Chest
Volume 105, Issue 1, January 1994, Pages 190-194
Journal home page for Chest

Clinical Investigations: Miscellaneous
N-Acetylcysteine Enhances Recovery From Acute Lung Injury in Man: A Randomized, Double-Blind, Placebo-Controlled Clinical Study

https://doi.org/10.1378/chest.105.1.190Get rights and content

Objective

To determine the effects of intravenous N-acetylcysteine (NAC) on the development of severe adult respiratory distress syndrome (ARDS) and mortality rate in patients with mild-to-moderate acute lung injury and to analyze the duration of ventilatory support and FIo2 required as well as the evolution of the lung injury score.

Setting

Three university hospital ICUs and one regional ICU in Switzerland.

Patients

Sixty-one adult patients presenting with mild-to-moderate acute lung injury and various predisposing factors for ARDS received either NAC, 40 mg/kg/d, or placebo intravenously for 3 days.

Measurements

Respiratory dysfunction was assessed daily according to the need for mechanical ventilation and FIO2, the evolution of the lung injury score, and the PaO2/FIo2 ratio. The cardiovascular state, liver function, and kidney function were also monitored. Data were collected at admission (day 0), during the first 3 days, and on the day of discharge from the ICU.

Results

The NAC and placebo groups (32 and 29 patients, respectively) were comparable at ICU admission for severity of illness assessed by the simplified acute physiology score (SAPS) (10.8 ± 4.6 vs 10.9 ± 4.8) and lung injury score (LIS) (1.39 ± 0.95 vs 1.11 ± 1.08) (mean ± SD). Three patients in each group developed ARDS. The 1-month mortality rate was 22 percent for the NAC group and 35 percent for the placebo group (difference not statistically significant). At admission, 22 of 32 patients (69 percent) in the NAC group were mechanically ventilated compared with 22 of 29 (76 percent) in the placebo group. At the end of the treatment period (day 3), 5 of 29 (17 percent) in the NAC group and 12 of 25 (48 percent) in the placebo group were still receiving ventilatory support (p = 0.01), The FIo2 was 0.37 less than admission value (day 0) in the NAC group, and 0.20 less in the placebo group (p < 0.04); the oxygenation index (PaO2/FIo2) improved significantly (p < 0.05) from day 0 to day 3 only in the NAC-treated group. The LIS showed a significant regression (p = 0.003) in the NAC-treated group during the first 10 days of treatment: no change was observed in the placebo group. No adverse effects were observed during the treatment with NAC.

Conclusions

Intravenous NAC treatment during 72 h improved systemic oxygenation and reduced the need for ventilatory support in patients presenting with mild-to-moderate acute lung injury subsequent to a variety of underlying diseases. Development of ARDS and mortality were not reduced significantly by this therapy.

Section snippets

Subjects and Protocol

During a 12-month period, patients with risk factors known to predispose to the development of ARDS (see below), and presenting with mild-to-moderate acute lung injury, were included in the trial in the four participating intensive care units (ICUs) in Switzerland (Geneva, Lausanne, Basel, Locarno).

In order to collect patients with comparable lung dysfunction for a pharmacologic treatment regimen, we used the expanded definition suggested by Murray et al,22 and only considered patients

Characterization of Patients

A total of 61 patients (47 men and 14 women) were recruited for the study (Table 1). All were considered evaluable for data analysis. Thirty-two patients received NAC and 29 received placebo. The two groups were well matched for demographic characteristics on trial entry. The SAPS for severity of disease26 was 10.8 ± 4.6 in the NAC group and 10.9 ± 4.8 in the placebo group (x ± SD, not significant [NS]). On admission, the lung injury score22 was 1.39 ± 0.95 in the NAC group, a value not

Discussion

Despite major improvements in patient care, ARDS still remains a formidable clinical challenge and carries a high mortality rate.27 Recent clinical studies suggest that patients with ARDS undergo relevant oxidative stress.12, 13, 14,16,19,28 Toxic oxygen products cause cellular and subcellular damage and activate epithelial cells, macrophages, or endothelial cells. Oxygen radicals are also recognized as mediators between primary and secondary effectors, either directly or via cytokine release (

ACKNOWLEDGMENTS

We would express our thanks to R. Ruffmann, M.D., Head of the Medical Division of Inpharzam SA, Zambon Group, for stimulating discussions and collaboration, and to G. Krejci, Ph.D., Clinical Investigations, Ltd, London, U.K., for the statistical analysis.

References (33)

  • RepineJ.E.

    Neutrophils, oxygen radicals and the adult respiratory distress syndrome

  • HeffnerJ.E. et al.

    Pulmonary strategies of antioxydant defense

    Am Rev Respir Dis

    (1989)
  • HarlanJ.M. et al.

    Neutrophilmediated endothelial injury in vitro

    J Clin Invest

    (1981)
  • ShasbyD.M. et al.

    Granulocyte mediate acute edematous lung injury in rabbits and in isolated rabbit lungs perfused with phorbol myristate acetate: role of oxygen radicals

    Am Rev Respir Dis

    (1982)
  • TateR.M. et al.

    Oxygen-radical mediated permeability edema and vasoconstriction in isolated perfused rabbit lung

    Am Rev Respir Dis

    (1982)
  • JohnsonK.J. et al.

    Wang PA. In vitro damage of rat lungs by oxygen metabolites

    J Clin Invest

    (1981)
  • Cited by (0)

    View full text