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.

Trial registration: ClinicalTrials.gov NCT01283009.

Keywords: Community-acquired pneumonia; Glucocorticoids; Intensive care; Methylprednisolone; Randomized clinical trial.

Fig. 1

Enrollment, randomization, and follow-up. ¥Participants who were consented improperly are not included in this diagram. §The reasons for failing eligibility criteria were “select all that apply,” so one patient may have more than one reason for exclusion. Five patients who did not meet eligibility criteria (three did not meet inclusion criteria and two met exclusion criteria) were randomized. *Reasons for study drug withdrawal were check all that apply. ¶Active gastrointestinal bleeding requiring transfusion of at least 5 units of PRBC’s. ¶¶Such as exacerbation of COPD or asthma, and vasculitis

Fig. 2

Kaplan–Meier estimate of survival. Kaplan–Meier estimates of survival are shown in the overall population (A), in patients who were receiving mechanical ventilation at randomization (Patients on MV; B), and in those not receiving mechanical ventilation at randomization (Patients not on MV; C). The inset in each panel shows the same data on an enlarged y axis and up to day 60

Fig. 2

Kaplan–Meier estimate of survival. Kaplan–Meier estimates of survival are shown in the overall population (A), in patients who were receiving mechanical ventilation at randomization (Patients on MV; B), and in those not receiving mechanical ventilation at randomization (Patients not on MV; C). The inset in each panel shows the same data on an enlarged y axis and up to day 60

Fig. 3

60-day all-cause mortality according to subgroup. The odds ratios and 95% confidence intervals are based on logistic regression with treatment as the single covariate. The widths of the confidence intervals have not been adjusted for multiplicity and therefore cannot be used to infer treatment effects