1. LSU Journal Club Corticosteroid Therapy for Patients Hospitalized With Community-Acquired Pneumonia A Systematic Review and Meta-analysis Scott Hebert, MD April 21, 2016

2. Background Community-acquired pneumonia is common and often severe. Estimated incidence of CAP range from 4-5 million cases per year with about 25% requiring hospitalization. About 50,000 deaths per year. 30 day mortality in hospitalized patients is about 30%

3. Background Pneumonia occurs when components of the innate immune system fail to clear a pathogen from the lower respiratory tract. Although local and cytokine mediated systematic inflammatory responses may help clear bacterial pathogens, they may also cause harm. Local inflammation exacerbates pulmonary dysfunction by impairing alveolar gas exchange. The severe systemic inflammation contributes to sepsis and end-organ dysfunction

4. Research purpose To examine the effect of adjunctive corticosteroid therapy on mortality, morbidity, and duration of hospitalization in patients with CAP.

5. Study Design Meta-analysis reviewing randomized trials of systemic corticosteroids in hospitalized adults with CAP.

6. Methods: Study Selection Selected studies randomly assigned adults with CAP to oral or intravenous corticosteroid therapy versus placebo or no treatment – Steroid selections (ranging from 1 dose to 10 days): dexamethasone prednisone prednisolone methylprednisolone hydrocortisone

7. Study Selection: Inclusion Criteria Studies included those that reported on at least 1 of the following outcomes: – All-cause mortality – Need for mechanical ventilation – Need for ICU admission – Development of ARDS – Duration of hospitalization – Time to clinical stability

8. Study Selection: Exclusions Studies with the following were excluded: – Ventilator-associated pneumonia – Aspiration pneumonia or Pneumocystis jirovecii pneumonia – Studies limited to patients with chronic obstructive pulmonary disease

9. Study Selection: 13 randomized control trials were included for a total of 2005 patients.

10. Outcomes: All-Cause Mortality

11. Outcomes: Mechanical Ventilation

12. Outcomes: ICU Admission

13. Outcomes: Progression to Acute Respiratory Distress Syndrome

14. Outcomes: Duration of Hospitalization

15. Outcomes: Time to Clinical Stability

16. Results All-cause mortality: – the meta-analysis shows a possible reduction in mortality with use of corticosteroids of 3%, but the certainty of the effect is diminished by subgroups of severe pneumonia demonstrating a much higher benefit. Progression to mechanical ventilation: – moderate certainty of absolute reduction of ~5%

17. Results ICU admission: – results limited by small number of incidences Progression to ARDS: – moderate certainty of absolute reduction of ~5% Duration of hospitalization: – high certainty of reduction of time by 1 day Time to clinical stability: – high certainty of reduction of time by 1 day

18. Conclusion The results provide high quality evidence for the benefits of adjunctive corticosteroids in CAP. For low risk of bias studies, results are consistent across a broad range of patients with CAP.

19. Questions