Continuous KRT: A Contemporary Review

Abstract

AKI is a common complication of critical illness and is associated with substantial morbidity and risk of death. Continuous KRT comprises a spectrum of dialysis modalities preferably used to provide kidney support to patients with AKI who are hemodynamically unstable and critically ill. The various continuous KRT modalities are distinguished by different mechanisms of solute transport and use of dialysate and/or replacement solutions. Considerable variation exists in the application of continuous KRT due to a lack of standardization in how the treatments are prescribed, delivered, and optimized to improve patient outcomes. In this manuscript, we present an overview of the therapy, recent clinical trials, and outcome studies. We review the indications for continuous KRT and the technical aspects of the treatment, including continuous KRT modality, vascular access, dosing of continuous KRT, anticoagulation, volume management, nutrition, and continuous KRT complications. Finally, we highlight the need for close collaboration of a multidisciplinary team and development of quality assurance programs for the provision of high-quality and effective continuous KRT.

Figure 1

CKRT achieves superior volume control than intermittent HD in patients with critical illness. (A) Fluid accumulation over time in patients on CKRT and on intermittent HD. Percentage of fluid accumulation was calculated as fluid balance (fluid intake in liters minus total output in liters) divided by baseline body weight (in kilograms). Data from the Program to Improve Care in Acute Renal Disease (PICARD) study. (B) Twenty-four–hour total fluid balance (I/Os, in milliliters) during the first 3 days of KRT in patients on intermittent HD and CVVHD therapy. Shown are median values with interquartile range (box borders) and extreme values (whiskers). CKRT, continuous KRT; CVVHD, continuous venovenous hemodialysis; HD, hemodialysis. (A) Reprinted from ref. , with permission. (B) Reprinted from ref. , with permission.

Figure 2

CKRT is less likely than intermittent HD to exacerbate intracranial hypertension or to decrease cerebral perfusion pressure. (A) In a patient with kidney failure after neurosurgical evacuation of a subdural hematoma, the start of intermittent HD is associated with a significant fall in mean arterial BP (MAP) and a significant rise in intracranial pressure (ICP). Cerebral perfusion pressure (CPP) in patients with intracranial hypertension is the difference between MAP and ICP (i.e., CPP=MAP–ICP) and is represented in this figure by the gray shaded area. The dual effects of decreased MAP and increased ICP with intermittent HD initiation can combine to produce a dramatic reduction in CPP. (B) Changes in mean ICP during intermittent HD and continuous venovenous hemodiafiltration (CVVHDF). In contrast to intermittent HD, CKRT, due to slower solute removal and more gradual changes in plasma osmolality, has minimal effect on ICP. (C) Reduction in plasma osmolality after 1 hour of treatment with intermittent HD and continuous venovenous hemofiltration (CVVH) at a total effluent dose of approximately 2 L/h. Shown are means (bars) and SEM (whiskers). *P<0.05 for comparison with intermittent HD. Reprinted or adapted from refs. and , with permission.

Figure 3

Modalities of CKRT utilize primarily convective clearance (hemofiltration), diffusive clearance (hemodialysis), or both. (A) In hemofiltration, solute clearance occurs primarily by convection. In convection, solutes are transported across the hemofilter membrane along with plasma water as a result of a hydrostatic pressure (i.e., transmembrane pressure) generated on the blood side of the membrane. Solutes cleared by convection include urea and other small molecules along with larger “middle molecules.” (B) In HD, solute clearance occurs primarily by diffusion, which is driven by a concentration gradient across the semipermeable membrane. Small solutes in high concentration in the blood diffuse across the membrane into the dialysate, which contains either little (e.g., potassium) or none (e.g., urea) of the solutes being cleared. Small solutes in higher concentration in the dialysate (e.g., bicarbonate) diffuse into the blood. Dialysate runs across the HD membrane countercurrent to the direction of blood flow to maintain a concentration gradient for removal of small solutes along the entire length of the semipermeable membrane. Modern hemodialyzers are virtually all “high-flux” dialyzers, which clear substances larger than historical low-flux dialyzers. However, unlike hemofiltration, HD does not effectively clear larger middle molecules. Ultrafiltration can be performed with HD by applying a transmembrane pressure across the membrane, but, in contrast to the high volume of ultrafiltration used to achieve significant solute clearance in hemofiltration, the volumes of ultrafiltration performed in HD are relatively small, contribute little to solute clearance, and are instead used only to achieve net volume removal. (C) In CVVH, a high volume of ultrafiltrate is generated and is replaced with an equal or (if net volume removal is desired) a somewhat smaller amount of physiologic crystalloid solution to effect net solute removal. The physiologic solution may be infused before the hemofilter (prefilter replacement fluid), into the return line (postfilter replacement fluid), or both. The net ultrafiltration rate (UF) is equal to the difference between the effluent rate and the replacement fluid rates (Qr), and it is adjusted to achieve net volume removal as desired. A typical CVVH prescription is shown, which, for a 70-kg patient, would provide a total dose of 30 ml/kg per hour and a net ultrafiltration rate of 100 ml/h (1.4 ml/kg per hour). To maintain efficient solute clearance in CVVH, blood flow rate (Qb) should be kept approximately five to six times higher than the replacement fluid rates. (D) In CVVHD, dialysate is driven through the dialyzer across the membrane from the blood flow in a direction countercurrent to blood flow. In most settings, the dialysate solution used in CVVHD is very similar or identical to the replacement fluid used in CVVH. In contrast to CVVH, ultrafiltration in CVVHD makes only minor contribution to solute removal but is performed primarily for the purposes of volume management, with ultrafiltrate generated at a rate equal to the desired rate of fluid removal. The effluent consists of both the spent dialysate and ultrafiltrate, and the net ultrafiltration rate is equal to the difference between the total effluent flow rate and the dialysate flow rate (Qd). A typical CVVHD prescription is shown, which, for a 70-kg patient, again provides a total dose of 30 ml/kg per hour and a net ultrafiltration rate of 100 ml/h (1.4 ml/kg per hour). To maintain efficient solute clearance in CVVHD, blood flow rate should be kept approximately 2.5 times higher than the dialysate flow rate. (E) CVVHDF combines a high volume of ultrafiltration coupled with replacement fluid (to achieve solute clearance by convection) with dialysate perfused across the membrane countercurrent to blood flow (to achieve solute clearance by diffusion). As in CVVH, ultrafiltrate volume in excess of the desired rate of fluid removal is replaced with a physiologic crystalloid solution that may be infused before the hemofilter (prefilter replacement fluid), into the return line (postfilter replacement fluid), or both. The effluent consists of both the spent dialysate and ultrafiltrate with the net ultrafiltration rate equal to the difference between the total effluent flow rate and the sum of dialysate and total replacement fluid flow rates. A typical CVVHD prescription is shown, which, for a 70-kg patient, again provides a total dose of 30 ml/kg per hour and a net ultrafiltration rate of 100 ml/h (1.4 ml/kg per hour). Adapted from refs. and , with permission.

Figure 4

Net ultrafiltration rate is independently associated with mortality in patients treated with CKRT. The relationship between mortality and net ultrafiltration (UF_NET) in patients in the intensive care unit (ICU) with AKI is J shaped. In a post hoc analysis of >1400 patients from the Randomized Evaluation of Normal versus Augmented Level Replacement Therapy study comparing high versus low dose of CKRT for AKI in the ICU, low UF_NET rates <1.01 ml/kg per hour and high UF_NET rates >1.75 ml/kg per hour were associated with higher risk-adjusted 90-day mortality compared with UF_NET rates in a middle range of 1.01–1.75 ml/kg per hour. It has been proposed that these effects are mediated by harms of organ edema in those treated with low UF_NET rates and by organ ischemia in those treated with high UF_NET rates, but no prospective trial data yet exist to demonstrate that targeting a moderate rate of UF_NET improves outcomes. Data from Murugan et al. Reprinted from ref. , with permission.