Severity of illness before the commencement of ECMO was assessed on the basis of ventilatory parameters, arterial blood gas values and chest radiograph findings.The primary outcome measure was the development of VAHS and VAHS-related mortality. Secondary outcome variables included the duration of mechanical ventilation, selleck chemical ECMO support and the duration of viral shedding.Standard treatmentsAntiviral treatment consisted of oral oseltamivir at doses of 75 to 150 mg twice daily and/or intravenous zanamivir at a dose of 600 mg twice daily (individually provided on a compassionate use basis by GlaxoSmithKline, Munich, Germany) . The standard therapeutic course for each compound lasted 5 days. If ongoing viral shedding was present, additional treatment courses were administered until A/H1N1/2009 infection was no longer detectable by RT-PCR assay.
Early corticosteroid treatment was not routinely used in this patient population.Patients with VAHS were intended to be treated according to the recommendations of the Histiocyte Society with a modified HLH-94 protocol which consisted of intravenous etoposide (100 to 150 mg/m2 once weekly) and intravenous dexamethasone (8 mg/m2 once daily) [22-24].Our diagnostic and therapeutic approach was approved by the local institutional review board (Ethics Committee of the Hannover Medical School, Reference 953-2011). In agreement with local regulations, informed consent was waived, as all patients were treated according to the standards of care in our center.Statistical analysisDescriptive analysis was performed using medians and interquartile ranges (IQR).
All statistical parameters were tested for normal distribution using the Shapiro-Wilk test of normality. Discrete variables were compared using Pearson’s ��2 test or Fisher’s exact test. For normally distributed data, continuous variables of patients with and without VAHS were analyzed using the Welch two-sample t-test. Otherwise, the Wilcoxon rank-sum test was used. Probability of survival was determined on the basis of survival curves using the Kaplan-Meier method. Differences between groups were calculated using a stratified log-rank test (Fleming-Harrington G�� family). Hazard ratios for the development of VAHS as a time-dependent variable were evaluated by using a Cox proportional regression model. Last survival status for all patients was assessed on 31 March 2010.
Two-sided P values <0.05 were considered statistically significant differences. R-Project software version 2.10.1 for Brefeldin_A Linux was used for statistical computation.ResultsCharacteristics of patientsBetween 5 October 2009 and 4 January 4 2010, 25 adult patients (22 Caucasian, 2 Turkish and 1 Arabian) fulfilled the study’s eligibility criteria. All patients were admitted with severe respiratory failure requiring invasive mechanical ventilation (n = 25, 100%) and venovenous ECMO support (n = 17, 68%).