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.

OBJECTIVE: 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.
METHODS: 7 healthy horses.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.

Vascular injections of stem cells are a pertinent alternative to direct intralesional injections when treating multiple or extensive lesions or with lesions impossible to reach directly. Extensive research using stem cell tracking has shown that intra-arterial injections without the use of a tourniquet should be preferred over venous or arterial regional limb perfusion techniques using a tourniquet. The median artery is used for the front limbs and the cranial tibial artery for the hind limbs. Proper efficacy studies are still lacking but early clinical work seems promising.

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.

In this case report, two horses with chronic refractory infections in the tuber calcanei were successfully managed via intravenous antibiotic regional limb perfusion through the lateral saphenous vein after failure of conventional treatment approaches, including surgery and intravenous regional limb perfusion using the cranial branch of the medial saphenous vein. Surgical delay in these cases may have allowed the development of chronic infection, which prevented the conventional regional perfusion from working effectively. The spatial difference of the vessels relative to the tuber calcanei possibly contributed to the treatment outcome in these horses. This report describes a novel approach for regional antimicrobial perfusion to the equine plantar hock region using the lateral saphenous vein.

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.

Pododermatitis and wing lesions are commonly reported issues in captive crane species. Regional limb perfusion has been used as a treatment for distal limb infections in several avian species, as systemic antibiotic therapy is often prolonged and unrewarding. A black-necked crane (Grus nigricollis), Siberian crane (Leucogeranus leucogeranus), and wattled crane (Bugeranus carunculatus) were treated with amikacin (5-10 mg/kg IV infusion) regional limb perfusion for cellulitis and osteomyelitis of hind limb digits and alular osteomyelitis and septic arthritis of the carpus, respectively, with a range of 1-3 treatments per case. Clinical signs of infection resolved within 10-40 days following regional limb perfusion combined with oral or parental antibiotic therapy. No side effects were observed following regional limb perfusion. This is the first report of regional limb perfusion in cranes and the first report of intravenous regional limb perfusion in a wing of an avian species.

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.

Septic synovitis is a critical orthopedic condition in horses. Early intervention is key, with antibiotic therapy typically initiated prior to culture and susceptibility reports becoming available. The pharmacokinetics of several antibiotics have been studied in horses for use in intravenous regional limb perfusion (IVRLP) for septic synovitis, including the carbapenem antibiotic, meropenem. For a variety of factors, some veterinary clinicians may select IVRLP meropenem as therapy for these cases. Meropenem is a vital antibiotic in human medicine, making veterinary use divisive. However, verifying the efficacy of meropenem contrasted to other IVRLP antibiotics is essential for appropriate antimicrobial stewardship. To investigate this, equine patient medical records at a single veterinary teaching hospital were examined. Cases treated with meropenem or gentamicin via IVRLP for septic synovitis were retrospectively analyzed for demographics, diagnostics, treatments, outcomes, and adverse effects. Twenty-three meropenem and 37 gentamicin treated horses were analyzed; demographic information was similar between groups. In the meropenem group, nine horses received meropenem only; the remainder received another antibiotic initially then changed to meropenem. Structures infected included joints (meropenem = 13, gentamicin = 17), tendon sheaths (meropenem = 5, gentamicin = 8) and navicular bursae (meropenem = 2, gentamicin = 6). Overall survival to discharge was 86% (52/60), with meropenem 91% (21/23) and gentamicin 84% (31/37), with no statistically significant differences noted between meropenem or gentamicin groups for overall survival to discharge or outcome after discharge. Twenty-four of 26 bacterial isolates obtained from culture were reported as sensitive to imipenem, a carbapenem antibiotic similar to meropenem. Reported susceptibility to other antibiotics such as ceftiofur (n = 22/26), ampicillin (n = 18/26), amikacin (n = 15/26), or gentamicin (n = 12/26) was also frequently present. In the population of this study, antimicrobial activity augmented with IVRLP using either meropenem or gentamicin both appear to be an effective treatment for septic synovial structures, therefore, less critical antimicrobials may be a viable and more judicious treatment option.

Small ruminants are increasing in popularity as production and companion animals in the United States, and among sheep, goats, and camelids there are many disease processes and management techniques that have the potential to result in painful or noxious stimuli. In these species, many medications and therapeutic techniques can be used to reduce or eliminate the long-term consequences of pain. In this second portion of the review, we focus on the application of pain management in these species. These strategies include mono- and multimodal and the use of precision pain management, such as epidural drug administration, regional perfusions, and transdermal applications.