Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia

Abstract

Purpose Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes. Methods This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72–96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up. Results Between January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57–1.40). There were no significant differences in secondary outcomes or complications. Conclusions In patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-022-06684-3.

ERS/ESICM/ESCMID/ALAT guidelines for the management of severe community-acquired pneumonia

“…Our systematic searches retrieved 267 references, of which six relevant RCTs. The data used for this recommendation include a recent RCT published by MEDURI et al [79] which has more patients than all other RCTs combined. This RCT included 584 patients with sCAP (ATS/IDSA criteria) and was a double-blind placebo-controlled study with methylprednisolone for 21 days (40 mg methylprednisolone for 7 days, 20 mg for 7 days, 12 mg for 7 days).…”

Severe community-acquired pneumonia

“…The most recent and largest study about corticosteroids in sCAP was a trial done with USA veterans; it was not, however, included in the last meta-analysis because it had not been published at the time [ 63 ]. This RCT was performed exclusively in patients with sCAP meeting minor or major ATS criteria.…”

“…Nonetheless, in a post hoc analysis, the duration of mechanical ventilation was significantly reduced by 3 days in the intervention arm. It would be extremely useful to include results obtained from the RCT done on veterans [ 63 ] in another meta-analysis to see if the effect of corticosteroids on mortality is maintained. This is the largest RCT performed in sCAP and changes our perspective on the effect of corticosteroids on decreasing mortality as a standard of care.…”

“…The saga on corticosteroids in sCAP continues, despite the last negative trial from M eduri et al [ 63 ]. Perhaps biomarkers will shed further light and provide the final answer.…”

Corticosteroids for severe community-acquired pneumonia: a story without an ending

“…It is in this context that Meduri and colleagues have published the ESCAPe RCT in Intensive Care Medicine evaluating low dose methylprednisolone in critically ill patients with severe community-acquired pneumonia [8]. As part of this trial, adult patients admitted to an intensive care unit (ICU) presenting with a clinical diagnosis of severe CAP (one major or three minor modified ATS/IDSA criteria for severe pneumonia), who were within 72-96 h of hospital presentation, were randomized to receive methylprednisolone or placebo for 20 days following a decremental dosing schedule.…”