Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients With Severe Community-Acquired Pneumonia and High Inflammatory Response

Abstract

IMPORTANCE In patients with severe community-acquired pneumonia, treatment failure is associated with excessive inflammatory response and worse outcomes. Corticosteroids may modulate cytokine release in these patients, but the benefit of this adjunctive therapy remains controversial. OBJECTIVE To assess the effect of corticosteroids in patients with severe communityacquired pneumonia and high associated inflammatory response. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized, double-blind, placebo-controlled trial conducted in 3 Spanish teaching hospitals involving patients with both severe community-acquired pneumonia and a high inflammatory response, which was defined as a level of C-reactive protein greater than 150 mg/L at admission. Patients were recruited and followed up from June 2004 through February 2012. INTERVENTIONS Patients were randomized to receive either an intravenous bolus of 0.5 mg/kg per 12 hours of methylprednisolone (n = 61) or placebo (n = 59) for 5 days started within 36 hours of hospital admission. MAIN OUTCOMES AND MEASURES The primary outcome was treatment failure (composite outcome of early treatment failure defined as [1] clinical deterioration indicated by development of shock, [2] need for invasive mechanical ventilation not present at baseline, or [3] death within 72 hours of treatment; or composite outcome of late treatment failure defined as [1] radiographic progression, [2] persistence of severe respiratory failure, [3] development of shock, [4] need for invasive mechanical ventilation not present at baseline, or [5] death between 72 hours and 120 hours after treatment initiation; or both early and late treatment failure). In-hospital mortality was a secondary outcome and adverse events were assessed. RESULTS There was less treatment failure among patients from the methylprednisolone group (8 patients [13%]) compared with the placebo group (18 patients [31%]) (P = .02), with a difference between groups of 18% (95% CI, 3% to 32%). Corticosteroid treatment reduced the risk of treatment failure (odds ratio, 0.34 [95% CI, 0.14 to 0.87]; P = .02). In-hospital mortality did not differ between the 2 groups (6 patients [10%] in the methylprednisolone group vs 9 patients [15%] in the placebo group; P = .37); the difference between groups was 5% (95% CI, −6% to 17%). Hyperglycemia occurred in 11 patients (18%) in the methylprednisolone group and in 7 patients (12%) in the placebo group (P = .34). CONCLUSIONS AND RELEVANCE Among patients with severe community-acquired pneumonia and high initial inflammatory response, the acute use of methylprednisolone compared with placebo decreased treatment failure. If replicated, these findings would support the use of corticosteroids as adjunctive treatment in this clinical population.

Association of Inhaled Corticosteroids with Incident Pneumonia and Mortality in COPD Patients; Systematic Review and Meta-Analysis

“…A recently published RCT on the role of systemic corticosteroids among patients hospitalized for community-acquired pneumonia with high inflammatory response has indicated a protective effect of corticosteroids. 47 This paradoxical beneficial effect of corticosteroids that has been earlier suggested 15, 46 might be further supported by the higher adherence among ICS users in RCTs. A sensitivity analysis by PP strategy, which accounted for the imbalance in drop-out rates in RCTs, showed that patients in ICS arms had significantly decreased unadjusted overall mortality compared to patients in non-ICS arms.…”

Endothelial and Microcirculatory Function and Dysfunction in Sepsis

“…This assessment of baseline microvascular status could be based upon bedside intravital microscopy (with its accompanying technical limitations) or systemic markers of endothelial damage (with their accompanying logistic concerns as point-of-care tests). The promise of such personalized approaches to infection treatment has been demonstrated in recent studies of pneumonia, in which a benefit of adjunctive corticosteroids existed largely in patients with baseline evidence of systemic inflammation 120,121 .…”

Severe Pneumococcal Pneumonia Causes Acute Cardiac Toxicity and Subsequent Cardiac Remodeling

“…Community-acquired pneumonia (CAP) and influenza infections together are the fourth most prevalent cause of death worldwide (3). The morbidity, mortality, and costs associated with CAP have remained unchanged in recent decades, despite availability of antibiotic treatments and preventive strategies with immunizations (4,5).…”