Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: A prospective, randomized trial Catherine S. C. Bouman, MD; Heleen M. Oudemans-van Straaten, MD, PhD; Jan G. P. Tijssen, MD, PhD; Durk F. Zandstra, MD, PhD; Jozef Kesecioglu, MD, PhD O liguric acute renal failure (ARF) is a frequent complica- tion in patients with septic or cardiogenic shock. Pending recovery of renal function, temporary re- nal replacement therapy is required in most cases. In daily practice, there is sub- stantial variation in the policies regard- ing initiation time of renal replacement therapy and in the way it is performed. Apart from intermittent hemodialysis, other techniques, including peritoneal dialysis, continuous arteriovenous hemo- (dia)filtration, and continuous veno- venous hemo(dia)filtration, are being used. It is generally accepted that in in- tensive care patients with ARF, the con- tinuous techniques are superior to inter- mittent hemodialysis, in particular with respect to hemodynamic stability (1, 2). Despite the implementation of continu- ous techniques, patient outcome is still very poor. Most studies of ARF in inten- sive care patients reported a mortality between 60% and 80% (3– 6). Low clear- ance techniques were used in these stud- ies, and renal replacement was started late in the course of renal failure. Non- randomized studies suggest that both earlier initiation of renal replacement therapy and the use of higher ultrafiltrate rates might improve survival and recov- ery of renal function (7, 8). In a recent prospective randomized study, improve- ment of survival was reported by increas- ing the ultrafiltrate rate (9). The aim of the present study was to evaluate the effects of initiation time of hemofiltration and of ultrafiltrate rate in patients with circulatory and respiratory insufficiency and early ARF. The primary end points were mortality at 28 days and recovery of renal function. METHODS The study was designed as a randomized trial comparing three treatment strategies: early high-volume hemofiltration (EHV), early low-volume hemofiltration (ELV), and late low-volume hemofiltration (LLV). The Aca- demic Medical Center, a university hospital with a 30-bed closed-format multidisciplinary intensive care unit (ICU), and the Onze Lieve Vrouwe Gasthuis, a teaching hospital with an 18-bed closed-format multidisciplinary ICU, participated in the study. Both centers prac- From the Departments of Intensive Care (CSCB) and Clinical Epidemiology (JGPT), Academic Medical Center, Amsterdam, The Netherlands; the Department of Anesthesiology, Cardiothoracic and Neurosurgical Intensive Care Unit, University Medical Center, Utrecht, The Netherlands (JK); and the Department of Intensive Care, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands (HMOvS, DFZ). Address requests for reprints to: Catherine S. C. Bouman, MD, Academic Medical Center, Department of Intensive Care, Meibergdreef 9, Amsterdam NL- 1105 AZ, The Netherlands. E-mail: C.S.Bouman@ AMC.uva.nl Copyright © 2002 by Lippincott Williams & Wilkins DOI: 10.1097/01.CCM.0000030444.21921.EF Objective: To study the effects of the initiation time of contin- uous venovenous hemofiltration and of the ultrafiltrate rate in patients with circulatory and respiratory insufficiency developing early oliguric acute renal failure. The primary end points were mortality at 28 days and recovery of renal function. Design: A randomized, controlled, two-center study. Setting: The closed-format multidisciplinary intensive care units of a university hospital (30 beds) and a teaching hospital (18 beds). Patients and Interventions: A total of 106 ventilated severely ill patients who were oliguric despite massive fluid resuscitation, inotropic support, and high-dose intravenous diuretics were ran- domized into three groups. Thirty-five patients were treated with early high-volume hemofiltration (72–96 L per 24 hrs), 35 patients with early low-volume hemofiltration (24 –36 L per 24 hrs), and 36 patients with late low-volume hemofiltration (24 –36 L per 24 hrs). Results: Median ultrafiltrate rate was 48.2 (42.3–58.7) mL·kg 1 ·hr 1 in early high-volume hemofiltration, 20.1 (17.5– 22.0) mL·kg 1 ·hr 1 in early low-volume hemofiltration, and 19.0 (16.6 –21.1) mL·kg 1 ·hr 1 in late low-volume hemofiltration. Sur- vival at day 28 was 74.3% in early high-volume hemofiltration, 68.8% in early low-volume hemofiltration, and 75.0% in late low-volume hemofiltration (p  .80). On average, hemofiltration started 7 hrs after inclusion in the early groups and 42 hrs after inclusion in the late group. All hospital survivors had recovery of renal function at hospital discharge, except for one patient in the early low-volume hemofiltration group. Median duration of renal failure in hospital survivors was 4.3 (1.4 –7.8) days in early high-volume hemofiltration, 3.2 (2.4 –5.4) days in early low-vol- ume hemofiltration, and 5.6 (3.1– 8.5) days in late low-volume hemofiltration (p  .25). Conclusions: In the present study of critically ill patients with oliguric acute renal failure, survival at 28 days and recovery of renal function were not improved using high ul- trafiltrate volumes or early initiation of hemofiltration. (Crit Care Med 2002; 30:2205–2211) KEY WORDS: hemofiltration; acute renal failure; survival; ultra- filtrate; mechanical ventilation; shock; oliguria 2205 Crit Care Med 2002 Vol. 30, No. 10