Biomarkers for outcome following cardiac arrest without therapeutic hypothermia treatment

Authors/year	Population	N	Biomarker	Sample source	Findings
Molecules of CNS Origin
Zandbergen, 2006	Post cardiac arrest, unconscious >24 h after CPR	407	NSE, s100β	Serum	100 % of patients with NSE > 33 μg/L at any time had a poor outcome (40 % PPV; 0 % FPR) s100β > 0.7 μg/L at 24–72 h post cardiac arrest predicts poor outcome (47 % PPV; 2 % FPR) Performance of clinical tests was inferior to SSEP and NSE in predicting outcome
Meynaar, 2003	Post cardiac arrest, comatose post CPR	110	NSE	Serum	NSE at 24 and 48 h after CPR was significantly higher in patients who did not regain consciousness versus those who did No one with NSE > 25 μg/L at any time regained consciousness (100 % specificity)
Pfeifer, 2005	Post cardiac arrest within 12 h of ROSC, survived >48 h	97	NSE, s100β	Serum	NSE > 65 μg/L predicted increased risk of death and persistent vegetative state at 28 days post CPR (97 % PPV) s100β > 1.5 μg/L predicts poor outcome (96 % PPV)
Rosen, 2001	Out of hospital cardiac arrest	66	s100β, NSE	Serum	s100β > 0.217 μg/L and NSE > 23.2 μg/L at 2 days post cardiac arrest predicted poor 1-year outcome (100 % PPV)
Bottiger, 2001	Non-traumatic out of hospital cardiac arrest	66	s100β	Serum	Significant differences in s100β level between survivors and non-survivors after cardiac arrest were observed from 30 min to 7 days post cardiac arrest s100β > 1.10 μg/L at 48 h post cardiac arrest predicted brain damage (100 % specificity)
Martens, 1998	Post cardiac arrest, unconscious and ventilated for >24 h	64	NSE, s100β	Serum	s100β and NSE were significantly higher in patients who did not regain consciousness compared of those who did s100β > 0.7 μg/L is a predictor of not regaining consciousness after cardiac arrest (95 % PPV; 96 % specificity) NSE > 20 μg/L predicted poor outcome (51 % sensitivity; 89 % specificity)
Hachimi-Idrissi, 2002	Post cardiac arrest	58	s100β	Serum	s100β > 0.7 μg/L at admission predicted not regaining consciousness (85 % specificity; 66.6 % sensitivity; 84 % PPV; 78 % NPV; 77.6 % accuracy)
Schoerkhuber, 1999	Non-traumatic out of hospital cardiac arrest	56	NSE	Serum	NSE was significantly higher in patients who had poor 6 month outcome at 12, 24, 48, and 72 h after ROSC NSE cutoffs for poor outcome were: NSE > 38.5 μg/L at 12 h, NSE > 40 μg/L at 24 h, NSE > 25.1 μg/L at 48 h, and NSE > 16.4 μg/L at 72 h (100 % specificity) NSE > 27.3 μg/L at any time predicted poor outcome (100 % specificity)
Molecules of non-CNS origin
Nagao, 2004	Age > 17 years, out of hospital cardiac arrest of presumed cardiac origin	401	BNP	Blood	Rate of survival to hospital discharge decreased in dose-dependent fashion with increasing quartiles of BNP on admission BNP > 100 pg/mL predicted lack of survival until hospital discharge (83 % sensitivity; 96 % NPV)
Kasai, 2011	Post cardiac arrest	357	Ammonia	Blood	Elevated ammonia on ER arrival is associated with decreased odds for good outcome at hospital discharge (OR 0.98 [0.96–0.99]) Ammonia > 192.5 μg/dL had 100 % NPV for good outcome at discharge 61 patients were treated with TH
Sodeck, 2007	Post cardiac arrest, comatose	155	BNP	Blood	Highest quartile BNP on admission is associated with poor outcome as compared to lowest quartile BNP > 230 pg/mL predicts unfavorable neurological outcome (OR 2.25 [1.05–4.81]) and death at 6 months (OR 4.7 [1.27–17.35])
Shinozaki, 2011	Non-traumatic out of hospital cardiac arrest with ROSC	98	Ammonia, lactate	Blood	Elevated ammonia and lactate on admission were associated with poor outcome Ammonia > 170 μg/dL predicted poor outcome (90 % sensitivity; 58 % specificity) Lactate > 12 mmol/L predicted poor outcome (90 % sensitivity; 52 % specificity)
CSF biomarkers
Roine, 1989	Out of hospital VF arrest who survived >24 h	67	NSE, CKBB	CSF	NSE and CKBB at 20–26 h post CPR were elevated in patients who did not regain consciousness compared with those who did All patients with NSE > 24 μg/L remained unconscious or died at 3 months (74 % sensitivity; 100 % specificity) CKBB > 17 μg/L predicted poor outcome (52 % sensitivity; 98 % specificity)
Sherman, 2000	Comatose cardiac arrest patients with SSEP studies	52	CKBB	CSF	CKBB > 205U/L predicted non-awakening (49 % sensitivity; 100 % specificity) CSF sampling time not standardized
Martens, 1998	Post cardiac arrest, unconscious, and ventilated for >48 h	34	NSE, s100β	CSF	s100β and NSE were both significantly higher in patients who did not regain consciousness compared of those who did NSE > 50 μg/L (89 % sensitivity; 83 % specificity) and s100β > 6 μg/L (93 % sensitivity; 60 % specificity) predicted death or vegetative state CSF sampling time is not standardized
Rosen, 2004	Post cardiac arrest, survive > 12 days post ROSC	22	NFL	CSF	CSF sampled at 12–30 days after cardiac arrest NFL > 18,668 μg/L predicted dependency in ADL at 1 year (100 % specificity; 46 % sensitivity)
Karkela, 1993	VF or asystolic arrest	20	CKBB, NSE	CSF	Case controlledCSF collected at 4, 28, and 76 h after resuscitation Elevated CKBB at 4 and 28 h, and elevated NSE at 28 and 76 h after cardiac arrest were associated with not regaining consciousness
Oda, 2012	Out of hospital cardiac arrest of presumed cardiac	14	HMGB1, s100β	CSF	CSF sampled at 48 h after ROSC HMGB1 and s100β were significantly higher in poor outcome group compared to good outcome group and to normal controls
Tirschwell, 1997	Post cardiac arrest with CSF CKBB measured	351	CKBB	CSF	Retrospective study CSF sampling time not standardized CKBB > 205U/L predicted non-awakening at hospital discharge (100 % specificity; 48 % sensitivity) Only nine patients with CKBB > 50U/L awakened and none regained independent ADLs

All studies are prospective observational unless otherwise noted

NPV negative predictive value, PPV positive predictive value, FPR false positive rate, OR odds ratio, ROSC return of spontaneous circulation, SSEP somatosensory evoked potential, TH therapeutic hypothermia, VF ventricular fibrillation