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Prediction of cognitive dysfunction after resuscitation from out-of-hospital cardiac arrest using serum neuron-specific enolase and protein S-100
  1. Neil R Grubb (neil.grubb{at}btopenworld.com)
  1. Royal Infirmary of Edinburgh, United Kingdom
    1. Catriona Simpson
    1. Royal Infirmary of Edinburgh, United Kingdom
      1. Roy Sherwood
      1. Kings College Hospital, London, United Kingdom
        1. Hagosa Abraha
        1. Kings College Hospital, London, United Kingdom
          1. Stuart M Cobbe
          1. University of Glasgow, United Kingdom
            1. Ronan E O'Carroll
            1. University of Stirling, United Kingdom
              1. Ian Deary
              1. University of Edinburgh, United Kingdom
                1. Keith A Fox
                1. University of Edinburgh, United Kingdom

                  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.

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