Abstract

Background More than 50% of patients initially resuscitated from out-of-hospital cardiac arrest die in hospital, many as a result of hypoxic brain injury. Of those who survive, more than one third suffer significant cognitive impairment. This study investigated the prognostic value of estimations of serum protein S-100 and neuron-specific enolase (NSE) concentrations for predicting (i) memory impairment at discharge, and (ii) in-hospital death, in patients admitted after resuscitation from out-of-hospital cardiac arrest.

Methods In a prospective study of 143 consecutive survivors of out-of-hospital cardiac arrest, serum samples were obtained within 12 hours of the event (time A), and 24-48 (time B) and 72-96 hours (time C) afterwards, if the patient survived. S-100 and NSE concentrations were measured. Pre-discharge cognitive assessment of patients who consented and survived to discharge (n=49) utilised the Rivermead Behavioural Memory Test (RBMT). We examined the relationship between biochemical brain marker concentrations and RBMT scores, and between marker concentrations and the risk of in-hospital death.

Results A moderate negative relationship was found between S-100 concentration and memory test score, at all time points (time A: r=-0.349, p=0.015; time B: r=-0.480, p=0.001; time C: r=-0.318, p=0.033). The relationship between NSE and memory test scores was weaker : time A: r=-0.015, p=0.917; time B: r=-0.304, p=0.035; time C: r=-0.241, p=0.111. A S-100 concentration greater than 0.29 mg l-1 at time B predicted moderate to severe memory impairment with absolute specificity (42.8 percent sensitivity). S-100 remained an independent predictor of memory function after adjustment for clinical variables and cardiac arrest timing indices. <BR> NSE and S-100 concentrations were greater in patients who survived than in those who died, at all time points. Median [range] S-100 concentrations at time B were 0.15 [0.00 - 1.10] versus 0.53 [0.01 - 9.20] mg/L, p<0.001 respectively. NSE concentrations at time B were 15.1 [8.3 - 70.9] versus 29.4 [10.4 - 197.0] mg/L, p<0.001. Both NSE and S-100 remained predictors of in-hospital death after adjustment for clinical variables and cardiac arrest timing indices. The threshold concentrations that yielded 100 percent specificity for in-hospital death (were S-100: 1.20 mg/L (sensitivity 44.8 percent); NSE 71.0 mg/L (sensitivity 14.0 percent).

Conclusions Estimation of serum S-100 concentration after out-of-hospital cardiac arrest can be used to identify patients at risk of significant cognitive impairment at discharge. Serum S-100 and NSE concentrations measured 24-48 hours after cardiac arrest provide useful adjunctive prognostic information, along with clinical assessment, to identify cardiac arrest victims with a high likelihood of in-hospital death. These markers now require prospective evaluation against neurophysiological predictive tests to further define their clinical application.