Effect of N-acetylcystein on microalbuminuria and organ failure in acute severe sepsis.

Herbert Spapen, Marc Diltoer, Nam NGUYEN Duc, Luc Huyghens, [No Value] Chest (Redacteur)

Onderzoeksoutput: Articlepeer review


Background and objective : Acute inflammation is characterized by increased microalbuminuria. 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), an anti-oxidant wit ant-inflammatory actions in the systemic and microvascular circulation, has been shown to decrease capillary leakage in experimental sepsis. The present study intended to investigate the effect of early treatment with NAC on microalbuminuria and organ dysfunction in clinical severe sepsis.

Design and setting : Prospective, randomised, placebo-controlled study in a 24-bed University Intensive Care Unit.

Patient population : Thirty-five patients, included within 4 to 6h of diagnosis of severe sepsis.

Interventions and measurements : Patients were randomly assigned to receive either NAC (continuous infusion starting with 50 mg/kg/4h followed by 100 mg/kg/24h for 44h ; n = 18) or placebo (n = 17) in addition to standard therapy. Urine samples for measurement of microalbuminuria/creatinine ratio (MACR) and blood samples for routine laboratory and arterial blood gas measurements were collected on inclusion and after 4, 24 and 48h.

Serverity of illness and degree of organ dysfunction were determined by using respectively the Acute Physiology And Chronic Health Evaluation (APACHE II) score and the Sequential Organ Failure Assessment (SOFA) score.

Results : Patients in both treatment groups were comparable between ?????
age, gender, causes of sepsis, APACHE II and baseline SOFA score. MACR did not change over time in the placebo-treated group and decreased slightly but non-significantly during NAC infusion. Compared to baseline values (6.2 + 3.9 vs. 6.5 + 2.7, NAC vs. placebo ; p = 0.6), the SOFA score increased in NAC-treated patients (7.9 + 3.7 and 7.7 + 3.8, respectively at 24h and 48h ; both p <0.05 vs. baseline) but decreased in placebo-treated subjects (5.1 + 2.1 at 48h ; p <0.01).

Conclusions : Early NAC administration does not influence the course of MACR in severe clinical sepsis, suggesting that NAC might not decrease or attenuate endothelial damage in clinical sepsis. As shown by the rise of the SOFA score, NAC treatment may even aggravate sepsis-induced organ damage.

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