Extracorporeal Blood Purification Techniques: From Dialysis to Plasm Apheresis
Blood purification techniques have gained a lot of interest for the treatment of small animal diseases in recent years. These therapies have evolved from empiric procedures adapted from the human medicine to experience- and study-based protocols adjusted or developed to meet the specific needs of small animals. In parallel, their spectrum of indications has progressed from the treatment of uremia to include the treatment of exogenous poisoning and the modulation of inflammation or the suppression of pathological immune responses in sepsis or immune-mediated diseases. The wider availability of these techniques and our better understanding of their indications and limitations have increased the interest of small animal clinicians so that they can now be viewed as belonging to the standard of advanced care for dogs and cats.
Types of Therapy
Intermittent hemodialysis (IHD), the original blood purification technique for the treatment of the uremic animal, has long been the reference therapy for dogs and cats with severe acute kidney injury (AKI). By using diffusion-based solute removal, the blood is progressively purified and the concentration of uremic solutes decreased. Hemodialysis therapy is typically performed on an intermittent basis with, initially, daily sessions of 3–5 hours followed by 3 treatments of 4–5 hours per week until recovery of sufficient renal function to be discontinued.
An alternative form of renal replacement not requiring expensive equipment and the extracorporeal circulation of blood is the peritoneal dialysis (PD) for which a solute (dialysate) is infused directly into the peritoneal cavity where the blood through the peritoneal membrane. Despite an apparent technical simpleness (does not require a machine), this form of therapy still requires experience and expertise to guide the therapy. Low efficiency, slow correction of the azotemia and risk of iatrogenic infections are among the main drawbacks of this therapy, although it is perfectly adequate for use in small animals and in particular very small patients.
Modifications of the basic principles of solute and water removal and adaptation of the hemodialysis technique to the unstable severely azotemic patient of very small size have evolved to the continuous renal replacement therapies (CRRT). In these techniques, removal of uremic solutes is mainly based on the principle of convection, where water is pulled through the dialysis membrane by hydrostatic pressure difference, dragging along the targeted plasma solutes. The main advantage of this more active form of solute removal is the possibility to shift the spectrum of those solutes to include also middle molecules such as certain inflammatory mediators. This technique is therefore considered particularly indicated in the inflamed animal with AKI, although a real advantage in this regard has not yet been proven. By allowing very low rates of clearance on a continuous form, these therapies are particularly adapted to the very small animal with very high levels of azotemia. The advantage of the continuous nature of the therapy is however counterbalanced by its disadvantages, including the need for continuous monitoring of very long treatments (several days or until renal recovery).
Newer dialysis delivery systems have been developed to provide various forms of treatment with enough versatility to allow easy switching between the available modalities, so that almost all conceivable combinations can be designed. Intermittent therapies can now provide a convenient combination of diffusion and convection (so-called hemodiafiltration) and machines designed to provide intermittent low-clearance therapies can now be used for intermittent therapies even in larger dogs (so-called prolonged intermittent renal replacement therapy).
Alternative forms of therapy rely mainly on the principle of adsorption with binding of unwanted solutes to a bed of activated charcoal or of other synthetic polymers. The technique of hemoperfusion (HP) is mainly conceived for the treatment of severe intoxications with highly protein-bound toxins (i.e., non-steroidal antiinflammatory drugs). The blood is either perfused directly over a bed of charcoal or polymer beads treated with a special coating to improve their hemocompatibility or it undergoes first a separation step and only the plasma or plasma water is brought in direct contact with the adsorptive substance before being mixed again with the blood cells (cascade HP). Main limitations of these techniques in veterinary medicine include the large size of the devices requiring large volumes of extracorporeal circuits, the limited availability of the technique, and the limited experience of most centers with this technique in small animals.
A further extension of the dialysis technology includes the use of filters with much higher filtration cutoffs to include molecules as large as immunoglobulins. The filtered fluid is therefore whole plasma that can be replaced with fresh plasma in order to decrease non-specifically the concentration of antibodies in immune-mediated diseases. This filtration-based therapeutic plasma exchange can now be provided safely to small animals, a welcome extension of our therapeutic possibilities for refractory immune diseases. Here also, a cascade technique allows the extracorporeal treatment of plasma before it is returned to the animal, decreasing markedly the amount of plasma needed as a replacement. Centrifugation-based techniques can also be used for plasma separation but they require different machines that on the other side also provide the possibilities to harvest other blood elements, including stem cells or platelets.
Although essential to provide renal replacement therapy, the availability of a dedicated machine is actually rarely the main factor limiting the development of a dialysis program. Far more restrictive is the availability of a dedicated and well-trained staff that can provide these forms of therapy in often very critical patients, realizing that most treatments are performed on an emergency basis after regular working hours.
Technically, our ability to provide renal replacement therapy requires an adequate vascular access, typically a large-bore double-lumen central venous catheter. Since this catheter represents the lifeline of the dialysis-dependent animal, it is essential not to use it for other purposes and to reserve it strictly for the dialysis treatments. It has to be handled aseptically and with adequate care, and it is usually locked with a concentrated heparin or citrate solution between the treatments. The volume of the extracorporeal circulation often defines which animal can be treated and it is preferred to restrict this volume to 15% of the animal's blood volume, although in special cases this can be extended to over 30% with appropriate priming fluids. The choice of the type of artificial kidney depends therefore most often on their respective blood side volume, more than on other technical characteristics.
The circulating blood typically remains in the circuit for 1–6 minutes depending on the blood flow chosen for a defined treatment. It therefore needs to be appropriately anticoagulated with either a systemic or a regional technique. Traditionally systemic heparinisation has been the anticoagulation method of choice for most animals and the animal receives a continuous rate infusion of unfractionated heparin after an initial bolus. Alternatively, particularly in animals with active bleeding, only the extracorporeal blood is anticoagulated with an infusion of trisodium citrate in the line to decrease the ionized calcium concentration in the extracorporeal blood to uncoagulable levels. A calcium infusion into the returning blood restores normocalcemia in the animal. This system of regional citrate anticoagulation allows the treatment of animals with active bleeding or immediately before/after surgery, but it also requires a close monitoring of the ionized calcium concentration to be provided safely.
Furthermore, cardiovascular, respiratory, and neurologic monitoring are essential parts of a safe procedure. Monitoring of the dialysis patient resembles in many aspects that of a critical patient undergoing anesthesia. A safe procedure will usually anticipate and prevent most complications and an adequately designed monitoring will help recognize potentially dangerous trends as early as possible.
Realistic expectations and appropriate communication with the animal's owner are essential for a satisfactory outcome. It is for example critical for the owner to realize that the procedure itself will have almost no effect on actual renal recovery, except by providing a more favorable body environment and more ample time for that recovery to happen (if it can happen). However is should be clear that only the most benign form of AKI have a reasonable chance to recover sufficiently in the minimal time available when only conventional therapy is available.
1. Cowgill LD. Urea kinetics and intermittent dialysis prescription in small animals. Vet Clin North Am Small Anim Pract. 2011;41(1):193–225.
2. Eatroff AE, et al. Long-term outcome of cats and dogs with acute kidney injury treated with intermittent hemodialysis: 135 cases (1997–2010). J Am Vet Med Assoc. 2012;241(11):1471–1478.
3. Cowgill LD, Francey T. Hemodialysis. In: DiBartola SP, ed. Fluid Therapy in Small Animal Practice. 4th edition. 2011.