How to Select Cases and Perform Field Technique for Regional Limb Perfusion

1. Introduction

Vascular isolation of a limb, or part of a limb, through the use of a proximal tourniquet for isolated drug delivery to the distal limb, was first used in humans for regional anesthesia, commonly known as a Bier block, after August Bier. The technique of regional limb perfusion (RLP) for local antimicrobial delivery in horses was first described in 1990.1 Since 1990, equine RLP has been thoroughly investigated by several scientific publications and has become a part of routine equine practice. It is likely that RLP has found such great acceptance among equine practitioners largely because of the horse’s tendency for distal limb injury, the relatively dirty environment in which the horse lives, and the difficulty and expense of treating distal limb bacterial infections that can often be life- and/or career-threatening.

The most striking benefit of RLP is that high antimicrobial concentrations can be achieved in distal limb tissues, including synovial fluid, with a low antimicrobial dose (relative to systemic dose) and maintained above the minimum inhibitory concentration (MIC) for most organisms for up to and exceeding 24 hours.²  Other benefits include relative ease of the technique once learned, no need for specialized equipment, minimal invasiveness, minor significance of most complications, minimal patient resistance, and the limited time required to complete the procedure (approximately 40 minutes). In the author’s hospital, RLP is nearly a daily occurrence in the treatment or prevention of distal limb infection. 

Mechanism

Antimicrobial drug delivery for most water-soluble, non–protein-bound drugs is a pressure and concentration gradient–dependent phenomenon, in which passive diffusion across a gradient occurs until equilibrium is reached. The equilibration rate is affected by the surface area to volume ratio (SA:V); whereas a high surface area (endothelium) to low volume (interstitial fluid) results in rapid equilibration to most tissues. This explains the apparent poor delivery to synovial structures where delivery is actually not inhibited but slow, due to a low SA:V ratio. In the joint, the surface area of the synovium is low relative to a high volume of synovial fluid volume (low SA:V ratio), resulting in delayed and probably reduced total drug delivery to the synovial fluid.

During RLP, equilibration to the tissues and the synovial fluid is enhanced in three ways: a change in pressure (1) and concentration (2) gradients and by a mechanical effect (3) to the endothelium. A tourniquet-induced rise in blood pressure results in dilation of venous capillaries and post-capillary venules (but not the arterioles), causing widening of the gaps between endothelial cells³ and an increased pressure gradient, improving drug diffusion to all tissues. This is able to overcome slow synovial delivery (due to low SA:V ratio) for synovial fluid. Vascular isolation by the proximal tourniquet maintains a very high drug concentration within the vascular space of the limb. The high concentration and wide concentration gradient speeds tissue and synovial fluid equilibration to a much higher plasma drug concentration. One final mechanism, unrelated to the RLP technique itself, for successful maintenance of high intra-articular drug concentrations (after RLP or IA injection) is again the effect of SA:V ratio on equilibration down a concentration gradient. The low SA:V ratio (low surface area of synovium to high volume of plasma) delays drug clearance by equilibration, allowing maintenance of high drug levels within the synovial fluid for longer periods, compared with other distal limb tissues.

Case Selection

Clinical application of RLP is most often performed in the treatment and prevention of musculoskeletal infections, including infections involving bones, joints, tendon sheaths, foot tissues, and soft tissues of the distal limb. There is clear benefit of RLP over systemic antimicrobials alone in synovial infections, especially when tissues are too swollen for intra-articular injection or in tissues with reduced perfusion, such as blunt trauma or skin flaps, where improved drug delivery would be paramount to prevent and treat infection. Even when intra-articular injection is possible, the two techniques can be combined (with same antimicrobial for both routes) for added clinical benefit; intra-articular injection will result in significantly higher synovial concentrations, RLP will result in significantly high interstitial and soft tissue concentrations, and both techniques will contribute equally to very high bone concentrations (see Reference 19). Although not routine, use of RLP as a stand-alone therapy for antimicrobial administration, without systemic antimicrobials, has been successful in cases in which antimicrobials are avoided because of antimicrobial-associated diarrhea or expense. Most often however, RLP is used in combination with systemic antimicrobial treatment as well as surgical debridement, topical therapy, and joint lavage when required.

There have been a few reports of successful RLP in foals,^4,5 and RLP has been successfully used in the author’s hospital in young foals (Figure 1). When RLP is used in the young foal, systemic anti-microbials should be always used concurrently to limit theoretical RLP-induced septicemia.⁶ If RLP with an aminoglycoside is elected in foals, it is critical to time RLP to coincide with administration of the systemic dose. Additionally, the RLP dose should be subtracted from the total body dose to derive the remaining drug dose to be given systemically. These measures are taken to avoid perturbing the normal drug trough levels, protecting against nephrotoxicity when using aminoglycosides.
 

Technique

Briefly, under heavy sedation, the vasculature of a limb is isolated through tourniquet application (proximal or proximal and distal tourniquets), so that perfusate (venous blood plus injected drug solution) leakage under the tourniquet to the systemic circulation is minimized. Distal to the tourniquet, an aseptically prepared vein is catheterized and antimicrobial solution is injected by slow infusion over 2 to 3 minutes. The site of venipuncture is wrapped to prevent extravasation of perfusate during RLP. The tourniquet is left in place and the patient is maintained in a stationary and sedated state for 25 to 30 minutes. After the perfusion period, the tourniquet is removed and the technique is repeated daily until local antimicrobial delivery is no longer required (Figure 2). [...]