High clearance continuous renal replacement therapy with a modified dialysis machine
Authors: Christian Schlaeper, Richard Amerling, Markus Manns, Nathan W. Levin
Journal: Kidney International (1999)

High clearance continuous renal replacement therapy with a modified dialysis machine. Recent studies suggest that the dialysis dose significantly affects survival in acute renal failure (ARF) patients and that bicarbonate dialysate improves acid-base balance during continuous renal replacement therapy (CRRT). These data inspired us to use slow continuous dialysis (SCD) in the treatment of ARF. SCD is defined by the following parameters: (a) blood flow (QB) = 100 to 200 ml/min, (b) dialysate flow (QD) = 100 to 300 ml/min, (c) the use of a modified hemodialysis machine with controlled ultrafiltration and online production of bicarbonate-based dialysate, and (d) continuous or extended daily treatment for 8 to 24 hours. SCD provides a urea clearance in the 70 to 80 ml/min range. Preliminary data from an ongoing clinical trial demonstrate the safety, efficiency, and simplicity of the treatment. High clearance continuous renal replacement therapy with a modified dialysis machine. Recent studies suggest that the dialysis dose significantly affects survival in acute renal failure (ARF) patients and that bicarbonate dialysate improves acid-base balance during continuous renal replacement therapy (CRRT). These data inspired us to use slow continuous dialysis (SCD) in the treatment of ARF. SCD is defined by the following parameters: (a) blood flow (QB) = 100 to 200 ml/min, (b) dialysate flow (QD) = 100 to 300 ml/min, (c) the use of a modified hemodialysis machine with controlled ultrafiltration and online production of bicarbonate-based dialysate, and (d) continuous or extended daily treatment for 8 to 24 hours. SCD provides a urea clearance in the 70 to 80 ml/min range. Preliminary data from an ongoing clinical trial demonstrate the safety, efficiency, and simplicity of the treatment. Acute renal failure (ARF) in critically ill patients has a high mortality. Repeated episodes of hypotension during intermittent hemodialysis (IHD) and the blood–dialyzer membrane interaction with complement and leukocyte activation can further injure the kidneys and delay recovery from ARF1Manns M. Sigler M.H. Teehan B.P. Intradialytic renal hemodynamics: Potential consequences for the management of the patient with acute renal failure.Nephrol Dial Transplant. 1997; 12: 870-872Crossref PubMed Scopus (76) Google Scholar,2Hakim R. Winagrad R.L. Parker R.A. Effect of dialysis membrane in the treatment of patients with acute renal failure.N Engl J Med. 1994; 331: 1338-1342Crossref PubMed Scopus (346) Google Scholar. Recent research has focused on whether the dialysis dose, biocompatible membranes, continuous renal replacement therapy (CRRT), or bicarbonate dialysate have an impact on morbidity and mortality in ARF3Manns M. Sigler M.H. Teehan B.P. Continuous renal replacement therapies: An update.Am J Kidney Dis. 1998; 32: 185-207Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar. Studies indicate that the dialysis dose significantly affects survival rate in ARF4Paganini E.P. Tapolyai M. Goormastic M. Halstenberg W. Kozlowski L. Leblanc M. Lee J.C. Moreno L. Sakai K. Establishing a dialysis therapy/patient outcome link in intensive care unit acute dialysis for patients with acute renal failure.Am J Kidney Dis. 1996; 28: S81-S89Abstract Full Text PDF Scopus (198) Google Scholar and that bicarbonate dialysate improves acid-base balance during CRRT5Leblanc M. Moreno L. Robinson O.P. Tapolyai M. Paganini E.P. Bicarbonate dialysate for continuous renal replacement therapy in intensive care unit patients with acute renal failure.Am J Kidney Dis. 1995; 26: 910-917Abstract Full Text PDF PubMed Scopus (37) Google Scholar. Based on these observations, we decided to use slow continuous dialysis (SCD) to treat ARF patients. The method combines the advantages of traditional continuous venovenous hemodialysis (CVVHD), which are gradual solute and volume removal and improved hemodynamic stability, with the advantages of IHD, which are high urea clearance, precise ultrafiltration control, and bicarbonate dialysate. We used a modified dialysis machine, the 2008H (Fresenius Medical Care, Lexington, MA, USA), for SCD. Special software was developed to permit dialysate flow rates down to 100 ml/min (range 100 to 800 ml/min) while maintaining temperature control. Patients were treated continuously with a blood flow (QB) of 100 to 200 ml/min and a dialysate flow (QD) of 100 ml/min. F40 or AV400S polysulfone hemofilters (Fresenius Medical Care), each with surface areas of 0.7 m2 and standard dialysis tubing, were used. The hemofilter and blood lines were changed every 24 to 36 hours or more frequently according to clinical circumstances. Dialysate was produced online using acid and bicarbonate concentrate and tap water treated with activated charcoal and reverse osmosis (RO). Dialysate was enriched with potassium to give a final concentration of 4 mEq/liter. The calcium concentration was 2.5 mEq/liter, and the glucose concentration was 2 g/liter. The dialysate bicarbonate concentration was adjusted to between 25 and 35 mEq/liter, depending on the acid-base status of the patient. Electrolytes, including calcium, phosphorous, and magnesium, were checked every six hours. Heparin was used for anticoagulation and was titrated to achieve a partial thromboplastin time (PTT) of twice the control level. Phosphate and magnesium were replaced as needed, and parenteral nutrition was adjusted to compensate for amino acid losses in the dialysate. The system was set up by the nephrology staff, who also initiated and discontinued the treatment. The intensive care unit nursing staff was trained to monitor the treatment, adjust ultrafiltration rate, handle routine alarms, watch for clotting, and perform saline flushes (used when anticoagulation was contraindicated). Slow continuous dialysis with the 2008H machine has been under evaluation for the past 15 months in an ongoing clinical trial. As of this writing, over 30 critically ill patients with acute and chronic renal failure (CRF) have been treated. Preliminary results from this center have been reported elsewhere (abstract; Amerling et al, J Am Soc Nephrol 9:166A, 1998). Of the first 23 patients, 20 patients had oliguric ARF and three had complicated CRF. Causes of ARF were postcardiac surgery acute tubular necrosis (ATN) in 10 patients, sepsis in three patients, cardiogenic shock in two patients, liver failure in three patients, pancreatitis in one patient, and gastrointestinal bleeding in one patient. The mean treatment time was 58 (range 12 to 144) hours. Fluid removal was varied according to the clinical circumstances and averaged 5.8 ± 1.7 liters. No replacement fluid was used. The metabolic control achieved during SCD was excellent, as judged by serum levels of potassium, blood urea nitrogen, creatinine, and phosphorus. Acid-base balance was maintained throughout the treatment. Treatment was stopped after 48 and 72 hours because of frequent clotting in two patients who were treated with F8 membranes. Thirteen patients survived over 30-days post-treatment, 11 of whom went home. Of these 11, eight recovered renal function. Thus, 30-day survival was 57%, and longer-term survival was 48%. Because the treatment was provided mainly to those patients judged to be too ill or unstable for intermittent hemodialysis (IHD), these results are impressive. Nursing acceptance was high, as the procedure was less labor intensive than traditional CRRT. Alarms (low transmembrane pressure [TMP], conductivity) occurred relatively infrequently and were easily resolved by the intensive care unit nursing personnel. Slow continuous dialysis provides superior small solute clearance compared with other continuous renal replacement therapies or IHD. Because the blood flow during conventional CVVHD is very much greater than the dialysate flow (QB = 100 ml/min, QD = 16 to 25 ml/min), the dialysate is fully saturated with urea. Thus, the urea clearance in CVVHD equals the dialysate flow rate plus the ultrafiltration rate. Roughly, 24 to 30 liters of plasma are typically cleared per day during CVVHD. If the dialysate flow is increased to 4 liter/hr, urea clearance increases to 3 liter/hr, as the dialysate is not completely saturated at higher dialysate flow rates6Bonnardeaux A. Pichette V. Ouimet D. Geadah D. Habel F. Cardinal J. Solute clearance with high dialysate flow rates and glucose absorption from the dialysate in continuous arteriovenous hemodialysis.Am J Kidney Dis. 1992; 19: 31-38Abstract Full Text PDF PubMed Scopus (60) Google Scholar. SCD using the F40 dialyzer with a QD of 6 liter/hr (100 ml/min) and a QB of 100 to 300 ml/min provides urea clearance of at least> 3.5 liter/hr (>84 liter/day). We simultaneously measured blood and dialysate urea nitrogen concentrations to determine the extraction ratio for SCD in several patients. Results ranged from 0.6 to 0.9. Thus, urea clearances may be as high as 90 ml/min (130 liter/day) in some patients. Because of the higher clearance, SCD can better tolerate interruptions (clotting, interventions) and still provide excellent dialysis. Some centers perform SCD for 8 to 12 hours during the day or night to avoid nighttime troubleshooting of the dialysis circuit or, conversely, to allow unrestricted access to the patient during the day (abstracts; Marshall et al, Blood Purif 17:24, 1999; and Hu et al, Blood Purif 17:15, 1999). According to Leblanc, Bonnardeaux, and Cardinal, CAVHD with a dialysate flow of 4 liter/hr yields a daily Kt/V of 2.0, or 14 per week, assuming nonstop therapy7Leblanc M. Bonnardeaux A. Cardinal J. Kt/V in continuous dialysis techniques.Semin Dial. 1995; 8: 51-52Crossref Scopus (28) Google Scholar. Shaver et al. used a 12-hour daily SCD to achieve a mean Kt/V of 1.64 per treatment (abstract; Shaver et al, Blood Purif 17:31, 1999). In our experience, SCD delivered over 24 hours provided a daily Kt/V of 2.4 (16.8 weekly), assuming a urea clearance of 60 ml/min and a volume of 36 liters. This compares favorably to other continuous or intermittent therapies, which deliver a weekly Kt/V of 6.2 (for low flow CRRT) or 7.5 (for daily IHD7Leblanc M. Bonnardeaux A. Cardinal J. Kt/V in continuous dialysis techniques.Semin Dial. 1995; 8: 51-52Crossref Scopus (28) Google ScholarTable 1.Table 1Comparison of different renal replacement modalities for ARFIHDSCDCRRTBlood flow ml/min200–300100–300100–200Dialysate flow ml/min500–80010015–35Dialysate bufferbicarbonatebicarbonatelactateDaily urea clearance liters3680–90aCalculated for 24 hr treatment20–40cDaily urea clearance is slightly lower than dialysate flow to account for down timeDaily Kt/V1.12.4bAssuming urea clearance 60 ml/min and V of 36 liters0.9–1.4Weekly Kt/V7.516.8bAssuming urea clearance 60 ml/min and V of 36 liters6–10Daily dialysate cost (US$)610dFrom abstract; Martin et al, Blood Purif 17:19, 1999, calculated for 24 hr treatment50–100dFrom abstract; Martin et al, Blood Purif 17:19, 1999, calculated for 24 hr treatmentAbbreviations are: IHD, daily intermittent hemodialysis with a dialyzer urea clearance of 175 ml/min7Leblanc M. Bonnardeaux A. Cardinal J. Kt/V in continuous dialysis techniques.Semin Dial. 1995; 8: 51-52Crossref Scopus (28) Google Scholar; SCD, slow continuous dialysis; CRRT, continuous renal replacement therapya Calculated for 24 hr treatmentb Assuming urea clearance 60 ml/min and V of 36 litersc Daily urea clearance is slightly lower than dialysate flow to account for down timed From abstract; Martin et al, Blood Purif 17:19, 1999, calculated for 24 hr treatment Open table in a new tab Abbreviations are: IHD, daily intermittent hemodialysis with a dialyzer urea clearance of 175 ml/min7Leblanc M. Bonnardeaux A. Cardinal J. Kt/V in continuous dialysis techniques.Semin Dial. 1995; 8: 51-52Crossref Scopus (28) Google Scholar; SCD, slow continuous dialysis; CRRT, continuous renal replacement therapy This may be clinically important, as Tapolyai et al observed an inverse correlation between Kt/V and mortality rate in 58 critically ill patients treated with IHD (abstract; Tapolyai et al, J Am Soc Nephrol 5:530, 1994). More recent data from the same group showed that the dialysis dose has a strong influence on survival in patients with moderate severity scores, independent of the manner with which the dialysis dose was provided (IHD vs. CRRT)4Paganini E.P. Tapolyai M. Goormastic M. Halstenberg W. Kozlowski L. Leblanc M. Lee J.C. Moreno L. Sakai K. Establishing a dialysis therapy/patient outcome link in intensive care unit acute dialysis for patients with acute renal failure.Am J Kidney Dis. 1996; 28: S81-S89Abstract Full Text PDF Scopus (198) Google Scholar. The available data suggest that a daily Kt/V for urea of >1.0 is required to achieve a significant impact on mortality8Sigler M.H. Transport characteristics of the slow therapies: Implications for achieving adequacy of dialysis in acute renal failure.Adv Renal Replace Ther. 1997; 4: 68-80PubMed Google Scholar. Preliminary data from Hu et al suggest that SCD may be superior to CVVH with regards to clotting and heparin requirement (900 units/hr for SCD vs. 1200 units/hr for CVVH; abstract; Hu et al, Blood Purif 17:15, 1999). However, SCD ran for only eight hours daily. Golper et al observed clotting during 12-hour SCD treatments, with an F8 dialyzer in 3 of 13 treatments (abstract; Chatoth et al, Blood Purif 17:16, 1999). Our experience suggests that large surface area dialyzers might not be advantageous, as both of our patients who were treated with the F8 dialyzer (surface area of 1.8 m2) experienced frequent clotting. This prompted us to switch to the smaller F40 dialyzer (surface area of 0.7 m2). Hu et al compared the hemodynamic stability of SCD (N = 5) and CVVH (N = 2; abstract; Hu et al, Blood Purif 17:15, 1999). Mean arterial pressure, hypotensive episodes, and vasopressor requirements were comparable in both groups. Golper et al performed SCD in six critically ill patients who had failed conventional hemodialysis because of hypotension (abstract; Chatoth et al, Blood Purif 17:16, 1999). The 12-hour SCD treatments were hemodynamically well tolerated, but 2 of 13 treatments were terminated because of hypotension. Slow continuous dialysis uses bicarbonate-buffered dialysate, whereas in the United States, CVVHD is traditionally performed using lactate-buffered peritoneal dialysis fluid as the dialysate. The use of the latter is problematic. First, the high glucose concentration in peritoneal dialysate may produce hyperglycemia9Reynolds H.N. Borg U. Belzberg H. Wiles C.E. Efficacy of continuous arteriovenous hemofiltration with dialysis in patients with renal failure.Crit Care Med. 1991; 19: 1387-1394Crossref PubMed Scopus (32) Google Scholar. Second, these solutions contain lactate in concentrations of 35 to 45 mmol/liter in order to compensate for bicarbonate losses in the filtrate. Under physiological conditions, lactate is converted to bicarbonate on an equimolar basis at a rate of roughly 100 mmol/hr. Severe impairment of lactate metabolism or enhanced lactate production in patients with severe hypoxia, sepsis, or liver failure may result in lactate accumulation with decreased myocardial performance10Saman S. Opie L.H. Mechanism of reduction of action potential duration of ventricular myocardium by exogenous lactate.J Mol Cell Cardiol. 1984; 10: 659-662Abstract Full Text PDF Scopus (23) Google Scholar, 11Mizock A. Falk J.L. Lactic acidosis in critical illness.Crit Care Med. 1992; 20: 80-93Crossref PubMed Scopus (500) Google Scholar, 12Davenport A. Will E.J. Davison A.M. Hyperlactaemia and metabolic acidosis during hemofiltration using lactate-buffered fluids.Nephron. 1991; 59: 461-465Crossref PubMed Scopus (70) Google Scholar, 13Davenport A. Will E.J. Davison A.M. Paradoxical increase in arterial hydrogen ion concentration in patients with hepatorenal failure given lactate-based fluids.Nephrol Dial Transplant. 1990; 5: 342-346Crossref Scopus (13) Google Scholar. In addition, an efflux of bicarbonate may worsen or cause a metabolic acidosis. A comparison of 13 patients treated with lactate and bicarbonate dialysate suggests that the bicarbonate solution may be associated with an improved acid-base status5Leblanc M. Moreno L. Robinson O.P. Tapolyai M. Paganini E.P. Bicarbonate dialysate for continuous renal replacement therapy in intensive care unit patients with acute renal failure.Am J Kidney Dis. 1995; 26: 910-917Abstract Full Text PDF PubMed Scopus (37) Google Scholar. The possible negative metabolic and hemodynamic effects of lactate make the physiologic buffer bicarbonate preferable. However, other investigators have not confirmed that elevated levels of lactate during hemofiltration cause any deterioration in acid-base status or hemodynamics14Nimmo G.R. Mackenzie S.J. Walker S. Nicol M. Grant I.S. Acid-base responses to high-volume haemofiltration in the critically ill.Nephrol Dial Transplant. 1993; 8: 854-857PubMed Google Scholar,15Thomas A.N. Guy J.M. Kishen R. Geraghty I.F. Bowles B.J.M. Vadgama P. Comparison of lactate and bicarbonate buffered haemofiltration fluids: use in critically ill patients.Nephrol Dial Transplant. 1997; 12: 1212-1217Crossref PubMed Scopus (65) Google Scholar. There are some logistical barriers to online production of dialysate that make the system more complex than conventional CRRT systems. However, the increased complexity is compensated for by decreased dialysate cost and nursing workload (abstracts; Hall et al, Blood Purif 17:30, 1999; Merz et al, Blood Purif 17:52, 1999; and Martin et al, Blood Purif 17:19, 1999). Access to tap water and the availability of a RO unit are essential. Depending on the quality of the tap water, water pretreatment may be required to achieve Association for the Advancement of Medical Instrumentation (AMII) standard water quality. Contamination of the dialysate with endotoxins is another potential hazard. Meticulous cleaning of the machine and the water purification system every 24 to 48 hours can minimize this risk. To add an extra level of safety, the dialysate can be filtered through a dialysate filter (for example, Diasafe®; Fresenius Medical Care). This will ensure the production of ultrapure dialysate with microbial counts <1 CFU/ml and endotoxin concentration <0.06 IU/ml16Lonnemann G. Schindler R. Ultrafiltration using the polysulfone membrane to reduce the cytokine-inducing activity of contaminated dialysate.Clin Nephrol. 1994; 42: S37-S43Google Scholar. To our knowledge, this is the first description of the use of SCD with a modified hemodialysis machine for ARF in critically ill patients. SCD is defined by the following parameters: (a) QB = 100 to 300 ml/min, (b) QD = 100 to 300 ml/min, (c) utilization of a modified hemodialysis machine with controlled ultrafiltration and online production of bicarbonate-based dialysate, (d) continuous or daily treatment for at least 8 to 12 hours. Slow continuous dialysis provides a sustained high rate of solute clearance in the range of 70 to 80 ml/min. Possible clinical advantages of this technique are being evaluated in an ongoing clinical trial. Preliminary data demonstrate the safety, efficiency, and simplicity of the treatment.