Mark J. Acierno, MBA, DVM, DACVIM
Continuous Renal Replacement Therapy (CRRT) is a new blood purification modality that is rapidly gaining acceptance for the treatment of acute kidney injury in people and companion animals. As its name implies, CRRT is a slow, gradual process that results in the removal of uremic toxins as well as the correction of electrolyte, acid-base and fluid imbalances. Unlike intermittent dialysis, where the patient is treated for a specific time period several days a week, once a patient starts CRRT, the therapy continues until renal function recovers, or the patient is transitioned to intermittent dialysis. Both intermittent dialysis and CRRT utilize semi-permeable membranes contained within a dialyzer to purify blood; however, while intermittent dialysis is primarily a diffusive therapy, CRRT utilizes both convection and diffusion. This allows CRRT to remove larger molecules than can be achieved with intermittent dialysis.
Continuous Renal Replacement Therapy has several treatment and operational advantages over intermittent dialysis. First, CRRT's continuous, gradual nature and ability to remove larger molecules more closely resembles normal renal function.1 In addition, studies have shown that CRRT provides better control of electrolyte and acid-base balance.2 Intermittent dialysis attempts to make large hematologic changes in relatively short periods of time primarily utilizing diffusion. As a result, these systems require large amounts of sterile dialysate, which must be produced "on-site."3 This requires the operation and maintenance of complex water purification equipment. CRRT's more gradual nature combined with its efficient use of convection and diffusion allows the use of purchased, pre-packaged fluids. This allows the CRRT unit to be used "cage side" eliminating the need for separate dialysis rooms.
Since the first successful canine dialysis in 19134, the basis of all blood purification has been the division of a patient's blood into many straw-like, semi-permeable membranes and surrounding the membranes with dialysate. By adjusting the composition of the dialysate, substances can be made to enter or leave the blood by diffusion. In CRRT, blood purification also takes place in a dialyzer; however, CRRT can utilize both diffusion and convection.5,6 Convection puts blood within the dialyzer under pressure resulting in fluid being forced out of the blood and across the semi-permeable membrane.6,7 Toxins, electrolytes and other small molecules are carried with the fluid (ultrafiltrate) and removed. Convection is technically challenging as the ultrafiltrate and associated electrolytes must be replaced with great accuracy or the patient can quickly become dehydrated, over hydrated, or suffer electrolyte imbalances. The primary benefits of convection are that larger molecules can be removed and that there is a more economic use of fluid than with diffusion.6,8
Modes of Operation
CRRT combines the principals of diffusion and convection to provide four distinct treatment modalities: Slow continuous ultrafiltration (SCUF), continuous veno-venous hemofiltration (CVVH), continuous veno-venous hemodialysis (CVVHD) and continuous veno venous hemodiafiltration (CVVHDF). SCUF is a purely convective modality in which fluids removed from the patient are not returned. SCUF has been used to treat non-diuretic responsive fluid overload in people (Figure 1).6
Like SCUF, continuous veno-venous hemofiltration (CVVH) is a purely convective modality (Figure 2); however, in CVVH, the ultrafiltrate is replaced with a sterile, balanced, electrolyte solution.9 This solution can be added either before or after the dialyzer.10 Adding the fluid after the dialyzer is significantly more efficient in removing toxins; however, as the blood becomes increasingly hemoconcentrated within the semi-permeable membranes, there is an increased risk of sludging and clot formation. Since 20%-25% of blood volume can be safely removed without a significant decrease in filter life, we typically use a post-filter configuration. Regardless of whether the fluid is added before or after the dialyzer it is referred to as "replacement fluids." Interestingly, until recently, there were no FDA approved replacement fluids and CRRT dialysate fluids were used in an off-label manner. Even today this practice is quite common.
Continuous veno-venous hemodialysis (CVVHD) is a diffusive therapy, which is similar to intermittent dialysis except prepackaged fluids are utilized (Figure 3).11
Continuous veno-venous hemodiafiltration (CVVHDF) combines the diffusive aspects of CVVHD with the convective properties of CVVH (Figure 4).11 Convective forces force fluid out of the blood and across the semi-permeable membrane while the dialysate bathing the membranes results in the movement of smaller molecules by diffusion.
It is unclear which CRRT modality provides the most effective blood purification. Research has shown that the convective components of CVVH and CVVHDF provide a significant advantage in the removal of larger molecules from the blood; however, diffusive modalities such as CVVHD are just as effective at removing smaller molecules such as creatinine and urea. Currently, the role of larger molecules in patients with acute renal injury is unclear. Nevertheless, we have had good successes treating patients with CVVH and CVVHDF.
Proper anticoagulation is essential in preventing clotting of the CRRT circuit. This is important as a clotted circuit can result in the loss of a significant about of patient blood, require replacement of the costly CRRT circuit, and represents time in which the patient's blood is not purified. There are two commonly used methods of anticoagulation. One involves systemic anticoagulation of the patient with heparin the other involves localized anticoagulation of the CRRT circuit by the chelation of serum calcium. Both methods are associated with significant side effects. Heparin is associated with hemorrhage while calcium chelation can cause hypocalcemia and metabolic alkalosis. Based on and personal experience, ease of monitoring and cost, our facility uses heparin as an anticoagulant.
Indications for Use
The most common indication for employing CRRT is in cases of acute kidney injury where there is a belief that reasonable kidney function will return in a relatively short period of time (days to weeks). We have used CRRT to treat animals with kidney injury secondary to Leptospirosis, melamine toxicity and heatstroke. This has made managing anuric and oliguric renal injury significantly easier and given time for sufficient renal function to return. CRRT can also be used in acute kidney injury cases where renal function is not expected to recover in the immediate future so these cases can be transferred to a center that performs intermittent dialysis. While acute kidney injury is the primary indication for CRRT, it can be utilized to treat a toxin exposure or drug overdose. The ability of CRRT to remove these substances is dependent on the compounds' characteristics including: size, protein binding, and volume of distribution.12 Up-to-date listings of which drugs and toxins can be effectively removed by CRRT or dialysis are available.
Providing properly trained, technically competent patient care twenty-four hours a day is one of the most difficult aspects of performing CRRT. Since an advanced knowledge of renal physiology and the mechanics of the CRRT unit are essential for treatment decisions, the pool of capable doctors and support staff is likely to be limited. In our hospital, a doctor and a technician or trained veterinary student is always by the patient's side. When patients require more than a few days of treatment, the staffing issues can become challenging.
CRRT is a new set of tools for providing support to animals with acute kidney injury. Its primary use is in cases where there is reasonable evidence that the kidneys will return to function in the short term or for stabilization of patients that are to be transitioned to intermittent dialysis. Treatment of toxicosis is another use for CRRT. Although time, resource and personnel intensive, our experience has been that treating acute kidney injury patients with CRRT can be very rewarding.
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Figure 1. Slow continuous ultrafiltration (SCUF) Circuit. Used with permission: Veterinary learning systems.
Figure 2. Veno-venous hemofiltration (CVVH) circuit. Used with permission: Veterinary learning systems.
Figure 3. Continuous veno-venous hemodialysis (CVVHD) circuit. Used with permission: Veterinary learning systems.
Figure 4. Continuous veno-venous hemodiafiltration (CVVHDF) circuit. Used with permission: Veterinary learning systems.
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