Infections and the inflammatory response in acute respiratory distress syndrome.

STUDY OBJECTIVE: Systemic inflammatory response syndrome (SIRS) and infections are frequently associated with the development and progression of acute respiratory distress syndrome (ARDS) and multiple organ dysfunction syndrome (MODS). We investigated, at onset and during the progression of ARDS, the relationships among (1) clinical variables and biological markers of SIRS, (2) infections defined by strict criteria, and (3) patient outcome. Biological markers of SIRS included serial measurements of inflammatory cytokines (IC)-tumor necrosis factor-alpha (TNF-alpha) and interleukins (IL) 1 beta, 2, 4, 6, and 8-in plasma and BAL fluid.

METHODS: We prospectively studied two groups of ARDS patients: 34 patients treated conventionally (group 1) and nine patients who received glucocorticoid rescue treatment for unresolving ARDS (group 2). Individual SIRS criteria and SIRS composite score were recorded daily for all patients. Plasma IC levels were measured by enzyme-linked immunosorbent assay on days 1, 2, 3, 5, 7, 10, and 12 of ARDS and every third day thereafter while patients received mechanical ventilation. Unless contraindicated, bilateral BAL was performed on day 1, weekly, and when ventilator-associated pneumonia was suspected. Patients were closely monitored for the development of nosocomial infections (NIs).

RESULTS: ICU mortality was similar among patients with and without sepsis on admission (54% vs 40%; p < 0.45). Among patients with sepsis-induced ARDS, mortality was higher in those who subsequently developed NIs (71% vs 18%; p < 0.05). At the onset of ARDS, plasma TNF-alpha, IL-1 beta, IL-6, and IL-8 levels were significantly higher (p < 0.0001) in nonsurvivors (NS) and in those with sepsis (p < 0.0001). The NS group, contrary to survivors (S), had persistently elevated plasma IC levels over time. In 17 patients, 36 definitive NIs (17 in group 1 and 19 in group 2) were diagnosed by strict criteria. No definitive or presumed NIs caused an increase in plasma IC levels above patients' preinfection baseline. Daily SIRS components and SIRS composite scores were similar among S and NS and among patients with and without sepsis-induced ARDS, were unaffected by the development of NI, and did not correlate with plasma IC levels.

CONCLUSIONS: Sepsis as a precipitating cause of ARDS was associated with higher plasma IC levels. However, NIs were not associated with an increase in SIRS composite scores, individual SIRS criteria, or plasma IC levels above patients' preinfection baseline. SIRS composite scores over time were similar in S and NS. SIRS criteria, including fever, were found to be nonspecific for NI. Irrespective of etiology of ARDS, plasma IC levels, but not clinical criteria, correlated with patient outcome. These findings suggest that final outcome in patients with ARDS is related to the magnitude and duration of the host inflammatory response and is independent of the precipitating cause of ARDS or the development of intercurrent NIs.