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Evolving Evidence for Steroids in ARDS

Updated: Oct 7, 2022



The topic of steroid use in ARDS remains a continued interest and debate. DEXA-ARDS and the COVID-19 RECOVERY trials have reintroduced this topic for discussion. Numerous studies have been published and multiple meta-analyses have been conducted over the past three decades. I have listed the prominent studies in the above graph with their results starting in 2006. Studies prior to 2006 were excluded as ventilator management has changed significantly. I also excluded the COVID-19 trials as they include a specific subgroup of ARDS patients.


The most recent trial by Villar et al (DEXA-ARDS) demonstrated a 60-day mortality benefit in the group treated with 20-mg dexamethasone daily for 5 d followed by 10 mg daily for 5 d, compared to placebo (21% vs 36%; P = .0047). More ventilator-free days were observed in the intervention group (12 vs 7; P < .0001). However, study results may have been confounded by the high percentage of patients with pneumonia and septic shocks, conditions for which other trials have indicated benefit with steroids [1].


A recent meta-analysis included nine studies with 1371 participants. The pooled analysis revealed that glucocorticoid use was associated with reduced mortality [relative risk (RR), 0.83; 95% confidence interval (CI) 0.74-0.93; P < 0.01; I2 = 37] and the statistical power was confirmed by trial sequential analysis [2].


It is difficult to interpret and apply the findings of use of steroids ARDS clinical trials to the bedside due to multiple reasons that include any of the following:

  1. ARDS is a heterogeneous clinical syndrome that may result from a variety of underlying diseases, such as pneumonia, sepsis, aspiration, pancreatitis, shock, trauma, drug intoxication, drowning, fat emboli, and blood transfusion.

  2. Despite Berlin's straightforward definition of ARDS, there is still little agreement on ARDS diagnoses across clinicians and it is difficult to identify ARDS cases with consistency.

  3. Clinical progress of ARDS differs among patients. Nearly 10% of patients diagnosed with ARDS improve rapidly and are extubated within one day only [3].

  4. Many cases of ARDS are caused by pneumonia and septic shock where steroids have shown a mortality benefit in these subgroups of patients.

  5. Diffuse alveolar damage which is the pathologic correlate of ARDS, is seen on autopsy only in 45% of patients clinically diagnosed with ARDS [4].

Therefore, it is unlikely that we find a therapeutic intervention or medication that is going to benefit the wide spectrum of ARDS patients. More likely, we will need to target therapies to specific subgroups. Steroid therapy is one of these interventions that may benefit a subgroup of ARDS patients. A good example of this conclusion is the use of steroids in viral pneumonia. Studies of steroid use have shown completely different outcomes for H1N1 ARDS cases compared to COVID-19 ARDS patients. The RECOVERY trial [5] demonstrated a better mortality outcome in COVID-19 severe cases with hypoxemia, whereas a systematic review for patients with influenza pneumonia showed that corticosteroid use was associated with higher mortality [6].


REFERENCES

1. 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.


2. Lin P, Zhao Y, Li X, Jiang F, Liang Z. Decreased mortality in acute respiratory distress syndrome patients treated with corticosteroids: an updated meta-analysis of randomized clinical trials with trial sequential analysis. Crit Care. 2021 Mar 26;25(1):122. doi: 10.1186/s13054-021-03546-0. PMID: 33771216; PMCID: PMC7995395.


3. Schenck EJ, Oromendia C, Torres LK, Berlin DA, Choi AMK, Siempos II. Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials. Chest. 2019 Mar;155(3):474-482. doi: 10.1016/j.chest.2018.09.031. Epub 2018 Oct 22. PMID: 30359616; PMCID: PMC6414787.


4. Hensley MK, Sjoding MW, Prescott HC. COUNTERPOINT: Should Corticosteroids Be Routine Treatment in Early ARDS? No. Chest. 2021 Jan;159(1):29-33. doi: 10.1016/j.chest.2020.07.059. PMID: 33422201.


5. RECOVERY Collaborative Group, Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.


6. Ni, YN., Chen, G., Sun, J. et al. The effect of corticosteroids on mortality of patients with influenza pneumonia: a systematic review and meta-analysis. Crit Care 23, 99 (2019). doi.org/10.1186/s13054-019-2395-8




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