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Virus-associated hemophagocytic syndrome as a major contributor to death in patients with 2009 influenza A (H1N1) infection

Gernot Beutel1*, Olaf Wiesner2, Matthias Eder1, Carsten Hafer3, Andrea S Schneider4, Jan T Kielstein3, Christian Kühn5, Albert Heim6, Tina Ganzenmüller6, Hans-Heinrich Kreipe7, Axel Haverich5, Andreas Tecklenburg8, Arnold Ganser1, Tobias Welte2 and Marius M Hoeper2

Author Affiliations

1 Departments of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany

2 Department of Respiratory Medicine, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany

3 Department of Nephrology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany

4 Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany

5 Department of Cardio-, Thoracic-, Transplantation and Vascular Surgery, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany

6 Institute for Virology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany

7 Institute for Pathology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany

8 Hospital Administration, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany

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Critical Care 2011, 15:R80  doi:10.1186/cc10073


See related letter by Linthorst et al., http://ccforum.com/content/15/5/440

Published: 2 March 2011

Abstract

Introduction

Virus-associated hemophagocytic syndrome (VAHS) is a severe complication of various viral infections often resulting in multiorgan failure and death. The purpose of this study was to describe baseline characteristics, development of VAHS, related treatments and associated mortality rate of consecutive critically ill patients with confirmed 2009 influenza A (H1N1) infection and respiratory failure.

Methods

We conducted a prospective observational study of 25 critically ill patients with 2009 influenza A (H1N1) infection at a single-center intensive care unit in Germany between 5 October 2009 and 4 January 2010. Demographic data, comorbidities, diagnosis of VAHS, illness progression, treatments and survival data were collected. The primary outcome measure was the development of VAHS and related mortality. Secondary outcome variables included duration of mechanical ventilation, support of extracorporeal membrane oxygenation and duration of viral shedding.

Results

VAHS developed in 9 (36%) of 25 critically ill patients with confirmed 2009 influenza A (H1N1) infection, and 8 (89%) of them died. In contrast, the mortality rate in the remaining 16 patients without VAHS was 25% (P = 0.004 for the survival difference in patients with or without VAHS by log-rank analysis). The patients were relatively young (median age, 45 years; interquartile range (IQR), 35 to 56 years of age); however, 18 patients (72%) presented with one or more risk factors for a severe course of illness. All 25 patients received mechanical ventilation for severe acute respiratory distress syndrome and refractory hypoxemia, with a median duration of mechanical ventilation of 19 days (IQR, 13 to 26 days). An additional 17 patients (68%) required extracorporeal membrane oxygenation for a median of 10 days (IQR, 6 to 19 days).

Conclusions

The findings of this study raise the possibility that VAHS may be a frequent complication of severe 2009 influenza A (H1N1) infection and represents an important contributor to multiorgan failure and death.