The effects of N-acetylcysteine and deferoxamine on plasma cytokine and oxidative damage parameters in critically ill patients with prolonged hypotension: a randomized controlled trial

J Clin Pharmacol. 2012 Sep;52(9):1365-72. doi: 10.1177/0091270011418657. Epub 2011 Nov 1.

Abstract

Reactive oxygen species and inflammation have been implicated in renal tubule cell injury. However, there is some controversy concerning whether antioxidants might attenuate oxidative damage and inflammation in humans after hypotension in the setting of critical illness. This study was a prospective, randomized, double-blinded, placebo-controlled study that included patients with hypotension. Patients were randomized to receive either N-acetylcysteine (NAC; 50 mg/kg by 4 hours followed by 100 mg/kg/d for 48 hours diluted in 5% glucose) and deferoxamine (DFX; at a single dose of 1000 mg diluted in 5% glucose) or placebo. The primary study outcome was the serum levels of markers of oxidative damage and inflammatory response. Secondary outcomes included the incidence of acute renal failure, serum creatinine at hospital discharge, intensive care unit length of stay, and length of hospital stay. Thirty patients were enrolled in the study. The use of NAC plus DFX decreased the oxidative damage parameters but not plasma interleukin-6 levels. In contrast, plasma nitrite levels increased 24 hours after NAC plus DFX administration. On analysis of secondary outcomes, it was observed that creatinine levels at hospital discharge were lower in patients receiving NAC plus DFX when compared with placebo. NAC plus DFX administration was able to decrease plasma markers of oxidative damage and creatinine levels at hospital discharge.

Trial registration: ClinicalTrials.gov NCT00870883.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Acute Kidney Injury / blood
  • Acute Kidney Injury / drug therapy
  • Acute Kidney Injury / etiology
  • Adult
  • Aged
  • Antioxidants / pharmacology*
  • Critical Illness
  • Deferoxamine / pharmacology*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypotension / blood
  • Hypotension / complications
  • Hypotension / drug therapy*
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Nitrites / blood
  • Oxidative Stress / drug effects
  • Siderophores / pharmacology*

Substances

  • Antioxidants
  • Interleukin-6
  • Nitrites
  • Siderophores
  • Deferoxamine
  • Acetylcysteine

Associated data

  • ClinicalTrials.gov/NCT00870883