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. 2020 Apr 29;2(4):e0111.
doi: 10.1097/CCE.0000000000000111. eCollection 2020 Apr.

Rationale for Prolonged Corticosteroid Treatment in the Acute Respiratory Distress Syndrome Caused by Coronavirus Disease 2019

Jesús Villar  1   2   3 , Marco Confalonieri  4 , Stephen M Pastores  5 , G Umberto Meduri  6   7
Affiliations

Rationale for Prolonged Corticosteroid Treatment in the Acute Respiratory Distress Syndrome Caused by Coronavirus Disease 2019

Jesús Villar et al. Crit Care Explor. .
No abstract available

Keywords: acute respiratory distress syndrome; coronavirus disease 2019; corticosteroids; intensive care unit; mechanical ventilation; mortality.

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Conflict of interest statement

Dr. Villar is funded by grants from the Instituto de Salud Carlos III, Madrid, Spain (CB06/06/1088, PI16/0049), the European Regional Development’s Funds, and the Asociación Científica Pulmón y Ventilación Mecánica. Canary Islands, Spain. Dr. Meduri received support for article research from the Veteran Administration. The remaining authors have disclosed that they do not have any potential conflicts of interest.

Figures

Figure 1.
Figure 1.
Randomized trials investigating prolonged corticosteroid treatment (CST) in acute respiratory distress syndrome (ARDS) (n = 1,093): impact (treated vs control) on (a) duration ventilator dependence and ventilator-free days. Data obtained from prior meta-analysis (randomized controlled trials [RCTs] 9; n = 816) used for the Corticosteroid Guideline Task Force of the Society of Critical Care Medicine and European Society of Intensive Care Medicine released guidelines for CST in critically ill patients including those with ARDS (5), with the addition of the new DEXA-ARDS RCT (n = 277) (6). A, Mean difference and 95% CI for increase in mechanical ventilation (MV)-free days by day 28 (7). The reduction in duration of MV in the four RCTs investigating methylprednisolone treatments was strikingly similar (methylprednisolone vs control: 10.4 ± 19.2 vs 20.2 ± 26.6, p = 0.051; 10.6 ± 2.9 vs 21.2 ± 2.2, p < 0.001; 18.6 ± 24.4 vs 27.3 ± 26.6, p = 0.43; and 27.3 ± 26.6 vs 14.1 ± 1.7, p = 0.006) (7). B, Mean (sd) difference in methylprednisolone treatment versus control (–10.10; –13.12 to 7.08; p < 0.001) and dexamethasone versus control (–5.3; –8.4 to –2.2; p = 0.0009).
Figure 2.
Figure 2.
Hospital mortality for patients randomized before day 14 of acute respiratory distress syndrome in randomized trials investigating prolonged corticosteroid treatment. ID = identification, RR = relative risk.
Figure 3.
Figure 3.
Corticosteroid treatment protocols: methylprednisolone and dexamethasone. A, Methylprednisolone treatment. The dosage is adjusted to ideal body weight and round up to the nearest 10 mg (i.e., 77 mg round up to 80 mg). Day 0, IV bolus (80 mg in 50 cc normal saline) over 30 min. Day 0-to ICU discharge: infusion is obtained by adding the daily dosage to 240 cc of normal saline and run at 10 cc/hr. If necessary, infusion can be changed to bolus every 6 hr (1/4 daily dose) or in the last 6 d very 12 hr (1/2 daily dose). Five days after the patient can ingest medications, methylprednisolone is administered orally in one single daily equivalent dose. Enteral absorption of methylprednisolone, and likely other corticosteroids, is compromised for days after extubation. If between days 1 to 14, the patient is extubated, the patient is advanced to day 15 of drug therapy and tapered according to schedule. Monitor anti-inflammatory response with daily measurements of C-reactive protein levels in addition to severity scores of acute respiratory distress syndrome and multiple organ dysfunction. Rapid tapering can be associated with reconstituted systemic inflammation in the presence of suppressed adrenal function with worsening lung physiology and increased mortality risk (28). Urgent reinstitution of corticosteroid treatment is necessary to be followed after improvement by slow tapering. B, Dexamethasone treatment. Patients in the dexamethasone group received an IV 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. Treatment was maintained for a maximum of 10 d after randomization or until extubation (if occurring before day 10). An updated protocol mandates to give dexamethasone for a maximum of 10 d after randomization, independently of the intubation status. This protocol does not mandate further tapering for few days to minimize the risk for reconstituted systemic inflammation.
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