There was no evidence of secondary septic complications, Lapatinib mw and VAHS was identified as the most likely cause of multiorgan failure. Therefore, we systematically and prospectively assessed all further patients with A/H1N1/2009 admitted to our intensive care unit (ICU) for the development of VAHS.This report describes a series of 25 consecutive critically ill patients with severe A/H1N1/2009 infection in whom VAHS was found to be a leading contributor to death.Materials and methodsStudy design and patient eligibilityBetween 5 October 2009 and 4 January 2010, we prospectively studied 25 adult patients (22 Caucasian, 2 Turkish and 1 Arabian) with confirmed severe A/H1N1/2009 infection admitted to the medical ICU at Hannover Medical School, Hannover, Germany.

All critically ill patients were defined as those requiring invasive mechanical ventilation, having a fraction of inspired oxygen level greater than 60% or receiving intravenous infusion of vasopressor or inotropic medication. Additional venovenous ECMO support was necessary in 17 patients. In each case, the diagnosis of A/H1N1/2009 infection was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay [17].Data collectionData collection included patient demographics as well as the presence of the number of predefined comorbidities. Presumed infectious organisms from upper and lower respiratory tract specimens were identified by performing A/H1N1/2009 RT-PCR assays within 48 hours of admission. Further viral, microbiological and fungal surveillance included twice-weekly nasopharyngeal swabs, bronchial lavage, and twice-weekly analysis of blood and urine cultures.

In addition to daily routine laboratory analysis, which included C-reactive protein (CRP), procalcitonin, and lactate dehydrogenase (LDH) levels, thrice-weekly measurements of serum ferritin and sIL-2R levels as well as weekly measurements to detect triglyceridemia and hypofibrinogenemia were performed. VAHS was suspected when patients developed fever, cytopenia affecting at least two lineages, hepatitis or splenomegaly and/or when serum levels of sIL-2R and ferritin were increased. The presence of two or more of these features triggered the performance of bone marrow aspiration and biopsy.

The diagnosis of VAHS was made according to established HLH diagnostic criteria if Anacetrapib three of four major criteria (fever, cytopenia, hepatitis or splenomegaly) and at least one minor criterion (evidence of hemophagocytosis in bone marrow samples or increase in serum level of sIL-2R or ferritin, respectively) were present [18].We further obtained information regarding the total duration of hospitalization, mechanical ventilation and ECMO support, as well as the duration and use of antiviral, antibiotic and antifungal treatments.