title: Prognostic value of cell-free plasma DNA in patients with cardiac arrest outside the hospital: an observational cohort study.
abstract: BACKGROUND
  Many approaches have been examined to try to predict patient outcome after cardiopulmonary resuscitation. It has been shown that plasma DNA could predict mortality in critically ill patients but no data are available regarding its clinical value in patients after out-of-hospital cardiac arrest. In this study we investigated whether plasma DNA on arrival at the emergency room may be useful in predicting the outcome of these patients.
  
  
  METHODS
  We performed a prospective study of out-of-hospital patients with cardiac arrest who achieved return of spontaneous circulation after successful resuscitation. Cardiovascular co-morbidities and resuscitation history were recorded according to the Utstein Style. The outcome measures were 24 h and overall in-hospital mortality. Cell-free plasma DNA was measured by real-time quantitative PCR assay for the beta-globin gene in blood samples drawn within two hours after the arrest. Descriptive statistics, multiple logistic regression analysis, and receiver operator characteristic (ROC) curves were calculated.
  
  
  RESULTS
  Eighty-five consecutive patients were analyzed with a median time to return of spontaneous circulation of 27 minutes (interquartile range (IQR) 18 to 35). Thirty patients died within 24 h and 58 died during the hospital course. Plasma DNA concentrations at admission were higher in non-survivors at 24 h than in survivors (median 5,520 genome equivalents (GE)/ml, vs 2810 GE/ml, P < 0.01), and were also higher in patients who died in the hospital than in survivors to discharge (median 4,150 GE/ml vs 2,460 GE/ml, P < 0.01). Lactate clearance at six hours was significantly higher in 24 h survivors (P < 0.05). The area under the ROC curves for plasma DNA to predict 24-hour mortality and in-hospital mortality were 0.796 (95% confidence interval (CI) 0.701 to 0.890) and 0.652 (95% CI 0.533 to 0.770). The best cut-off value of plasma DNA for 24-h mortality was 4,340 GE/ml (sensitivity 76%, specificity 83%), and for in-hospital mortality was 3,485 GE/ml (sensitivity 63%, specificity 69%). Multiple logistic regression analysis showed that the risk of 24-h and of in-hospital mortality increased 1.75-fold and 1.36-fold respectively, for every 500 GE/ml increase in plasma DNA.
  
  
  CONCLUSIONS
  Plasma DNA levels may be a useful biomarker in predicting outcome after out-of hospital cardiac arrest.
authors.affiliation: Emergency Medicine Department, Internal Medicine Service, Hospital Universitario La Paz, IDIPaz, Paseo de la Castellana 261, Madrid, Spain. farnalich.hulp@salud.madrid.org
authors.forename: Francisco
authors.initials: F
authors.lastname: Arnalich
authors.forename: Marta
authors.initials: M
authors.lastname: Menéndez
authors.forename: Verónica
authors.initials: V
authors.lastname: Lagos
authors.forename: Enrique
authors.initials: E
authors.lastname: Ciria
authors.forename: Angustias
authors.initials: A
authors.lastname: Quesada
authors.forename: Rosa
authors.initials: R
authors.lastname: Codoceo
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Vazquez
authors.forename: Eduardo
authors.initials: E
authors.lastname: López-Collazo
authors.forename: Carmen
authors.initials: C
authors.lastname: Montiel
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016887:Cardiopulmonary Resuscitation; D015331:Cohort Studies; D015897:Comorbidity; D004247:DNA / Q000097:blood*; D005260:Female; D006323:Heart Arrest / Q000097:blood / Q000401:mortality / Q000628:therapy*; D017052:Hospital Mortality / Q000639:trends; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D019370:Observation; D017063:Outcome Assessment, Health Care / Q000379:methods; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012372:ROC Curve; D055544:beta-Globins / Q000032:analysis
chemical_list: D015415:Biomarkers; D055544:beta-Globins; D004247:DNA