Rolando Claure-Del Granado

Effluent Volume in Continuous Renal Replacement Therapy Overestimates the Delivered Dose of Dialysis

BACKGROUND AND OBJECTIVES Studies examining dose of continuous renal replacement therapy (CRRT) and outcomes have yielded conflicting results. Most studies considered the prescribed dose as the effluent rate represented by ml/kg per hour and reported this volume as a surrogate of solute removal. Because filter fouling can reduce the efficacy of solute clearance, the actual delivered dose may be substantially lower than the observed effluent rate. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Data were examined from 52 critically ill patients with acute kidney injury (AKI) requiring dialysis. All patients were treated with predilution continuous venovenous hemodiafiltration (CVVHDF) and regional citrate anticoagulation. Filter performance was monitored during the entire course of therapy by measuring blood urea nitrogen (BUN) and dialysis fluid urea nitrogen (FUN) at initiation and every 12 hours. Filter efficacy was assessed by calculating FUN/BUN ratios every 12 hours of filter use. Prescribed urea clearance (K, ml/min) was determined from the effluent rate. Actual delivered urea clearance was determined using dialysis-side measurements. RESULTS Median daily treatment time was 1413 minutes (1260 to 1440) with a total effluent volume of 46.4 ± 17.4 L and urea mass removal of 13.0 ± 7.6 mg/min. Prescribed clearance overestimated the actual delivered clearance by 23.8%. This gap between prescribed and delivered clearance was related to the decrease in filter function assessed by the FUN/BUN ratio. CONCLUSIONS Effluent volume significantly overestimates delivered dose of small solutes in CRRT. To assess adequacy of CRRT, solute clearance should be measured rather than estimated by the effluent volume.

Understanding kidney care needs and implementation strategies in low- and middle-income countries: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference

Evidence-based cinical practice guidelines improve delivery of uniform care to patients with and at risk of developing kidney disease, thereby reducing disease burden and improving outcomes. These guidelines are not well-integrated into care delivery systems in most low- and middle-income countries (LMICs). The KDIGO Controversies Conference on Implementation Strategies in LMIC reviewed the current state of knowledge in order to define a road map to improve the implementation of guideline-based kidney care in LMICs. An international group of multidisciplinary experts in nephrology, epidemiology, health economics, implementation science, health systems, policy, and research identified key issues related to guideline implementation. The issues examined included the current kidney disease burden in the context of health systems in LMIC, arguments for developing policies to implement guideline-based care, innovations to improve kidney care, and the process of guideline adaptation to suit local needs. This executive summary serves as a resource to guide future work, including a pathway for adapting existing guidelines in different geographical regions.

Fluid overload in the ICU: evaluation and management

BackgroundFluid overload is frequently found in acute kidney injury patients in critical care units. Recent studies have shown the relationship of fluid overload with adverse outcomes; hence, manage and optimization of fluid balance becomes a central component of the management of critically ill patients.DiscussionIn critically ill patients, in order to restore cardiac output, systemic blood pressure and renal perfusion an adequate fluid resuscitation is essential. Achieving an appropriate level of volume management requires knowledge of the underlying pathophysiology, evaluation of volume status, and selection of appropriate solution for volume repletion, and maintenance and modulation of the tissue perfusion. Numerous recent studies have established a correlation between fluid overload and mortality in critically ill patients. Fluid overload recognition and assessment requires an accurate documentation of intakes and outputs; yet, there is a wide difference in how it is evaluated, reviewed and utilized. Accurate volume status evaluation is essential for appropriate therapy since errors of volume evaluation can result in either in lack of essential treatment or unnecessary fluid administration, and both scenarios are associated with increased mortality. There are several methods to evaluate fluid status; however, most of the tests currently used are fairly inaccurate. Diuretics, especially loop diuretics, remain a valid therapeutic alternative. Fluid overload refractory to medical therapy requires the application of extracorporeal therapies.SummaryIn critically ill patients, fluid overload is related to increased mortality and also lead to several complications like pulmonary edema, cardiac failure, delayed wound healing, tissue breakdown, and impaired bowel function. Therefore, the evaluation of volume status is crucial in the early management of critically ill patients. Diuretics are frequently used as an initial therapy; however, due to their limited effectiveness the use of continuous renal replacement techniques are often required for fluid overload treatment. Successful fluid overload treatment depends on precise assessment of individual volume status, understanding the principles of fluid management with ultrafiltration, and clear treatment goals.

Effluent volume and dialysis dose in CRRT: time for reappraisal

The results of several studies assessing dialysis dose have dampened the enthusiasm of clinicians for considering dialysis dose as a modifiable factor influencing outcomes in patients with acute kidney injury. Powerful evidence from two large, multicenter trials indicates that increasing the dialysis dose, measured as hourly effluent volume, has no benefit in continuous renal replacement therapy (CRRT). However, some important operational characteristics that affect delivered dose were not evaluated. Effluent volume does not correspond to the actual delivered dose, as a decline in filter efficacy reduces solute removal during therapy. We believe that providing accurate parameters of delivered dose could improve the delivery of a prescribed dose and refine the assessment of the effect of dose on outcomes in critically ill patients treated with CRRT.

Toward the optimal dose metric in continuous renal replacement therapy

Purpose: There is no consensus on the optimal method to measure delivered dialysis dose in patients with acute kidney injury (AKI). The use of direct dialysate-side quantification of dose in preference to the use of formal blood-based urea kinetic modeling and simplified blood urea nitrogen (BUN) methods has been recommended for dose assessment in critically-ill patients with AKI. We evaluate six different blood-side and dialysate-side methods for dose quantification. Methods: We examined data from 52 critically-ill patients with AKI requiring dialysis. All patients were treated with pre-dilution CVVHDF and regional citrate anticoagulation. Delivered dose was calculated using blood-side and dialysis-side kinetics. Filter function was assessed during the entire course of therapy by calculating BUN to dialysis fluid urea nitrogen (FUN) ratios q/12 hours. Results: Median daily treatment time was 1,413 min (1,260–1,440). The median observed effluent volume per treatment was 2,355 mL/h (2,060–2,863) (p<0.001). Urea mass removal rate was 13.0±7.6 mg/min. Both EKR (r2=0.250; p<0.001) and KD (r2=0.409; p<0.001) showed a good correlation with actual solute removal. EKR and KD presented a decline in their values that was related to the decrease in filter function assessed by the FUN/BUN ratio. Conclusions: Effluent rate (mL/kg/h) can only empirically provide an estimated of dose in CRRT. For clinical practice, we recommend that the delivered dose should be measured and expressed as KD. EKR also constitutes a good method for dose comparisons over time and across modalities.

Assessing and Delivering Dialysis Dose in Acute Kidney Injury

Assessing and delivering dialysis dose in acute kidney injury (AKI) has emerged as an important issue in the management of critically ill patients. There is ongoing debate on how dose of dialysis should be expressed and measured. Most studies have focused on clearance of small molecules (blood urea nitrogen) as a marker of delivered dose and for establishing dose–outcome relationships. Recent evidence has shown that other markers may also be important to consider, as acid–base balance and fluid overload have emerged as important factors contributing to outcomes. In this review, we provide an evaluation of current approaches to prescribing and delivering dialysis dose in AKI, identify gaps in practice and propose an integrated approach to optimize dose delivery in dialysis with a goal to improve outcomes.

Anticoagulation, delivered dose and outcomes in CRRT: The program to improve care in acute renal disease (PICARD)

Delivered dialysis dose by continuous renal replacement therapies (CRRT) depends on circuit efficacy, which is influenced in part by the anticoagulation strategy. We evaluated the association of anticoagulation strategy used on solute clearance efficacy, circuit longevity, bleeding complications, and mortality. We analyzed data from 1740 sessions 24 h in length among 244 critically ill patients, with at least 48 h on CRRT. Regional citrate, heparin, or saline flushes was variably used to prevent or attenuate filter clotting. We calculated delivered dose using the standardized Kt/Vurea. We monitored filter efficacy by calculating effluent urea nitrogen/blood urea nitrogen ratios. Filter longevity was significantly higher with citrate (median 48, interquartile range [IQR] 20.3–75.0 hours) than with heparin (5.9, IQR 8.5–27.0 hours) or no anticoagulation (17.5, IQR 9.5–32 hours, P < 0.0001). Delivered dose was highest in treatments where citrate was employed. Bleeding complications were similar across the three groups (P = 0.25). Compared with no anticoagulation, odds of death was higher with the heparin use (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.02–3.32; P = 0.033), but not with citrate (OR 1.02 95% CI 0.54–1.96; P = 0.53). Relative to heparin or no anticoagulation, the use of regional citrate for anticoagulation in CRRT was associated with significantly prolonged filter life and increased filter efficacy with respect to delivered dialysis dose. Rates of bleeding complications, transfusions, and mortality were similar across the three groups. While these and other data suggest that citrate anticoagulation may offer superior technical performance than heparin or no anticoagulation, adequately powered clinical trials comparing alternative anticoagulation strategies should be performed to evaluate overall safety and efficacy.

Withholding and Withdrawing Renal Support in Acute Kidney Injury

Management of critically ill patients with acute kidney injury (AKI) is mainly limited to supportive therapy, with dialysis as one of the main components. Whether or not to offer dialysis and when to withdraw dialysis is a one of the many choices physicians face in daily clinical practice. Withholding or withdrawing renal replacement therapy is a complex decision and depends on many interacting factors, which are unique for each patient and their families and for the care team. An evidence‐based guideline with nine specific recommendations for managing patients has been available however is infrequently employed to help clinical decision making. In this review, we discuss the important issues affecting decisions to withhold or withdraw dialysis in AKI patients and provide an approach for making these decisions for patient management.

Principles of Anticoagulation in Extracorporeal Circuits

Abstract Intermittent and continuous dialysis therapies depend on adequate anticoagulation in their extracorporeal circuit (ECC) to maximize circuit and filter longevity, which will increase clearance and lessen costs and nurse time requirements. Insufficient anticoagulation results in decreased filter performance, clotting, and blood loss. Excessive anticoagulation leads to bleeding complications, which occur in 5% to 26% of treatments. Patients with acute kidney injury (AKI) are at risk for hemorrhagic and thrombotic complications. The goal of the nephrologist remains prolongation of ECC life in the safest manner possible for the patient. Use of replacement fluids in prefilter mode and avoidance of excessive ultrafiltration and blood flow reductions also can lead to improved circuit patency. Although unfractionated heparin remains the most commonly used anticoagulant, there are now an increasing number of other options; these include low-molecular-weight heparin, heparinoids, direct thrombin inhibitors, prostanoids, and serine protease inhibitors. When choosing the type of anticoagulation for renal replacement therapies in AKI, the clinician must consider several aspects, such as the half-life, how to monitor, how to reverse the effect in case of severe bleeding, if the anticoagulant is dialyzable or not, and how to balance the benefits and risk of each drug.

Components of Fluid Balance and Monitoring

Abstract Fluid administration is frequently used in hospitalized patients. The most common reasons for fluid administration include hypotension, shock, sepsis, hypovolemia, replacement of fluid losses, and oliguria. Prompt resuscitation of patients with hypoperfusion with intravenous fluids has been shown to improve outcomes. However, approximately 50% of hemodynamically unstable patients will respond to fluid administration. For many clinicians, the current approach to fluid resuscitation focuses on blood pressure and cardiac output (CO). Bedside echocardiographic assessment also can be useful. If a patient responds to a fluid challenge of 250 mL by a 10% to 15% increase in stroke volume (SV) or CO, further fluids can be given as long as there is a positive response. This approach allows avoiding excessive fluid administration, which has been associated with worse cardiopulmonary and kidney outcomes, delayed wound healing, and decreased survival. Therefore, even if an initial fluid resuscitation is required, subsequent approaches aiming for neutral and negative fluid balance can be required, including conservative fluid administration, diuretics, and/or dialysis. In conclusion, fluid therapy in critically ill patients is a dynamic process. Individual assessment of fluid requirements and timing of fluid administration are needed, as well as frequent reassessment of response and ongoing needs. Studies are required to assess the benefits of conservative, hemodynamically guided fluid resuscitation strategy and early use of vasopressors, as well as to optimize techniques to manage fluid overload. In this chapter, we review physiologic aspects related to fluid status, the four phases of fluid resuscitation, and assessment of fluid volume, fluid responsiveness, and fluid overload. We also summarize the pathogenesis of fluid overload and its association with adverse outcomes and comment on practical issues regarding fluid administration, removal, and monitoring.