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Intensive Care Med (2010) 36:33–41 DOI 10.1007/s00134-009-1727-6


Adolfo Maximo Quispe-Laime Jonas Daniel Bracco Patricia Alejandra Barberio Claudio German Campagne ´ Veronica Edith Rolfo Reba Umberger Gianfranco Umberto Meduri

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

Abstract Purpose: Duringthe 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 metaanalysis 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 andsuspected H1N1 influenza. Methods: From June 24 through 12 July A. M. Quispe-Laime Á J. D. Bracco Á 2009, 13 patients with suspected P. A. Barberio Á C. G. Campagne Á H1N1 pneumonia and ALI-ARDS V. E. Rolfo Medical Intensive Care Unit, Dr. Leonidas were admitted to the intensive care Lucero Acute Municipal Hospital, unit (ICU) of a tertiary care hospital. Universidad Nacional del Sur, H1N1 influenzawas confirmed with Bahia Blanca, Argentina real-time reverse transcriptase-polymerase chain reaction assay in eight R. Umberger Á G. U. Meduri Memphis Veterans Affairs Medical Center, patients. Oseltamivir and corticosteroid treatment were initiated Memphis, TN, USA concomitantly at ICU admission; G. U. Meduri ()) those with severe ARDS received Division of Pulmonary, Critical Care,methylprednisolone (1 mg/kg/day), and Sleep Medicine, and others received hydrocortisone University of Tennessee Health Science (300 mg/day) for a duration of Center, 956 Court Avenue, Room E222B, 21 ± 6 days. Results: Patients with Memphis, TN 38163, USA and without confirmed H1N1 e-mail: umeduri@utmem.edu
Received: 19 September 2009 Accepted: 30 October 2009 Published online: 19 November 2009 Ó Copyrightjointly hold by Springer and ESICM 2009

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 andmortality 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 findingsprovide the rationale for developing a randomized trial. Keywords H1N1 influenza A virus Á Acute respiratory distress syndrome Á Corticosteroid treatment Á Mechanical ventilation Á Mortality


and multiple organ dysfunction (MODS), associated with prolonged intensive care unit (ICU) stay and high During the 2009 H1N1 influenza A virus pandemic, a (17–54%) mortality [1–7]. In influenza,including minority of patients have developed severe pneumonia H1N1, experimental and clinical studies have identified leading to acute respiratory distress syndrome (ARDS) dysregulated systemic inflammation as an important


pathogenetic mechanism correlating with disease severity and progression [1, 8–11]. There has been significant advancement in our understanding of the cellular mechanismsof corticosteroid action [12] and the interaction between corticosteroids and transcription factors for inflammatory cytokines in critical illness and ARDS [13, 14]. Within this new pathogenetic construct [15], an extensive rationale was recently provided for low-tomoderate dose prolonged corticosteroid treatment as an adjunct to antiviral therapy in severe cases of H5N1 influenza [8]. In the...
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