key: cord-0005887-7r5szacw
authors: Hernu, Romain; Chroboczek, Tomasz; Madelaine, Thomas; Casalegno, Jean-Sebastien; Lina, Bruno; Cour, Martin; Argaud, Laurent
title: Early oseltamivir therapy improves the outcome in critically ill patients with influenza: a propensity analysis
date: 2017-10-12
journal: Intensive Care Med
DOI: 10.1007/s00134-017-4953-3
sha: 954003d6e5fa19d642523400fff061b6280958ad
doc_id: 5887
cord_uid: 7r5szacw

nan

neurological failure (n = 7, 3.5%). Infections were mostly caused by type A influenza virus (n = 171, 85%), with A(H1N1)pdm encountered in half of cases (n = 100, 50%). Other characteristics of the patients are presented in Table 1 . Only 40 (20%) patients received antiviral treatment by oseltamivir within 2 days of the onset of symptoms. Day-28, ICU, and in-hospital mortalities were 18% (37/201), 21% (43/201), and 26% (53/201), respectively. Survivors were more likely to have received early oseltamivir therapy, with a significant trend in proportions of in-hospital mortality with increasing time from onset of symptoms to initiation of treatment (p = 0.01). Oseltamivir administration within 2 days of the onset of symptoms appeared as the sole independent determinant of a favorable outcome (OR 0.26; 95% CI 0.08-0.79, p = 0.02). After propensity score-matched analysis, oseltamivir therapy within 2 days of the onset of symptoms was associated with reduced in-hospital mortality (Supplementary Table 1 ).

The present study emphasizes the delay in oseltamivir administration as a major risk factor for in-hospital mortality. Influenza is a public health problem that, each year, causes both severe illness and deaths in high-risk populations [1] . With the exception of the 2009 pandemic, data on critical illnesses attributable to influenza are scarce. Thus, we designed the present study to provide current information on influenza disease in ICUs in the real situation of a specific territory. Concerning the severity of the patients' illness or the risk factors of death, our cohort is in agreement with previous studies on influenza-associated critical illness mainly drawn from 2009 pandemic studies [2, 3] . Nevertheless, our study does not confirm the negative impact on patients' outcomes of the influenza A(H1N1)pdm virus subtype. Importantly, as confirmed by propensity analysis, oseltamivir administration was associated with better outcomes when administrated within 2 days of the onset of symptoms. This is the key message of our work, consistent with recent studies in non-severe forms of the disease, including meta-analysis of randomized clinical trials [4] . Indeed, the recent literature highlights the efficacy of oseltamivir to reduce the duration of symptoms, respiratory tract complications, and hospital admittance [4, 5] . Our results extend to the ICU setting the relationship between the delay of oseltamivir administration and the effectiveness of the treatment in patients with either A(H1N1)pdm or other influenza virus subtypes.

In conclusion, this real-life study emphasizes oseltamivir efficacy on in-hospital outcome when administrated within 2 days of the onset of symptoms. Even if physicians' awareness of the influenza disease has been undeniably enhanced since the last pandemic, many efforts are still required to improve influenza-infected patient management in ICUs, including early oseltamivir administration.

The online version of this article (doi:10.1007/s00134-017-4953-3) contains supplementary material, which is available to authorized users. 

Influenza-Associated Hospitalizations in the United States

Critically ill patients with 2009 influenza A(H1N1) infection in Canada

Critical care services and 2009 H1N1 influenza in Australia and New Zealand

Oseltamivir treatment for influenza in adults: a meta-analysis of randomised controlled trials

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data