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Purpose: To evaluate the efficacy of the novel oXiris® membrane in critically ill adult patients., Methods: We systematically searched MEDLINE, EMBASE, and CENTRAL from inception to 01/06/2023 for relevant randomised controlled trials (RCTs) and non-randomised studies of intervention (NRSI). The primary outcome was overall mortality. Random effect meta-analyses were conducted in RevMan 5.4.1. Study quality was evaluated using Cochrane's risk of bias tool. (PROSPERO: CRD42023389198)., Results: Ten studies (2 RCTs and 8 NRSIs) with 481 patients were included. None had low risk of bias. Treatment using oXiris® was associated with reduced overall mortality (RR 0.78, 95%CI 0.62-0.98; p = 0.03; 6 NRSI). One RCT reported 28-day mortality, finding no significant difference between groups. Besides, pooled NRSIs results showed significant reductions in SOFA scores, norepinephrine dosage, and several inflammatory biomarkers (C-reactive protein [CRP], lactate, and interleukin-6 [IL-6]) post oXiris® treatment. However, other clinical outcomes (ICU and hospital length of stay, mechanical ventilation duration) were similar between groups., Conclusion: In critically ill patients, the use of oXiris® membrane was associated with reduced overall mortality, norepinephrine dosage, CRP, IL-6, lactate levels, along with improved organ function. However, the certainty of evidence was very low, necessitating high-quality RCTs to further evaluate its efficacy in this population., Competing Interests: Declaration of competing interest None., (Copyright © 2023. Published by Elsevier Inc.)

Sepsis is the primary cause of acute kidney injury in critically ill patients. During the past decades, several extracorporeal blood purification techniques have been developed for sepsis and sepsis-induced acute kidney injury management. These therapies could act on both the infectious agent itself and the host immune response. In this article, we review the available literature discussing the different extracorporeal blood purification techniques, including high-volume hemofiltration, cascade hemofiltration, hemoperfusion, coupled plasma filtration adsorption, plasma exchange, and specific optimized renal replacement therapy membranes., (Copyright © 2019. Published by Elsevier Inc.)

Purpose: To determine the effect on strong ion difference of citrate as an anticoagulant during continuous veno-venous hemofiltration (CVVH)., Materials and Methods: ICU patients with renal failure and CVVH were included. Patients were treated with either nadroparin (N) or sodium citrate (C) as an anticoagulant. Strong ion difference (SID) apparent (SIDa) and SID effective (SIDe) and strong ion gap (SIG) were calculated at t = 0 and t = 24 h. Citrate concentration was measured in the citrate treated patients., Results: Ten patients with N and nine with C were included. In both groups the SIDa did not change significantly. SIG decreased significantly with N (11.4 ± 4.2 to 4.0 ± 3.1 meq/l; p = 0.005) but not with C (9.3 ± 1.9 to 8.1 ± 2.4 meq/l; p = 0.097). The decrease was significantly greater for N compared to C; p = 0.014. This is reflected by the SIDe which increased significantly (p = 0.022) more from 24.7 ± 4.5 to 32.9 ± 3.9 (p = 0.005) for N and from 26.3 ± 5.8 to 29.6 ± 1.6 for C (p = 0.058)., Conclusion: Citrate anticoagulation results in a persistently high SIG during CVVH compared to nadroparin. This is associated with the presence of unmeasured anions such as citrate in the systemic circulation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objectives: This study was designed to determine whether venovenous extracorporeal membrane oxygenation (VV ECMO) reduced mortality in patients with influenza-related acute respiratory distress syndrome (ARDS)., Design: A retrospective cohort study was performed. Baseline characteristics of participants were compared and Kaplan-Meier survival analysis was used to compare survival at last medical center follow-up. Cox proportional hazards modeling also was performed to test for univariate associations between salient variables and mortality., Setting: A single-center ECMO referral university hospital., Participants: All patients admitted with influenza-related ARDS during the 2015 to 2016 influenza season., Interventions: Mechanical ventilation alone versus mechanical ventilation and ECMO cannulation., Measurements and Main Results: A total of 26 patients with influenza-related ARDS were included in the cohort. Thirteen patients were treated with VV ECMO while 13 were not. Twelve of the ECMO patients and 8 of the non-ECMO patients were transferred from outside hospitals. Patients treated with ECMO were younger and had less hypertension and diabetes mellitus. There was no difference in baseline sequential organ failure assessment score between the 2 groups. In-hospital mortality for ECMO patients was 15.4% versus 46.7% for patients not treated with ECMO. Survival at last medical center follow-up was better in patients treated with ECMO (p = 0.02). Age, highest blood carbon dioxide level, and treatment without ECMO were all associated with increased mortality., Conclusions: Influenza-related ARDS has a high mortality rate and patients treated only with mechanical ventilation have worse outcome than those managed with VV ECMO. More liberal use of ECMO should be considered in patients with influenza-related ARDS., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Acute kidney injury (AKI) occurs frequently in the surgical intensive care unit and results in significant morbidity and mortality. AKI needs to be identified early and underlying causes treated or eliminated. Sepsis, major surgery such as coronary artery bypass, and hypovolemia are the most common causes and patients with underlying comorbidities have increased susceptibility. Treatment should begin by ensuring that patients are adequately resuscitated and all contributing causes are replaced or eliminated. After stabilization of hemodynamic status and elimination of contributing causes, treatment becomes largely supportive and may require the use of a renal replacement therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of ultrafiltration on interleukins, TNF-α levels, and pulmonary function in patients undergoing coronary artery bypass grafting (CABG)., Design: Prospective, randomized, controlled trial., Setting: University hospital., Participants: Forty patients undergoing CABG were randomized into a group assigned to receive ultrafiltration (UF) during cardiopulmonary bypass (CPB) or into another group (control) that underwent the same procedure but without ultrafiltration., Methods: Interleukins and TNF-α levels, pulmonary gas exchange, and ventilatory mechanics were measured in the preoperative, intraoperative, and postoperative periods. Interleukins and TNF-α also were analyzed in the perfusate of the test group., Measurements and Main Results: There were increases in IL-6 and IL-8 at 30 minutes after CPB and 6, 12, 24, and 36 hours after surgery, along with an increase in TNF-α at 30 minutes after CPB and 24, 36, and 48 hours after surgery in both groups. IL-1 increased at 30 minutes after CPB and 12 hours after surgery, while IL-6 increased 24 and 36 hours after surgery in the UF group. The analysis of the ultrafiltrate showed the presence of TNF-α and traces of IL-1β, IL-6, and IL-8. There were alterations in the oxygen index, alveolar-arterial oxygen difference, deadspace, pulmonary static compliance and airway resistance after anesthesia and sternotomy, as well as in airway resistance at 6 hours after surgery in both groups, with no difference between them., Conclusions: Ultrafiltration increased the serum level of IL-1 and IL-6, while it did not interfere with gas exchange and pulmonary mechanics in CABG., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Extended daily dialysis (EDD) has been suggested as an effective renal replacement therapy for acute kidney injury. However, results from studies comparing EDD to continuous renal replacement therapy (CRRT) are inconclusive., Study Design: A systematic review and meta-analysis was performed by searching in MEDLINE, EMBASE, the Cochrane Library, Google Scholar, and a Chinese database (SinsoMed)., Setting & Population: Patients with acute kidney injury., Selection Criteria for Studies: Randomized controlled trials (RCTs) and observational studies were included. EDD was defined as extended hemodialysis or hemodiafiltration for more than 6 but less than 24 hours per session using a conventional hemodialysis machine., Intervention: Renal replacement therapy comparing EDD with CRRT., Outcomes: Mortality, kidney recovery, and fluid removal., Results: We included 17 studies from 2000 to 2014: 7 RCTs and 10 observational studies involving 533 and 675 patients, respectively. Meta-analysis of RCTs showed no difference in mortality rates between EDD and CRRT (relative risk, 0.90; 95% CI, 0.74-1.11; P=0.3). However, EDD was associated with lower mortality risk compared with CRRT in observational studies (relative risk, 0.86; 95% CI, 0.74-1.00; P=0.05). There was no evidence of heterogeneity in RCTs (I(2)=0%) or observational studies (I(2)=15%). In both RCTs and observational studies, there were no significant differences in recovery of kidney function, fluid removal, or days in the intensive care unit, and EDD showed similar biochemical efficacy to CRRT during treatment (serum urea, serum creatinine, and serum phosphate)., Limitations: The survival benefit of EDD is dependent on only observational studies and might have been affected by allocation or selection bias., Conclusions: EDD is associated with similar outcomes to CRRT in RCTs. The finding that EDD is associated with a lower mortality rate relies on data from observational studies, which are potentially subject to allocation or selection bias, making further high-quality RCTs desirable., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Acute kidney injury (AKI) is a well-known complication in critically ill patients. Little is known about the timing and the ultrafiltration dose after initial resuscitation. In vivo microscopy of the microcirculation has been suggested as alternative for the assessment of volume status. Previous studies contribute to the understanding that intravascular hypovolemia is reflected by microcirculatory blood flow changes not detected by conventional methods. The aim of our study was to assess microcirculatory blood flow changes during negative fluid balance ultrafiltration in patients with oliguric AKI., Materials and Methods: Patients with oliguric AKI on renal replacement therapy were included after hemodynamic stabilization. Target was a predefined negative fluid balance; subsequently, a stepwise decrease in amount of substitution fluid was achieved. The data were recorded at baseline and after each change., Results: Fifteen patients were included in the study. Microcirculatory blood flow index did not change significantly between baseline and endpoint (2.90 [2.87-3.00] vs 2.90 [2.75-3.00], P=.57). During treatment, heart rate decreased from 96 (80-111) to 94 (79-110) beats per minute (P=.01), without a significant change in mean arterial blood pressure (80 [68-95 mm Hg] vs 79 [65-91 mm Hg], P=.5)., Conclusion: Microcirculatory blood flow is not altered by reduced substitution during renal replacement therapy., (Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.)

Patients with hypervolemic hyponatremia and kidney failure pose a special therapeutic challenge. Hemodialysis to correct volume overload, azotemia, and abnormal electrolyte levels will result in rapid correction of serum sodium concentration and place the patient at risk for osmotic demyelination syndrome. We present a patient with acute kidney injury and severe hypervolemic hypotonic hyponatremia (serum sodium<100 mEq/L) who was treated successfully with continuous venovenous hemofiltration. This teaching case illustrates the limitations of hemodialysis and demonstrates how to regulate the sodium correction rate by single-pool sodium kinetic modeling during continuous venovenous hemofiltration. Two methods to adjust the replacement fluid to achieve the desired sodium concentration are outlined., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the clinical effects of a combined ultrafiltration strategy on the surgical treatment of pediatric patients with congenital heart diseases., Design: A prospective, randomized, controlled study., Setting: A single-institution study in an affiliated hospital of a university., Participants: Sixty-five pediatric patients who underwent open heart surgery with cardiopulmonary bypass (CPB) to treat congenital heart disease were enrolled. The participants were randomized into 2 groups: conventional + modified ultrafiltration (MUF) (CM) group and prime + zero-balanced + MUF (PZM) group., Interventions: In the CM group (n = 33), conventional ultrafiltration was performed after removal of the aortic clamp, and MUF was performed after the completion of CPB. In the PZM group (n = 32), ultrafiltration was performed for the circuit prime solution, zero-balance ultrafiltration was performed after removal of the aortic clamp, and MUF was performed after the completion of CPB., Measurements and Main Results: The blood gas parameters and tumor necrosis factor alpha content in the priming solution and perioperative blood samples were analyzed. Postoperative parameters, including mechanical ventilation time, respiratory indices, intensive care unit time, and hospital time, also were recorded. One hospital death occurred in each group. No severe complications occurred in either group. The lactic acid, glucose, and tumor necrosis factor alpha contents in the priming solution and perioperative blood samples were significantly lower in the PZM group compared with the CM group. The respiratory indices were statistically significantly better in the PZM group compared with the CM group in the early postoperative period. No significant differences were found between the 2 groups regarding the postoperative ventilation time, inotropic support, homologous blood transfusion, drainage, intensive care unit time, or postoperative hospital time., Conclusion: The combined use of ultrafiltration of prime solution, zero-balance ultrafiltration, and MUF strategy is associated with a modest improvement in pulmonary function compared with the combination of conventional and MUF strategies in the early postoperative period, but the principal clinical outcomes are similar., (Copyright © 2013 Elsevier Inc. All rights reserved.)

ESRD patients are admitted more frequently to intensive care units (ICUs) and have higher mortality risks than the general population, and the main causes of critical illness among ESRD patients are cardiovascular events, sepsis, and bleeding. Once in the ICU, hemodynamic stabilization and fluid-electrolyte management pose major challenges in oligoanuric patients. Selection of renal replacement therapy (RRT) modality is influenced by the outpatient modality and access, as well as severity of illness, renal provider experience, and ICU logistics. Currently, most patients receive intermittent hemodialysis or continuous RRT with temporary vascular access catheters. Acute peritoneal dialysis (PD) is less frequently utilized, and utility of outpatient PD is reduced after an ICU admission. Thus, preservation of current vascular accesses, while limiting venous system damage for future access creations, is relevant. Also, dosing of small-solute clearance with urea kinetic modeling is difficult and may be supplanted by novel online clearance techniques. Medication dosing, coordinated with delivered RRT, is essential for septic patients treated with antibiotics. A comprehensive, standardized approach by a multidisciplinary team of providers, including critical care specialists, nephrologists, and pharmacists, represents a nexus of care that can reduce readmission rates, morbidity, and mortality of vulnerable ESRD patients., (Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Heart failure is a syndrome in which myocardial function is incapable of providing for normal physiologic needs. In the acute care setting, cardiac dysfunction primarily manifests with volume perturbations and presents with signs and symptoms of vascular congestion. Thus, in acute heart failure volume assessment is crucial in diagnosing and improving the prognosis. Also, goal-directed therapy relies on accurate volume assessment to minimize the adverse outcomes of inappropriate, ineffective, or excessive diuresis. Currently, in most institutions clinical methods of volume assessment are the mainstay. However, these methods are highly dependent on the practitioners' skill level. In fact, there is a high variability between experienced physicians when assessing volume. As adjuncts, objective methods of volume assessment are being developed and used such as natriuretic peptides, bioimpedance analysis, and imaging., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Acute decompensated heart failure and fluid overload are the most common causes of hospitalization in heart failure patients and they often contribute to disease progression. Initial treatment encompasses intravenous diuretics, although there might be a percentage of patients refractory to this pharmacologic approach. New technologies have been developed to perform extracorporeal ultrafiltration in fluid-overloaded patients. Newer simplified devices permit ultrafiltration to be performed with peripheral venous access and low blood flows, making ultrafiltration feasible at most hospitals and acute care settings. Extracorporeal ultrafiltration then is prescribed and conducted by specialized teams and fluid removal is planned to restore a status of hydration close to normal. Recent clinical trials, and European and North American practice guidelines, suggest that ultrafiltration is reasonable for patients with refractory congestion not responding to medical therapy and assigned to this recommendation a class IIa, level of evidence B. It seems that a close collaboration between nephrologists and cardiologists may be the key for a collaborative therapeutic effort in heart failure patients. Further studies suggest that wearable technologies might become available soon to treat patients in ambulatory and de-hospitalized settings. These new technologies may help to cope with the increasing demand for care of chronic heart failure patients., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: In continuous venovenous hemofiltration (CVVH) issues like timing and dose remain controversial, particularly in sepsis. The objective of this study is to examine which CVVH characteristic best predicts mortality in sepsis-induced acute kidney injury (AKI)., Materials and Methods: We retrospectively studied all consecutive patients with sepsis-induced AKI requiring CVVH in a 1.5-year period. Patient, sepsis, and CVVH characteristics, including timing, dose, mode, type of substitution fluid and of anticoagulation, and azotemic control were evaluated. Primary outcome was survival at day 28 after the start of CVVH., Results: Of the 97 patients, 43 (44%) died up to day 28 after the start of CVVH. In univariate analyses, the delivered dose of CVVH was about 10% higher in survivors than nonsurvivors (median, 23 vs 20 mL kg(-1) h(-1), P = .01). In multivariate analyses, a lower delivered CVVH dose contributed to predict higher mortality, independently of disease severity, type of substitution fluid, and azotemic control. In a Kaplan-Meier curve, a delivered dose less than 19.7 mL kg(-1) h(-1) was associated with shorter survival (P = .006)., Conclusion: Our retrospective data suggest that in sepsis-induced AKI requiring CVVH, delivered dose, rather than timing, mode of administration, and azotemic control, is an independent predictor of mortality. A lower delivered dose is associated with higher mortality., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Studies investigating the metabolic effects of citrate-based substitution fluids are lacking. This study aims to compare the effect of citrate- vs bicarbonate-based substitution fluid used during continuous venovenous hemofiltration (CVVH) for acute kidney injury on acid-base balance and electrolytes in critically ill patients., Methods: This was a prospective sequential cohort study in patients with a contraindication for systemic anticoagulation. The first cohort was treated by bicarbonate-based CVVH (n = 10) and the second cohort was treated by CVVH with citrate-based substitution fluid (n = 19). Flow of the latter was coupled to blood flow, and ionized calcium concentrations were monitored and kept constant by calcium-glubionate infusion., Results: No major differences between the 2 groups were found in baseline acid-base parameters. In both groups, arterial pH increased after initiation of treatment and normalized on the average within 18 hours in either group. No differences were found in bicarbonate concentrations. Electrolyte control was comparable for the groups., Conclusion: Citrate-based substitution fluid is comparable to bicarbonate-based substitution fluid during CVVH in critically ill patients with acute kidney injury, concerning acid-base balance and electrolyte control. This implies complete conversion of citrate to bicarbonate in the patients studied., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Given the paucity of prospective randomized controlled trials assessing comparative performances of different dialysis techniques, we compared on-line high-flux hemofiltration (HF) with ultrapure low-flux hemodialysis (HD), assessing survival and morbidity in patients with end-stage renal disease (ESRD)., Study Design: An investigator-driven, prospective, multicenter, 3-year-follow-up, centrally randomized study with no blinding and based on the intention-to-treat principle., Setting & Participants: Prevalent patients with ESRD (age, 16 to 80 years; vintage > 6 months) receiving renal replacement therapy at 20 Italian dialysis centers., Interventions: Patients were centrally randomly assigned to HD (n = 32) or HF (n = 32)., Outcomes & Measurements: All-cause mortality, hospitalization rate for any cause, prevalence of dialysis hypotension, standard biochemical indexes, and nutritional status. Analyses were performed using the multivariate analysis of variance and Cox proportional hazard method., Results: There was significant improvement in survival with HF compared with HD (78%, HF versus 57%, HD) at 3 years of follow-up after allowing for the effects of age (P = 0.05). End-of-treatment Kt/V was significantly higher with HD (1.42 +/- 0.06 versus 1.07 +/- 0.06 with HF), whereas beta(2)-microglobulin levels remained constant in HD patients (33.90 +/- 2.94 mg/dL at baseline and 36.90 +/- 5.06 mg/dL at 3 years), but decreased significantly in HF patients (30.02 +/- 3.54 mg/dL at baseline versus 23.9 +/- 1.77 mg/dL; P < 0.05). The number of hospitalization events for each patient was not significantly different (2.36 +/- 0.41 versus 1.94 +/- 0.33 events), whereas length of stay proved to be significantly shorter in HF patients compared with HD patients (P < 0.001). End-of-treatment body mass index decreased in HD patients, but increased in HF patients. Throughout the study period, the difference in trends of intradialytic acute hypotension was statistically significant, with a clear decrease in HF (P = 0.03)., Limitations: This is a small preliminary intervention study with a high dropout rate and problematic generalizability., Conclusion: On-line HF may improve survival independent of Kt/V in patients with ESRD, with a significant decrease in plasma beta(2)-microglobulin levels and increased body mass index. A larger study is required to confirm these results.

Background: Renal replacement therapies other than intermittent hemodialysis are often required in hemodynamically unstable patients. Continuous renal replacement therapies use a slow blood flow rate, necessitating anticoagulation and prolonged treatment times that may create difficulties with staffing and limit patient diagnostic and therapeutic procedures. We developed an alternative strategy based on a higher blood flow rate that allows increased rates of hemofiltration, no anticoagulation, and a shorter ("accelerated") treatment period. We report our technical and clinical experience with accelerated venovenous hemofiltration (AVVH)., Study Design: Case series., Setting & Participants: Hemodynamically unstable patients requiring renal replacement therapy in the medical or surgical intensive care unit of an academic medial center., Outcomes & Measurements: Achieved dose, blood flow rate, mean arterial pressure, serum chemistry test results, patient weight, filter clotting, and patient survival., Results: 100 patients received 457 AVVH treatments (average, 4.1 treatments/patient during 5.6 days). Mean Acute Physiology, Age, and Chronic Health Evaluation II score was 24 +/- 7.1. Treatment consisted of 36 L of predilution hemofiltration during 9 hours. Mean blood flow was 362 mL/min, and net fluid removal was 2.5 L/treatment. Anticoagulation was not used and filter clotting was seen in only 3.3% of treatments. 86% of patients received the prescribed dose. Pre- and post-AVVH chemistry test results showed a significant decrease in blood urea nitrogen (from 69.6 +/- 24.8 to 50.7 +/- 22.0 mg/dL) and serum creatinine levels (from 4.3 +/- 2.0 to 2.9 +/- 1.3 mg/dL). Weight was decreased significantly (from 98.8 +/- 26.4 to 93.4 +/- 23.1 kg). Pre- and post-AVVH mean arterial pressure comparison showed an increase from 72.8 +/- 13.6 to 74.4 +/- 15.2 mm Hg. Patient survival rate was 53%., Limitations: Retrospective analysis, absence of a comparison group., Conclusion: AVVH is an alternate renal replacement therapy for patients in the intensive care unit and appears to provide adequate volume and solute control without the need for anticoagulation. The shorter treatment period offers flexibility for staffing and other patient diagnostic and therapeutic procedures.

Introduction: The benefit of hemofiltration (HF) as an adjunctive treatment of sepsis or the systemic inflammatory response syndrome (SIRS) in critically ill patients is a subject of severe debate. Firm conclusions on this subject are hampered by the heterogeneity in study populations and HF treatments, and the lack of adequately sized randomized controlled clinical trials. The aim of this review was to determine the importance of ultrafiltration dose and timing on the physiologic and clinical effects of HF in sepsis and SIRS. In addition, we discuss the issue of filter pore size., Methods: Literature search was done in Embase and PubMed database for animal and human studies., Results: Animal studies suggest beneficial effects of HF on hemodynamics; gas exchange; sepsis-induced immunoparalysis; histology of gut, lung, and kidney; and (short-term) survival. These effects were more prominent with "very high" ultrafiltrate rates (> or =100 mL/kg per hour) and early initiation of HF (ie, before or very early after the septic challenge). Three small randomized studies and 3 observational studies in patients with sepsis or SIRS show beneficial effects of short-term or pulse HF using very high ultrafiltrate rates and/or early initiation of HF on physiologic endpoints and survival. However, the studies were underpowered for survival. The first observations of high permeability HF (pore size, about 10 nm; in vitro cutoff, 100 kd) are promising, but so far, it has not been sufficiently examined to allow strong conclusions., Conclusion: Human and animal studies suggest that early initiation and high ultrafiltrate volumes are determinants of the beneficial physiologic and clinical effect of HF in sepsis and SIRS. As yet, the evidence in humans is too low to recommend HF as an adjunctive therapy for critically ill patients with sepsis or SIRS. Regarding the many uncertainties about optimal volume (high or very high) and type of membrane, clinical studies should first focus on endpoints as recovery from organ failure and length of treatment before survival studies are started.

Background: Linezolid is being used increasingly for life-threatening vancomycin-resistant infections in critically ill patients. Limited data suggest that linezolid is cleared by intermittent hemodialysis. However, information on clearance of linezolid by continuous renal replacement therapy is limited. A patient undergoing continuous venovenous hemodiafiltration (CVVHDF) was evaluated to determine linezolid clearance through CVVHDF., Methods: A 33-year-old man with necrotizing fasciitis and acute-on-chronic renal failure requiring CVVHDF was treated with linezolid, 600 mg every 12 hours, for a vancomycin-resistant urinary tract infection. The study was performed on day 4 of therapy after a 1-hour infusion of linezolid. A series of blood samples and all urine and diafiltrate were collected during a 12-hour period. Linezolid concentrations were determined by using high-performance liquid chromatography assay. Linezolid clearance through CVVHDF was determined by using 2 methods. Method 1 evaluated the amount of drug recovered in diafiltrate. Method 2 evaluated plasma drug concentrations in prefilter and postfilter (PAN-10 Hemofilter; Asahi Medical Co, Tokyo, Japan) samples., Results: Clearance of linezolid through CVVHDF was 15.6 mL/min by method 1 and 21.6 mL/min by method 2. Total-body clearance was 189 mL/min. The amount of linezolid recovered in diafiltrate was 50 mg (8.3% of the dose)., Conclusion: Clearance of linezolid through CVVHDF in this patient was marginal. It does not appear that supplemental dosing of linezolid is necessary in patients undergoing CVVHDF.

A 53-year-old woman was admitted to the hospital with ischemic colitis and underwent a subtotal colectomy. She developed acute renal failure, severe hyperbilirubinemia, and intense pruritus resistant to medical treatment. Extracorporeal albumin dialysis using a Molecular Adsorbent Recirculating System (MARS; Gambro Co, Lund, Sweden) has been used to treat liver failure and reduce total serum bilirubin (SB) levels. A trial of extracorporeal albumin dialysis with continuous renal replacement therapy (RRT) was instituted to achieve net removal of SB. A 25% albumin solution was mixed with conventional dialysate to yield a dialysate concentration of 1.85% or 5.0% albumin. The patient underwent 2 continuous RRT sessions using extracorporeal albumin dialysis (1.85% and 5.0% albumin dialysate). Pretreatment and posttreatment SB levels were determined, and total bilirubin concentration (TB) also was measured in each of the collection bags during conventional and albumin dialysis. Pretreatment and posttreatment SB levels were 50.4 mg/dL (862 micromol/L) and 39.0 mg/dL (667 micromol/L) with 1.85% albumin dialysate and 47.1 mg/dL (805 micromol/L) and 39.7 mg/dL (679 micromol/L) with 5.0% albumin dialysate, respectively. The collected dialysate TB level was 0.3 mg/dL (5 micromol/L) during nonalbumin RRT and increased to 1.37 +/- 0.06 mg/dL (23 +/- 1 micromol/L) with 1.85% albumin dialysis. The collected dialysate fluid TB level was 0.3 mg/dL (5 micromol/L) during the nonalbumin RRT and increased to 1.38 +/- 0.15 mg/dL (24 +/- 3 micromol/L) during 5.0% albumin RRT. Single-pass albumin dialysis with continuous RRT cleared SB better than standard continuous RRT. Single-pass albumin dialysis with continuous RRT is feasible and may be a viable alternative in centers that do not have access to MARS therapy. This modality merits additional evaluation for its efficacy in clearing albumin-bound serum toxins.

Background: The objective is to study the population pharmacokinetics of lorazepam and midazolam in critically ill patients with acute renal failure who are treated with continuous venovenous hemofiltration (CVVH)., Methods: Twenty critically ill patients with acute renal failure on CVVH therapy were administered either lorazepam (n = 10) or midazolam (n = 10) by continuous infusion. CVVH was performed with an ultrafiltrate flow of 2 L/h with filtrate substitution in the predilution or postdilution mode. Blood flow through the 1.9-m 2 cellulose triacetate membrane filter was 180 mL/min. For 48 hours, multiple blood and ultrafiltrate samples were obtained for determination of concentrations of the drug and its metabolites., Results: The pharmacokinetics of lorazepam is described best by a 1-compartment model. No significant covariates were identified. Total-body clearance was 6.4 L/h, and volume of distribution was 376 L. Ultrafiltration clearance was 0.31 L/h, equivalent to approximately 5% of total clearance. Average degree of plasma protein binding was 82.9% for lorazepam, with a sieving coefficient of 0.16 +/- 0.03. For lorazepamglucuronide, degree of plasma protein binding was 39.5%, and sieving coefficient was 0.48 +/- 0.07. The pharmacokinetics of midazolam is described best by a 1-compartment model. No significant covariates were identified. Total-body clearance was 8.5 L/h, and volume of distribution was 157 L. Clearance by ultrafiltration was 0.055 L/h, equivalent to approximately 0.7% of total clearance. Average degree of plasma protein binding was 95.8%, with a sieving coefficient of 0.04 +/- 0.03. For the metabolite 1-hydroxymidazolamglucuronide, average degree of plasma protein binding was 43.4%, with a sieving coefficient of 0.45 +/- 0.06., Conclusion: Neither lorazepam nor midazolam is removed efficiently by CVVH. CVVH contributes significantly to the removal of the glucuronide metabolites lorazepamglucuronide and 1-hydroxymidazolamglucuronide.

Linezolid is a new oxazolidinone antibiotic active against most Gram-positive microorganisms the renal elimination of which accounts for about 30% to 35% of all the clearance. Its pharmacokinetic ability was assessed during continuous venovenous hemofiltration (CVVH) in 2 anuric patients with severe postsurgical intraabdominal infections who were receiving standard dosages (600 mg intravenously twice a day). Blood samples for quantification of linezolid in plasma and in filtrate were collected after more than 4 days of therapy before dosing and at 0, 0.5, 1, 2, 3, 5, 7, 9, and 11 hours after the morning 1-hour intravenous infusion, and concentrations were determined by means of high-performance liquid chromatography. Linezolid was partially cleared by CVVH in both the patients (hemofiltration clearance [CL CVVH ] = 0.38 and 0.35 mL/min/kg), with high sieving coefficient values (0.76 to 0.92). Efficacious plasma exposure for time-dependent antibacterial activity of linezolid, either in terms of trough levels above minimum inhibitory concentration (MIC) at which 90% of the isolates are inhibited (Cmin >MIC90 ) or of area under the plasma concentration time curve to MIC90 ratio (AUC/MIC90 ) >100 hours, was ensured during CVVH in both patients. However, despite similar CL CVVH , significant interindividual pharmacokinetic variability was found in the 2 patients (AUC during the observational period [AUC 0-tau ] 334.71 versus 109.34 mg/L x h), mainly owing to substantial differences in non-CVVH-related clearance of linezolid (total CL, 0.55 versus 1.21 mL/min/kg). Our findings indicate that linezolid, although partially removed, does not warrant dosage modification during the first 48 hours when CVVH (with polysulfide hemofilter) at standard 2,000 mL/h substitution flow rate in predilution is applied to anuric patients. Thereafter, this choice is a reasonable one with the exception of those patients who have other features of linezolid toxicity and in which non-CVVH-related clearance might be impaired, although further evaluations are warranted.

Background: Continuous venovenous hemofiltration (CVVH) may be preferable over continuous venovenous hemodialysis (CVVHD) in sepsis; however, CVVH use is limited by the lack of commercially produced bicarbonate replacement solutions in the United States. Anticoagulation used for hemofiltration traditionally has been either heparin or citrate based, but to date, citrate protocols have been used predominately in CVVHD. When CVVH has been used with citrate anticoagulation, replacement solutions have had to be custom made in the pharmacy., Methods: We describe a protocol used in a series of 9 children with sepsis who underwent CVVH with the use of a commercially available bicarbonate solution (Normocarb; Dialysis Solutions Inc, Richmond Hill, Ontario, Canada) and a commercially available citrate solution (Anticoagulant Citrate Dextrose Solution Formula A [ACD-A]; Baxter Health Care, Deerfield, IL). This simplified approach to citrate anticoagulation with CVVH used Normocarb as a prefilter replacement solution under provisions of the 1997 Food and Drug Administration Modernization Act., Results: All patients had acceptable levels of solute and ultrafiltration clearance with this approach. CVVH circuit life averaged 71 hours (range, 37 to 131 hours), influenced in part by the industry recommendation to change the circuit at 72 hours, whereas no complications from this protocol were identified., Conclusion: Similar to CVVHD, this protocol is effective and simple in its components, using industry-produced solutions, avoiding the need for pharmacy-made solutions, and limiting cost and potential risk for compounding errors. Although not the purpose of this report, the patient survival rate was 55%.

The relationship between dialyzer fiber bundle volume (FBV), dialyzer life span, and small-solute clearance has yet to be clearly defined in continuous venovenous hemodialysis (CVVHD). This study sought to define this relationship using novel ultrasound dilution technology. We studied 55 sessions in 31 intensive care unit patients on CVVHD therapy. A session was defined as the life span of a single dialyzer. The following variables were assessed every 6 hours throughout each session, starting within 1 hour of initiation of that session: FBV, access recirculation, extracorporeal blood flow rate, effluent (EUN) to blood urea nitrogen (BUN) concentration ratio, effluent creatinine to blood creatinine concentration ratio, and urea nitrogen and creatinine clearances. Data were analyzed using random-effects linear models to estimate trends. Several dialysis-related and solute-removal parameters were analyzed for association with each other. Systemic or dialysis circuit heparin was administered in 28 of 55 sessions. One hundred seventy sets of FBV, 101 sets of urea clearance, and 102 sets of creatinine clearance measurements were performed. There was a declining trend for FBV (0.8 mL/h), heart rate (0.25 beats/min/h), and measured blood flow (0.33 mL/min/h; P < 0.05). Apart from dialysate inflow rate (P = 0.044), there was no significant correlation with EUN-BUN ratio. Session duration was associated with dialysis access site; the femoral access provided longer dialysis sessions than subclavian and internal jugular accesses (P = 0.029). We conclude that small-solute removal remains stable over the course of our CVVHD system life spans despite significant loss of hemodialyzer FBV., (Copyright 2002 by the National Kidney Foundation, Inc.)

Current renal substitution therapy with hemodialysis or hemofiltration has been an important life-sustaining technology, but it still has suboptimal clinical outcomes in patients with end-stage renal disease or acute renal failure. This therapy replaces the small solute clearance function of the glomerulus but does not replace the metabolic and endocrinologic functions of the tubular cells. This article shows that the combination of a synthetic hemofiltration cartridge and a renal tubule cell assist device (RAD) containing human cells in an extracorporeal circuit replaces filtration, metabolic, and endocrinologic functions in acutely uremic dogs. The RAD maintained excellent performance and durability characteristics for 24 hours of continuous use in the uremic animals. The RAD increased ammonia excretion, glutathione metabolism, and 1,25-dihydroxyvitamin D3 production. Cardiovascular stability in the animals was documented in these studies during this extracorporeal treatment. With these results, clinical evaluation of this device in the treatment of severely ill patients with acute renal failure in an intensive care unit has been initiated., (Copyright 2002 by the National Kidney Foundation, Inc.)

Cefazolin dialytic clearance has not been determined in patients undergoing hemodialysis with high-efficiency or high-flux dialyzers. The objective of this study is to determine the pharmacokinetics and dialytic clearance of cefazolin and develop dosing strategies in these patients. Twenty-five uninfected subjects undergoing chronic thrice-weekly hemodialysis were administered a single dose of intravenous cefazolin (15 mg/kg) after their standard hemodialysis session. Fifteen subjects underwent hemodialysis with high-efficiency hemodialyzers, and 10 subjects underwent hemodialysis with high-flux hemodialyzers. Blood and urine samples were collected serially over the interdialytic period, during the next intradialytic period, and immediately after the next hemodialysis session. Serum and urine concentrations of cefazolin were determined by high-performance liquid chromatography. Differential equations describing a two-compartment model were fit to the cefazolin serum concentration-time data over the study period, and pharmacokinetic parameters were determined. Mean dialytic clearance values for cefazolin were significantly greater in the high-flux group compared with the high-efficiency group (30.9 +/- 6.52 versus 18.0 +/- 6.26 mL/min, respectively; P: < 0.05). Cefazolin reduction ratios were significantly greater (0.62 +/- 0.08 versus 0.50 +/- 0.07; P: < 0.005) in the high-flux group compared with the high-efficiency group and correlated well with equilibrated urea reduction. The pharmacokinetic model developed from patient data was used to simulate cefazolin serum concentration data for high-efficiency and high-flux dialyzers. Cefazolin doses of 15 or 20 mg/kg after each hemodialysis session maintained adequate serum concentrations throughout a 2- or 3-day interdialytic period regardless of hemodialyzer type.

Lithium intoxication is an important complication of its frequent use and narrow therapeutic index. Intermittent hemodialysis has been the treatment of choice when emergent extracorporeal lithium clearance is indicated, but postdialysis rebound elevations in lithium concentration with recurrent toxicity have been documented. We report a case of intentional acute on chronic lithium intoxication in which continuous venovenous hemodiafiltration was successfully used. This modality offers the advantage of slow sustained removal of lithium without hemodynamic instability or rebound elevations in lithium concentration.

Objective: To determine whether the use of modified ultrafiltration during pediatric cardiopulmonary bypass (CPB) diminishes the load of circulating endotoxins., Design: Single-arm prospective observational study., Setting: A university hospital operating room and intensive care unit., Participants: Twenty children undergoing CPB for correction of various congenital heart diseases., Interventions: The amount of endotoxins in plasma was measured during CPB and before and after modified ultrafiltration. The ultrafiltrate was assayed for the presence of endotoxins. Postoperatively, the children were followed with relevant infectious parameters and cultures., Measurements and Main Results: The amount of endotoxins increased significantly during the CPB procedure (from a median of 1.3 ng [range, 0 to 13.7 ng] to 24.2 ng [range, 2.1 to 75.9 ng]). After termination of CPB, modified ultrafiltration was shown to lower the amount of circulating endotoxins in blood (from a median of 24.2 ng [range, 2.1 to 75.4 ng] to 9.0 [range, 0.1 to 40.6 ng]). The major bulk of this reduction in endotoxin load was retrieved in the ultrafiltrate (median of 11.9 ng [range, 0 to 12.1 ng])., Conclusion: This study strongly suggests that modified ultrafiltration decreases the amount of circulating endotoxins in children undergoing cardiac surgery.

Advances in technology have made it possible to deliver a high Kt/V in a shorter time. The realization that duration of dialysis may be an important predictor of survival independent of dialysis dose has resulted in the popularity of prolonged slow dialysis (PHD). The longer duration and increased frequency of dialysis achieve excellent small- and middle-molecular weight solute clearance and also attenuate the peak concentration of uremic toxins. The slow dialysis process enables the equilibration of tissue and vascular compartments, resulting in better clearance and decreased postdialysis rebound increase in solutes. Gentle, persistent ultrafiltration allows the control of hypertension with minimal antihypertensive use. The intense and more frequent dialysis improves appetite and permits liberalization of diet. This greater dietary protein intake results in a progressive increase in serum albumin level and dry weight. Nocturnal hemodialysis achieves control of hyperphosphatemia without phosphate binders and a significant reduction in serum beta(2)-microglobulin levels. Normalization of extracellular volume, better clearance of uremic toxins, and improved nutrition result in a significant improvement in survival. The flexible time schedule with home hemodialysis and improvement of sleep and neurocognitive function allow better rehabilitation. The available evidence indicates PHD may be closer to the concept of an ideal dialysis, but there is lingering uncertainty about the consequence of prolonged immune stimulation, catabolism, and loss of essential solutes with these therapies.

Objective: To evaluate whether combined zero-balanced and modified ultrafiltration affects the systemic inflammatory response in coronary artery bypass graft (CABG) patients., Design: Randomized and controlled., Setting: University-affiliated heart center., Participants: Forty-three patients scheduled for elective CABG., Interventions: In the ultrafiltration group (UF group; n = 21), zero-balanced ultrafiltration was performed during rewarming and modified ultrafiltration immediately after the end of cardiopulmonary bypass (CPB). A control group of patients (n = 22) was treated identically to the treatment group except no ultrafiltration process was performed., Measurements and Main Results: Immediately after CPB (ie, after zero-balanced ultrafiltration), and again after the modified ultrafiltration, the concentrations of interleukin-6 and interleukin-8 were significantly less (p < 0.05) in the UF group compared with the control group. Both proinflammatory cytokine levels peaked at 2 and 4 hours after CPB, at which time no difference between the two groups could be observed. The levels of measured anti-inflammatory mediators (interleukin-10 and interleukin-1 receptor antagonist) did not show any difference between the two groups. Intrapulmonary shunt fraction decreased in the course of the modified ultrafiltration from 31% +/- 1.2% to 25% +/- 1.3% (p < 0.01), whereas mean arterial pressure increased (69 +/- 1.8 to 80 +/- 2.8 mmHg; p < 0.01); neither parameter changed in the control group. Time to extubation was shorter in the UF group (6.1 +/- 0.5 v 8.6 +/- 0.7 hours; p < 0.05)., Conclusion: It was concluded that the use of ultrafiltration diminished inflammatory response in a very limited time period immediately after CPB and, probably as a consequence, slightly improved clinical parameters.

A patient with leptospirosis who developed oliguric renal failure, massive pulmonary haemorrhage and respiratory failure is described. The patient's clinical condition and arterial oxygenation failed to improve despite vigorous supportive measures. Nitric oxide inhalation and haemofiltration resulted in a marked clinical improvement and subsequent full recovery. We suggest that the addition of haemofiltration and nitric oxide inhalation therapy should be considered in patients with pulmonary haemorrhage and renal failure caused by leptospirosis, in whom conventional therapy fails.

Orthotopic heart transplantation (OHT) is an accepted treatment for heart failure refractory to medical management. International registry data reported a 1-year survival after OHT of 79%. The risk factors associated with requiring continuous venovenous hemofiltration or hemodialysis and mortality in patients requiring continuous venovenous hemofiltration (CVVH)/hemodialysis (HD) have not been studied, since improvements have been made in OHT. We tested the hypothesis that requiring CVVH/HD in the immediate posttransplantation period increases mortality after OHT. We studied pretransplantation factors to predict those patients who would need CVVH/HD. Patients undergoing OHT from 1995 to 1996 were studied. Fifty-two patients underwent OHT. Eight patients (15%) needed CVVH/HD. Initial immunosuppression included cyclosporine, azathioprine, and solumedrol. Patients were changed to antilymphocyte therapy if they had oliguric acute renal failure, T or B cell incompatibility, or biopsy-proven rejection. Overall, survival at 1 year was 84.6%. Survival in patients not needing CVVH/HD was 91%, and survival in patients needing CVVH/HD was 36.5%. For each year of age over 55 years, patients had a relative risk of requiring CVVH/HD of 7.

Continuous renal replacement modalities have found widespread use and acceptance over the last decade. The various modalities differ in the kind of access (arteriovenous v venovenous); in the application of convective clearance (continuous hemofiltration), diffusive clearance (continuous hemodialysis), or a combination of both (continuous hemodiafiltration); and in the location where the replacement fluid enters the circuit (predilution v postdilution). Continuous therapies incorporate several advantages, such as improved hemodynamic stability, the possibility for unlimited alimentation, optimal fluid balance, and gradual urea removal without fluctuations. However, it has not yet been shown whether these advantages have a significant impact on outcome and prognosis, the ultimate measure of treatment efficiency. Major disadvantages of continuous therapies are the ongoing necessity for continuous anticoagulation, immobilization of the patient, and possible side effects from lactate-containing replacement fluid or dialysate. Continuous renal replacement procedures have certainly made the management of critically ill patients easier. In particular, oligoanuric patients with diuretic resistant volume overload and hemodynamically unstable patients with acute renal failure and concomitant sepsis or multiorgan failure appear to benefit most from continuous treatment. The role of continuous hemofiltration as a method of removing serum cytokines in septic patients without renal failure is still controversial and needs further clinical assessment. Due to slow efficacy, continuous renal replacement is indicated only in rare circumstances for intoxication; this therapy also is of rather limited use in severe hyperkalemia or acidosis. Noncritically ill patients with uncomplicated renal failure (eg, due to the use of dye or antibiotics) should be treated with intermittent hemodialysis or peritoneal dialysis. Furthermore, intermittent hemodialysis is preferable in patients with hemorrhagic diathesis because it can be easily performed without anticoagulants.

The objective of this study was to determine the outcome of acute renal failure (ARF) treated by continuous venovenous high-flux dialysis in patients with ventilator-dependent respiratory failure treated in a single center and to examine the importance of primary diagnosis in determining survival. We retrospectively reviewed 408 consecutively treated patients in the multidisciplinary intensive care unit (ICU) of a large teaching hospital. All ventilated patients requiring dialysis support over a 5-year period (January 1, 1991 to December 31, 1995) were included in the study. Patient age, APACHE II score, primary diagnosis, inotrope requirement, and survival to discharge from the ICU, from the hospital, and at 6 months were recorded for 408 consecutively treated patients. The mean age was 54 years, the median APACHE II score was 29, and the ICUs, hospital, and 6-month survival rates were 48%, 38%, and 36%, respectively. Inotropic support was required in 75%. Liver disease was the primary diagnosis in 35%. Logistic regression analysis indicated that increasing age and APACHE II, use of inotropes, and presence of liver disease were all associated with increased mortality. Eight percent of survivors (3% of the total population) required long-term renal replacement therapy. In conclusion, in our experience, continuous venovenous high-flux dialysis can be universally adopted in the ICU management of ARF associated with multiorgan failure. Patient survival is related to primary diagnosis, and a knowledge of case mix is essential in considering outcome of ARF in any reported series.

Gram-negative bacterial sepsis remains a challenging diagnostic and therapeutic dilemma to the practicing clinician. Bacterial-derived products (eg, gram-negative bacterial lipopolysaccharide or endotoxin) and host inflammatory mediators (eg, tumor necrosis factor-alpha and interleukin-1) are believed to play a pivotal role in the pathogenesis of sepsis and septic shock. Despite the many advances in the treatment of sepsis, mortality rates in septic patients remain high. Indeed, numerous clinical trials using biologically engineered immunotherapies targeting specific inflammatory mediators have proven unsuccessful. This lack of success has led to a renewed interest in blood purification techniques using extracorporeal therapies. During sepsis, circulating bacterial-derived products as well as inflammatory mediators can be reduced and/or eliminated by various extracorporeal adjunctive therapies such as plasma exchange, continuous renal replacement, and adsorbent-based therapies. Adsorbents have commonly been used orally for gastrointestinal removal of toxins or drugs. However, their potential use in sepsis has received little attention. The incorporation of adsorbents in hemoperfusion columns has allowed their use for the removal of toxic compounds from the circulatory system. Adsorbents developed for use in sepsis can bind toxins in a nonselective (eg, charcoal), selective (eg, polymyxin B-immobilized polystyrene-derivative fiber), or specific (eg, antibody-coated microsphere-based detoxification system) way. However, despite an explosive development in the experimental use of these promising therapies, randomized clinical trials are currently lacking. In summary, a multi-disciplinary complex therapeutic approach remains a prerequisite to the successful treatment of sepsis.

Sepsis can be considered a systemic inflammatory response syndrome (SIRS) caused by infection. When an excessive and/or persistent activation of humoral and cellular mechanisms of host defense is present, an exaggerated and generalized activation of inflammatory mechanisms can lead to a multiple organ dysfunction syndrome. Mediators thought to be involved in this syndrome include the major plasma cascade systems (complement, coagulation, and fibrinolytic systems) and soluble cell-derived mediators (cytokines, reactive oxygen species, platelet-activating factor (PAF), arachidonic acid metabolites, and nitric oxide and related compounds). Several findings indicate that among these mediators, PAF may exert an important role in the pathophysiology of septic shock. Evidence is accumulating that in human sepsis this scenario is far more complicated and that removal of inflammatory mediator excess from plasma, rather than blockade of their potentially beneficial local production, might provide a rationale for the use of continuous renal replacement therapy (CRRT). There is an emerging view that CRRT should be considered in the light of broader concept (ie, the use of blood purification for the treatment of sepsis). Recent studies, performed in an experimental model of continuous arteriovenous hemofiltration with exogenous PAF, demonstrated that polysulfone membranes can adsorb substantial amounts of biologically active PAF. These studies also showed that the removal of this mediator occurs by a two-step process involving early adsorption followed by ultrafiltration. Although the removal of cytokines, such as tumor necrosis factor-alpha (TNF-alpha), remains controversial, mainly because of differences in membrane used, operational conditions, and inter- and intra-assay variability, the crucial point is that no evidence has yet been given to show real benefit from CRRT in significantly reducing the plasma concentration of cytokines. The net advantage of CRRT, however, may not only be the removal of cytokines per se, but also the simultaneous elimination of cytokine-inducing substances. Experimental and human studies will be discussed as to whether extracorporeal treatments may remove an excess of circulating cytokines, either by increasing the turnover rate (the so-called high-volume hemofiltration), or by using sorbent systems to regenerate plasma filtrate.

The emergence of dialytic support for patients with reversible renal failure was one of the most significant advances in critical care medicine. Supporting a patient with a failed organ till organ recovery has not had the same success with other organ failures. Despite the indispensable nature of the support, dialysis was intermittent at best, and carried its own morbidity. The emergence of a "continuous" dialysis delivery system, originally through an arteriovenous access and later through veno-venous methodology, began to simulate the continuity of the natural kidney, and lifted much of the fluid and drug restrictions imposed by the intermittent nature of standard dialytic therapies. Components of the system were next reviewed for improvement and biocompatability. Differences in patient outcome were documented with various component comparisons, and disparate patient tolerance of delivery modality was also clearly proven. The hemodynamic stability of continuous treatment created utilization to be focused on the more unstable, the more severely compromised patient group. In this context, comparative studies with intermittent delivery methods showed improved hemodynamic stability among patients treated with continuous renal replacement therapies (CRRT), but no clear difference in patient mortality. Patient characteristics and severity scoring have recently been undertaken to better describe the population, and attempts at dialysis dosing is currently being developed for ARF dialysis recipients. Early results seem to point toward a dialysis dose effect on mortality in certain groups of ICU acute renal failure patients. However, the dialytic process is only depurative and artificial. Plastic membrane bio-incompatibility, human physiological responses to foreign material exposure, either in the circuit material itself or introduced from therapy methodology, pose practical and theoretical problems. Recent advances in the field of bio-artificial technology have allowed the development of functioning hybrid "blood processors," which function as a renal tubule and may be able to not only "clean" blood, but also allow for other cellular functions not currently possible with dead membrane technology. Combining living cells with a continuous delivery method may be the next significant step toward a fully functional renal replacement therapy.