Table 2.

Biomarkers for outcome following cardiac arrest with therapeutic hypothermia treatment

Authors/year/Ref	Study design	Population	N	Bio-marker	Sample source	Findings
Tiainen/2003/[27]	RCT	Witnessed VF or VT arrest, ≤60 min between collapse to ROSC	70	NSE, s100β	Serum	NSE levels were lower in TH compared to normothermia NSE did not reach 100 % specificity in TH, whereas it does in normothermia TH: NSE >31.2 μg/L at 24 h, >26 μg/L at 36 h, and >25 μg/L at 48 h predicted poor outcome (96 % specificity) Normothermia: NSE >13.3 μg/L at 24 h, >12.6 μg/L at 36 h, and >8.8 μg/L at 48 h had 100 % specificity for poor outcome TH: s100β >0.21 μg/L at 24 h (100 % specificity), s100β >0.21 μg/L at 36 h, and s100β >0.23 μg/L at 48 h (96 % specificity) predicted poor outcome
Cronberg/2011/[29]	Pro	Post cardiac arrest with GCS <8 after ROSC	111	NSE	Serum	Elevated NSE was associated with worse outcome, DWI changes on MRI, and worse neuropathology All patients with NSE >33 μg/L at 48 h died without regaining consciousness NSE >27 μg/L predicted poor outcome at 6 months (100 % specificity)
Rundgren/2009/[25]	Pro	In- or out-of-hospital cardiac arrest, GCS ≤7	107	NSE, s100β	Serum	NSE >28 μg/L at 48 h predicted poor 6-month outcome (100 % specificity; 67 % sensitivity). s100β >0.51 μg/L at 24 h predicted poor 6-month outcome (96 % specificity; 62 % sensitivity)
Daubin/2011/[24]	Pro	In- or out-of-hospital cardiac arrest, comatose >48 h	97	NSE	Serum	Elevated NSE correlated with worse outcome at 3 months. NSE >47 μg/L predicted poor 3-month outcome (84 % specificity; 72 % sensitivity) NSE >97 μg/L predicted poor outcome (100 % PPV)
Shinozaki/2009/[23]	Pro	In- or out-of-hospital non-traumatic cardiac arrest with ROSC >20 min, with GCS ≤8	80	NSE, s100μ	Serum	s100β and NSE are both elevated in poor outcome group. s100β had better predictive performance than NSE s100β cutoff for poor outcome are as follows: s100β >1.41 μg/L at admission, s100β >0.21 μg/L at 6 h, and s100β >0.05 μg/L at 24 h post cardiac arrest (100 % specificity)
Stammet/2013/[28]	Pro	Post cardiac arrest	75	NSE, s100μ	Serum	Elevated s100β and NSE levels are associated with poor outcome at 6 months Adding s100β to Bispectral index improved predictive value for poor outcome
Rossetti/2012/[21]	Pro	Post cardiac arrest, comatose	61	NSE	Serum	5 cardiac arrest survivors, including 3 with good outcome, had NSE >33 μg/L
Mortberg/2011/[30]	Pro	Post cardiac arrest, SBP >80 mmHg x > 5 min, GCS ≤7, <6 h following ROSC	31	NSE, s100β, BDNF, GFAP	Serum	No association between BDNF and GFAP levels and outcome NSE >4.97 μg/L at 48 h and NSE >3.22 μg/L at 96 h post cardiac arrest predicted poor outcome at 6 months (93 % specificity) s100β >1.0 μg/L at 2 h (93 % specificity), and s100β >0.18 μg/L at 24 h (100 % specificity) post-cardiac arrest predicted poor outcome

PPV positive predictive value, Pro prospective observational, RCT randomized controlled trial, ROSC return of spontaneous circulation, TH therapeutic hypothermia, VF ventricular fibrillation, VT ventricular tachycardia