N-acetylcysteine for patients with prolonged hypotension as prophylaxis for acute renal failure (NEPHRON)

Background: Acute renal failure is a common complication in critically ill patients and carries an increased morbidity and mortality. N-acetylcysteine is an antioxidant and anti-inflammatory agent that may counteract some of the pathophysiologic derangements in shock states. Objective: To test whether the administration of N-acetylcysteine, compared with placebo, reduces the incidence of acute renal failure in hypotensive patients. Design. Prospective, randomized, double-blinded, placebo-controlled study. Setting., Intensive care units of a university tertiary care hospital. Patients. One hundred forty-two patients with new onset (within 12 hrs) of at least >= 30 consecutive minutes of hypotension and/or vasopressor requirement. Interventions: Patients were randomized to receive either N-acetylcysteine or placebo for 7 days, in addition to standard supportive therapy. Measurements and Main Results: Patients who received N-acetylcysteine had an incidence of acute renal failure (>= 0.5 mg/dL increase in creatinine) of 15.5%, compared with 16.9% in those receiving placebo (p =.82, not significant). There were no significant differences between treatment arms in any of the secondary outcomes examined, including incidence of a 50% increase in creatinine, maximal rise in creatinine, recovery of renal function, length of intensive care unit and hospital stay, requirement for renal replacement therapy, and mortality. Among patients receiving N-acetylcysteine, there were trends toward reduced incidence of acute renal failure in patients with baseline Sequential Organ Failure Assessment (SOFA) score >8 (p =.12), lower SOFA scores during the first 4 days of treatment (p =.28), and reduced mortality in patients <65 yrs of age (p =.20). Conclusions. There were no significant differences in any of our primary or secondary end points between patients treated with N-acetylcysteine or placebo. Trends toward reduced incidence of acute renal failure in patients with baseline SOFA score >8, reduced SOFA scores during the first 4 days, and reduced mortality in patients <65 yrs of age are provocative but require further study to determine their clinical significance.