Nephrol Dial Transplant (2000) 15: 1189-1193
© 2000 European Renal Association-European Dialysis and Transplant Association
Extended daily veno-venous high-flux haemodialysis in patients with acute renal failure and multiple organ dysfunction syndrome using a single path batch dialysis system
1 Medizinische Hochschule Hannover, Abteilung Nephrologie, 2 Klinik für Nieren-, Hochdruck-und Gefäßkrankheiten, Klinikum Hannover Oststadt, 3 Medizinische Klinik II, RWTH Aachen, and 4 Gemeinschaftspraxis für Nephrologie/Dialyse, Langenhagen, Germany
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Abstract |
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Background. In the treatment of acute renal failure in patients with multiple organ dysfunction syndrome (MODS), continuous renal replacement therapies (CRRT) are increasingly used because of excellent volume control in the presence of improved cardiovascular stability. Patients with MODS, however, are frequently catabolic and have a high urea generation rate requiring either cost-intensive high-volume CRRT or additional intermittent haemodialysis to provide adequate clearance of small-molecular waste products. We tested the closed-loop batch haemodialysis system (called Genius®) for the treatment of acute renal failure in patients with MODS in the intensive care unit.
Methods. Blood flow and countercurrent dialysate flow were reduced to 70 ml/min. Thus the 75 l dialysate tank of the Genius® system lasts for 18 h of extended single-path high-flux haemodialysis (18 h-HFD) using polysulphous F60 S® dialysers. Blood pressure, body temperature, and venous blood temperature in the extracorporeal circuit (no heating of the dialysate), ultrafiltration rate, serum urea levels, dialyser urea clearance, and total urea removal were monitored. In addition we tested the bacteriological quality of the spent dialysate at the end of 18-h treatments.
Results. Twenty patients with acute renal failure and MODS were investigated. Averaged dialyser urea clearance was 59.8 ml/min (equal to 3.6 l/h or 64.8 l/day). Total removal of urea was 14.1±6.5 g/day keeping serum levels of urea below 13 mmol/l. Mean arterial pressure remained stable during the 18-h treatments with a mean ultrafiltration rate of 120 ml/h. The temperature in the venous blood tubing dropped by 5±0.5°C during the 18-h treatment (0.28°C/h) in the presence of unchanged core temperature in the patients. There was no bacterial growth in 2.5 l of spent dialysate (<0.0004 colony forming units/ml).
Conclusions. Extended high-flux dialysis using the Genius® system combines the benefits of CRRT (good cardiovascular stability, sterile dialysate) with the advantages of intermittent dialysis (high urea clearance, low treatment costs). High efficiency, simplicity and flexibility of the system offers the unique opportunity to use the same dialysis machine for extended time periods (18 h) as well as for shorter intermittent renal replacement therapy in critically ill patients.
Keywords: acute renal failure; cardiovascular stability; dialysate temperature; extended daily high-flux haemodialysis; multiple organ dysfunction syndrome; sterile dialysate
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Introduction |
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The technique of extracorporeal treatment of acute renal failure in patients with multiple organ dysfunction syndrome (MODS) bears significant implications for the outcome of critically ill patients. These patients suffer from oliguria, azotaemia, hypercatabolism, cardiovascular instability, and disturbances of electrolyte and acid–base homeostasis. Pathophysiological changes due to failure of excretory and regulatory kidney functions contribute importantly to the mortality of MODS, which remains high at about 80% if more than three organ systems fail in spite of numerous improvements in intensive care [1,2].
Renal replacement therapy in intensive care needs to fulfil the following requirements: (i) removal of volume overload by ultrafiltration rates which are tolerated by patients with cardiovascular instability (ii) sufficient extracorporeal clearance of urea, creatinine, etc., meeting the excessive production in catabolic patients; and (iii) restoration of frequently extremely disturbed electrolyte- and acid–base homeostasis. Principally, haemodialysis (HD), haemofiltration (HF), or a combination of these called haemodiafiltration (HDF) are applicable. All modalities can be used intermittently for 3–5 h on 3–7 days a week or continuously. Studies comparing intermittent to continuous therapies with respect to mortality in this population are not conclusive, most probably due to too many non-matched variables in the different study populations [3,4]. The total amount of clearance provided to the patient seems to be the most important factor. A weekly Kt/V of 5.6 is necessary to achieve sufficient clearance of small molecular substances in patients with acute renal failure [5]. This goal could be reached either by continuous venovenous haemofiltration (CVVH) with an exchange volume (ultrafiltrate replaced by substitution fluid) of 36 l a day, or by intermittent HD 5x4 h per week. It is also clear that intermittent HD of 3x4 h per week will result in underdialysis of critically ill patients with acute renal failure [3,5].
Because of the need of parenteral nutrition, antibiotics, vasopressors and other medication given intravenously, ultrafiltration of up to 4 l is required every day to keep the balance between fluid intake and output in oligo-anuric patients with acute renal failure. Even if intermittent haemodialysis or haemofiltration is performed daily, removal of 4 l in 4 h (ultrafiltration rate of 1000 ml/h) will often not be tolerated by patients requiring vasopressors. With respect to fluid removal, extended treatment times will reduce ultrafiltration rates/hour and improve cardiovascular stability. CVVH is associated with excellent blood pressure stability because removal of 4 l in 24 h reduces the ultrafiltration rate to less than 200 ml/h, which is well tolerated even by septic patients under vasopressors.
A disadvantage of CVVH is the need of 36 and more litres of sterile substitution fluid which is usually provided in 4.5 l bags. Today, bicarbonate-buffered substitution fluid is recommended, which has to be mixed from two components just before use. Bags have to be mixed and replaced every 3 h, which increases the work-load as well as the treatment cost of CVVH as compared to intermittent HD. A further disadvantage is that substitution fluid contains a fixed composition of electrolytes, including the buffer, so that individual prescriptions according to the needs of the patient are not possible.
In order to combine the benefits of intermittent haemodialysis (high diffusive clearance, flexibility in the composition of dialysate, low costs of dialysate preparation) and those of continuous haemofiltration (cardiovascular stability due to continuous control of volume and acid–base status, convective clearance of middle molecules), we adapted a batch haemodialysis system developed by B. Tersteegen for chronic intermittent HD for the treatment of acute renal failure in the intensive care unit. This so called Genius® system (Fresenius) has been described recently in detail in this journal by W. Fassbinder [6].
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Subjects and methods |
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Genius extended daily high-flux HD
Preparation of the dialysate and filling of the dialysate tank of the Genius® machine requires a special procedure using a Genius® specific preparation set up. The dialysis machine including the acetate-free bicarbonate buffered dialysate is prepared in the dialysis unit by dialysis nurses from sterile reverse osmosis water and prepacked salts (NaCl, KCl, CaCl2, MgCl2, NaHCO3). The dialysate is heated to a temperature of 38–40°C during the filling process of the 75-l tank of the dialysis machine [6]. The dialysate composition (Na+ 135–145 mmol/l, HCO3- 25–45 mmol/l, K+ 1–4 mmol/l, Ca2+ 1.0–2.0 mmol/l, Mg2+ 0.3–1.2 mmol/l, glucose 0–11 mmol/l) can be chosen and changed every day following the prescription of the nephrologist for each individual patient. Fresh dialysate is pumped from the top of the tank into the dialysate compartment of the high-flux dialyser (F60 S, polysulphone, Fresenius). In the closed dialysate loop, spent dialysate is pumped through a central tube to the bottom of the tank. By this technique, spent dialysate on the bottom of the tank does not mix with fresh dialysate on top. Only one roller pump with two pump-segments is present in the extracorporeal system recirculating blood and dialysate with the same speed of 70 ml/min. This reduced pump speed as compared to 250 ml/min in intermittent HD offers the possibility of prolonging a treatment session from 5 to 18 h with 75 l of dialysate without interruption. An ultrafiltrate line is connected to the closed dialysate compartment with an adjustable pump allowing ultrafiltration rates between 20 and 1000 ml/h. Because of a slightly positive pressure in the closed dialysate circuit solute transport across the high-flux dialyser membrane is by diffusion and internal filtration/backfiltration. The Genius® treatment modality of almost continuous renal replacement therapy is best described as extended daily high-flux HD (HFD), which has previously been described by C. Ronco [7]. Extended HFD with F60S dialysers and the Genius® system were performed daily for 18 h (usually overnight from 2 p.m. to 8 a.m.) and the whole system including the dialyser was changed once a day.
Patients
Twenty patients (14 men, 6 women) with oliguric acute renal failure and MODS were included in the study. All patients were on mechanical ventilation, thus two organ systems (lung and kidney) had failed in all patients. The accompanying or underlying diseases included pancreatitis (n=2), oesophageal carcinoma (n=1), pneumonia (n=6), bowel obstruction with perforation (n=5), endocarditis (n=3), and liver failure (n=3). The median APACHE II score was 26 (range 22–30). All patients were on parenteral nutrition providing approximately 30–35 kcal/kg body weight including 1.2–1.5 g protein/kg body weight/day. Twelve patients were in the need of vasopressors (dopamine, noradrenaline).
Parameters
The dialyser urea clearance was measured 1 h after start of treatment and at the end of an 18-h HFD by obtaining pre-and post-dialyser plasma samples. The dialyser clearance was calculated by the formula: dialyser urea clearance=(A-V)/AxQB, where ‘A’ is the plasma urea level pre-dialyser, ‘V’ is urea serum level post-dialyser, and QB represents the blood flow which was 70 ml/min. Plasma urea levels were also measured every day before and after the 18-h HFD treatment. At the end of the 18-h treatment, spent dialysate was mixed thoroughly in the 75-l tank of the Genius® machine and a dialysate sample was taken to measure urea concentration in order to calculate the total mass of urea removed.
The dose of heparin needed per treatment for adequate anticoagulation was documented. Blood pressure, ultrafiltration rate, rectal body temperature and venous blood temperature in the extracorporeal circuit were monitored continuously.
Dialysate bacteriology
At the end of the 18-h HFD treatment, 2.5 l of the mixed dialysate in the 75-l tank were pumped through a Swinnex filter holding a 0.22 µm membrane. The filter membrane was incubated up-side-down on nutrient-poor culture agar (tryptone glucose extract, TGE, Oxoid, Unipath Ltd) for 5 days at 25°C and colony-forming units (c.f.u.) were counted. Bacterial growth in spent dialysate was expressed as c.f.u./ml.
All measurements were done under steady-state conditions, at the third to fifth 18-h HFD treatment.
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Results |
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Urea clearance
The averaged in vivo dialyser urea clearance of the F60 high-flux dialyser under the chosen conditions with a blood flow equal to countercurrent dialysate flow of 70 ml/min was 59.8 ml/min 1 h after start of 18-h HFD and did not drop significantly until the end of the 18-h treatment. Theoretically this could be extrapolated to an urea clearance of approximately 3.6 l/h and to 64.6 l/18 h. With this volume of urea clearance provided every day, plasma urea levels were (n=20, means±SD): 36.2±17.3 mg/dl (12.9±6.2 mmol/l) before and 26.6±10.5 mg/dl (9.5±3.8 mmol/l) at the end of the 18-h HFD treatment. The total mass of urea removed into the dialysate was 14.1±6.5 g/day.
Cardiovascular stability during 18 h of extended high-flux HD
The mean of the mean arterial pressure (MAP) and the cumulative ultrafiltration volume during the 18-h HFD are depicted in Figure 1
. The mean ultrafiltration rate was 120 ml/h (range 20–300 ml/h) during 18 h of extended high-flux dialysis resulting in an average total ultrafiltration volume of 2.2±1.1 l/day. In the presence of this volume removal there was a remarkable arterial blood pressure stability during the 18-h treatment. The MAP was 71.1±5.9 mmHg at the start of Genius® HFD and remained stable until the end when the mean MAP was 79.1±4.3 mmHg.
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Temperature loss during extended high-flux HD
The blood temperature in the venous blood line of the extracorporeal circuit dropped from (mean±SD) 35.3±0.7°C to 30.2±0.8°C during 18 h, which is equal to an averaged temperature loss of 0.28°C/h. As indicated in Figure 2, the decrease in temperature was not linear and a higher loss was noted during the first 3–6 h followed by a less pronounced loss during the last 12 h of treatment. The core temperature of the patients did not drop significantly (36.8±0.6°C at the start of treatment vs 36.2±0.3°C after 18 h of Genius® HFD) (Figure 2).
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Anticoagulation
In all patients unfractionated heparin was used for anticoagulation. A bolus injection of 1000 U before the start of treatment was followed by continuous heparinization of 500 U/h. The total dose was 10000 U per 18-h HFD treatment. There was no clotting of the extracorporeal circuit in the 20 treatments described and no severe bleeding complication was observed.
Microbiological quality of spent dialysate
There was no bacterial growth in any of the 15 dialysate samples tested. Therefore the dialysate contained less than 1 c.f.u./2500 ml, which is <0.0004 c.f.u./ml.
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Discussion |
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In 1997 we started to use the Genius® system in the intensive care unit in order to replace both intermittent HD for 3–5 h with standard HD machines as well as CVVH performed with 36 l of bicarbonate-buffered substitution fluid per day. Over the last 2 years, more than 2500 treatments have been performed using double-lumen venous catheters for blood access. In more than 1000 treatments, 18-h HFD has been performed with a blood flow equal to the countercurrent dialysate flow of 70 ml/min. In the present paper we present the results of additional measurements in 20 critically ill patients during 18 h of extended high-flux haemodialysis using the Genius® system. Under the conditions of slow blood and dialysate flow a relatively high dialyser urea clearance (85% of blood flow) was achieved. More important than the calculated dialyser clearance is the total mass of urea nitrogen removed into the dialysate. In the Genius® machine, the total removal of urea can easily be determined because the dialysate is recirculated in a closed loop and a representative sample from the tank allows exact quantitative measurements of urea removal. Our data indicate that during 18 h of extended high-flux dialysis a mean of 14 g of urea (range 6–27 g) were removed. This amount of urea removal is sufficient to balance urea nitrogen appearance which is in the range of 10–20 g per day in critically ill patients depending on the protein intake and the degree of catabolic protein degradation. In our anuric patients the urea clearance provided by daily 18-h HFD was able to keep serum urea levels below 13 mmol/l. This high clearance of small solutes cannot be achieved in catabolic patients using conventional CVVH with a volume exchange of up to 36 l per day.
The predominant transport mechanism across the dialyser membrane during Genius HFD is diffusion. In addition, a phenomenon of internal filtration and backfiltration inside the high-flux dialyser occurs which may add removal of small and middle molecules by convection. Using a HD system with high diffusive clearance, the cardiovascular stability during treatment is of special importance because it has been proposed that the improved tolerance of ultrafiltration during CVVH might be due to the fact that in CVVH diffusion is negligible and convection is the almost exclusive mechanism of solute removal from blood. We therefore monitored arterial blood pressure during Genius® HFD and found stable MAP in all 20 patients in the presence of a continuous mean ultrafiltration rate of 120 ml/h (Figure 1
). We conclude that during Genius® HFD ultrafiltration is well tolerated in the presence of diffusion.
There are several possible reasons contributing to this good cardiovascular stability. First, dialysate temperature and the blood temperature in the extracorporeal blood circuit dropped by 5±0.5°C during the 18-h treatment (0.28°C/h) in the presence of unchanged core temperature in the patients. It has been shown that cooling of the dialysate temperature increases peripheral resistance and improves blood pressure stability in chronic HD patients [8]. One may assume that also in critically ill patients reinfusion of cooler blood from the extracorporeal circulation may increase peripheral resistance and improve cardiovascular stability as well. It has to be pointed out that we used a reduced blood flow of 70 ml/min in the Genius® system. In other CRRT treatment modalities with higher blood flows reinfusion of cooler blood may result in decreased core temperature as well. It remains to be elucidated whether the beneficial effect of low temperature on cardiovascular stability is accompanied by negative effects on tissue perfusion leading to ischaemic damage. Second, the bacteriological quality of the Genius® dialysate was very high, even after an 18-h treatment. Thus, the spent dialysate almost fulfils the standard of sterility (<10-6 c.f.u./ml). Since backfiltration of pyrogens from contaminated dialysate into the blood may induce a drop in blood pressure in high-flux HD, the high bacteriological quality of the Genius® dialysate may contribute to cardiovascular stability during extended high-flux HD. Third, the dialysate buffer influences the blood pressure during HD. Acetate-buffered dialysate in particular has been associated with hypotensive episodes during CVVH [9]. As in the Genius® system acetate-free bicarbonate dialysate is used, this fact may also contribute to the good blood pressure control during the 18-h treatment.
Blood clotting in the extracorporeal circuit could be a problem, in particular when blood flow is reduced like in the present study. In all 20 patients there was no increased requirement of heparin during 18 h of Genius® HFD compared to our own previous experience with CVVH. Severe bleeding complications attributable to the Genius® treatment were not observed. Compared to several CVVH/HD systems there is an important difference in the extracorporeal blood circuit of the Genius® machine: the blood lines do not include an air-trap-chamber or bubble catcher, thus avoiding a blood–air contact which is thought to promote blood coagulation [10]. It has to be mentioned, however, that there was no contraindication for the use of heparin in the 20 patients studied. If anticoagulation has to be avoided completely, clotting occurs after a variable period of time and it is not possible to run an 18-h treatment without changing the dialyser and the blood tubings.
Some data in the recent literature suggest that continuous renal replacement therapies may improve outcome of critically ill patients with acute renal failure and MODS [11]. Improved clearances of known waste products (urea, creatinine) as well as unknown uraemic toxins or circulating mediators of inflammation and sepsis may play a role. Although still controversial, it has been proposed that high-volume CVVH using exchange volumes (ultrafiltration vs substitution) of up to 100 l/day may be superior to standard CVVH with respect to improved cardiovascular stability and outcome. Since sterile i.v. substitution fluid has to be used in CVVH, the costs of high-volume CVVH increases dramatically with the volume of substitution fluid used. In contrast, the Genius® system uses 75 l of online-produced sterile dialysate, which is much less expensive than 75 l of sterile substitution fluid. The removal of circulating mediators of sepsis (proinflammatory cytokines such as TNF
) is discussed as an indication for high-volume CRRT in patients with MODS [11]. However the amount of cytokines that can be removed during high-volume extracorporeal treatments including extended Genius® HFD is negligible compared to the high endogenous clearance of these mediators and does not result in a significant reduction of cytokine plasma levels [12]. There is, however, a different aspect with respect to cytokine production in patients with sepsis. The ability of circulating mononuclear cells to produce and release proinflammatory cytokines in response to endotoxin is severely suppressed in sepsis. Preliminary studies in patients with acute renal failure and sepsis demonstrated that compared to standard CVVH with 36-l substitution per day, Genius® 18-h HFD is superior in improving the endotoxin-induced whole-blood production of proinflammatory cytokines [13]. We speculate that Genius® HFD is at least as effective as high-volume CVVH in the treatment of critically ill patients with acute renal failure and sepsis.
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Conclusion |
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We describe a single-path batch HD system (Genius®) for the treatment of acute renal failure in patients with MODS as an alternative to established techniques of continuous renal replacement therapies such as CVVH. We conclude that the Genius® system is a simple and easy to handle technique combining the benefits of CVVH (good cardiovascular stability, sterile substitution fluid) with the advantages of intermittent dialysis (high urea clearance, variable dialysate composition, low cost). Simplicity and flexibility of the system offers the unique opportunity to use the same dialysis machine for extended daily as well as intermittent renal replacement therapy.
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Notes |
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Correspondence and offprint requests to: PD Dr med. Gerhard Lonnemann, Gemeinschaftspraxis für Nephrologie/Dialyse, Eickenhof 15, D-30851 Langenhagen, Germany.
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References |
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- Schwilk B, Wiedeck H, Stein B, Reinelt H, Treiber H, Bothner U. Epidemiology of acute renal failure and outcome of haemodiafiltration in intensive care. Intens Care Med1997; 23: 1204–1211[Web of Science][Medline]
- Jones CH, Richardson D, Goutcher E et al. Continuous venovenous high-flux dialysis in multiorgan failure: a 5-year single-center experience. Am J Kidney Dis1998; 31: 227–233[Web of Science][Medline]
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Ronco C, Brendolan A, Bellomo R. Continuous versus intermittent renal replacement therapy in the treatment of acute renal failure. Nephrol Dial Transplant1998; 13 [Suppl 6]: 79–85
[Free Full Text] - Clark WR, Mueller BA, Alaka KJ, Macias WL. A comparison of metabolic control by continuous and intermittent therapies in acute renal failure. J Am Soc Nephrol1994; 4: 1413–1420[Abstract]
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[Free Full Text] - Ronco C. Continuous renal replacement therapies in the treatment of acute renal failure in intensive care patients. Part 1. Theoretical aspects and techniques. Nephrol Dial Transplant1994; 9[Suppl 4]: 191–200
- Van Kuijk WHM, Hillion D, Savoiu C, Leunissen KML. Critical role of the extracorporeal blood temperature in the hemodynamic response during hemofiltration. J Am Soc Nephrol1997; 8: 949–955[Abstract]
- Wynckel A, Wuillai A, Bene B, Cornillet J, Randoux C, Chanard J. Assessment of acetate free continuous veno-venous hemofiltration in acute renal failure. ASAIO J1998; 44: M606–609[Medline]
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Revision received 23. 3.00.
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