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Heart rhythm disorders and pacemakers
Prediction of cognitive dysfunction after resuscitation from out-of-hospital cardiac arrest using serum neuron-specific enolase and protein S-100
  1. Neil R Grubb1,
  2. Catriona Simpson2,
  3. Roy A Sherwood3,
  4. Hagosa D Abraha3,
  5. Stuart M Cobbe4,
  6. Ronan E O’Carroll5,
  7. Ian Deary6,
  8. Keith A A Fox2
  1. 1
    Department of Cardiology, Royal Infirmary of Edinburgh, Edinburgh, UK
  2. 2
    University of Edinburgh Cardiovascular Research Unit, UK
  3. 3
    Kings College Hospital, London, UK
  4. 4
    Department of Medical Cardiology, Glasgow Royal Infirmary, UK
  5. 5
    University of Stirling, UK
  6. 6
    University of Edinburgh, UK
  1. Dr N R Grubb, Department of Cardiology, Royal Infirmary of Edinburgh, 31 Little France Crescent, Edinburgh EH16 4SA, UK; neil.grubb{at}


Background: More than 50% of patients initially resuscitated from out-of-hospital cardiac arrest die in hospital.

Objective: To investigate the prognostic value of serum protein S-100 and neuron-specific enolase (NSE) concentrations for predicting (a) memory impairment at discharge; (b) in-hospital death, 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, 24–48 and 72–96 hours after the event. S-100 and NSE concentrations were measured. Pre-discharge cognitive assessment of patients (n = 49) was obtained by the Rivermead Behavioural Memory Test (RBMT). The relationship between biochemical brain marker concentrations and RBMT scores, and between marker concentrations and the risk of in-hospital death was examined.

Results: A moderate negative relationship was found between S-100 concentration and memory test score, at all time points. The relationship between NSE and memory test scores was weaker. An S-100 concentration >0.29 μg/l at time B predicted moderate to severe memory impairment with absolute specificity (42.8% sensitivity). S-100 remained an independent predictor of memory function after adjustment for clinical variables and cardiac arrest timing indices. NSE and S-100 concentrations were greater in patients who died than in those who survived, at all time points. Both NSE and S-100 remained predictors of in-hospital death after adjustment for clinical variables and cardiac arrest timing indices. The threshold concentrations yielding 100% specificity for in-hospital death were S-100: 1.20 μg/l (sensitivity 44.8%); NSE 71.0 μg/l (sensitivity 14.0%).

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 additional information.

  • cardiac arrest
  • hypoxia–ischaemia (brain)
  • cognitive function

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  • Competing interests: Dr NR Grubb was reimbursed for consultancy work for St Jude Medical between 2005 and 2006. He was also reimbursed for consultancy work for CardioDigital, a signal analysis company, between 2003 and 2006. Dr Grubb does not hold shares in either company.

  • Abbreviations:
    cardiopulmonary resuscitation
    coefficient of variation
    Glasgow Coma Score
    National Adult Reading Test
    neurone-specific enolase
    Rivermead Behavioural Memory Test
    receiver operating characteristic