When I asked about a dozen ED docs, internists, ID specialists and intensivists whether or not they used steroids for community acquired pneumonia, I did not receive one definitive clear answer. But when I asked them whether or not they would use steroids for COVID pneumonia, they all clearly and definitively said a resounding “yes” (and most of them added that it was the only drug besides oxygen that was effective for COVID pneumonia). So this got me thinking – what are the indications for steroids in patients with pneumonia besides those with concurrent COPD exacerbations, ARDS or adrenal shock? This is Journal Jam – so, the other question is: what is the evidence for benefit for steroids in CAP, the flu and COVID pneumonia? And if there is benefit, do those benefits outweigh the potential harms? To help us sort this out, Justin and Anton have the mighty return of a special guest – Dr. Andrew Morris in this Journal Jam podcast…

Steroids are thought to curb the inflammatory response in CAP, improve symptoms, reduce the frequency of acute respiratory distress syndrome, and decrease the length of illness.

Articles discussed in this Journal Jam podcast on steroids and pneumonia

Community Acquired Pneumonia (CAP)

Stern A, Skalsky  K, Avni  T, Carrara  E, Leibovici  L, Paul  M. Corticosteroids for pneumonia. Cochrane Database of Systematic Reviews 2017, Issue 12. Art. No.: CD007720.

Confalonieri M, Urbino R, Potena A, Piattella M, Parigi P, Puccio G, Della Porta R, Giorgio C, Blasi F, Umberger R, Meduri GU. Hydrocortisone infusion for severe community-acquired pneumonia: a preliminary randomized study. Am J Respir Crit Care Med. 2005 Feb 1;171(3):242-8.

Meijvis SC, Hardeman H, Remmelts HH, Heijligenberg R, Rijkers GT, van Velzen-Blad H, Voorn GP, van de Garde EM, Endeman H, Grutters JC, Bos WJ, Biesma DH. Dexamethasone and length of hospital stay in patients with community-acquired pneumonia: a randomised, double-blind, placebo-controlled trial. Lancet. 2011 Jun 11;377(9782):2023-30. doi: 10.1016/S0140-6736(11)60607-7. Epub 2011 Jun 1. PMID: 21636122.

Nafae, R. M. et al. Adjuvant role of corticosteroids in the treatment of community-acquired pneumonia. Egyptian Journal of Chest Diseases and Tuberculosis. 62(3), 7-2013, 439-445.

Torres A, Sibila O, Ferrer M, et al. Effect of Corticosteroids on Treatment Failure Among Hospitalized Patients With Severe Community-Acquired Pneumonia and High Inflammatory ResponseA Randomized Clinical TrialJAMA. 2015;313(7):677–686.

Blum CA, Nigro N, Briel M, Schuetz P, Ullmer E, Suter-Widmer I, Winzeler B, Bingisser R, Elsaesser H, Drozdov D, Arici B, Urwyler SA, Refardt J, Tarr P, Wirz S, Thomann R, Baumgartner C, Duplain H, Burki D, Zimmerli W, Rodondi N, Mueller B, Christ-Crain M. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015 Apr 18;385(9977):1511-8.

Lloyd M, Karahalios A, Janus E, Skinner EH, Haines T, De Silva A, Lowe S, Shackell M, Ko S, Desmond L, Karunajeewa H; Improving Evidence-Based Treatment Gaps and Outcomes in Community-Acquired Pneumonia (IMPROVE-GAP) Implementation Team at Western Health. Effectiveness of a Bundled Intervention Including Adjunctive Corticosteroids on Outcomes of Hospitalized Patients With Community-Acquired Pneumonia: A Stepped-Wedge Randomized Clinical Trial. JAMA Intern Med. 2019 Jul 8;179(8):1052–60.

Influenza

Lansbury  L, Rodrigo  C, Leonardi‐Bee  J, Nguyen‐Van‐Tam  J, Lim  WS. Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database of Systematic Reviews 2019, Issue 2. Art. No.: CD010406.

COVID Pneumonia

Angus DC, Derde L, Al-Beidh F, Annane D, Arabi Y, Beane A, et al. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1317-1329. doi: 10.1001/jama.2020.17022.

Dequin PF, Heming N, Meziani F, Plantefève G, Voiriot G, et al; CAPE COVID Trial Group and the CRICS-TriGGERSep Network. Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1298-1306.

RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, et al. Dexamethasone in Hospitalized Patients with Covid-19 – Preliminary Report. N Engl J Med. 2020 Jul 17:NEJMoa2021436.

Tomazini BM, Maia IS, Cavalcanti AB, Berwanger O, et al; COALITION COVID-19 Brazil III Investigators. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. JAMA. 2020 Oct 6;324(13):1307-1316.

WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, et al. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020 Oct 6;324(13):1330-1341.


Initial steroid dosing options for CAP and COVID pneumonia in the ED include

  • Dexamethasone 6-20mg IV
  • Methylprednisolone 40mg IV
  • Hydrocortisone 50-200mg IV

Take home points on steroids for community acquired pneumonia, influenza and COVID pneumonia

  • Steroids do not offer benefit in patients with confirmed influenza pneumonia, mild bacterial community acquired pneumonia or COVID pneumonia patients who do not require supplemental oxygen
  • There is a signal of benefit for the sickest bacterial pneumonia patients heading for the ICU, although there is no clear data on the timing of those steroids – so the decision to give steroids may be left to the ICU (unless there is a long delay to admission from the ED)
  • A meta-analysis is only as good as the studies that it includes; in the case of CAP, the Cochrane meta-analysis claiming benefit of steroids included studies that were either small with poor methodology or adequately sized but without significant benefit for patient-oriented outcomes
  • The 4 trials reviewed here looked at steroids in COVID pneumonia; taken together, there is some evidence to suggest that steroids may benefit COVID pneumonia patients who require supplemental oxygen to maintain an oxygen saturation >90%.
    • RECOVERY trial – dexamethasone 6mg daily (max 10 days) showed an overall statistically significant mortality benefit, with the largest benefit in those patients requiring mechanical ventilation who had symptoms for at least 7 days, and a non-statistically significant increase in mortality in those patients who did not require supplemental oxygen
    • CoDEX trial – dexamethasone 20mg IV daily x 5 days, then 10mg IV daily x 5 days in ICU showed more ventilator-free days, SOFA score was significantly lower in the dexamethasone group at 7 days suggesting lower organ dysfunction in the dexamethasone group; however, there was no significant difference in all-cause mortality at 28 days
    • CAPE COVID trial – hydrocortisone 200mg/day x 7 days, then 100mg/day x 4 days, then 50mg/day for 3 days showed no statistically significant difference in treatment failure on day 21, defined as death or persistent dependency on mechanical ventilation or high-flow oxygen therapy; hydrocortisone did not significantly reduce the proportion of patients receiving mechanical ventilation on day 21 and did not increase in the rate of secondary infections
    • REMAP-CAP trial – ICU patients in shock given hydrocortisone 50mg IV q6h x 7 days showed no statistically significant difference in respiratory and cardiovascular organ support-free days, up to day 21.

Other FOAMed resources on steroids for pneumonia

EM Cases Episode 130 Community Acquired Pneumonia: ED Management

Justin Morgenstern, “Steroids for COVID-19”, First10EM blog, December 7, 2020. Available at: https://first10em.com/steroids-for-covid-19/.

REBELEM on steroid in COVID-19

PulmCrit – Dexamethasone & COVID – a study in immunopathology, evidence-based medicine, and ourselves

The Bottom Line on REMAP-CAP trial