Erythropoietin therapy after out-of-hospital cardiac arrest: A systematic review and meta-analysis

Table 1 Characteristics of the included studies

Name of study	Cariou et al[9], 2008	Grmec et al[10], 2009	Cariou et al[11], 2016
Study design	Single center, case-control	Single center, case-control	Multicenter, single blind RCT
Total dose of Epo administered	200000 IU	90000 IU	200000 IU
Timing of Epo administration	Immediately after ROSC	Within 1 or 2 min of physician assisted CPR	Immediately after ROSC
No. of participants, n (intervention/control)	18/40	24/48	234/242
Mean age, yr (intervention/control)	59/58	59/60	60.5/58.6
Male gender, n (intervention/control)	16/39	16/34	192/184
Initial rhythm PEA/asystole, n (intervention/control)	2/8	12/17	94/100
Initial rhythm shockable (VF/VT), n (intervention/control)	16/32	12/31	115/110
Perfusing rhythm after bystander defibrillation, n (intervention/control)	0/0	0/0	24/31
Unknown rhythm, n (intervention/control)	0/0	0/0	1/3
Follow-up duration	28 d	Till hospital discharge	60 d

RCT: Randomized control trial; Epo: Erythropoietin; IU: International units; ROSC: Return of spontaneous circulation; CPR: Cardiopulmonary resuscitation; PEA: Pulseless electrical activity; VF: Ventricular fibrillation; VT: Ventricular tachycardia.

Table 2 Assessment of quality for the included studies

Newcastle-Ottawa scale for bias assessment for case-controlled studies
Newcastle-Ottawa scale for bias assessment	Cariou et al[9], 2008	Grmec et al[10], 2009
Selection	3	2
Comparability	2	2
Exposure	3	3
Cochrane Risk of Bias tool for the Randomized controlled study (Cariou et al[11])
Entry	Judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: “Patients were randomly assigned in a 1:1 ratio to the intervention or the control group”
Allocation concealment (selection bias)	Low risk	Quote: “Randomization was performed centrally with the use of a computer-generated assignment sequence Intervention assignments were made in permuted blocks of varying size and were stratified according to site”
Blinding of participants and personnel (performance bias)	High risk	Comment: Probably done
		Quote: “Single-blinded”; “physicians performing neurological follow-up and final outcome measurement, as well as study administrators and statisticians, were unaware of the intervention assignments”
		Comment: Probably done. However, only single blinding performed
Blinding of outcome assessment (detection bias) (patient-reported outcomes)	Low risk	Quote: “Single-blinded”
		Comment: Probably done
Blinding of outcome assessment (detection bias) (mortality)	Low risk	Obtained from medical records; Quote “CPC was assessed by face-to-face contact with patients still hospitalized, and through phone interviews in discharged patients using a standardized protocol”
		Review authors do not believe this will introduce bias
Incomplete outcome data addressed (attrition bias) (Longer-term outcomes, > 6 wk)	Low risk	60 d: 1/234 missing from intervention group (“lost to follow-up”); 0/242 missing from control group
Selective reporting (reporting bias)	Low risk	A single scale to assess neurological outcomes was used and reported (CPC score)

Table 3 Baseline demographics of study population

Baseline characteristic	Epo	No Epo	n	Studies (n)	P for overall effect
Age, yr	59.5	58.9	606	3	0.22
Males, %	79.2	81.4	606	3	0.93
Initial rhythm PEA/asystole, %	33.8	32.2	606	3	0.85
Initial rhythm VF/VT, %	62.7	63.3	606	3	0.45

Epo: Erythropoietin; PEA: Pulseless electrical activity; VF: Ventricular fibrillation; VT: Ventricular tachycardia.