Corticosteroids in H1N1 pneumonia – damned if you do, and damned if you don’t?

We are in the middle of yet another H1N1 epidemic in India. Karnataka has been particularly affected, with several new cases being reported every day. Several deaths have been reported so far, and the toll is likely to mount in the days to come. The current epidemic shares several common features with the global pandemic of 2009, with predominance in young adults and dense lung infiltrates leading to severe problems with gas exchange. Several rescue interventions have been resorted to, including the use of extracorporeal membrane oxygenation with a view to tide over the crisis until natural healing occurs.

Against this background, we reconsider the use of corticosteroids – considered savior by many and maligned by others in many different clinical situations. Several anecdotal reports of dramatic improvement were noted with corticosteroid therapy during the 2009 epidemic; subsequently, many observational studies have been published with no clear-cut answers; however, some studies suggest worse outcomes with the use of corticosteroids. To my knowledge, there has been no robust, prospective controlled study that has addressed this question. The World Health Organization is reasonably categorical in its H1N1 treatment guidelines, suggesting that “Patients who have severe or progressive clinical illness, including viral pneumonitis, respiratory failure, and ARDS due to influenza virus infection, should not be given systemic corticosteroids unless indicated for other reasons or as part of an approved research protocol”.

I tried to pool the limited data available so far, through a PubMed search using a combination of search terms including “corticosteroids and H1N1”, “steroids and H1N1”, “methylprednisonlone and H1N1”, “hydrocortisone and H1N1”, and “dexamethasone and H1N1”. I retrieved nine studies that analyzed mortality as the endpoint. I chose mortality for the longest period reported in each study as the outcome. This is what I found.

Fig 1. Pooled data on mortality from nine observational studies with the use of corticosteroids in H1N1 infection

The pooled data from these observational studies seem to suggest that the use of corticosteroids use in H1N1 infection may lead to increased mortality. Two previous meta-analyses have also reported similar results. (1,2)

However, how much importance do we attach pooled data in a clinical situation fraught with poor outcomes with conventional measures? We have also seen a dramatic improvement on the odd occasion with steroids when we were with our backs to the wall. Several important questions remain unanswered especially when data is pooled across heterogeneous patient populations. Specifically, would steroids be helpful in 1) the most severe forms of the disease 2) would the timing matter – early vs. late? 3) Is there a preferred corticosteroid preparation (methylprednisolone vs. hydrocortisone)? 4) Would corticosteroids improve outcomes in severe ARDS due to H1N1 infection?

Unfortunately, these questions are difficult to answer; it is an onerous if not impossible task to prospectively study specific patient populations who are likely to benefit from corticosteroid administration. Perhaps, when faced with similar difficult clinical situations when a clear-cut answer is not forthcoming, we should continue to have equipoise and keep an open mind.

Have you been taking your flu booster shots?

References:

1. Zhang Y, Sun W, Svendsen ER, Tang S, MacIntyre RC, Yang P, et al. Do corticosteroids reduce the mortality of influenza A (H1N1) infection? A meta-analysis. Crit Care. 2015;19(1):46.
2. Rodrigo C, Leonardi-Bee J, Nguyen-Van-Tam JS, Lim WS. Effect of Corticosteroid Therapy on Influenza-Related Mortality: A Systematic Review and Meta-analysis. J Infect Dis. 2015 Jul 15;212(2):183–94.