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. 2011;15(2):R80.
doi: 10.1186/cc10073. Epub 2011 Mar 2.

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

Gernot Beutel  1 , Olaf Wiesner, Matthias Eder, Carsten Hafer, Andrea S Schneider, Jan T Kielstein, Christian Kühn, Albert Heim, Tina Ganzenmüller, Hans-Heinrich Kreipe, Axel Haverich, Andreas Tecklenburg, Arnold Ganser, Tobias Welte, Marius M Hoeper
Affiliations

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

Gernot Beutel et al. Crit Care. 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.

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Figures

Figure 1
Figure 1
Predicted hazard ratio for the development of virus-associated hemophagocytic syndrome (VAHS) revealed a 12-fold increase (log-hazard ratio, 2.5) within the first 16 days after symptom onset.
Figure 2
Figure 2
Bone marrow smears showing large histiocytes with vacuolated cytoplasm phagocytic granulocytes (a) and containing nucleated red blood cells (erythrophagocytosis (b)) (Wright-Giemsa stain; original magnification, ×600).
Figure 3
Figure 3
Kaplan-Meier curve showing estimated survival rates of patients with 2009 influenza A (H1N1) infection with or without virus-associated hemophagocytic syndrome (VAHS). P = 0.004 by log-rank analysis.
See this image and copyright information in PMC

Comment in

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