Furosemide does not improve renal recovery after hemofiltration for acute renal failure in critically ill patients: A double blind randomized controlled trial Peter H. J. van der Voort, MD, PhD, MSc; E. Christiaan Boerma, MD; Matty Koopmans, RN; Marie ¨ t Zandberg, MD; Joke de Ruiter, MD; Rik T. Gerritsen, MD; Peter H. M. Egbers, MD; W. Peter Kingma, MD; Michae ¨ l A. Kuiper, MD, PhD, FCCP, FCCM T he incidence of acute renal failure (ARF) in patients with severe sepsis or septic shock is 16% to 51% (1). ARF in patients with multiple-organ dysfunc- tion syndrome is associated with a mor- tality of 50% to 70% (2). A substantial percentage of multiple-organ dysfunc- tion syndrome patients with ARF re- quire renal replacement therapy (3). Whether in that case intermittent or continuous renal replacement therapy (CRRT) should be given is addressed by several studies (4 – 6). Which patients with ARF will regain urine output and renal function and at what time remains unpredictable. The proportion of patients who remain dialy- sis dependent varies in the literature be- tween 1% and 16% (7–10). Little is known about the proper time to withdraw CRRT and how to proceed in the recovery phase of ARF. During CRRT, many pa- tients show oliguria or anuria. Because of that, physicians may be tempted to give diuretics when CRRT ends. Continuous infusion of a loop diuretic, such as furo- semide, is the most logical choice to in- crease urine production (11). The dimin- ished capacity to concentrate urine after ARF may necessitate a higher urinary vol- ume to increase clearance. In addition, loop diuretics can lower oxygen demand in the medullary thick ascending limb and they are capable of reducing the se- verity of ARF in animal studies (12, 13). However, in critically ill patients, loop diuretics do not prevent the progression from early kidney failure to more ad- vanced stages of ARF (11). In a meta- analysis, loop diuretics did reduce the duration of renal replacement therapy in ARF but critically ill patients were poorly represented in these studies (11). Fur- thermore, the use of furosemide may be associated with increased mortality (14). This observational study may suffer from statistical flaws and is, therefore, debated by others (15). The role of loop diuretics in the recov- ery phase of ARF in critically ill patients with multiple-organ failure is poorly studied. Despite this lack of data, a large multicenter study showed that in the overall management of ARF diuretics are used by 67% of the intensive care and nephrology clinicians (16). Thirty-four percent of them used diuretics in the recovery phase of ARF (16). On the basis of these considerations, we studied the effect of continuous furo- semide infusion when compared with pla- From the Department of Intensive Care (PHJvdV, MK), Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands; and Department of Intensive Care, (PHJvdV, ECB, MK, MZ, JdR, RTG, PHME, WPK, MAK) Medical Center Leeuwarden, Amsterdam, The Netherlands. Clinical Trials # NCT00298454; the study was not commercially funded. For information regarding this article, E-mail: phjvdvoort@chello.nl Copyright © 2009 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0b013e318195424d Objective: To study the potential beneficial role of furosemide in resolving renal failure after hemofiltration in mechanically ventilated critically ill patients. Design: Single-center randomized, double blind, placebo-con- trolled study. Setting: A 13-bed mixed intensive care unit (ICU) in a teaching hospital. Patients: Patients who had been treated with continuous veno- venous hemofiltration were included. Interventions: After the end of continuous venovenous hemofiltra- tion, the urine of the first 4 hours was collected for measuring creatinine clearance. Patients were subsequently randomized for furosemide (0.5 mg/kg/hr) or placebo by continuous infusion. To prevent hypovolemia, the rate of fluid infusion was adapted every hour and was set as the urinary production of the previous hour. Measurements and Main Results: End points were renal re- covery (creatinine clearance more than 30 mL/min or stable serum creatinine without renal replacement therapy) in the ICU and in the hospital. Seventy-two patients were included and 71 were eligible for the analysis. The 36 furosemide-treated patients had a significantly increased urinary volume compared with the 35 placebo-treated patients (median 247 mL/hr (interquartile range [IQR] 774 mL/hr) vs. 117 mL/hr (IQR 158 mL/hr), p  0.003) and greater sodium excretion (median 73 mmol/L (IQR 48) vs. 37 (IQR 48) mmol/L, p  0.001). In the furosemide group 25 patients and in the placebo group 27 patients showed recovery of renal function at ICU discharge (p  0.46). Two patients of the furo- semide group needed long-term dialysis dependency (p  0.23). Conclusion: Furosemide by continuous infusion in the recovery phase of hemofiltration-dependent acute kidney failure did in- crease urinary volume and sodium excretion but did not lead to a shorter duration of renal failure or more frequent renal recovery. (Crit Care Med 2009; 37:000 – 000) KEY WORDS: furosemide; acute renal failure; hemofiltration; re- covery; critically ill; mechanical ventilation 1 Crit Care Med 2009 Vol. 37, No. 2