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Effects of N-acetylcysteine on Microalbuminuria and Organ Failure in Acute Severe Sepsis^*

Results of a Pilot Study

^* From the Intensive Care Department, Academic Hospital, Vrije Universiteit Brussel, Brussels, Belgium.

Correspondence to: Herbert D. Spapen, MD, PhD, FCCP, Intensive Care Department, Academic Hospital, Vrije Universiteit Brussel, Laarbeeklaan, 101, B-1090 Brussels, Belgium; e-mail: herbert.spapen{at}az.vub.ac.be

Abstract

Study objective: The level of microalbuminuria is thought to reflect the severity of inflammation-induced systemic vascular permeability and may have prognostic value with regard to organ dysfunction and survival. N-acetylcysteine (NAC) has been shown to decrease capillary leakage in experimental sepsis. The present study investigated the effect of early treatment with NAC on microalbuminuria and organ dysfunction in severe clinical sepsis.

Design: Prospective, randomized, placebo-controlled study.

Setting: A 24-bed multidisciplinary ICU in a university teaching hospital.

Patients: Thirty-five patients included within 4 h of fulfilling consensus criteria of severe sepsis.

Interventions: Patients were randomly assigned to receive either NAC (continuous infusion starting with 50 mg/kg/4 h followed by 100 mg/kg/24 h for 44 h; n = 18) or placebo (n = 17) in addition to standard therapy.

Measurements and results: Urine samples for measurement of microalbuminuria/creatinine ratio (MACR) were collected on inclusion and after 4 h, 24 h, and 48 h. Severity of illness and degree of organ failure were determined by using, respectively, the APACHE (acute physiology and chronic health evaluation) II score and the sequential organ failure assessment (SOFA) score. The MACR did not differ over time between the placebo- and the NAC-treated groups. SOFA scores were comparable between both treatment groups at baseline (6.2 ± 3.9 vs 6.5 ± 2.7, NAC vs placebo; p = 0.6) and increased during treatment in the NAC-treated patients but not in the placebo group (7.9 ± 3.7 vs 5.9 ± 2.5, p = 0.09 and 7.7 ± 3.8 vs 5.1 ± 2.1, p < 0.05; NAC vs placebo, respectively, at 24 h and at 48 h). The cardiovascular SOFA score progressively increased during NAC treatment, reaching higher values as compared to time-matched scores in the placebo group.

Conclusions: Early NAC administration does not influence the course of MACR in severe clinical sepsis, suggesting that NAC might not attenuate endothelial damage in this condition. NAC treatment even aggravated sepsis-induced organ failure, in particular cardiovascular failure.

Key Words: antioxidants • cardiac performance • microalbuminuria • N-acetylcysteine • organ failure • severe sepsis

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