In the penultimate episode in our ARDS Rapid Fire Journal Club Summer Series we are talking about the DEXA-ARDS trial (published in Lancet Respiratory Medicine in 2020). This trial evaluated the impact of dexamethasone in the treatment of ARDS.

Article and Reference

Today we’re discussing the DEXA-ARDS trial published in Lancet Respiratory Medicine in 2020. This trial evaluated the impact of dexamethasone on mortality and duration of mechanical ventilation for patients with ARDS.

Villar J, Ferrando C, Martínez D, Ambrós A, Muñoz T, Soler JA, Aguilar G, Alba F, González-Higueras E, Conesa LA, Martín-Rodríguez C, Díaz-Domínguez FJ, Serna-Grande P, Rivas R, Ferreres J, Belda J, Capilla L, Tallet A, Añón JM, Fernández RL, González-Martín JM; dexamethasone in ARDS network. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020 Mar;8(3):267-276. doi: 10.1016/S2213-2600(19)30417-5. Epub 2020 Feb 7. PMID: 32043986.

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Article Notes

• DEXA-ARDS; Lancet Respiratory Medicine, 2020
  • DOI:10.1016/S2213-2600(19)30417-5
  • Link: https://doi.org/10.1016/s2213-2600(19)30417-5
  • Background: ARDS is an intense inflammatory process without proven, specific pharmacotherapies. Previous work and a recent meta-analysis demonstrated improvements in inflammation, gas exchange, and ventilator and ICU liberation but did not adequately address mortality.
  • Study Design (design, primary outcome, participants, etc)
    • Design: investigator-initiated, multicenter, unblinded, randomized controlled trial in 17 academic ICUs in Spain, conducted from 3/2013 to 12/2018
    • Primary Outcome
      • VFD at 28d
      • Secondary:
        • 60d mortality
        • Actual duration of ventilation in ICU survivors
        • ICU acquired infections
    • Participants
      • Inclusion ARDS with P/F < 200 for < 24hr on LTVV
      • Exclusion:
        • Already receiving steroids or immunosuppression
        • CHF
        • Severe COPD
        • DNR
      • Summary: Middle aged, mostly male patients with < 24hr of moderate to severe ARDS receiving LPV without chronic heart or lung disease
        • Like many ARDS trials, just over 3/4 of patients’ ARDS was caused by PNA or sepsis. Mean P/F was ~140
  • Intervention/Limitations
    • N = 277, stratified by center and then randomized
    • Intervention: dexamethasone 20mg qd for 5d followed by 10mg qd for 5d
      • Stopped early for extubation before day 10
      • First dose given no more than 30 hours after P/F < 200
    • Control: no placebo, just SOC
    • All patients received LTVV
  • Outcomes/Safety
    • Power: with N = 314 (actual N = 277), 80% power to detect 2 additional VFD and 15% mortality reduction
      • As an aside, this seems to be a theme in ICU trials: massively ambitious proposed benefits during power calculations and then under-enrolling for that power calculation ultimately resulting with a point estimate that favors the intervention but is not statistically significant.
    • Efficacy:
      • 60d mortality: 21% vs 36%, P = 0.0047
        • NNT of just < 7!
      • VFD at 28d: 12.3 vs 7.5, P < 0.0001
      • Actual duration of ventilation in ICU survivors: 14.2d vs 19.5d (P = 0.0009)
    • Safety:
      • Hyperglycemia: 76% vs 70%, P = 0.33
        • Always interesting in steroid trials when no change in glucose control is seen. This isn’t the most EBM thing I’ll ever say, but frankly I disregard this and assume steroids will cause hyperglycemia regardless of the trial results.
      • ICU acquired infections: 24% vs 25%, P = 0.75
  • Takeaway
    • In a narrowly selected population of patients without chronic heart or severe lung disease and with early, moderate ARDS (mostly from sepsis or pneumonia), dexamethasone reduced mortality and duration of mechanical ventilation.
      • If time, insert soap-box about etiology of ARDS being very important (EG, flu, fungal, parasitic, mycobacterial infections)

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This episode is launching our 2024 Rapid Fire Journal Club summer series on ARDS! This summer we will be talking about landmark ARDS trials that have defined the literature and shaped patient care. Journal clubs often focus on new trials, and so learners may have a less thorough understanding of the baseline literature that defines many of our ICU practices. The goal of this series is to provide a quick, but in-depth look at these papers so that learners understand the modern landscape of ARDS.

Today, we’re kicking this initiative off by looking at the ARMA or ARDSNet Trial published in the NEJM in 2000. Enjoy!

Article and Reference

We’re talking about the ARMA trial today which examined “Ventilation with Lower Tidal Volumes as Compared with Traditional Tidal Volumes for Acute Lung Injury and the Acute Respiratory Distress Syndrome.”

Reference: Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801. PMID: 10793162.

Infographic

Correction:

We mention a step-wise titration of tidal volume in the control group to achieve Pplats of 45-50. To clarify, there was no adjustment of Vt in the traditional Vt group unless Pplat > 50. If Vt had been decreased in the traditional Vt group because Pplat was > 50, it would not be subsequently increased back to 12 unless Pplat < 45 (to avoid a cycle of corrections and re-adjustments). Similarly in the lower Vt group, there was no adjustment (“titration”) of Vt unless Pplat > 30, and there was a similar protocol in place not to increase the Vt again unless the Pplat was < 25.

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