Dialysing the patient with acute renal failure in the ICU: the emperor's clothes?

Norbert Lameire, Wim Van Biesen and Raymond Vanholder

Renal Division, Department of Medicine, University Hospital, Gent, Belgium

Correspondence and offprint requests to: N. Lameire, Renal Division, University Hospital, De Pintelaan 185, 9000 Gent, Belgium.

Introduction

Acute renal failure (ARF) is one of the few causes of organ failure in which complete recovery is possible, provided the patient survives the associated comorbid conditions. The most serious forms of ARF are found in the intensive care unit (ICU), where up to 25% of new patients are reported to develop ARF. Despite the observation that mortality among ARF patients, compared with those without ARF but with comparable illness scores, is significantly higher [1], the majority of patients do not die directly from the renal failure, but from their comorbid conditions. Treatment of ARF can thus be seen as a bridge to recovery of kidney function.

The outcome in patients who are admitted in the ICU because of ARF is also better than that in patients who develop ARF as a complication of a nonrenal comorbid condition during their stay on the ICU (Figure 1Go; own observations). Attention should thus be paid to the prevention of ARF in patients already in the ICU. One may expect that in the future an increasing number of patients with numerous pre-existing comorbid conditions will be hospitalized in the ICU and will require renal replacement therapy (RRT) for ARF.



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Fig. 1. Survival of patients who developed ARF during 1997 either before (– – –) or during (— —) admission to ICU (University Hospital Gent, Belgium).

 
The `ideal' treatment modality for ARF in the ICU should thus not only aim at the preservation of `homeostasis', but should also preferably not increase the comorbidity or worsen the patient's underlying condition, as these are the main determinants of outcome. In view of the expected increase in patient numbers, the `ideal' technique should be inexpensive, simple to manage, and not place too much of a burden on the already often overworked nursing and medical ICU and dialysis staff.

Current dialysis strategies in ARF: the emperors

Until now, the literature on dialysis in ARF has focused mainly on the comparison of two major dialysis techniques: conventional intermittent haemodialysis (IHD) and continuous renal replacement therapy (CRRT). One difference between these two options is fairly evident: the time during which they are applied. CRRT is, in theory, applied continuously, whereas IHD, just like chronic haemodialysis, is applied for only a few hours during the day. Because of the short treatment time, IHD needs to deliver highly efficient therapy for toxin and fluid removal. In contrast, CRRT modalities are mostly rather low-efficiency techniques, and therapy needs to be continuous in order to be adequate. Some other important differences between these two techniques are less frequently emphasized in the literature. (i) IHD is mostly performed as a mainly diffusive therapy across a low-flux dialysis membrane, with a high dialysate flow, which necessitates on-line dialysate production, a water-treatment module and a dialysis monitor. (ii) In contrast, CRRT is performed mostly as convective therapy across a high-flux membrane, and using industry-prepared substitution fluid in bags. (iii) It is clear that the application of IHD needs the nursing and technical expertise of a dialysis team, whereas CRRT is technically less demanding.

Based on these differences, it must unfortunately be admitted that the choice between CRRT and IHD is often reduced to a question of whether the intensivist or nephrologist is responsible for the treatment of ARF in the ICU.

Although it has been claimed that CRRT is associated with a better outcome than IHD, to date no randomized prospective study has been able to prove this [24].

Most published studies have major draw-backs, such as differences in case-mix of patients, or the comparison of optimal CRRT (high volume) with less optimal IHD (limited treatment time, alternate day treatment). Many studies suggested a greater haemodynamic stability of the patient when CRRT is used rather than IHD [2,4]. Although statistically significant, the clinical relevance of the observed differences was low [5].

As far as we know, only one cross-over study has been performed to date, and this did not find a difference in the haemodynamic tolerance of CRRT compared with IHD. In this study, the frequency of hypotensive episodes with a decreases in mean arterial blood pressure with >10 mmHg was 25 and 26% in CRRT and IHD, respectively, and there was also no difference in vasopressor requirement [6].

It has been hypothesized that vasoconstriction, due to lowering of body temperature by the haemofiltration technique and the substitution of below-body-temperature substitution fluids, rather than the CRRT procedure itself, plays an important role in the better haemodynamic stability [2]. The role of temperature was addressed in a cross-over study in which haemodynamic measurements were determined in 11 chronic renal failure (CRF) patients who underwent cold haemofiltration, warm haemofiltration and combined ultrafiltration and haemodialysis [7].

When care was taken to ensure that haemofiltration and combined therapy were performed at equivalent warm temperatures, no difference in blood pressure or vascular reactivity was observed between the two modalities.

It has been claimed that IHD is not able to deliver adequate epuration in the highly catabolic ARF patient in the ICU. Clark et al. [8] developed a computer model allowing individualized RRT prescription for ARF patients, aiming for a desired level of metabolic control (expressed as BUN-levels). The model predicts that adequate metabolic control cannot be obtained with a 4-h IHD session in a patient weighing >90 kg; in contrast, adequate control can be obtained with CRRT, using a urea clearance rate of 2000 ml/h. The model assumes that an IHD session is limited to 4 h/day, and that CRRT is applied for 24 h/day, using a total ultrafiltrate volume of >50 l/day. It should be realized that it may take 5–6 days before the steady-state BUN target is reached. In addition, CRRT therapies are rarely applied in a continuous 24 h/day schedule. It has been reported in one study that the mean operation time of CCRT was only 21.8 h [9]. It has also been reported, however, in IHD that the delivered dialysis dose was below the prescribed dose [10].

The impact of the biocompatibility of the dialysis membrane upon the outcome in ARF patient is still debated, and has recently been discussed in this journal [11] and by us [2]. Although recent studies have suggested that biocompatible membranes are associated with better outcomes, including a lower incidence of sepsis when compared with typical cellulosic membranes, additional information is needed to verify these observations and to define the cause of this response, particularly as it applies to sepsis.

An effect of dialyser membranes on protein and amino acid losses has not been widely investigated as yet, however, in a small cross-over study, it was shown that amino acid losses with the use of high-flux polysulfone membranes exceeded those found with the use of low-flux cuprophane membranes [12]. If these results are confirmed its impact on the nutritional management of the ARF patient should be studied.

It is widely believed that CRRT can be useful in the treatment of lactic acidosis, a frequent complication in patients with multiple organ failure (MOF). Levraut et al. [13] calculated that the extracorporal clearance of lactate is fairly low in comparison with the internal metabolization, so that total lactate clearance and the severity of the metabolic acidosis are not always effected greatly by CRRT.

The role of CRRT in the removal of cytokines and other mediators of inflammation and sepsis has been discussed frequently over recent years and has been reviewed by us in this journal [14].

Although most of these molecules can be removed by either membrane adsorption and/or convection, it is clear that the rate of synthesis of these molecules and their whole-body turnover is high, and that extracorporal removal will not consistently decrease their plasma levels. In addition, anti-inflammatory cytokines are also removed, and the balance of pro- and anti-inflammatory molecule plasma levels remains unchanged [15].

The need for large quantities of industry-prepared dialysate, and for specially adapted artificial kidney sets make the application of CRRT more expensive compared with IHD. A financial analysis in 1995 [16] concluded that `regular' CRRT was ±400 US$/week more expensive than IHD.

New concepts for RRT in the ICU: ... and their clothes

The main advantages of either IHD or CRRT also constitute their major weaknesses; the high efficiency of IHD allows short, intermittent therapy, which can potentially lead to haemodynamic intolerance, poor fluid control and a `saw-tooth' pattern of metabolic control; the low efficiency CRRT assures smooth metabolic control, and perhaps better haemodynamic stability, but necessitates continuous treatment and thus continuous anticoagulation. For adequate metabolic control with CRRT, high ultrafiltrate volumes are needed, increasing the risk of errors in fluid-balance calculations. The need for on-line water treatment makes IHD more complicated, but at the same time reduces the cost. Its intermittent nature also reduces the burden for the nursing and medical staff, and creates time for other diagnostic and/or therapeutic out-of-unit procedures, often needed in this type of patient. CRRT increases the cost and its continuous nature has a heavy impact on the workload of the nurses, and may disturb the already complex ICU organization. These drawbacks of CRRT explain the evolution over recent years from very low efficiency, but easy-to-perform and cheap, continuous arteriovenous haemofiltration (CAVH) to highly efficient, but technically more complex and expensive, high volume continuous vevo-venous haemodialysis (CVVHD) treatment. Changes from arteriovenous to venovenous access, together with the array of CRRT modalities (haemofiltration, slow ultrafiltration, slow haemodialysis and slow haemodiafiltration) have necessitated the introduction of more sophisticated equipment, which includes blood and dialysate pumps, air-leak detectors, pressure monitors and blood-leak detectors. Some of the principle advantages of CRRT (the use of non-dialysis personnel and its simplicity) have been lost with these innovations.

It is thus not surprising that `hybrid techniques' have emerged to provide alternative answers in the polarized discussion between IHD and CRRT. These `slow, extended daily dialysis' (SLEDD) techniques all combine the advantages of CRRT and IHD by using a dialysis monitor and water-treatment module for on-line production of dialysate to perform slow, but extended and daily, haemodialysis. In SLEDD, dialysis is started at a blood flow of 100–150 ml/h, with a dialysate flow of 100–300 ml/min. Dialysis time varies between 6 and 12 h. The possible variations and adaptations of blood flow, haemofiltration rate and duration of dialysis time as a function of the needs of the patient are practically unlimited, and make SLEDD applicable in most ICU patients. Ultrafiltration control is usually tight and is easy to obtain using a dialysis monitor. The on-line production of dialysate by the dialysis monitor also allows tailoring of the dialysate composition for bicarbonate, calcium, potassium and sodium. The shorter treatment time reduces the need for anticoagulation and makes the application of alternative anticoagulation techniques, such as flushing or citrate-anticoagulation, more easy to perform.

In our experience, the use of a single type of machine for all types of dialysis treatment, the reduction in the workload and its intermittent nature make this technique very acceptable to the ICU nursing team.

To date, no large-scale studies on SLEDD are available; however, the technique is increasingly being used and the first preliminary reports are positive [17,18].

In conclusion, in the debate between CRRT and IHD, no randomized trials are available proving that one modality is superior to the other. In view of the high mortality rate of ICU patients with ARF, and the wide diversity in case-mix of comorbidity, such a study does not, in fact, seem realistic, so the controversy will probably never be solved. The dialysis treatment of ARF in ICU patients has evolved very quickly, whereby the two `alternatives', IHD and CRRT, have become more and more similar to each other. This adaptation has been driven by the recognition of the limitations of both techniques. In view of this, `new techniques', such as SLEDD, which are in fact logical modifications that combine the advantages of both techniques, have been developed and used contemporarily in different centres in Europe and the USA. Most modern haemodialysis machines offer possibilities to adapt dialysate flow rates and perform some degree of haemofiltration, and can thus be used for the SLEDD technique.

However, despite all the technical advances that have been developed over recent years, we firmly believe that to ensure optimal dialysis treatment for the ARF patient in the ICU, the skills and the experience of the physicians and nurses who perform dialysis are more important than the applied dialysis modalities.

References

  1. Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality. J Am Med Assoc 1996; 275: 1489–1494[Abstract]
  2. Lameire N, Van Biesen W, Vanholder R, Colardijn F. The place of intermittent hemodialysis in the treatment of acute renal failure in the ICU patient. Kidney Int 1998; 53 [Suppl. 66]: S110–S119[ISI]
  3. Mehta R, McDonald B, Gabbai F, Pahl M, Farkas A, Pascual M, Fowler W and Collborative Study Group. Continuous versus intermittent dialysis for acute renal failure in the ICU: results from a randomized multicenter trial. J Am Soc Nephrol 1996; 7: 1457 [Abstract]
  4. Manns M, Sigler MH, Teehan BP. Continuous renal replacement therapies: an update. Am J Kidney Dis 1998; 32: 185–207[ISI][Medline]
  5. Mehta RL. Continuous renal replacement therapies in the acute renal failure setting: current concepts. Adv Ren Replac Ther 1997; 4 [Suppl. 1]: 81–92
  6. Misset B, Timsit J, Renaud B, Tamion F, Carlet J. Comparison of hemodynamic tolerance of sequential hemodialysis and continuous hemofiltration during acute renal failure in ICU-patients: a randomized cross-over study. Intens Care Med 1996; 22: 742–746[ISI][Medline]
  7. van Kuijk WH, Hillion D, Savoiu C, Leunissen KM. Critical role of the extracorporeal blood temperature in the hemodynamic response during hemofiltration. J Am Soc Nephrol 1997; 8: 949–955[Abstract]
  8. Clark W, Mueller B, Kraus M, Macias W. Extracorporeal therapy requirements for patients with acute renal failure. J Am Soc Nephrol 1997; 8: 804–812[Abstract]
  9. Frankenfield DC, Reynolds HN, Wiles CE, Badellino MM, Siegel JN. Urea removal during continuous hemofiltration of conventional dialytic therapy and acute continuous hemodiafiltration in the management of acute renal failure in the critically ill. Renal Fail 1993; 15: 595–602[ISI][Medline]
  10. Evanson JH, Hakim RM, Wingard RL, Knights S, Schulman G, Ikizler TA, Himmelfarb J. Assessment of dose of dialysis in acute renal failure patients. J Am Soc Nephrol 1996; 7: 1512 (Abstract)
  11. Jacobs C. Membrane biocompatibility in the treatment of acute renal failure: what is the evidence in 1996? Nephrol Dial Transplant 1997; 12: 38–42[Free Full Text]
  12. Hynote ED, McCamish MA, Depner TA, Davis PA. Amino acid losses during hemodialysis: effects of high-solute flux and parenteral nutrition in acute renal failure. J Parent Enter Nutr 1995; 19: 15–21[Abstract]
  13. Levraut J, Ciebiera JP, Jambou P, Ichai C, Labib Y, Grimaud D. Effect of continuous venovenous hemofiltration with dialysis on lactate clearance in critically ill patients. Crit Care Med 1997; 25: 58–62[ISI][Medline]
  14. De Vriese AS, Vanholder RC, De Sutter JH, Colardijn FA, Lameire NH. Continuous renal replacement therapies in sepsis: where are the data? Nephrol Dial Transplant 1998; 13: 1362–1364[ISI][Medline]
  15. De Vriese AS, Colardijn FA, Philippe JJ, Vanholder RC, De Sutter JH, Lameire NH. Cytokine removal during continuous hemofiltration in septic patients. J Am Soc Nephrol 1999; 10: 846–853[Abstract/Free Full Text]
  16. van Bommel E, Bouvy N, So K, Zietse R, Vincent H, Bruining H, Weimar W. Acute dialytic support for the critically ill: intermittent hemodialysis versus continuous arteriovenous hemodiafiltration. Am J Nephrol 1995; 15: 192–200[ISI][Medline]
  17. Chatoth DK, Shaver MJ, Marshall MR, Golper TA. Daily 12-hour sustained low-efficiency hemodialysis (SLED) for the treatment of critically ill patients with acute renal failure: initial experience. Blood Purif 1999; 17: [Abstract 16]
  18. Hu KT, Yeun JY, Craig M, Tarne P, Depner TA. Extended daily dialysis: an alternative to continuous venovenous hemofiltration in the intensive care unit. Blood Purif 1999; 17: [Abstract 15]