Clinical benefits of corticosteroid administration during adult cardiopulmonary resuscitation: A systemic review and meta-analysis

Table 1 Characteristics of the included studies

Ref.	Age, yr	Study design, country/territory, enrollment period	Sample size (exposure/control)	Location	Shockable initial rhythm (exposure/control), %	Witnessed arrest (exposure/control), %	Bystander CPR (exposure/control), %	Intervention	Comparator	Outcomes of interest
Bolvardi et al[17], 2016	68.9 ± 16.0	RCT, Iran, 2015	50 (25/25)	OHCA	28 (20/36)	N/A	N/A	1 mg epinephrine plus 125 mg methylpredni-solone during the first cycle of resuscitation	1 mg epinephrine plus saline during the first cycle of resuscitation	Successful resuscitation; Survival to hospital discharge; Neurological outcomes at hospital discharge
Mentzelopoulos et al[9], 2009	67.4	RCT, Greece, Jul 2006 to Mar 2007	100 (48/52)	IHCA	14 (15/13)	81 (79/83)	N/A	1 IU vasopressin plus 1 mg epinephrine for the first 5 CPR cycles and 40 mg methylprednisolone. Shock after resuscitation was treated with stress-dose hydrocortisone (300 mg daily for 7 d with gradual tapering)	Placebo (saline) plus 1 mg epinephrine for the first 5 CPR cycles. Shock after resuscitation was treated with saline placebo	Sustained ROSC; Survival to hospital discharge
Mentzelopoulos et al[7], 2013	63.0	RCT, Greece, Sep 2008 to Oct 2010	268 (130/138)	IHCA	16.8 (16.7/16.9)	92.2 (91.3/93/1)	N/A	1 IU vasopressin plus 1 mg epinephrine for the first 5 CPR cycles and 40 mg methylprednisolone. Shock after resuscitation was treated with stress-dose hydrocortisone (300 mg daily for 7 d with gradual tapering)	Placebo (saline) plus 1 mg epinephrine for the first 5 CPR cycles. Shock after resuscitation was treated with saline placebo	ROSC ≥ 20 min; Survival to hospital discharge; Neurological outcomes at hospital discharge
Paris et al[10], 1984	N/A	RCT, United States, Mar 1982 to Jan 1983	83 (37/46)	OHCA	48.2 (41.3/56.8)	N/A	30.1 (36.9/21.6)	100 mg dexamethasone	The same volume of saline	Survival to hospital admission; Survival to hospital discharge
Tsai et al[11], 2007	72.5 ± 16.2	Prospective non-RCT, Taiwan, Oct 2004 to Jul 2005	97 (36/61)	Non-trauma, OHCA	10.3 (11/10)	75.3 (83/71)	N/A	100 mg hydrocortisone	Saline as placebo	Sustained ROSC; Survival to hospital discharge
Tsai et al[18], 2016	68.2	Retrospective, Taiwan, 2004-2011	145644 (2912/142732)	IHCA (at the ED)	20.6 (33.4/20.3)	N/A	N/A	Any forms of steroid use	No steroid use	Survival to hospital admission; Survival to hospital discharge; 1-yr survival

CPR: Cardiopulmonary resuscitation; ED: Emergency department; IHCA: In-hospital cardiac arrest; N/A: Not applicable; OHCA: Out-of-hospital cardiac arrest; RCT: Randomized-controlled trial; ROSC: Return of spontaneous circulation.

Table 2 Cochrane risk of bias assessment tool for randomized trials and the Good Research for Comparative Effectiveness checklist for nonrandomized trials

Randomized-controlled trials
Ref.	Randomization		Deviation from the intended interventions			Missing outcome data			Measurement of outcome			Selection of the reported result			Overall
Bolvardi et al[17], 2016	Low		High			Some concerns			Low			Some concerns			High
Mentzelopoulos et al[9], 2009	Low		Low			Low			Low			Low			Low
Mentzelopoulos et al[7], 2013	Low		Low			Low			Low			Low			Low
Paris et al[10], 1984	High		Low			Some concerns			Low			Some concerns			High
Non-randomized-controlled trials
Ref.	Adequate treatment	Adequate outcomes		Objective outcomes	Valid outcomes		Similar outcomes	Covariates recorded		New initiators	Concurrent comparators		Covariates accounted for	Immortal time bias		Sensitivity analysis
	D1	D2		D3	D4		D5	D6		M1	M2		M3	M4		M5
Tsai et al[11], 2007	+	+		+	+		+	+		+	+		+	+		+
Tsai et al[18], 2016	+	+		+	+		+	+		+	+		+	+		+