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.


METHODS
Prospective, randomized, double-blinded, placebo-controlled study.


METHODS
Intensive care units of a university tertiary care hospital.


METHODS
One hundred forty-two patients with new onset (within 12 hrs) of at least>or=30 consecutive minutes of hypotension and/or vasopressor requirement.


METHODS
Patients were randomized to receive either N-acetylcysteine or placebo for 7 days, in addition to standard supportive therapy.


RESULTS
Patients who received N-acetylcysteine had an incidence of acute renal failure (>or=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.
Komisarof
Jeffrey A
JA
Department of Medicine, Division of Nephrology, General Clinical Research Center, Oregon Health & Science University, Portland, OR, USA.
Gilkey
Gawain M
GM
Peters
Dawn M
DM
Koudelka
Caroline W
CW
Meyer
Mary M
MM
Smith
Stephen M
SM
D000111:Acetylcysteine / Q000627:therapeutic use*; D058186:Acute Kidney Injury / Q000209:etiology* / Q000517:prevention & control*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use*; D006801:Humans; D007022:Hypotension / Q000150:complications*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013997:Time Factors
D016166:Free Radical Scavengers; D000111:Acetylcysteine