Steroids in acute respiratory distress syndrome: A panacea or still a puzzle?

Table 1 Comparison of studies of steroids in non-coronavirus disease 2019 acute respiratory distress syndrome

Ref.	Country, number of participating sites	Number of patients	Type of patient population	Severity of ARDS	Intervention group	Control group	Primary outcome	Remarks
Meduri et al[8], 1998	United States, 4	24	Adults with ARDS who failed to improve lung injury score by the seventh day of respiratory failure on mechanical ventilation	Severe	IV Methylprednisolone 2 mg/kg loading dose followed by tapering dosage until day 32	Placebo	Improvement in lung function and mortality (both ICU and hospital mortality)	Trial stopped early due to huge benefits in corticosteroid group (leading to biases in the treatment effect)
Annane et al[9], 2006	France, 19	300	Adults with ARDS and septic shock on mechanical ventilation	Moderate-to-severe	IV Hydrocortisone 50 mg every 6th hourly plus oral 9-α-fludrocortisone for 7 d	Placebo	Mortality at 28 d in non-responders to short corticotropin test	Short corticotropin test with IV tetracosactrin 250 mcg prior to randomization
Steinberg et al[10], 2006	United States, 25 centres	180	Adults with ARDS of at least 7 d’ duration on mechanical ventilation with P/F ration less than 200	Moderate-to-severe	IV Methylprednisolone 2 mg/kg loading dose followed by tapering dosage until day 21	Placebo	All-cause mortality at 60 d	Long recruitment time, high incidence of neuromyopathy in both groups
Meduri et al[11], 2007	United States, 5	91	Adults with ARDS on mechanical ventilation	Any severity	IV Methylprednisolone 1 mg/kg loading dose followed by tapering dosage until day 28	Placebo	Reduction in lung injury score by 1-point or successful extubation by day 7	Baseline higher number of patients in placebo group with ‘catecholamine-dependant shock’ may have biased the results
Rezk et al[12], 2013	Kuwait, 1	27	Adults with ARDS on mechanical ventilation	Any severity	IV Methylprednisolone 1 mg/kg loading dose followed by tapering dosage until day 28	Placebo	Improvement in clinical and laboratory parameters	Underpowered, extremely small sample size, ill-defined primary and secondary outcomes
Tongyoo et al[13], 2016	Thailand, 1	206	Adults with ARDS and severe sepsis	Any severity	IV Hydrocortisone every 6th hourly for 7 d	Placebo	All-cause mortality at 28 d	Single centre, limited generalizability
Villar et al[7], 2020	Spain, 17	277	Adults with ARDS	Moderate-to-severe	IV Dexamethasone 20 mg once daily (day 1 to 5) followed by 10 mg once daily (day 6 to 10)	Placebo	VFD at 28 d	Largest RCT till date, insufficient implementation of prone ventilation in both groups

ARDS: Acute respiratory distress syndrome; VFD: Ventilator-free days; RCT: Randomised controlled trial; ICU: Intensive care unit.