Use of steroids in CAP is highly debated topic for a long time. Recent evidences in this field sheds answers to this question.
CAPE-COD (NEJM.2023) Trial is a multicenter, double-blind, placebo-controlled trial in 31 French ICUs evaluating 200 mg/day infusion of hydrocortisone for 8 or 14 days with a planned taper in patients admitted in ICU with severe non-viral CAP. Yet the trial was stopped early due to the COVID-19 pandemic, the authors reported a significant decrease in mortality, with 6.2% of the hydrocortisone group and 11.9% of the placebo group dead at 28 days (absolute difference −5.6% [95%CI: −9.6 to −1.7%], p = 0.006). In subgroup analyses of the CAPE COD trial, hydrocortisone was most effective in inflammatory patients with CRP > 150 mg/L (relative risk −7.4, [95%CI −12.9−1.7%]
ESCAPe (Intensive Care Med. 2022) is a randomized 586 critically ill patients in 42 American hospitals to receive 40 mg/day of methylprednisolone or placebo for 20 days with a tapering plan within 72–96 h of hospital presentation and observed no significant difference in 60-day mortality (16% vs. 18% [95%CI: -8−5%], p = 0.61) or any other secondary outcomes.
DEXA-ARDS (Lancet.2020), a randomized multicenter study involving 17 ICUs in Spain, showed an increase of 4.8 ventilator-free days ([95%CI: 2.5–7.03], p < 0001) within 28 days in the intervention arm as well as a decreased mortality rate. Patients in the dexamethasone group received an intravenous dose of 20 mg once daily from day 1 to day 5, which was reduced to 10 mg once daily from day 6 to day 10. Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS.
Torres et al (JAMA.2015) did multicentric, double blinded RCT to assess the effect of corticosteroids in patients with severe community-acquired pneumonia and high associated inflammatory response. 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. 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)
Mechanism of steroids in CAP
- Recent studies have shown that steroids are beneficial when started early in severe CAP. This can be explained its action on glucocorticoid receptors.
- Glucocorticoid Receptors (GR) is a transcription factor expressed in most cells. After binding steroids, the GR translocates to the nucleus and exerts both genomic and non-genomic effects (notably in mitochondria). During inflammation, epigenetic modifications alter the possibility for GR to regulate the transcription of inflammatory genes. During the first hours of inflammation, steroids reduce inflammatory cytokine production, neutrophils, and T cell recruitment and adhesion . In later days, steroids can have opposite effects on the inflammatory response by reducing anti-inflammatory cytokines secretion or increasing phagocytic capacity.
Current Guidelines in CAP
- ATS 2019 don't recommend routine use of Steroids in non severe or severe pneumonia. Steroids can be used in CAP for refractory shock.
- ERS/ESICM 2023 Guidelines state that in patients with sCAP, we suggest the use of corticosteroids if shock is present.
- Present guidelines recommends steroids in CAP only for refractory shock, but from recent evidence it may be reasonable for early administration of steroids in severe bacterial pneumonia . Further studies are required to confirm these findings.
Reference
Bouras M, Rello J, Roquilly A. Steroids in severe community-acquired pneumonia: dangerous, worthless, or miracle cure? The roller coaster of clinical trials. Anaesth Crit Care Pain Med. 2023 Aug;42(4):101253. doi: 10.1016/j.accpm.2023.101253. Epub 2023 May 26. PMID: 37245688; PMCID: PMC10214762.
