Higher Nitric Oxide Levels Increase Survival In ALI/ARDS Trial

In a large-scale, multi-center trial of patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), researchers showed that higher levels of nitric oxide (NO) in patient urine were strongly associated with improved survival, more ventilator-free days, and decreased rates of organ failure.

The results appear in the first issue for February 2007 of the American Journal of Respiratory and Critical Care Medicine, published by the American Thoracic Society.

Michael Matthay, M.D., of the University of California, San Francisco, and five associates measured NO in the urine of 566 patients enrolled in the National Heart, Lung, and Blood Institute's Acute Respiratory Distress Syndrome Network trial, which was designed to look at several different levels of respiratory support.

In humans, NO is involved in oxygen transport to the tissues, the transmission of nerve impulses and a variety of other physiological processes. A product of cellular metabolism, NO serves as a crucial physiologic messenger molecule.

ARDS is the rapid onset of respiratory failure--the inability to adequately oxygenate the blood - that often occurs in the critically ill. ALI precedes ARDS as severe respiratory illnesses progress. Both conditions can be life-threatening.

Among participants, the problems that led to ALI involved aspiration, pneumonia, sepsis (from which 25 percent suffered), and other serious medical difficulties.

The average age of the subjects was 52, with 57 percent being male and 74 percent classified as white.

By the third day of the three-day study, 62 ALI/ARDS patients had died. All of the remaining survivors had significantly higher NO levels. Lower tidal volume respiration was associated with higher levels of urine NO and fewer deaths.

The authors speculated that NO has a beneficial effect on ALI since it scavenges oxygen free radicals that are generated during oxidative stress. Since NO increases microcirculation, it helps to better perfuse tissue beds in the lungs.

The investigators offered an alternative hypothesis to explain their findings: NO created inside the body may have a beneficial effect on organs other than the lung during ALI. It might help prevent further tissue damage by improving oxygen and nutrient delivery to the tissues, while helping to decrease the amount of toxic oxygen species. The authors also speculated that NO might have antibacterial effects that could be important in infectious conditions that predispose patients to ALI.

Dr. Matthay noted that results from animal models of ALI used in prior studies could differ significantly from those associated with human physiology. He added that prior studies had been performed with a smaller number of patients associated with a single research center.

The researchers concluded that they have provided a "reasonable reflection of whole-body NO levels compared with a single organ measurement, which could have been obtained by measuring bronchoalveolar lavage fluid from the lung."

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Contact: Michael Matthay, M.D., University of California, San Francisco, 505 Parmassus Avenue, Rm. 917, San Francisco, California 94143-0130

Contact: Suzy Martin
American Thoracic Society