title: Brain biomarkers and management of uncertainty in predicting outcome of cardiopulmonary resuscitation: a nomogram paints a thousand words.
abstract: OBJECTIVE
  Use of brain biomarkers for predicting death after cardiopulmonary resuscitation (CPR) is limited by a research focus on the discriminative ability of each biomarker and ethical/cultural controversy concerning the likelihood of misclassification of potential survivors. We illustrate an approach to address these limitations by creating a dynamic nomogram with four levels of sensitivity (0.8, 0.9, 0.95 and 1.0) selected to represent different degrees of certainty in correct identification of survivors.
  
  
  METHODS
  A prolective observational study conducted in a single 850-bed hospital. Admission serum S100beta (S100B) and neuron-specific enolase (NSE) were determined for all adult survivors of non-traumatic out-of-hospital arrest and CPR.
  
  
  RESULTS
  158 patients were included, 126 (80%) died in hospital, 32 (20%) survived. Non-survivors had higher admission biomarker levels than survivors (p≤0.001 for both S100B and NSE). Presenting rhythm (VT/VF vs. other) and logarithmic-transformed S100B and NSE levels were statistically significant in the multivariable model predicting survival. The area under the model ROC curve was 0.868 (95%CI 0.80, 0.936). Plots for predicting survival for each combination of biomarker levels were generated for each sensitivity with and without VT/VF, allowing clinicians to select their option in terms of survival probability. In this modest-sized illustrative study the model misclassified 1/19 patients with Cerebral Performance Category 1-2 for sensitivity >0.80.
  
  
  CONCLUSIONS
  We demonstrate how brain biomarkers can serve as decision support tools after CPR despite ethical/cultural differences in defining futility. Data from larger and diverse samples are required for stable estimates prior to clinical implementation of such a tool.
authors: Surgical Intensive Care, Shaare Zedek Medical Center, and Hebrew University-Hadassah Faculty of Medicine, Ein-Kerem, Jerusalem, Israel. einav_s@szmc.org.il
authors: Sharon
authors: S
authors: Einav
authors: Nechama
authors: N
authors: Kaufman
authors: Nurit
authors: N
authors: Algur
authors: Nurith
authors: N
authors: Strauss-Liviatan
authors: Jeremy D
authors: JD
authors: Kark
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D001921:Brain / Q000378:metabolism*; D016887:Cardiopulmonary Resuscitation / Q000009:adverse effects / Q000706:statistics & numerical data; D003661:Decision Support Techniques; D005260:Female; D006801:Humans; D007557:Israel / Q000453:epidemiology; D008297:Male; D018447:Medical Futility / Q000941:ethics; D008875:Middle Aged; D049451:Nomograms; D058687:Out-of-Hospital Cardiac Arrest / Q000097:blood / Q000401:mortality / Q000628:therapy; D017063:Outcome Assessment, Health Care; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D012372:ROC Curve; D018570:Risk Assessment / Q000941:ethics / Q000379:methods*; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood*; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D064568:S100 Calcium Binding Protein beta Subunit; D010751:Phosphopyruvate Hydratase
keywords: Biological markers; Cardiopulmonary resuscitation; Decision support techniques; Epidemiology; Evidence-based medicine; Heart arrest; Neuron-specific enolase; Prognosis; S-100 calcium-binding protein beta subunit