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.

Pharmacokinetics of regional limb perfusion using a combination of amikacin and penicillin in standing horses.

The objectives of this study were to evaluate the compatibility and the pharmacokinetic properties of combined amikacin and penicillin administration by intravenous regional limb perfusion (IVRLP) in horses. A tourniquet was applied proximal to the carpus of 7 clinically healthy adult horses and 2 g of amikacin and 10 × 106 IU of penicillin (100 mL total volume) were sequentially injected into the cephalic vein just distal to the tourniquet. Synovial samples were collected from the joint at several times after injection. All samples were analyzed for amikacin and penicillin concentration. The mean maximum concentration (Cmax) of both amikacin and penicillin was over 10-fold the relevant minimal inhibitory concentration (MIC) for all horses and remained above those MICs for at least 24 hours. The results of this study indicate that combining amikacin with penicillin during IVRLP in normal horses delivers high therapeutic synovial concentrations of both drugs.

Pharmacocinétique de la perfusion régionale des membres en utilisant une combinaison d'amikacine et de pénicilline chez des chevaux debout. Les objectifs de cette étude consistaient à évaluer la compatibilité et les propriétés pharmacocinétiques de l'administration combinée d'amikacine et de pénicilline par perfusion intraveineuse régionale des membres (PIRM) chez les chevaux. Un tourniquet a été appliqué proximalement au carpe de sept chevaux adultes en bonne santé clinique et 2 g d'amikacine et 10 × 106 UI de pénicilline (volume total de 100 ml) ont été injectés en séquence dans la veine céphalique légèrement distale au tourniquet. Des échantillons synoviaux ont été prélevés de l'articulation plusieurs fois après l'injection. Tous les échantillons ont été analysés pour la concentration d'amikacine et de pénicilline. La concentration maximale moyenne (Cmax) de l'amikacine et de la pénicilline était plus de 10 fois supérieure à la concentration inhibitrice minimale (CIM) pertinente pour tous les chevaux et est demeurée au-dessus de ces CIM pendant au moins 24 heures. Les résultats de cette étude indiquent que la combinaison de l'amikacine avec la pénicilline durant la PIRM chez des chevaux en santé offre des concentrations synoviales thérapeutiques élevées des deux médicaments.(Traduit par Isabelle Vallières).

Pharmacokinetics of ceftazidime after regional limb perfusion in standing horses.

OBJECTIVE: To determine the metacarpophalangeal joint fluid concentrations of ceftazidime administered via regional limb perfusion (RLP). ANIMALS: Eight healthy horses. METHODS: RLP was performed by injecting 2 g of ceftazidime and 60 mL of perfusate volume in the cephalic vein of standing, sedated horses. Serum and synovial fluid from the metacarpophalangeal joint were collected before perfusion and at 0.5, 2, 6, 12, 24 hours postperfusion. Ceftazidime concentrations were measured via liquid chromatography. Maximal concentration (Cmax ), area under the curve (AUC), half-life of the drug (T ½), and the timing of Cmax (Tmax ) were determined to assess ceftazidime as a candidate drug for RLP. Continuous parameters were compared with the Mann-Whitney U test. P value ≤ .05 was considered statistically significant. RESULTS: The Cmax of ceftazidime in synovial fluid (235 µg/mL) was 15 times higher than the minimal inhibitory concentration (MIC) for most bacteria involved in orthopedic infections, including resistant pathogens such as Pseudomonas aeruginosa (MIC = 16 µg/mL). However, synovial concentrations decreased quickly and remained above the MIC in only 1 horse by 6 hours postperfusion. CONCLUSION: RLP generated high synovial fluid concentrations of ceftazidime in the distal limb, but these concentrations decreased rapidly below the deliberately high MIC selected. CLINICAL RELEVANCE: Once daily RLP, as applied in our study, with 2 g ceftazidime in standing horses, cannot be recommended for use in a clinical setting.

Surgical management and long-term outcome of umbilical infection in 65 foals (2010-2015).

OBJECTIVE: To report the short- and long-term outcomes of surgical management of umbilical infection in foals. STUDY DESIGN: Retrospective case series. ANIMALS: Foals (n = 65). METHODS: Medical records (2010-2015) of foals up to 1 month of age, surgically treated for an umbilical infection were reviewed. Short-term (at the time of discharge from hospital) and long-term (1 year after surgery) survival rates were obtained. Clinical variables influencing survival were assessed. Chi-square or Fisher's exact test were used to evaluate the relationship between the data retrieved and outcome. P ≤ .05 was considered statistically significant. RESULTS: Sixty-five foals were included in the study, representing 17.2% of all foals admitted to the hospital. Fifty foals were discharged from hospital (77%) and 43 foals (66%) were alive 1 year after surgery. Lower long-term survival rates were associated with: younger age at presentation, septic joints, multiple pathologies, higher creatinine level, higher heart rate, umbilical infection diagnosed at the hospital rather than prior to referral, prolonged hospitalization, longer period between arrival and surgery, and postoperative complications. The most common surgical findings were urachal enlargement followed by right arterial enlargement. CONCLUSION: Younger foals with worse systemic condition and concurrent disorders are at higher risk for treatment failure. Early diagnosis improves the outcome. Surgical treatment yields good results and should be considered upon diagnosis, after taking into account the clinical situation. CLINICAL SIGNIFICANCE: Based on the results of this study, diagnosis and surgical management of umbilical infection in neonatal foals should be performed as early as possible, and a good outcome can be expected after surgery.

The Effect of Perfusate Volume on Amikacin Concentration in the Metacarpophalangeal Joint Following Cephalic Regional Limb Perfusion in Standing Horses.

OBJECTIVE: To determine the influence of 3 perfusate volumes on amikacin concentration in the metacarpophalangeal joint following cephalic regional limb perfusion (RLP) in standing horses. ANIMALS: Seven healthy horses. METHODS: Three perfusate volumes (100, 60, and 30 mL), containing 2 grams of amikacin, were tested during intravenous RLP at the cephalic vein, placing the tourniquet at mid antebrachium, in standing sedated horses. Synovial fluid was collected from the metacarpophalangeal joint before perfusion and at 30 and 120 minutes after perfusion. Serum samples were taken from the jugular vein at the same time points. Samples were analyzed for amikacin concentrations and a repeated measures ANOVA, followed by least squares difference pairwise comparisons to identify differences in amikacin concentration across perfusate volumes. Differences were considered significant at P<.05. RESULTS: The mean amikacin concentration in synovial fluid at 30 minutes after perfusion was significantly higher following perfusate volume of 100 mL (579 µg/mL), compared to volumes of 60 mL (227 µg/mL) or 30 mL (282 µg/mL) (P<.05). When a threshold of 160 µg/mL was used, more horses reached the synovial therapeutic threshold following perfusate volume of 100 mL (100%), than horses receiving 60 mL (43%) and 30 mL (57%) at 30 minutes after injection. CONCLUSION: The use of 100 mL volume for RLP at the cephalic vein in standing horses resulted in higher concentration of amikacin in the synovial fluid and is recommended for use in clinical cases.