Corticosteroids in Pneumonia

Corticosteroids in Pneumonia _

Corticosteroids inhibit the expression and action of many molecules involved in the acute inflammatory response associated with severe pneumonia as a result of their molecular mechanisms of action76,77 and increase gene transcription of different anti-inflammatory molecules (eg, lipocortin 1, b-2 receptors) in a mechanism called transactivation.

In addition, corticosteroids decrease gene transcription of several inflammatory molecules, such as cytokines, chemokines, or adhesion molecules, in a mechanism called transrepression.77 Different experimental studies have shown that acute administration of corticosteroids reduces inflammatory cytokines in severe CAP.78,79

Few studies have evaluated the impact of corticosteroid treatment on severe CAP in clinical practice. A pilot study by Monton and colleagues80 on patients with pneumonia requiring mechanical ventilation detected the possible immunosuppressive effect of corticosteroids in severe pneumonia. In this study, a decrease in proinflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-a, was observed in serum and in bronchoalveolar lavage of patients who received corticosteroids as coadjuvant treatment to the antibiotic treatment. Furthermore, in the group of patients receiving corticosteroids, a trend to lower mortality was also observed. However, the study was limited by the small sample size (n 5 20). A retrospective study with 308 patients with severe CAP (defined as PSI score class IV and V) showed that mortality decreased in patients who received simultaneous administration of systemic corticosteroids with antibiotic treatment (OR 0.28, 95% CI 0.113–0.732).81

Several randomized controlled trials have evaluated the effect of corticosteroids on CAP. Confalonieri and colleagues82 assessed the efficacy and safety of continuous infusion of hydrocortisone in 46 patients with CAP requiring ICU admission. Twentythree patients received an intravenous bolus of 200 mg of hydrocortisone followed by an infusion of 10 mg/h for 7 days. These investigators demonstrated a reduction in mortality in the group treated with hydrocortisone, better modulation of systemic inflammatory response (determined by serum C-reactive protein), and significant improvement in clinical end points, such as chest radiographs, multiple organ dysfunction syndrome severity scale, PaO2/FiO2 ratio, and ICU and hospital stay.

However, the small sample size and differences among groups at admission (placebo group had lower PaO2/FiO2 ratio and lower levels of C-reactive protein) limited the generalizability of the results.

Other randomized controlled trials on patients with less severe CAP who required hospitalization have conflicting results. Snijeder and colleagues83 studied the impact of 40 mg of prednisolone once daily for 7 days compared with placebo among 213 patients hospitalized with CAP. The investigators found no differences regarding the rate of 30-day mortality, time to clinical stability, or length of hospital stay. However, patients treated with corticosteroids had faster decline in serum C-reactive protein levels compared with placebo. By contrast, late clinical failure (>72 hours from admission) was more common in the corticosteroid group. The investigators performed a subanalyses on patients with severe CAP, and found no differences among groups.

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