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Critical Care
Published in: Critical Care 1/2016

Open Access 01-12-2016 | Research

The influence of corticosteroid treatment on the outcome of influenza A(H1N1pdm09)-related critical illness

Authors: Jesse W. Delaney, Ruxandra Pinto, Jennifer Long, François Lamontagne, Neill K. Adhikari, Anand Kumar, John C. Marshall, Deborah J. Cook, Philippe Jouvet, Niall D. Ferguson, Donald Griesdale, Lisa D. Burry, Karen E. A. Burns, Jamie Hutchison, Sangeeta Mehta, Kusum Menon, Robert A. Fowler, on behalf of the Canadian Critical Care Trials Group H1N1 Collaborative

Published in: Critical Care | Issue 1/2016

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Abstract

Background

Patients with 2009 pandemic influenza A(H1N1pdm09)-related critical illness were frequently treated with systemic corticosteroids. While observational studies have reported significant corticosteroid-associated mortality after adjusting for baseline differences in patients treated with corticosteroids or not, corticosteroids have remained a common treatment in subsequent influenza outbreaks, including avian influenza A(H7N9). Our objective was to describe the use of corticosteroids in these patients and investigate predictors of steroid prescription and clinical outcomes, adjusting for both baseline and time-dependent factors.

Methods

In an observational cohort study of adults with H1N1pdm09-related critical illness from 51 Canadian ICUs, we investigated predictors of steroid administration and outcomes of patients who received and those who did not receive corticosteroids. We adjusted for potential baseline confounding using multivariate logistic regression and propensity score analysis and adjusted for potential time-dependent confounding using marginal structural models.

Results

Among 607 patients, corticosteroids were administered to 280 patients (46.1 %) at a median daily dose of 227 (interquartile range, 154–443) mg of hydrocortisone equivalents for a median of 7.0 (4.0–13.0) days. Compared with patients who did not receive corticosteroids, patients who received corticosteroids had higher hospital crude mortality (25.5 % vs 16.4 %, p = 0.007) and fewer ventilator-free days at 28 days (12.5 ± 10.7 vs 15.7 ± 10.1, p < 0.001). The odds ratio association between corticosteroid use and hospital mortality decreased from 1.85 (95 % confidence interval 1.12–3.04, p = 0.02) with multivariate logistic regression, to 1.71 (1.05–2.78, p = 0.03) after adjustment for propensity score to receive corticosteroids, to 1.52 (0.90–2.58, p = 0.12) after case-matching on propensity score, and to 0.96 (0.28–3.28, p = 0.95) using marginal structural modeling to adjust for time-dependent between-group differences.

Conclusions

Corticosteroids were commonly prescribed for H1N1pdm09-related critical illness. Adjusting for only baseline between-group differences suggested a significant increased risk of death associated with corticosteroids. However, after adjusting for time-dependent differences, we found no significant association between corticosteroids and mortality. These findings highlight the challenges and importance in adjusting for baseline and time-dependent confounders when estimating clinical effects of treatments using observational studies.
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Metadata
Title
The influence of corticosteroid treatment on the outcome of influenza A(H1N1pdm09)-related critical illness
Authors
Jesse W. Delaney
Ruxandra Pinto
Jennifer Long
François Lamontagne
Neill K. Adhikari
Anand Kumar
John C. Marshall
Deborah J. Cook
Philippe Jouvet
Niall D. Ferguson
Donald Griesdale
Lisa D. Burry
Karen E. A. Burns
Jamie Hutchison
Sangeeta Mehta
Kusum Menon
Robert A. Fowler
on behalf of the Canadian Critical Care Trials Group H1N1 Collaborative
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Critical Care / Issue 1/2016
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-016-1230-8

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