Acute lung injury : incidence and predictors of outcome with special reference to inhaled nitric oxide

• Main Author: Luhr, Owe
• Format: Doctoral or Postdoctoral Thesis
• Language: unknown
• Published: Karolinska Institutet, Danderyds Sjukhus / Karolinska Institutet at Danderyds Hospital 1999
• Subjects: Respiratory distress syndrome; Adult; -drug-therapy; -mortality; Treatment; -outcome; Nitric oxide; therapeutic-use; administration-and-dosage; -adverse effects; Mutagenicity; tests; Chromosome aberrations; Risk factors; Logistic models; Prospective studies; Meier; Iceland
• Online Access: http://hdl.handle.net/10616/44122

This work started out as a critical examination of the initial clinical experiences with inhalation of nitric oxide (INO) to patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) in Scandinavia 1991-1994. During this examination, we found that epidemiological data and prognostic factors were lacking in Scandinavia for these patient groups, making it difficult to evaluate new therapies. In addition, no studies addressing genotoxicity of INO in humans were found. Objectives: 1. Retrospectively determine mortality and identify potential risks with INO in patients with ALI/ARDS treated outside clinical studies in Scandinavia 1991-1994, and evaluate possible long-term adverse effects on pulmonary function in survivors. 2. In a human test-model study potential genotoxic, adverse effects after a 2-hour INO exposure. 3. Prospectively determine incidence and 90-day mortality of acute respiratory failure (ARF), and ALVARDS in Scandinavia. 4. Compare the compatibility of two proposed definitions of ARDS. 5. Prospectively determine whether evaluation of respiratory variables recorded in the first week of ICU care, could predict outcome in ARF and ARDS. Measurements and results: We identified and analyzed all patients (n=56) treated with INO in Scandinavia 1991-1994. Survivors (n=16) were tested with pulmonary function tests > 8 months after the acute episode. To assess genotoxicity, ten healthy volunteers were exposed for INO with scoring of chromosome aberrations in peripheral blood lymphocytes prior to and after exposure. We also performed an 8-week prospective epidemiological cohort study in Sweden, Denmark and Iceland gathering data on 1,515 patients with ARF, and identified patients with ALI (n=287) and ARDS (n=221) using the American-European Consensus Conference on ARDS criteria. We calculated Kaplan-Meier survival curves and tested for significance by log-rank test. Factors independently contributing to mortality were analyzed using a Cox regression model. Patients included in ...