial cutaneous antebrachial nerves was performed prior, and an 8 cm rubber tourniquet was placed on the proximal radius for 30 minutes following the infusion. The first infusion consisted of 2 g of amikacin sulphate and 10 mg of dexamethasone phosphate diluted with 0.9% NaCl to a total volume of 100 ml. The second perfusion was performed after a 2-week washout period, the same protocol was used but without dexamethasone phosphate. Synovial fluid samples were collected from the metacarpophalangeal joint at T = 0, 0.5, 2, 12, 24 and 36 h post-infusion. Synovial fluid amikacin sulphate concentrations were determined by use of liquid chromatography/tandem mass-spectrometry. All horses (n = 8) remained healthy throughout the study, and no adverse effects associated with the study were encountered. No statistically significant differences were found in synovial fluid amikacin sulphate concentrations between the treatment and the control group at any of the time points. In conclusion, dexamethasone phosphate can be used in IVRLP concomitantly with amikacin sulphate in cases of distal limb inflammation and pain without decreasing the synovial fluid concentration of amikacin sulphate.

Synovial Concentration of Trimethoprim-Sulphadiazine Following Regional Limb Perfusion in Standing Horses.

The aim of this study was to investigate the safety and pharmacokinetics of trimethoprim-sulphadiazine administered via intravenous regional limb perfusion (IVRLP) into the cephalic vein. According to the hypothesis, the drug could be administered without adverse effects and the synovial concentrations would remain above the minimum inhibitory concentration (MIC) for trimethoprim-sulphadiazine (0.5 and 9.5 µg/mL) for 24 h. Ten (n = 10) horses underwent cephalic vein IVRLP with an Esmarch tourniquet applied for 30 min. Four grams (4 g) of trimethoprim-sulphadiazine (TMP-SDZ) were diluted at 0.9% NaCl for a total volume of 100 mL. Synovial fluid and blood samples were obtained immediately before IVRLP and at 0.25, 0.5, 2, 6, 12 and 24 h after the initiation of IVRLP. Trimethoprim and sulphadiazine concentrations were determined using a method based on liquid chromatography/tandem mass spectrometry. The Cmax (peak drug concentration) values were 36 ± 31.1 and 275.3 ± 214.4 µg/mL (TMP and SDZ). The respective tmax (time to reach Cmax) values were 20 ± 7.8 and 26.4 ± 7.2 min. The initial synovial fluid concentrations were high but decreased quickly. No horse had synovial concentrations of trimethoprim-sulphadiazine above the MIC at 12 h. Severe vasculitis and pain shortly after IVRLP, lasting up to one week post-injection, occurred in five out of 10 horses. In conclusion, IVRLP with trimethoprim-sulphadiazine cannot be recommended due to the low concentrations of synovial fluid over time and the frequent severe adverse effects causing pain and discomfort in treated horses. Thus, in cases of septic synovitis with bacteria sensitive to trimethoprim-sulphadiazine, other routes of administration should be considered.

The Concentration of Metronidazole in the Distal Interphalangeal Joint following Intravenous Regional Limb Perfusion via the Cephalic Vein in Standing Horses.

OBJECTIVE: The aim of this study was to determine the concentration of metronidazole in the distal interphalangeal joint (DIPJ) of the thoracic limb after administering metronidazole to standing horses by intravenous regional limb perfusion (IVRLP). METHODS: Eleven healthy horses had a wide rubber tourniquet applied to the proximal aspect of the antebrachium for 0.5 hours and 500 mg of metronidazole diluted in physiologic saline solution to a total volume of 108 mL was administered by cephalic IVRLP. Synovial fluid samples were collected from the DIPJ before perfusion and at 0.25, 0.5, 2, 12 and 24 hours. Blood samples were obtained at the same time points for serum analysis. Concentrations of metronidazole were determined by liquid chromatography/tandem mass spectrometry. RESULTS: Four horses were excluded due to low synovial fluid concentrations and not completing the full tourniquet application time. The C max in the synovial fluid was 327 ± 208 µg/mL, and the t max was 26 ± 7 minutes. Only the concentrations of metronidazole at time points 0.25 and 0.5 hours were significantly different (p < 0.001) from synovial concentration before perfusion. The serum C max was 1.78 ± 0.93 µg/mL, and the t max was 76 ± 52min. CONCLUSION: Metronidazole administered by IVRLP reached high concentrations in the synovial fluid at 0.5 hours. However, the concentrations rapidly decreased below the minimum inhibitory concentration of potential target pathogens. Effectiveness of metronidazole administered by IVRLP as a sole therapy against anaerobic infections of synovial structures of the distal limb cannot be determined by a pharmacokinetic study. However, the present study serves as the basis for future carefully planned clinical trials.

Intraincisional medical grade honey decreases the prevalence of incisional infection in horses undergoing colic surgery: A prospective randomised controlled study.

BACKGROUND: Medical grade honey has previously been described as a prophylactic treatment for wounds. Local prophylactic treatment may be valuable in preventing post-operative incisional infections in horses undergoing colic surgery but has not been evaluated. OBJECTIVES: To establish whether medical grade honey gel, applied on the linea alba intraoperatively, decreases the prevalence of incisional infections in horses undergoing colic surgery with no associated adverse effects. STUDY DESIGN: Prospective blinded randomised controlled clinical study. METHODS: Horses older than 4 months that underwent colic surgery between May 2017 and December 2018 and survived for >2 weeks were included in the study. Horses were allocated 1:1 to treatment or control by block randomisation. In the treatment group, following closure of the linea alba, medical grade honey gel (L-Mesitran Soft® ) was placed in the incision followed by apposition of subcutaneous tissue and skin. Information regarding the incision and post-operative complications was obtained at five time points (24 hours, 48 hours, 5 days, 14 days and 3 months). RESULTS: Eighty-nine horses were included in the study. No adverse effects associated with treatment were observed. Horses in the treatment group had a lower rate of incisional infection compared with the control group (8.2% vs. 32.5%, P = .02). The protective effect of MGH had a calculated adjusted odds ratio (OR) of 0.2 (95% CI:0.07-0.8, P = .03). The number of patients required to receive treatment to prevent one case of incisional infection (NNEB) was 4.7. Risk factors associated with infection included: younger age (OR = 27, 95% CI: 2.3 to 306, P = .008) and diarrhoea 48 hours post-operatively (OR = 20, 95% CI: 1.5 to 277, P = .02). MAIN LIMITATIONS: Follow-up was performed by different veterinary surgeons, hence not completely uniform. CONCLUSION: Local prophylactic treatment with medical grade honey gel in the abdominal incision during surgery is safe and may significantly decrease the prevalence of incisional infections in horses undergoing colic surgery.

Time to Peak Concentration of Amikacin in the Antebrachiocarpal Joint Following Cephalic Intravenous Regional Limb Perfusion in Standing Horses.

OBJECTIVE: The aim of this study was to determine the time (Tmax) to the maximum concentration (Cmax) of amikacin sulphate in synovial fluid of the radiocarpal joint (RCJ) following cephalic intravenous regional limb perfusion (IVRLP) using 2 g of amikacin sulphate. METHODS: Cephalic IVRLP was performed with 2 g of amikacin sulphate diluted in 0.9% NaCl to a total volume of 100 mL in six healthy adult mixed breed mares. An Esmarch's rubber tourniquet was applied for 30 minutes and the antibiotic solution was infused through a 23-gauge butterfly catheter. Synovial fluid was collected from the RCJ prior to the infusion and at 5, 10, 15, 20, 25 and 30 minutes after completion of IVRLP. The tourniquet was removed after the last arthrocentesis. Synovial fluid amikacin sulphate concentrations were determined by liquid chromatography/tandem mass spectrometry. RESULTS: The calculated mean Tmax occurred at 15 minutes (range: 10-20 minutes) post-perfusion. The highest synovial fluid amikacin sulphate concentration was noted at 10 minutes in 2 horses, 15 minutes in 2 horses and 20 minutes in 2 horses. The highest mean concentration was 1023 µg/mL and was noted at 20 minutes. Synovial mean concentrations were significantly different between 15 and 30 minutes. CLINICAL SIGNIFICANCE: In this study no Tmax occurred after 20 minutes; thus, 30 minutes of tourniquet application time appear to be excessive. The 20 minutes duration of tourniquet application appears sufficient for the treatment of the RCJ in cephalic IVRLP using 2 g amikacin sulphate in a total volume of 100 mL.