H1N1 influenza A virus-associated acute lung injury: response to combination oseltamivir and prolonged corticosteroid treatment

Abstract

Purpose: During the 2009 H1N1 influenza A virus pandemic, a minority of patients developed rapidly progressive pneumonia leading to acute lung injury (ALI)-acute respiratory distress syndrome (ARDS). A recent meta-analysis provides support for prolonged corticosteroid treatment in ALI-ARDS. We prospectively evaluated the response to oseltamivir and prolonged corticosteroid treatment in patients with ALI-ARDS and suspected H1N1 influenza.

Methods: From June 24 through 12 July 2009, 13 patients with suspected H1N1 pneumonia and ALI-ARDS were admitted to the intensive care unit (ICU) of a tertiary care hospital. H1N1 influenza was confirmed with real-time reverse transcriptase-polymerase chain reaction assay in eight patients. Oseltamivir and corticosteroid treatment were initiated concomitantly at ICU admission; those with severe ARDS received methylprednisolone (1 mg/kg/day), and others received hydrocortisone (300 mg/day) for a duration of 21 +/- 6 days.

Results: Patients with and without confirmed H1N1 influenza had similar disease severity at presentation and a comparable response to treatment. By day 7 of treatment, patients experienced a significant improvement in lung injury and multiple organ dysfunction scores (P < 0.001). Twelve patients (92%) improved lung function, were extubated, and discharged alive from the ICU. Hospital length of stay and mortality were 18.7 +/- 9.6 days and 15%, respectively. Survivors were discharged home without oxygen supplementation.

Conclusions: In ARDS patients, with and without confirmed H1N1 influenza, prolonged low-to-moderate dose corticosteroid treatment was well tolerated and associated with significant improvement in lung injury and multiple organ dysfunction scores and a low hospital mortality. These findings provide the rationale for developing a randomized trial.

Fig. 1

Changes in PaO₂:FiO₂ (top), lung injury (middle), and SOFA (bottom) scores during the first 7 days of treatment in patients with positive and negative H1N1 rRT-PCR (left) and in patients with and without severe ARDS (right). SOFA score Sequential Organ Failure Assessment score [29]. Patients with severe ARDS were treated with prolonged methylprednisolone treatment at an initial dose of 1 mg/kg/day; patients with ALI-ARDS were treated with hydrocortisone at an initial dose of 300 mg/day. PaO₂:FiO₂ reflect the worst daily value. From day 1 to day 7, the PaO₂:FiO₂ increased from 113 ± 21 to 198 ± 21 (P = 0.006) in H1N1 positive, from 82 ± 26 to 271 ± 26 (<0.0001) in H1N1 negative, from 78 ± 25 to 172 ± 25 (P = 0.01) in severe ARDS, and from 120 ± 23 to 272 ± 23 (P < 0.001) in ALI-ARDS. From day 1 to day 7, the LIS decreased from 2.83 ± 0.8 to 2.01 ± 0.5 (P = 0.003) in H1N1 positive, from 3.45 ± 0.3 to 2.15 ± 0.8 (P = 0.02) in H1N1 negative, from 3.58 ± 0.4 to 2.44 ± 0.7 (P = 0.009) in severe ARDS, and from 2.63 ± 0.6 to 1.73 ± 0.3 (P = 0.007) in ALI-ARDS. From day 1 to day 7, the SOFA score decreased from 5.9 ± 1.6 to 3.3 ± 2.0 (P = 0.01) in H1N1 positive, from 7.4 ± 4.1 to 3.0 ± 3.5 (P = 01) in H1N1 negative, from 8.2 ± 3.0 to 4.2 ± 2.9 (P = 0.04), and from 5.0 ± 1.5 to 2.3 ± 2.1 (P = 0.02) in ALI-ARDS