Regional Limb Perfusion Research Articles

Plasma and Tissue Amikacin Concentrations Following Regional Limb Perfusion of Chickens (Gallus gallus domesticus).

Intravenous regional limb perfusion (IVRLP) has been used in the treatment of pododermatitis and distal limb infections, which are significant causes of morbidity in avian species. This intravenous drug administration technique is designed to achieve high drug tissue concentrations while minimizing systemic toxic effects. Amikacin is commonly used for IVRLP in veterinary medicine, but dosing guidelines have not been established for its use in birds. The current study aimed to determine the tissue concentration of amikacin after a single IVRLP administration in healthy, euhydrated leghorn hen chickens (Gallus gallus domesticus). Chickens received a single IVRLP dose of 10 mg/kg amikacin and were euthanatized posttreatment at 1 hour (n = 6), 12 hours (n = 6), and 24 hours (n = 6) to assess tissue and synovial fluid concentrations of amikacin in the injected leg. Mean tissue concentrations were highest 1 hour post-IVRLP (synovial fluid = 153.0 µg/mL, metatarsal pad tissue = 26.05 µg/mL) before declining at the 12- and 24-hour time points. This indicates that administration of amikacin via IVRLP can reach minimum inhibitory concentrations of common bacterial isolates in tissues after a single treatment with 10 mg/kg amikacin. Regional limb perfusion every 24 hours is recommended, although the minimum days of treatment may be case dependent and vary based on response to therapy.

Best practices for use of regional limb perfusion in a field setting

Best practices for use of regional limb perfusion in a field setting

Morphine synovial fluid concentrations after intravenous regional limb perfusion in horses during standing sedation.

Addition of morphine to the perfusate while performing intravenous regional limb perfusion (IVRLP) may be helpful in treating painful infectious orthopaedic conditions of the distal limb. The main objective of this study was to determine synovial morphine concentrations following IVRLP with morphine alone or in combination with amikacin. Randomised cross-over in vivo experiment. Six horses underwent IVRLP with 0.1 mg/kg morphine sulphate diluted to 60 mL using 0.9% NaCl (M group) or combined with 2 g amikacin and 0.9% NaCl (MA group) with a 2-week washout period between treatments. Synovial fluid was collected from the radiocarpal joint (RCJ) at 10, 20, 30, 120, 240, 480, 720 and 1440 min after IVRLP. The tourniquet was removed after the 30-min sample was collected. Synovial concentrations of morphine and major metabolites were measured using liquid chromatography-tandem mass spectrometry. Amikacin concentrations were quantified by a fluorescence polarisation immunoassay. Measurable concentrations of morphine were apparent in the RCJ of all horses. Median CMAX of morphine in the M group was 4753.1 (2115.7-14 934.5) ng/mL and 4477 (3434.3-7363) ng/mL in the MA group (p = 0.5). Median CMAX of synovial amikacin was 322.6 (157.5-1371.6 μg/mL). Limitations include small sample size. Investigators were not blinded to the treatments and a third treatment group where amikacin alone was administered via IVRLP to the study population was not included. IVRLP using morphine is a feasible technique and synovial morphine concentrations were measurable following IVRLP and were not affected when used concurrently with amikacin. Administration of morphine via IVRLP may be beneficial as an analgesic technique for orthopaedic conditions of the distal limb while limiting potential serious systemic side-effects.

Faster perfusate instillation time results in more systemic leakage of amikacin sulfate when performing intravenous regional limb perfusion in horses.

To evaluate if a difference in synovial amikacin concentrations exists in the radiocarpal joint (RCJ) following different durations of instillation of an IV regional limb perfusion (IVRLP) perfusate. 7 healthy horses. Horses received 2 IVRLPs with 2 g amikacin diluted to 60 mL with 0.9% NaCl via the cephalic vein in a crossover study design with a wash-out period between procedures. Instillation of the perfusate was administered over a 1-minute (technique 1) and 5-minute (technique 5) period. Concentrations of amikacin within the RCJ were measured at time (T) 5, 10, 15, 20, 25, and 30 minutes after instillation of the perfusate. Systemic concentrations of amikacin were measured at T0, 5, 10, 15, 20, 25, 29 minutes, and 1 minute after tourniquet removal (T31). Amikacin concentrations were determined by fluorescence polarization immunoassay. The median maximum concentration (CMAX) of amikacin within the RCJ for technique 1 was 338.4 µg/mL (range, 60 to 4,925 µg/mL), while the median CMAX for technique 5 was higher at 694.8 µg/mL (range, 169.2 to 3,410 µg/mL; P = .398). There was a higher amikacin blood concentration over time for technique 1 compared to technique 5 (P = .004). Administration of perfusate at different rates did not significantly affect synovial concentration of amikacin within the RCJ when performing IVRLP. However, increased systemic leakage was noted when the perfusate was administered over 1 minute, which might affect synovial concentrations in a larger group of horses.

Phenylbutazone concentrations in synovial fluid following administration via intravenous regional limb perfusion in the forelimbs of six adult horses.

Pain management is critical to equine welfare with non-steroidal anti-inflammatory drugs (NSAID) commonly used in horses. However, systemic NSAID use is limited by harmful gastrointestinal and renal side effects. Intravenous regional limb perfusion (IVRLP) is a technique used in horses that produces high, local antibiotic concentrations while limiting systemic circulation. NSAID-IVRLP would be a novel method of local pain management while limiting systemic NSAID side effects. To date, NSAID-IVRLP administration has not been reported in horses. This study aimed to identify the pharmacokinetics and local complications associated with using the NSAID phenylbutazone (PBZ) for IVRLP in six standing adult horses. PBZ-IVRLP, at a dose of 2.2 mg/kg PBZ, was performed in a randomly assigned forelimb cephalic vein in 6 standing, healthy adult horses. A placebo-IVRLP was performed in the contralateral forelimb for comparison. Systemic serum and radiocarpal joint synovial fluid PBZ concentrations were identified at various timepoints (before IVRLP T-0 h, just after tourniquet removal T-0.5, 1.5, 3, 5, 12, 16, and 24 h post IVRLP) for non-compartmental pharmacokinetic analysis and concentration over time curves. Local complications associated with PBZ-IVRP were evaluated for up to 7 days following PBZ-IVRLP using physical and ultrasonographic assessment. On day 7 horses were humanely euthanized with histology performed on both forelimbs at PBZ-IVRLP and placebo-IVRLP administration sites. Non-compartmental pharmacokinetics for PBZ, and its major metabolite oxyphenbutazone (OBZ), were determined for serum and synovial fluid. Synovial PBZ concentrations (mean ± SD; 1.9 ± 2.1 μg/mL) were significantly lower (p = 0.03; CI,0.46-7.36) than serum PBZ concentrations (5.8 ± 5.1 μg/mL) at any time point. Physical and ultrasonographic measurements were not significantly different between PBZ- and placebo-IVRLP forelimbs. The most common histologic findings included focal deep dermal/subcutaneous hemorrhage and edema. Two horses showed perivasculitis and one horse showed a resolving thrombus in the cephalic vein of the PBZ-IVRLP limb. This horse also had severe perivasculitis and fibrinosuppurative dermatitis/panniculitis in the placebo-IVRLP limb. PBZ-IVRLP pharmacokinetics at a 2.2 mg/kg dose showed no benefit compared to systemic PBZ administration in standing adult horses. Local complications associated with PBZ-IVRLP were similar to placebo-IVRLP on physical and ultrasonographic evaluation.

Effects of a 10% dimethyl sulfoxide solution on radiocarpal joint amikacin pharmacokinetics during intravenous regional limb perfusion in standing sedated horses.

To determine the effect of a 10% dimethyl sulfoxide (DMSO) solution on the peak concentration (CMAX ) of amikacin in the radiocarpal joint (RCJ) during intravenous regional limb perfusion (IVRLP) compared with 0.9% NaCl. Randomized crossover study. Seven healthy adult horses. The horses underwent IVRLP with 2 g of amikacin sulfate diluted to 60 mL using a 10% DMSO or 0.9% NaCl solution. Synovial fluid was collected from the RCJ at 5, 10, 15, 20, 25, and 30 minutes after IVRLP. The wide rubber tourniquet placed on the antebrachium was removed after the 30 min sample. Amikacin concentrations were quantified by a fluorescence polarization immunoassay. The mean CMAX and time to peak concentration (TMAX ) of amikacin within the RCJ were determined. A one-sided paired t-test was used to determine the differences between treatments. The significance level was p < .05. The mean ± SD CMAX in the DMSO group was 1361.8 ± 593 μg/mL and in the 0.9% NaCl group it was 860 ± 481.6 μg/mL (p = .058). Mean TMAX using the 10% DMSO solution was 23 and 18 min using the 0.9% NaCl perfusate (p = .161). No adverse effects were associated with use of the 10% DMSO solution. Although there were higher mean peak synovial concentrations using the 10% DMSO solution no difference in synovial amikacin CMAX between perfusate type was detected (p = .058). Use of a 10% DMSO solution in conjunction with amikacin during IVRLP is a feasible technique and does not negatively affect the synovial amikacin levels achieved. Further research is warranted to determine other effects of using DMSO during IVRLP.

Clinical Efficacy of a Single Intravenous Regional Limb Perfusion with Marbofloxacin versus Ceftiofur Sodium to Treat Acute Interdigital Phlegmon in Dairy Cows.

The objective of the study was to compare the clinical efficacy of a single antimicrobial intravenous regional limb perfusion (IVRLP) with marbofloxacin versus ceftiofur sodium to treat naturally occurring interdigital phlegmon (IP) in dairy cows. The study had a randomized parallel-group design. Forty lactating Friesian cows clinically diagnosed with acute IP were enrolled, assigned to one of two treatment groups, and received a single IVRLP with the antimicrobial drug selected (M: 0.67 mg/kg of marbofloxacin; C: 500 mg/animal of ceftiofur sodium). Clinical data for the severity of lameness, digital swelling and local lesion appearance were assessed at diagnosis and at 5, 10 and 15 days post-IVRLP. Clinical resolution was defined as digital swelling disappearance, locomotion score reduction of at least 2/5 points, healed or healing local lesion and no relapse at 15 days after IVRLP. The total daily milk yield of each cow on the day before the clinical detection, on the day of diagnosis and on the day of the clinical follow-up post-IVRLP were registered. Lameness, digital swelling and local lesion severity were not significantly different between groups at any time-point. In both groups, on the fifteenth day after treatment, 17/20 (85%) cows showed a positive outcome, with no significant difference (p > 0.05). The daily milk production of all cows was adversely affected by the clinical onset of IP and gradually returned to a normal level after IVRLP in both groups. These preliminary results support the hypothesis that a single antimicrobial IVRLP procedure, irrespective of the antimicrobial selected (ceftiofur vs. marbofloxacin), has a high success rate and restores milk yield in cases of dairy cattle with acute IP lameness.

Long-term results of isolated limb perfusion with hyperthermia in patients with limb melanoma

Introduction. In patients with local recurrences of melanoma or with transit metastases of this tumor located distal to the axilla and inguinal region, the use of isolated regional limb perfusion is considered as one of the effective treatment options.Aim. To evaluate the long-term results of treatment extremities melanoma using the method of isolated regional perfusion of the extremities.Materials and methods. An analysis of the treatment and observation results of 72 patients (12 men and 60 women) with melanoma of the extremities was carried out, the median age was 56.7 years (from 25 to 78 years). All patients underwent isolated regional perfusion with hyperthermia using melphalan at doses of 10 mg/l volume for the lower limb and 13 mg/l volume for the upper limb. Patient survival for 5 years, the incidence of relapses and metastases of melanoma, as well as the frequency of limb amputation were assessed.Results. The rate of complete response to treatment was 13.9 %, in the vast majority of cases there was a partial regression – in 72.2 % of cases. There was no response to treatment in only 13.9 % of patients.Recurrence of transit metastases within 5 years developed in 52 (72.2 %) patients. Amputation was performed only in 11.1 % of cases. The 1-year survival rate was 91.7 %, the 5-year survival rate for melanoma patients who underwent isolated regional perfusion was 55.6 %.Сonclusion. Isolated regional perfusion under conditions of hyperthermia with melphalan is an effective and safe method of treatment in terms of long-term results of melanoma treatment, providing a 5-year patient survival rate of 55.6 %, a low rate of amputations and metastasis.

Treatment of Septic Tenosynovitis and Osteoarthritis in an American White Pekin (Anas platyrhynchos domesticus) with Repeated Intravenous Regional Limb Perfusion and Antibiotic-Impregnated Calcium Sulfate Beads.

A 2-year-old female American white pekin (Anas platyrhynchos domesticus) was assessed for a 2-month history of chronic lameness and swelling involving the left leg. Radiographic images of the left leg showed soft tissue swelling of the digits and tarsometatarsus with osteolysis of the tarsometatarsal-phalangeal joint. A complete blood count revealed marked leukocytosis and hyperproteinemia. A Streptococcus species was isolated from a bacterial culture of fluid obtained from the left tarsometatarsal-phalangeal joint. Biweekly intravenous regional limb perfusions of the left leg with ampicillin-sulbactam and amikacin were performed on the patient. Despite initial improvement in left leg lameness and swelling, follow-up radiographic images showed progressive osteolysis of the tarsometatarsal-phalangeal joint and associated digits. Surgical placement of antibiotic-impregnated calcium sulfate beads into the left tarsometatarsal-phalangeal joint was next performed with concurrent, repeated intravenous regional limb perfusion using the same antibiotic. Following the placement of antibiotic-impregnated beads and continued intravenous regional limb perfusion, the duck had decreased lameness and swelling of the left leg. Repeated antibiotic treatment through intravenous regional limb perfusion and concurrent placement of antibiotic-impregnated calcium sulfate beads is a practical treatment option for complicated distal limb infections in avian species. This therapeutic protocol has great potential in treating aggressive distal leg infections in many avian species because regional limb perfusion alone may not penetrate the joint adequately to achieve complete resolution of infection.

Current treatment and prevention of orthopaedic infections in the horse

SummaryOrthopaedic infections, including synovial sepsis, osteomyelitis and infection of orthopaedic implants are common in equine medicine. Infections can be caused by haematogenous spread of pathogens, trauma or penetrating injuries, extension of local infections and iatrogenic causes such as surgery and synovial injections. Horses with orthopaedic infections are generally markedly lame and often require aggressive and prolonged therapy. Early diagnosis can greatly impact treatment outcomes and can be facilitated by careful physical examinations, haematology, diagnostic imaging and timely synovial fluid sampling. Concerted efforts should always be made to obtain a positive bacterial culture and sensitivity. Treatment is focused on antimicrobial therapy with local therapy, including intravenous regional limb perfusion and intrasynovial injections, being employed whenever possible; lavage and debridement; and analgesia and supportive care. Responsible use of antimicrobials and antimicrobial stewardship are critical when treating orthopaedic infections. Prognosis will depend on the source and severity of the infection, the causative agent and the time to intervention. Foals and horses can respond well to treatment and return to soundness with early, aggressive and targeted treatment.

Evaluation of the Solution Volume Associated With Lidocaine for Intravenous Regional Limb Perfusion: A Venographic Study in Horse

• Studies on the vascular effects of 2% lidocaine on IVRLP in horses are absent. • The association of 2% lidocaine does not increase the number of filled vessels. • There is a different pattern of vascular filling with larger and smaller volumes. • It is suggested that higher volumes have a greater effect on vascular diameter.

Intravenous regional antibiotic perfusion as an adjunctive therapy to treat osteomyelitis in a common snapping turtle (Chelydra serpentina)

AbstractA wild, adult, male common snapping turtle (Chelydra serpentina) presented to North Carolina State University's Turtle Rescue Team (TRT) with injuries consistent with vehicular trauma. Injuries included head trauma with an associated superficial lesion of the head and an overpronated left forelimb with a necrotic wound on the palmar surface. Osteomyelitis localised to the left forelimb was considered the primary differential based on radiographic findings and clinical signs. To treat osteomyelitis, regional antibiotic limb perfusions were conducted approximately once per week. After conducting seven total regional antibiotic limb perfusions, the patient's ambulation and mentation improved significantly and there was no progression of osteomyelitis on repeated radiographs. The patient was released to the wild after 5 months under human care. This case report demonstrates the potential use of regional antibiotic limb perfusion as an adjunctive therapy for osteomyelitis in chelonians.

Clinicopathologic Findings in Chickens (Gallus gallus domesticus) Administered Amikacin Through Intravenous Regional Limb Perfusion.

Regional limb perfusion (RLP) has been used to treat cases of distal limb infections in avian species. Potentially nephrotoxic drugs, such as amikacin, may increase the risk of nephrotoxicity with RLP because of the presence of the renal portal system and direct venous blood flow from the pelvic limbs to the kidneys. In a randomized, blinded, placebo-controlled study, the safety of repeated amikacin administration (20 mg/kg q24h for 3 doses) via RLP was evaluated in healthy female chickens (Gallus gallus domesticus; n = 8 treatment, n = 8 saline control group). Plasma uric acid concentrations were not significantly elevated in treated birds compared with the control group at any time point following RLP. One week following the final RLP, birds were necropsied and the kidneys evaluated grossly and histologically. There was no significant difference in renal pathology scores between treated and control birds or between kidneys ipsilateral to the perfused limb and contralateral kidneys. This study concludes that RLP of amikacin at high doses produced no discernable renal pathology in healthy euhydrated chickens.

Evaluation of factors associated with surgical site infection in equine proximal interphalangeal joint arthrodesis: 54 cases (2010-2019).

BackgroundThe frequency of surgical site infection (SSI) following orthopaedic implant placement in horses has been reported but not compared with respect to specific antibiotic protocols administered.ObjectivesTo determine factors associated with SSI in horses undergoing proximal interphalangeal joint (PIPJ) arthrodesis including perioperative antibiotic protocols.MethodsRecords were evaluated (2010–2019), and horses undergoing PIPJ arthrodesis were identified. Patient signalment, supervising surgeon, reason for surgery, limb, implants placed, anaesthetic time, duration casting/coaptation postoperatively, antibiotic regimen and incidence/onset SSI were recorded. Bayesian and frequentist logistic regressions were used to estimate the contribution of covariates to infection occurrence.ResultsFifty‐four PIPJ arthrodeses were performed. SSI occurred in 2/54 (3.7%) on day 15,30. Arthrodesis was performed most commonly for osteoarthritis (33/54, 61.1%), fracture (11/54, 20.4%), and subluxation (5/54, 9.3%). Perioperative systemic antibiotics were administered 1–3 days (15/54, 27.8%) or > 3 days (39/54, 72.2%). Antibiotic protocols included cefazolin/gentamicin (20/54, 37%), cefazolin/gentamicin/doxycycline (14/54, 25.9%) and potassium penicillin/gentamicin (10/54, 18.5%). Regional limb perfusion was performed preoperatively 31/54 (57.4%) and postoperatively 7/54 (13%). Survival to dismissal was 98.1% (53/54 horses) with one horse euthanized due to support limb laminitis. No association was identified between antibiotic selection or duration (1–3 vs. > 3 days), pre‐operative regional antibiotic perfusion, intraoperative antibiotic lavage or anaesthetic time (< or > 3 h) and SSI; however, modelling was complicated by quasi‐complete or complete separation of the data. Bayesian analysis (but not frequentist analysis) indicated an association between post‐operative regional antibiotic perfusion and SSI. Limitations include the retrospective nature of data collection and the low rate of infection overall.ConclusionsThe prevalence of SSI in this population was lower than that in previous reports of equine orthopaedic internal fixation. There was no difference in SSI rate in cases administered systemic antibiotics for 1–3 days or >3 days, or for those horses that did or did not receive preoperative regional antibiotic perfusion.

Effects of regional limb perfusion technique on concentrations of antibiotic achieved at the target site: A meta-analysis.

Intravenous regional limb perfusions (RLP) are widely used in equine medicine to treat distal limb infections, including synovial sepsis. RLPs are generally deemed successful if the peak antibiotic concentration (Cmax) in the sampled synovial structure is at least 8-10 times the minimum inhibitory concentration (MIC) for the bacteria of interest. Despite extensive experimentation and widespread clinical use, the optimal technique for performing a successful perfusion remains unclear. The objective of this meta-analysis was to examine the effect of technique on synovial concentrations of antibiotic and to assess under which conditions Cmax:MIC ≥ 10. A literature search including the terms "horse", "equine", and "regional limb perfusion" between 1990 and 2021 was performed. Cmax (μg/ml) and measures of dispersion were extracted from studies and Cmax:MIC was calculated for sensitive and resistant bacteria. Variables included in the analysis included synovial structure sampled, antibiotic dose, tourniquet location, tourniquet duration, general anesthesia versus standing sedation, perfusate volume, tourniquet type, and the concurrent use of local analgesia. Mixed effects meta-regression was performed, and variables significantly associated with the outcome on univariable analysis were added to a multivariable meta-regression model in a step-wise manner. Sensitivity analyses were performed to assess the robustness of our findings. Thirty-six studies with 123 arms (permutations of dose, route, location and timing) were included. Cmax:MIC ranged from 1 to 348 for sensitive bacteria and 0.25 to 87 for resistant bacteria, with mean (SD) time to peak concentration (Tmax) of 29.0 (8.8) minutes. Meta-analyses generated summary values (θ) of 42.8 x MIC and 10.7 x MIC for susceptible and resistant bacteria, respectively, though because of high heterogeneity among studies (I2 = 98.8), these summary variables were not considered reliable. Meta-regression showed that the only variables for which there were statistically significant differences in outcome were the type of tourniquet and the concurrent use of local analgesia: perfusions performed with a wide rubber tourniquet and perfusions performed with the addition of local analgesia achieved significantly greater concentrations of antibiotic. The majority of arms achieved Cmax:MIC ≥ 10 for sensitive bacteria but not resistant bacteria. Our results suggest that wide rubber tourniquets and concurrent local analgesia should be strongly considered for use in RLP and that adequate therapeutic concentrations (Cmax:MIC ≥ 10) are often achieved across a variety of techniques for susceptible but not resistant pathogens.

Increasing tourniquet number has no effect on amikacin concentration within the radiocarpal joint in horses undergoing intravenous regional limb perfusion.

To determine whether IV regional limb perfusion (IVRLP) performed in the cephalic vein with a wide rubber tourniquet (WRT) applied proximal and distal to the carpus results in a higher peak concentration (Cmax) of amikacin in the radiocarpal joint (RCJ), compared with the Cmax for IVRLP using a single WRT proximal to the carpus. 7 healthy adult horses. Horses underwent IVRLP using standing sedation with 2 g of amikacin sulfate diluted to 60 mL by use of saline (0.9% NaCl) solution in the cephalic vein with 2 different tourniquet techniques; proximal WRT (P) and proximal and distal WRT (PD). Synovial fluid was collected from the RCJ at 5, 10, 15, 20, 25, and 30 minutes after IVRLP. Tourniquets were removed after the 30-minute sample was collected. Blood samples from the jugular vein were collected at 5, 10, 15, 20, 25, 29, and 31 minutes after IVRLP. Amikacin concentration was quantified by a fluorescence polarization immunoassay. Median peak concentration (Cmax) of amikacin and time to maximum drug concentration (Tmax) within the RCJ were determined. Median peak concentration in the RCJ was 1331.4 μg/mL with technique P and 683.1 μg/mL with technique PD. Median Tmax occurred at 30 minutes with technique P and 25 minutes with technique PD. No significant (Cmax, P = 0.18; Tmax, P = 0.6) difference in amikacin Cmax or Tmax between techniques was detected. Placement of 2 WRTs offers no advantage to a single proximal WRT when performing IVRLP to deliver maximal amikacin concentrations to the RCJ using IVRLP.

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 2cm long butterfly catheter. Regional anaesthesia of the ulnar, median and medial cutaneous antebrachial nerves was performed prior, and an 8cm rubber tourniquet was placed on the proximal radius for 30minutes following the infusion. The first infusion consisted of 2g of amikacin sulphate and 10mg of dexamethasone phosphate diluted with 0.9% NaCl to a total volume of 100ml. 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 36h 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.

Effect of perfusate volume on amikacin concentrations after saphenous intravenous regional limb perfusion in standing, sedated horses.

To determine the influence of perfusate volume on synovial fluid amikacin concentrations in the joints of the hind limb after standing saphenous intravenous regional limb perfusion (IVRLP). Randomized crossover design. Six adult horses. Saphenous IVRLP was performed in 6 standing horses with 1 g of amikacin diluted with 0.9% NaCl to volumes of 10ml, 60 ml, and 120 ml. Samples of synovial fluid from the tarsocrural, metatarsophalangeal, and hind limb distal interphalangeal joints were collected at 15 and 30 min after perfusate administration. Concentrations of 40μg/ml and 160μg/ml were considered therapeutic for susceptible and resistant pathogens, respectively. No difference in synovial fluid amikacin concentrations was detected between volumes in any joint (P= .4). All synovial fluid amikacin concentrations were higher at 30 min compared to 15 min (P= .003). All median synovial fluid amikacin concentrations at 30 min were > 40μg/ml using the 60 ml and 120 ml volumes. Synovial fluid amikacin concentrations >40 μg/ml were only reached in the hind limb distal interphalangeal joint when the 10ml volume was used. All median synovial fluid amikacin concentrations observed were < 160μg/ml. Target concentrations for pathogens that were considered susceptible were consistently reached with perfusate volumes of 60 ml and 120 ml. However, median synovial fluid amikacin concentrations did not reach target levels for resistant pathogens. Perfusate volumes of 60 ml or 120 ml are recommended to treat infections due to susceptible pathogens in the joints of the distal hind limb. These results justify investigation of saphenous IVRLP with different perfusate volumes using higher doses of amikacin.

Evaluation of totally implantable catheters in healthy horses

BackgroundFor horses requiring prolonged daily cephalic intravenous regional limb perfusion (IVRLP), the use of a totally implantable catheter (TIC) could be indicated to reduce complications associated with frequent venipuncture or external catheterization. This study aims to evaluate the implantation technique of the TIC in the cephalic vein of horses for IVRLP, describe the complications associated with the device’s placement and use, and assess its viability up to 60 days after implantation. Totally implantable catheters, cut to 15 cm (n = 5) and 46 cm (n = 5) in length, were implanted into one cephalic vein in ten adult horses (n = 10). Twenty-four hours following placement, IVRLP with contrast was performed via the TIC and evaluated with radiography. Physical examinations, lameness evaluation, hematologic assessment, and the catheter patency tests were performed at scheduled intervals for the duration of catheterization (7–60 days).ResultsCatheters were implanted without difficulty and allowed for IVRLP 24 h post implantation. Complications resulted in removal of the catheters, with four maintained for 7 days, three in place for 15 days, and three catheters maintained for 60 days. Complications included lameness, limb swelling, catheter kinking, and venous thrombosis.ConclusionsThe implantation technique of the TIC in the cephalic vein of horses is feasible and requires minimal technical effort. Although TIC allows venous access without the need for repeated venipuncture, its long-term use presents complications. For horses requiring prolonged daily cephalic IVRLP, the use of a TIC could be indicated. However, the high incidence of venous thrombosis may limit clinical application.

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.