Chest
Volume 105, Issue 5, May 1994, Pages 1516-1527
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Clinical Investigations in Critical Care
Corticosteroid Rescue Treatment of Progressive Fibroproliferation in Late ARDS: Patterns of Response and Predictors of Outcome

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Pulmonary fibroproliferation (PFP) is directly or indirectly the leading cause of death in patients with late ARDS. We previously reported our experience using intravenous corticosteroids (IVC) in 8 patients with late ARDS and now have expanded our observation to a total of 25 patients with severe fibroproliferation (mean lung injury score [LIS] 3) and progressive respiratory failure (RF). Thirteen patients had open-lung biopsy before treatment. Patients were started on IVC treatment (IVCT) an average of 15±7.5 days into mechanical ventilation (MV). Significant physiologic improvement (SPI) to IVCT was defined as a reduction in LIS of greater than 1 point or an increase in PaO2: ratio of greater than 100. We observed three patterns of response: rapid responders (RR) had an SPI by day 7 (n=15); delayed responders (DR) had an SPI by day 14 (n=6); nonresponders (NR) were without SPI by day 14 (n=4). Overall, the following significant mean changes were seen within 7 days of IVCT: LIS from 3 to 2 (p=0.001), PaO2:FIo2 from 162 to 234 (p=0.0004), PEEP from 11 to 6.8 cm H2O (p=0.001), chest radiograph score from 3.8 to 3.0 (p=0.009), and VE from 16 to 13.6 L/min (p=0.01). Development of pneumonia was related to the pattern of response. Surveillance bronchoscopy was effective in identifying pneumonia in eight afebrile patients. Nineteen of 25 (76 percent) patients survived the ICU admission. Comparisons were made between survivors (S) and nonsurvivors (NS) and among the three groups of responders. At the time ARDS developed, no physiologic or demographic variable could discriminate between S and NS. At the time of IVCT, only liver failure was more frequent in nonsurvivors (p=0.035). Histologic findings at open-lung biopsy and pattern of physiologic response clearly predicted outcome. The presence of preserved alveolar architecture (p=0.045), myxoid type fibrosis (p=0.045), coexistent intraluminal bronchiolar fibrosis (p=0.0045), and lack of arteriolar subintimal fibroproliferation (p=0.045) separated S from NS. ICU survival rate was 86 percent in responders and 25 percent in nonresponders (p=0.03). Only one death resulted from refractory respiratory failure.

Section snippets

Patient Population

Twenty-five patients, 8 male and 17 female, received IVCT for late ARDS between July 1989 and September 1992. All patients met diagnostic criteria for ARDS as described by Fowler et al.5 Patients were considered candidates for IVCT if they had (1) evidence of progressive respiratory failure with worsening LIS, and (2) no evidence of active infection. ARDS was caused by a direct injury to the lung in 10 patients and indirect injury in 15 patients. Direct injuries leading to ARDS included

Results

Mean APACHE II score on admission was 20.4±1.7 (range, 11 to 31). Patients had severe respiratory failure with a mean LIS of 2.94±0.68 on day 1 of ARDS (highest value in the first 24 h), and all but four patients had an LIS>2.5. Table 2 shows demographics, type of ARDS, APACHE II score, LIS, and MOF score at the time ARDS developed. At the time ARDS developed, 50 percent of nonsurvivors and 11.1 percent survivors had liver failure with a total bilirubin ≥3 mg/dl (p=0.08). One of these four

Discussion

Adult respiratory distress syndrome (ARDS) is a clinical and pathophysiologic entity characterized by the acute and diffuse involvement of the endothelial and epithelial surface of the lung, which leads to respiratory failure. The term “late ARDS” refers to the clinical stage of ARDS in which the lung attempts to repair the initial or persistent injury to the respiratory units. Its histologic correspondent is termed “fibroproliferative phase” which, if unhalted, leads to extensive fibrosis.

Conclusions

The findings of this self-controlled, clinical, interventional study indicate that pulmonary fibroproliferation is potentially responsive to corticosteroid treatment and that responsiveness is associated with improved outcome. Treatment is more effective when administered early into fibroproliferation before dense acellular fibrosis with deranged alveolar architecture occurs. Unfortunately, monitoring of physiologic and clinical variables was not useful in discriminating patients with advanced

ACKNOWLEDGMENTS

We wish to thank Dr. David Armbruster for critique of the manuscript and Reba Umberger for data collection.

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