We reviewed the evidence regarding the effect of additional ('adjunctive') steroid treatment in individuals with influenza infection.
The majority of individuals with influenza have a fever, headache and a cough and get better without any specific treatment. However, a small proportion of people develop a more severe form of influenza, requiring admission to an intensive care unit in hospital. These patients are often prescribed steroids as part of their treatment, although the evidence that steroids are beneficial in these circumstances is controversial.
We searched for studies comparing additional steroid treatment with no additional steroid treatment in individuals with influenza. This evidence is current to June 2015. We identified a total of 19 studies with 3459 individuals; none of them were clinical trials. The majority of studies investigated adults admitted to hospital with pandemic influenza in 2009 and 2010.
We did not find any relevant clinical trials on this topic. The evidence available from existing observational studies was of very low quality. We found that patients with influenza who received additional steroid treatment might have had a greater risk of death compared to patients who did not receive steroid treatment. Hospital-acquired infection was the main 'side effect' related to steroid treatment that was reported in the included studies; all studies reported a greater risk of hospital-acquired infection in the group treated with steroids. However, it was not possible to be certain if patients with more severe influenza were selected to receive steroid treatment in the first place. Therefore, it is not possible to be certain whether additional steroid treatment in patients with influenza is truly harmful, or not. Clinical trials of additional steroids in the treatment of individuals with influenza are therefore warranted to clarify the situation. In the meantime, the use of steroids in influenza remains a clinical judgement call.
We did not identify any completed RCTs of adjunctive corticosteroid therapy for treating influenza. The available evidence from observational studies is of very low quality with confounding by indication a major potential concern. Although we found that adjunctive corticosteroid therapy was associated with increased mortality, this result should be interpreted with caution. In the context of clinical trials of adjunctive corticosteroid therapy in sepsis and pneumonia that report improved outcomes, including decreased mortality, more high-quality research is needed (both RCTs and observational studies). Currently, we do not have sufficient evidence in this review to determine the effectiveness of corticosteroids for patients with influenza.
Specific treatments for influenza are limited to neuraminidase inhibitors and adamantanes. Corticosteroids show evidence of benefit in sepsis and related conditions, most likely due to their anti-inflammatory and immunomodulatory properties. Although commonly prescribed for severe influenza, there is uncertainty over their potential benefit or harm.
To systematically assess the effectiveness and potential adverse effects of corticosteroids as adjunctive therapy in the treatment of influenza, taking into account differences in timing and doses of corticosteroids.
We searched CENTRAL (2015, Issue 5), MEDLINE (1946 to June week 1, 2015), EMBASE (1974 to June 2015), CINAHL (1981 to June 2015), LILACS (1982 to June 2015), Web of Science (1985 to June 2015), abstracts from the last three years of major infectious disease and microbiology conferences, and references of included articles.
We included randomised controlled trials (RCTs), quasi-RCTs and observational studies that compared corticosteroid treatment with no corticosteroid treatment for influenza or influenza-like illness. We did not restrict studies by language of publication, influenza subtypes, clinical setting or age of participants. We selected eligible studies in two stages: sequential examination of title and abstract, followed by full text.
Two pairs of review authors independently extracted data and assessed risk of bias. We pooled estimates of effect using random-effects meta-analysis models, where appropriate. We assessed heterogeneity using the I2 statistic and assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.
We identified 19 eligible studies (3459 individuals), all observational; 13 studies (1917 individuals) were suitable for inclusion in the meta-analysis of mortality. Of these, 12 studied patients infected with 2009 influenza A H1N1 virus (H1N1pdm09). Risk of bias was greatest in the 'comparability domain' of the Newcastle-Ottawa scale, consistent with potential confounding by indication. Data specific to mortality were of very low quality. Reported doses of corticosteroids used were high and indications for their use were not well reported. On meta-analysis, corticosteroid therapy was associated with increased mortality (odds ratio (OR) 3.06, 95% confidence interval (CI) 1.58 to 5.92). Pooled subgroup analysis of adjusted estimates of mortality from four studies found a similar association (OR 2.82, 95% CI 1.61 to 4.92). Three studies reported greater odds of hospital-acquired infection related to corticosteroid therapy; all were unadjusted estimates and we graded the data as very low quality.