Introduction
- Steroid use in ARDS has been a highly debated topic around dosing, which steroid, durations, when to initiate therapy. With the emergence of COVID-19, the debate has resurfaced along with numerous trials.
- The thought behind using steroids in this patient population is to use the anti-inflammatory and anti-proliferative effects of glucocorticoids to mitigate the progression and limit the severity of this inflammatory disease.
- Many studies have been conducted investigating which steroid is the most effective in patients with ARDS. Most have concluded that glucocorticoids possess the most benefit. However, the next questions that arise are what dose is the most appropriate and how long should patients receive steroid therapy.
Pharmacology
| Methylprednisolone | Dexamethasone | |
| Dose | Ranging from 0.125 mg/kg/day to 2 mg/kg/day Duration: 5 – 25 days | Ranging from 6 mg/day to 20 mg/day Duration: 5 – 10 days |
| Administration | IV | IV |
| PK/PD | Onset: within 1 hour Half-life: 15 minutes Metabolism: hepatic primarily | Onset: 30 minutes Half-life: 1 – 5 hours Metabolism: hepatic |
| Adverse Effects | Adrenal suppression, hyperglycemia, psychiatric/behavioral effects, osteoporosis, glaucoma | Adrenal suppression, hyperglycemia, psychiatric/behavioral effects, osteoporosis, glaucoma |
| Drug Interactions and warnings | CYP3A4 inducers or inhibitors (i.e. warfarin, verapamil, diltiazem, phenobarbital, phenytoin) | CYP3A4 inducers or inhibitors (i.e. warfarin, verapamil, diltiazem, phenobarbital, phenytoin) |
Overview of Evidence
| Author, year | Design/ sample size | Steroid & Comparison | Outcome |
| Steinberg et al, 2006 | RCT 180 participants | Methylprednisolone taper vs placebo in ARDS patients 7-13 days or 14-28 days after disease onset | There was no difference in 60-day mortality between groups, but there was a decrease in mechanical ventilator-free days and ICU-free days in patients that received MP |
| Meduri et al, 2007 | RCT 91 participants | Methylprednisolone vs placebo in patients with early ARDS | Patients receiving MP had an improvement in lung injury score, mechanical vent-free days, ICU LOS, and mortality |
| Villar et al, 2020 | RCT 277 participants | Dexamethasone* vs placebo in patients with acute to moderate ARDS * Dexamethasone 20 mg daily x 5 days, then 10 mg daily x 5 days | There was a significant increase in mechanical vent-free days at day 28 in patients who received dexamethasone There was also a decrease in all-cause mortality at day 60 and hospital mortality in dexamethasone patients compared to placebo |
| Horby et al, 2021 | RCT 6425 participants | Dexamethasone for 6mg daily for 10 days vs placebo in patients confirmed SARS-CoV-2 | There was a significant reduction in mortality at day 28 in patients receiving dexamethasone The greatest benefit was seen in patients that were requiring mechanical ventilation |
| Angus et al, 2020 | RCT 403 participants | Fixed-dose* vs shock-dependent** hydrocortisone vs usual care in adults with severe COVID-19 receiving either respiratory or cardiovascular support in the ICU *Hydrocortisone 100 mg q6h x 7 days **Hydrocortisone 50 mg q6h x 7 days | There was no difference in the number of organ-support free days between the groups A secondary analysis was conducted showing probability of superiority to no hydrocortisone. Both dosing regimens had probability of superiority above 80% |
| Tomazini et al, 2020 | RCT 299 participants | Dexamethasone* and usual care vs usual care alone in patients with COVID-19 and confirmed ARDS within 48 hours of symptoms *Dexamethasone 20 mg daily x 5 days, then 10 mg daily x 5 days | Patients receiving dexamethasone had significantly more mechanical-vent free days compared to usual care alone There was no difference in mortality or ICU-free days between groups |
Conclusions
- Some studies suggest the use of glucocorticoids in patients with ARDS with or without COVID-19 have a beneficial effect
- The most common reported benefit from steroid use in these patients is an increase in mechanical ventilator-free days
- In patients that have COVID-19 in addition to ARDS, studies suggest that there is a benefit to giving steroids with the greatest effect being in patients requiring oxygen supplementation
- There is not enough evidence to determine the optimal duration of steroid therapy
References
- Micromedex [Electronic version].Greenwood Village, CO: Truven Health Analytics. Retrieved February 4, 2022, from http://www.micromedexsolutions.com/
- Angus DC, Derde L, Al-Beidh F, 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. 10 06 2020;324(13):1317-1329. doi:10.1001/jama.2020.17022
- Horby P, Lim WS, Emberson JR, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. Feb 25 2021;384(8):693-704. doi:10.1056/NEJMoa2021436
- Meduri GU, Golden E, Freire AX, et al. Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial. Chest. Apr 2007;131(4):954-63. doi:10.1378/chest.06-2100
- Steinberg KP, Hudson LD, Goodman RB, et al. Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome. N Engl J Med. Apr 20 2006;354(16):1671-84. doi:10.1056/NEJMoa051693
- Tomazini BM, Maia IS, Cavalcanti AB, et al. 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. 10 06 2020;324(13):1307-1316. doi:10.1001/jama.2020.17021
- Villar J, Ferrando C, Martínez D, et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 03 2020;8(3):267-276. doi:10.1016/S2213-2600(19)30417-5
- Matthay MA, Zemans RL. The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol. 2011;6:147-63. doi:10.1146/annurev-pathol-011110-130158
