Prednisone … for Pneumonia?

The utility of antibiotics for eradication of bacterial pathogens from the lower respiratory tract is a given.  Use of steroids – also known for their immunosuppressive properties – not so much.

But, one can imagine clinical utility for steroids in acute infection.  Not every function of the immune system results in desirable patient-oriented effects.  Immunologic host responses include release of many inflammatory cytokines responsible for organ dysfunction, and steroids are already part of accepted therapy for several specific manifestations of pneumonia.  Based on prior results in smaller trials, these authors suspected use of steroids might be of benefit – both in mortality and in time to symptom resolution.

With 785 patients allocated in blinded fashion to 50 mg of prednisone daily or placebo, patients receiving prednisone reached “clinical stability” in a median of 3 days, compared to 4.4 days for the placebo cohort.  Hospital length-of-stay was reduced to 6 days from 7, and intravenous antibiotic use was cut by a day.  There were few important adverse effects overall, and the only consistent harm apparent in these data was increased hyperglycemia associated with corticosteroid use.

The accompanying editorial in The Lancet states adjunctive therapy with steroids is a therapy whose time has come, based on healthcare savings due to resource utilization.  In the context of other published studies, this observed reduction in time to vital sign normalization is valid.  However, whether the effect of steroids is truly beneficial or akin to simply masking the underlying clinical state by suppression of pro-inflammatory cytokine release is less certain.  Use of anti-pyretics blunts outward signs of systemic inflammatory response syndrome, and beta-blockers likewise reduce the tachycardia resulting from physiologic stress without specifically treating the underlying process.  It is hard to associate the outcomes measured in this trial with actual expedited clinical cure.

Reductions in length-of-stay and IV antibiotic use are reasonable patient-oriented and system-oriented outcomes, however, so the decision ultimately rests with the magnitude of harms – and the harms are certainly real.  Previous studies have suggested increased early recurrence or persistence of pneumonia, in addition to uncontrolled hyperglycemia.  These authors hoped to measure a 25% reduction in mortality – which was a bit of an odd expectation, given the ~2-4% expected absolute mortality – and no such suggestion of benefit was observed.

Simply put, this is not ready for prime-time or guideline-level adoption.  It is certainly worthy of further study, but steroids should not be used routinely outside the scope of prospective monitoring.

“Adjunct prednisone therapy for patients with community- acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial”
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62447-8/abstract

4 thoughts on “Prednisone … for Pneumonia?”

  1. Does anyone know the incidence of femoral head osteonecrosis per steroid treatment ?
    Very rare, delayed, and devastating.
    Never could know but I've seen a few. When I was a rheumatology resident so that is highly biased.

  2. So I looked it up.
    Scary legal paper:
    http://www.ecardiologynews.com/fileadmin/qhi_archive/ArticlePDF/CT/080040343.pdf

    Otherwise no reliable figures.
    10,000 to 20,000 osteonecrosis (ON ) cases per year in the USA
    10 percent of all total hip replacements are for osteonecrosis
    21 to 37 percent of ON cases are said to be steroid related
    comorbidity is important: alcoholism, SLE, transplantation, Sickle cell disease …
    Rarely happens with short courses but still does.
    High cumulative dose increases risk.
    The medicolegal paper above says we must tell and document.

    Now, not knowing the number of steroid courses per year in the USA , it is difficult to know the statistical risk for steroid induces ON.
    In the worst case scenario based on uncertain figures such as above there could occur up to 5000 steroid induced ON cases per year in the USA.
    But how many steroid courses ?
    Anyne with a guesstimate ?

  3. This study did not do any air flow measurments on patients. 18% did have COPD, and doubtless many more were undiagnosed asthmatics. It is likely, or even probable, that many of these patients had bronchial inflammation and bronchospasm and improved for that reason alone. Such a study should have done PFTs both before and after an albuterol challenge.

    Steve Smith

  4. That's definitely a concern – the under-treated or under-appreciated bronchospasm in these patients. There were 600-odd patients excluded from their selection due to an indication for steroids, so clearly there was some vigilance for this – but many could have slipped through. Or, you could view this as pragmatic – that treating clinicians, in general, are going to miss a certain amount of mild bronchospasm that would benefit from steroids in hospitalization, and the "empiric coverage" with steroids does more benefit than harm.

    It might also be possible to prospectively study this with better exclusions to reduce the number of patients at higher-risk of hyperglycemia events. Interesting – but definitely not the "idea whose time has come" as the accompanying editorial states.

Comments are closed.