Elsevier

The Lancet

Volume 356, Issue 9223, 1 July 2000, Pages 26-30
The Lancet

Articles
Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial

https://doi.org/10.1016/S0140-6736(00)02430-2Get rights and content

Summary

Background

Continuous veno-venous haemofiltration is increasingly used to treat acute renal failure in critically ill patients, but a clear definition of an adequate treatment dose has not been established. We undertook a prospective randomised study of the impact different ultrafiltration doses in continuous renal replacement therapy on survival.

Methods

We enrolled 425 patients, with a mean age of 61 years, in intensive care who had acute renal failure. Patients were randomly assigned ultrafiltration at 20 mL h−1 kg−1 (group 1, n=146), 35 mL h−1 kg−1 (group 2, n=139), or 45 mL h−1 kg−1 (group 3, n=140). The primary endpoint was survival at 15 days after stopping haemofiltration. We also assessed recovery of renal function and frequency of complications during treatment. Analysis was by intention to treat.

Results

Survival in group 1 was significantly lower than in groups 2 (p=0·0007) and 3 (p=0·0013). Survival in groups 2 and 3 did not differ significantly (p=0·87). Adjustment for possible confounding factors did not change the pattern of differences among the groups. Survivors in all groups had lower concentrations of blood urea nitrogen before continuous haemofiltration was started than non-survivors. 95%, 92%, and 90% of survivors in groups 1, 2, and 3, respectively, had full recovery of renal function. The frequency of complications was similarly low in all groups.

Interpretation

Mortality among these critically ill patients was high, but increase in the rate of ultrafiltration improved survival significantly. We recommend that ultrafiltration should be prescribed according to patient's bodyweight and should reach at least 35 mL h−1 kg−1.

Introduction

Acute renal failure occurs frequently in critically ill patients in intensive care.1 The disorder is defined as a sudden sustained decline in glomerular filtration rate, generally associated with azotaemia and a fall in urine output. The diagnosis of acute renal failure based on a change in urine output, blood urea nitrogen, or creatinine concentration alone should be made cautiously. Several disorders may lead to such disturbances, the most frequent being volume depletion.1 Blood urea nitrogen concentrations might be raised in patients who have gastrointestinal haemorrhages, severe catabolism, low urine flow rate, intravascular volume depletion, and after administration of drugs. Creatinine can be raised in the absence of acute renal failure in patients who have high muscle mass, or after traumatic muscle injury. For all these reasons, a complete clinical assessment is normally done before the diagnosis is made. Whatever the underlying cause of acute renal failure, ischaemic or toxic injuries to the kidneys represent the final common pathways leading to acute tubular necrosis.1

Acute renal failure, however, is frequently only one of several organ system failures that are present in intensive-care patients, and is generally seen as part of multiple-organ dysfunction syndrome. Such patients are critically ill, and receive various pharmacological and life-support treaments. The primary aim of renal replacement therapy in these circumstances is to achieve adequate correction of homoeostatic disorders with good clinical tolerance. Intermittent renal replacement and peritoneal dialysis have some limitations in efficiency and clinical tolerance.2, 3, 4 Continuous renal replacement therapy is increasingly being used to treat acute renal failure in critically ill patients.5 The advantages of continuous treatments are steady biochemical correction, slow continuous fluid removal, and excellent cardiovascular stability,4, 5, 6 and they are the most popular forms of renal replacement for critically ill patients in Europe and Australia.7 In the USA, there is still some resistance to wider application of these treatments, supported by claims that outcomes better than with other approaches have never been shown.8, 9 Even in countries where continuous treatments are widely used, however, there are substantial differences between facilities, and standards in procedures have not yet been achieved. Furthermore, there is no consensus on an adequate treatment dose9 or on the impact of dose delivery on outcome.10

In St Bartolo Hospital, Vicenza, Italy, continuous veno-venous haemofiltration has been the sole form of first-line renal replacement therapy in patients who have acute renal failure, in intensive care, since 1980. The long-term clinical experience led us to undertake a prospective randomised trial of the effects of different treatment doses on the survival of patients with acute renal failure treated by continuous haemofiltration. The study also assessed recovery of renal function and treatment complications.

Section snippets

Patients

We enrolled patients from two different intensive-care units of the same institution. Criteria for inclusion were admission to the intensive-care unit and the presence of acute renal failure, defined by abnormal concentrations of serum blood urea nitrogen and creatinine, and urine output of less than 200 mL in the preceding 12 h, despite fluid resuscitation and furosemide administration.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11 Fluid resuscitation was done, according to each intensive-careunit's

Results

Of the 492 patients considered for the study, 67 did not fit the entry criteria or refused to give their consent. Therefore, 425 patients (187 women, 238 men) were enrolled (figure 1). The origin of acute renal failure was mostly postsurgical, but in some patients causes were medical and trauma-related. Sepsis was present in 14%, 12%, and 11% of patients in groups 1, 2, and 3, respectively.

Small but significant differences were present for age, APACHE II score, and serum concentrations of blood

Discussion

In chronic haemodialysis patients, haemodialysis dose might affect morbidity and mortality.17 A similar correlation between outcome and dose of treatment in acute renal failure has been suggested.18 In previous analyses, the increase in ultrafiltration was significant, but maximum treatment dose was still low. We compared three medium to high doses of ultrafiltration volume.

The difficulty of doing this type of study on critically ill patients is the definition of criteria for severity of

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