Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design

BackgroundElectroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest, but its value is limited by varying definitions of pathological patterns and by inter-rater variability. The American Clinical Neurophysiology Society (ACNS) has recently proposed a standardized EEG-terminology for critical care to address these limitations.In the Target Temperature Management (TTM) trial, a large international trial on temperature management after cardiac arrest, EEG-examinations were part of the prospective study design. The main objective of this study is to evaluate EEG-data from the TTM-trial and to identify malignant EEG-patterns reliably predicting a poor neurological outcome.Methods/DesignIn the TTM-trial, 399 post cardiac arrest patients who remained comatose after rewarming underwent a routine EEG. The presence of clinical seizures, use of sedatives and antiepileptic drugs during the EEG-registration were prospectively documented.After the end of the trial, the EEGs were retrieved to form a central EEG-database.The EEG-data will be analysed using the ACNS EEG terminology. We designed an electronic case record form (eCRF). Four EEG-specialists from different countries, blinded to patient outcome, will independently classify the EEGs and report through the eCRF. We will describe the prognostic values of pre-specified EEG patterns to predict poor as well as good outcome. We hypothesise three patterns to always be associated with a poor outcome (suppressed background without discharges, suppressed background with continuous periodic discharges and burst-suppression). Inter- and intra-rater variability and whether sedation or level of temperature affects the prognostic values will also be analyzed.DiscussionA well-defined terminology for interpreting post cardiac arrest EEGs is critical for the use of EEG as a prognostic tool.The results of this study may help to validate the ACNS terminology for assessing post cardiac arrest EEGs and identify patterns that could reliably predict outcome.Trial registrationThe TTM-trial is registered at ClinicalTrials.gov (NCT01020916).

[1]  N. Yonemoto,et al.  Nationwide Improvements in Survival From Out-of-Hospital Cardiac Arrest in Japan , 2012, Circulation.

[2]  W. Freeman,et al.  Neuron-specific enolase correlates with other prognostic markers after cardiac arrest , 2011, Neurology.

[3]  S. M. Sumi,et al.  Predicting outcome in hypoxic-ischemic coma. A prospective clinical and electrophysiologic study. , 1991, Electroencephalography and clinical neurophysiology.

[4]  W. Haupt,et al.  Application of Electrophysiologic Techniques in Poor Outcome Prediction Among Patients With Severe Focal and Diffuse Ischemic Brain Injury , 2011, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[5]  M. Nuwer,et al.  American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology: 2012 version. , 2013, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[6]  Eric Marsh,et al.  Interobserver Reproducibility of Electroencephalogram Interpretation in Critically Ill Children , 2011, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[7]  A. Hart,et al.  Prediction of poor outcome within the first 3 days of postanoxic coma , 2006, Neurology.

[8]  H. Viertiö-Oja,et al.  Hypothermia-treated cardiac arrest patients with good neurological outcome differ early in quantitative variables of EEG suppression and epileptiform activity* , 2009, Critical care medicine.

[9]  J. Bache European Resuscitation Council Guidelines for Resuscitation , 1998 .

[10]  Foss Mv MANAGEMENT OF VIRUS HEPATITIS. , 1964 .

[11]  H. Sediri,et al.  Early EEG Monitoring for Detecting Postanoxic Status Epilepticus during Therapeutic Hypothermia: A Pilot Study , 2009, Neurocritical care.

[12]  B Jennett,et al.  Assessment of outcome after severe brain damage. , 1975, Lancet.

[13]  M. Ramsay,et al.  Evaluating and monitoring analgesia and sedation in the intensive care unit , 2008, Critical care.

[14]  C. Bassetti,et al.  [Prognostic value of electroencephalography in non-traumatic comas]. , 1990, Schweizerische medizinische Wochenschrift.

[15]  S. Chokroverty “Alpha‐like” rhythms in electroencephalograms in coma after cardiac arrest , 1975, Neurology.

[16]  A. Rossetti,et al.  Early Multimodal Outcome Prediction After Cardiac Arrest in Patients Treated With Hypothermia* , 2014, Critical care medicine.

[17]  Mauro Oddo,et al.  Prognostication after cardiac arrest and hypothermia: A prospective study , 2010, Annals of neurology.

[18]  C. Suter,et al.  Alpha‐pattern coma: 24 cases with 9 survivors , 1977, Annals of neurology.

[19]  P. Kaplan,et al.  Etiology, neurologic correlations, and prognosis in alpha coma , 1999, Clinical Neurophysiology.

[20]  L. Svensson,et al.  Increase in survival and bystander CPR in out-of-hospital shockable arrhythmia: bystander CPR and female gender are predictors of improved outcome. Experiences from Sweden in an 18-year perspective , 2011, Heart.

[21]  A. Rossetti,et al.  Predicting neurological outcome after cardiac arrest , 2011, Current opinion in critical care.

[22]  M. Kuiper,et al.  Target Temperature Management after out-of-hospital cardiac arrest--a randomized, parallel-group, assessor-blinded clinical trial--rationale and design. , 2012, American heart journal.

[23]  Alessio Farcomeni,et al.  Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia. , 2013, Resuscitation.

[24]  I. Rosén,et al.  Continuous amplitude-integrated electroencephalogram predicts outcome in hypothermia-treated cardiac arrest patients , 2010, Critical care medicine.

[25]  C. Bassetti,et al.  Prognostic value of EEG in post-anoxic coma after cardiac arrest. , 1987, European neurology.

[26]  Ingmar Rosén,et al.  Amplitude-integrated EEG (aEEG) predicts outcome after cardiac arrest and induced hypothermia , 2006, Intensive Care Medicine.

[27]  M. Wise,et al.  Targeted temperature management at 33°C versus 36°C after cardiac arrest. , 2013, The New England journal of medicine.

[28]  ELECTROENCEPHALOGRAPHIC CHANGES IN ACUTE CEREBRAL ANOXIA FROM CARDIAC OR RESPIRATORY ARREST. , 1966, Electroencephalography and clinical neurophysiology.

[29]  TakeshiKimura,et al.  Nationwide Improvements in Survival From Out-of-Hospital Cardiac Arrest in Japan , 2012 .

[30]  C. Callaway,et al.  Frequency and Timing of Nonconvulsive Status Epilepticus in Comatose Post-Cardiac Arrest Subjects Treated with Hypothermia , 2012, Neurocritical Care.

[31]  R. Emerson,et al.  The ACNS Subcommittee on Research Terminology for Continuous EEG Monitoring: Proposed Standardized Terminology for Rhythmic and Periodic EEG Patterns Encountered in Critically Ill Patients , 2005, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[32]  E. W. Nielsen,et al.  EEG should be performed during induced hypothermia. , 2006, Resuscitation.

[33]  Arthur C. Grant,et al.  EEG interpretation reliability and interpreter confidence: A large single-center study , 2014, Epilepsy & Behavior.

[34]  Y. Shon,et al.  The prognostic value of continuous amplitude-integrated electroencephalogram applied immediately after return of spontaneous circulation in therapeutic hypothermia-treated cardiac arrest patients. , 2013, Resuscitation.

[35]  C W Hess,et al.  Early prognosis in coma after cardiac arrest: a prospective clinical, electrophysiological, and biochemical study of 60 patients. , 1996, Journal of neurology, neurosurgery, and psychiatry.

[36]  P. Kochanek,et al.  Effects of hypothermia on drug disposition, metabolism, and response: A focus of hypothermia-mediated alterations on the cytochrome P450 enzyme system , 2007, Critical care medicine.

[37]  V. Synek EEG Abnormality Grades and Subdivisions of Prognostic Importance in Traumatic and Anoxic Coma in Adults , 1988, Clinical EEG.

[38]  G. Young,et al.  An Electroencephalographic Classification for Coma , 1997, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[39]  Lawrence J. Hirsch,et al.  Interrater Reliability of ICU EEG Research Terminology , 2012, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[40]  I. Stiell,et al.  Advanced cardiac life support in out-of-hospital cardiac arrest. , 2004, The New England journal of medicine.

[41]  M. Holtkamp,et al.  STATUS EPILEPTICUS: AN INDEPENDENT OUTCOME PREDICTOR AFTER CEREBRAL ANOXIA , 2008, Neurology.

[42]  B. Jennett,et al.  ASSESSMENT OF OUTCOME AFTER SEVERE BRAIN DAMAGE A Practical Scale , 1975, The Lancet.

[43]  J. Tibballs,et al.  Adult advanced life support , 1994 .

[44]  F. Donati,et al.  Postanoxic alpha (theta) coma: a reappraisal of its prognostic significance , 2000, Clinical Neurophysiology.

[45]  G. B. Young,et al.  Practice Parameter: Prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review) , 2006, Neurology.

[46]  T. Rea,et al.  Incidence of EMS-treated out-of-hospital cardiac arrest in Europe. , 2005, Resuscitation.

[47]  Roger D. White,et al.  The Role of EEG after Cardiac Arrest and Hypothermia , 2013, Epilepsy currents.

[48]  M. Kawai,et al.  Outcome From Therapeutic Hypothermia and EEG , 2011, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[49]  M. Kuiper,et al.  Acute posthypoxic myoclonus after cardiopulmonary resuscitation , 2012, BMC Neurology.

[50]  C. Wijman,et al.  Prognosis After Cardiac Arrest and Hypothermia: A New Paradigm , 2011, Current neurology and neuroscience reports.

[51]  Mauro Oddo,et al.  Early EEG correlates of neuronal injury after brain anoxia , 2012, Neurology.

[52]  Outcome after severe brain damage. , 1973, Lancet.

[53]  Greg Sinibaldi,et al.  Incidence of EMS-treated out-of-hospital cardiac arrest in the United States. , 2004, Resuscitation.

[54]  Gavin D Perkins,et al.  European Resuscitation Council Guidelines for Resuscitation 2010 Section 4. Adult advanced life support. , 2010, Resuscitation.

[55]  Postanoxic status epilepticus can be identified and treatment guided successfully by continuous electroencephalography. , 2013, Therapeutic hypothermia and temperature management.

[56]  M. Copass,et al.  Electroencephalographic rhythms of alpha frequency in comatose patients after cardiopulmonary arrest , 1974, Neurology.

[57]  E. Englund,et al.  The influence of induced hypothermia and delayed prognostication on the mode of death after cardiac arrest. , 2013, Resuscitation.

[58]  W. Freeman,et al.  PREDICTORS OF AWAKENING FROM POSTANOXIC STATUS EPILEPTICUS AFTER THERAPEUTIC HYPOTHERMIA , 2009, Neurology.

[59]  C. Callaway,et al.  Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: a systematic review and meta-analysis. Part 1: patients not treated with therapeutic hypothermia. , 2013, Resuscitation.

[60]  A. Faris,et al.  The electroencephalogram after resuscitation of cardiocirculatory arrest , 1973, Journal of neurology, neurosurgery, and psychiatry.

[61]  Peter W. Kaplan,et al.  STATUS EPILEPTICUS : AN INDEPENDENT OUTCOME PREDICTOR AFTER CEREBRAL ANOXIA. Authors' reply , 2008 .

[62]  Jan Claassen,et al.  Recommendations on the use of EEG monitoring in critically ill patients: consensus statement from the neurointensive care section of the ESICM , 2013, Intensive Care Medicine.

[63]  G. Ronquist,et al.  Prediction of outcome after cardiac arrest , 1987, Critical care medicine.