Prognostication in comatose survivors of cardiac arrest: An advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine.

OBJECTIVES: To review and update the evidence on predictors of poor outcome (death, persistent vegetative state or severe neurological disability) in adult comatose survivors of cardiac arrest, either treated or not treated with controlled temperature, to identify knowledge gaps and to suggest a reliable prognostication strategy. METHODS: GRADE-based systematic review followed by expert consensus achieved using Web-based Delphi methodology, conference calls and face-to-face meetings. Predictors based on clinical examination, electrophysiology, biomarkers and imaging were included. RESULTS AND CONCLUSIONS: Evidence from a total of 73 studies was reviewed. The quality of evidence was low or very low for almost all studies. In patients who are comatose with absent or extensor motor response at ≥72 h from arrest, either treated or not treated with controlled temperature, bilateral absence of either pupillary and corneal reflexes or N20 wave of short-latency somatosensory evoked potentials were identified as the most robust predictors. Early status myoclonus, elevated values of neuron-specific enolase at 48-72 h from arrest, unreactive malignant EEG patterns after rewarming, and presence of diffuse signs of postanoxic injury on either computed tomography or magnetic resonance imaging were identified as useful but less robust predictors. Prolonged observation and repeated assessments should be considered when results of initial assessment are inconclusive. Although no specific combination of predictors is sufficiently supported by available evidence, a multimodal prognostication approach is recommended in all patients.

Yield of intermittent versus continuous EEG in comatose survivors of cardiac arrest treated with hypothermia.

INTRODUCTION: Electroencephalography (EEG) has a central role in the outcome prognostication in subjects with anoxic/hypoxic encephalopathy following a cardiac arrest (CA). Continuous EEG monitoring (cEEG) has been consistently developed and studied; however, its yield as compared to repeated standard EEG (sEEG) is unknown. METHODS: We studied a prospective cohort of comatose adults treated with therapeutic hypothermia (TH) after a CA. cEEG data regarding background activity and epileptiform components were compared to two 20 minute sEEG extracted from the cEEG recording (one during TH, and one in early normothermia). RESULTS: In this cohort, 34 recordings were studied. During TH, the agreement between cEEG and sEEG was 97.1% (95% CI: 84.6 - 99.9%) for background discontinuity and reactivity evaluation, while it was 94.1% (95% CI 80.3 - 99.2%) regarding epileptiform activity. In early normothermia, we did not find any discrepancies. Thus, concordance was very good during TH (kappa 0.83), and optimal during normothermia (kappa=1). The median delay between CA and the first EEG reactivity testing was 18 hours (range: 4.75 - 25) for patients with perfect agreement and 10 hours (range: 5.75 - 10.5) for the three patients in whom there were discordant findings (P=0.02, Wilcoxon). CONCLUSION: Standard intermittent EEG has comparable performance than continuous EEG both for variables important for outcome prognostication (EEG reactivity) and identification of epileptiform transients in this relatively small sample of comatose survivors of CA. This finding has an important practical implication, especially for centers where EEG resources are limited.

Sudden cardiac death in athletes : the Lausanne recommendations

La mort subite d'origine cardiaque chez les sportifs : les Recommandations de Lausanne Résumé Objectifs : Cette étude collecte les données de la littérature scientifique concernant la mort subite d'origine cardiaque chez les sportifs et a pour but d'aboutir à un protocole d'investigation de préparticipation globalement acceptable, approuvé par la conférence de consensus du Comité International Olympique(CIO), et recommandé par ce dernier. Données cliniques : La mort subite chez les athlètes de moins de 35 ans, engagés dans des sports de compétition,. est un évènement bien connu, dont l'incidence est plus élevée (~2/100000/an) que chez les non-athlètes (2,5 :1). La cause est cardiovasculaire dans plus de 90% des cas. Méthodes : Une revue systématique de la littérature a mis en évidence les causes de mort subite d'origine cardiaque, le sexe, l'âge, les maladies cardiaques sous-jacentes et le type de sport, ainsi que les protocoles d'investigation de préparticipation utilisés. Les méthodes nécessaires pour détecter des anomalies cardiaques préexistantes sont discutées pour formuler un protocole d'investigation de préparticipation pour la commission médicale du CIO. (http://www.olympic.org/uk/organisation/commissions/medical/full_ story_ uk.asp?id=1182) Résultats: 1101 cas de mort subite d'origine cardiaque ont été rapportés (1966-2004) chez des athlètes de moins de 35 ans, 50% présentant des anomalies cardiaques congénitales et des cardiomyopathies et 10% une athérosclérose à début précoce. 40% des athlètes avaient moins de 18 ans, 33% moins de 16 ans ; le rapport femme/homme était de 1/9. La mort subite d'origine cardiaque était reportée dans presque tous les sports ; ceux impliqués le plus fréquemment étaient le football(30%), le basketball(25%), et la course à pied(15%). Les tests de préparticipation étaient de qualité et de contenu variables. La conférence de consensus du CIO a accepté les «Recommandations de Lausanne » proposées, basées sur cette recherche et des opinions d'experts. (http://multimedia.olympic.org/pdf/en_report_886.pdf) Conclusions : La mort subite d'origine cardiaque touche plus souvent qu'attendu les jeunes athlètes et est principalement due à des anomalies cardiaques congénitales préexistantes. Les atteintes athérosclérotiques précoces forment une autre cause importante de décès chez les jeunes adultes. L'acceptation par le CIO de «Recommandations de Lausanne » a permis d'aboutir à un protocole d'investigation de préparticipation globalement acceptable .

Prognostic value of continuous eeg monitoring during therapeutic hypothermia in patients with coma after cardiac arrest

INTRODUCTION: Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome. METHODS: From April 2009 to April 2010, we prospectively studied 34 consecutive comatose patients treated with TH after CA who were monitored with cEEG, initiated during hypothermia and maintained after rewarming. EEG background reactivity to painful stimulation was tested. We analyzed the association between cEEG findings and neurologic outcome, assessed at 2 months with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). RESULTS: Continuous EEG recording was started 12 ± 6 hours after CA and lasted 30 ± 11 hours. Nonreactive cEEG background (12 of 15 (75%) among nonsurvivors versus none of 19 (0) survivors; P < 0.001) and prolonged discontinuous "burst-suppression" activity (11 of 15 (73%) versus none of 19; P < 0.001) were significantly associated with mortality. EEG seizures with absent background reactivity also differed significantly (seven of 15 (47%) versus none of 12 (0); P = 0.001). In patients with nonreactive background or seizures/epileptiform discharges on cEEG, no improvement was seen after TH. Nonreactive cEEG background during TH had a positive predictive value of 100% (95% confidence interval (CI), 74 to 100%) and a false-positive rate of 0 (95% CI, 0 to 18%) for mortality. All survivors had cEEG background reactivity, and the majority of them (14 (74%) of 19) had a favorable outcome (CPC 1 or 2). CONCLUSIONS: Continuous EEG monitoring showing a nonreactive or discontinuous background during TH is strongly associated with unfavorable outcome in patients with coma after CA. These data warrant larger studies to confirm the value of continuous EEG monitoring in predicting prognosis after CA and TH.

Neurological Prognostication after Cardiac Arrest and Therapeutic Hypothermia: a Prospective Validation Study

Introduction: Clinical examination and electroencephalography study (EEG) have been recommended to predict functional recovery in comatose survivors of cardiac arrest (CA), however their prognostic value in patients treated with induced hypothermia (IH) has not been evaluated. Hypothesis: We aimed to validate the prognostic ability of clinical examination and EEG in predicting outcome of patients with coma after CA treated with IH and sought to derive a score with high predictive value for poor functional outcome in this setting. Methods: We prospectively studied 100 consecutive comatose survivors of CA treated with IH. Repeated neurological examination and EEG were performed early after passive rewarming and off sedation. Mortality was assessed at hospital discharge, and functional outcome at 3 to 6 months with Cerebral Performance Categories (CPC), and was dichotomized as good (CPC 1-2) vs. poor (CPC 3-5). Independent predictors of outcome were identified by multivariable logistic regression and used to assess the prognostic value of a Reproducible Electro-clinical Prognosticators of Outcome Score (REPOS). Results: Patients (20/100) with good outcome had all a reactive EEG background. Incomplete recovery of brainstem reflexes, myoclonus, time to return of spontaneous circulation (ROSC) > 25 min, and unreactive EEG background were all independent predictors of death and severe disability, and were added to construct the REPOS. Using a cut-off of 0 or 1 variables for good vs. 2 to 4 for poor outcome, the REPOS had a positive predictive value of 1.00 (95% CI: 0.92-1.00), a negative predictive value of 0.43 (95% CI: 0.29-0.58) and an accuracy of 0.81 for poor functional recovery at 3 to 6 months. Conclusions: In comatose survivors of CA treated with IH, a prognostic score, including clinical and EEG examination, was highly predictive of death and poor functional outcome at 3 to 6 months. Lack of EEG background reactivity strongly predicted poor neurological recovery after CA. Our findings show that clinical and electrophysiological studies are effective in predicting long-term outcome of comatose survivors after CA and IH, and suggest that EEG improves early prognostic assessment in the setting of therapeutic cooling.

Outcome Prediction after Cardiac Arrest Treated with Hypothermia

Rationale: Clinical and electrophysiological prognostic markers of brain anoxia have been mostly evaluated in comatose survivors of out hospital cardiac arrest (OHCA) after standard resuscitation, but their predictive value in patients treated with mild induced hypothermia (IH) is unknown. The objective of this study was to identify a predictive score of independent clinical and electrophysiological variables in comatose OHCA survivors treated with IH, aiming at a maximal positive predictive value (PPV) and a high negative predictive value (NPV) for mortality. Methods: We prospectively studied consecutive adult comatose OHCA survivors from April 2006 to May 2009, treated with mild IH to 33-34_C for 24h at the intensive care unit of the Lausanne University Hospital, Switzerland. IH was applied using an external cooling method. As soon as subjects passively rewarmed (body temperature >35_C) they underwent EEG and SSEP recordings (off sedation), and were examined by experienced neurologists at least twice. Patients with status epilepticus were treated with AED for at least 24h. A multivariable logistic regression was performed to identify independent predictors of mortality at hospital discharge. These were used to formulate a predictive score. Results: 100 patients were studied; 61 died. Age, gender and OHCA etiology (cardiac vs. non-cardiac) did not differ among survivors and nonsurvivors. Cardiac arrest type (non-ventricular fibrillation vs. ventricular fibrillation), time to return of spontaneous circulation (ROSC) >25min, failure to recover all brainstem reflexes, extensor or no motor response to pain, myoclonus, presence of epileptiform discharges on EEG, EEG background unreactive to pain, and bilaterally absent N20 on SSEP, were all significantly associated with mortality. Absent N20 was the only variable showing no false positive results. Multivariable logistic regression identified four independent predictors (Table). These were used to construct the score, and its predictive values were calculated after a cut-off of 0-1 vs. 2-4 predictors. We found a PPV of 1.00 (95% CI: 0.93-1.00), a NPV of 0.81 (95% CI: 0.67-0.91) and an accuracy of 0.93 for mortality. Among 9 patients who were predicted to survive by the score but eventually died, only 1 had absent N20. Conclusions: Pending validation in a larger cohort, this simple score represents a promising tool to identify patients who will survive, and most subjects who will not, after OHCA and IH. Furthermore, while SSEP are 100% predictive of poor outcome but not available in most hospitals, this study identifies EEG background reactivity as an important predictor after OHCA. The score appears robust even without SSEP, suggesting that SSEP and other investigations (e.g., mismatch negativity, serum NSE) might be principally needed to enhance prognostication in the small subgroup of patients failing to improve despite a favorable score.

Prognostic value of continuous EEG monitoring during therapeutic hypothermia after cardiac arrest.

Introduction: Continuous EEG (cEEG) is increasingly used to monitor brain function in neuro-ICU patients. However, its value in patients with coma after cardiac arrest (CA), particularly in the setting of therapeutic hypothermia (TH), is only beginning to be elucidated. The aim of this study was to examine whether cEEG performed during TH may predict outcome. Methods: From April 2009 to April 2010, we prospectively studied 34 consecutive comatose patients treated with TH after CA who were monitored with cEEG, initiated during hypothermia and maintained after rewarming. EEG background reactivity to painful stimulation was tested. We analyzed the association between cEEG findings and neurologic outcome, assessed at 2 months with the Glasgow-Pittsburgh Cerebral Performance Categories (CPC). Results: Continuous EEG recording was started 12 ± 6 hours after CA and lasted 30 ± 11 hours. Nonreactive cEEG background (12 of 15 (75%) among nonsurvivors versus none of 19 (0) survivors; P < 0.001) and prolonged discontinuous "burst-suppression" activity (11 of 15 (73%) versus none of 19; P < 0.001) were significantly associated with mortality. EEG seizures with absent background reactivity also differed significantly (seven of 15 (47%) versus none of 12 (0); P = 0.001). In patients with nonreactive background or seizures/epileptiform discharges on cEEG, no improvement was seen after TH. Nonreactive cEEG background during TH had a positive predictive value of 100% (95% confidence interval (CI), 74 to 100%) and a false-positive rate of 0 (95% CI, 0 to 18%) for mortality. All survivors had cEEG background reactivity, and the majority of them (14 (74%) of 19) had a favorable outcome (CPC 1 or 2). Conclusions: Continuous EEG monitoring showing a nonreactive or discontinuous background during TH is strongly associated with unfavorable outcome in patients with coma after CA. These data warrant larger studies to confirm the value of continuous EEG monitoring in predicting prognosis after CA and TH.

Contemporary approach to neurologic prognostication of coma after cardiac arrest.

Coma after cardiac arrest (CA) is an important cause of admission to the ICU. Prognosis of post-CA coma has significantly improved over the past decade, particularly because of aggressive postresuscitation care and the use of therapeutic targeted temperature management (TTM). TTM and sedatives used to maintain controlled cooling might delay neurologic reflexes and reduce the accuracy of clinical examination. In the early ICU phase, patients' good recovery may often be indistinguishable (based on neurologic examination alone) from patients who eventually will have a poor prognosis. Prognostication of post-CA coma, therefore, has evolved toward a multimodal approach that combines neurologic examination with EEG and evoked potentials. Blood biomarkers (eg, neuron-specific enolase [NSE] and soluble 100-β protein) are useful complements for coma prognostication; however, results vary among commercial laboratory assays, and applying one single cutoff level (eg, > 33 μg/L for NSE) for poor prognostication is not recommended. Neuroimaging, mainly diffusion MRI, is emerging as a promising tool for prognostication, but its precise role needs further study before it can be widely used. This multimodal approach might reduce false-positive rates of poor prognosis, thereby providing optimal prognostication of comatose CA survivors. The aim of this review is to summarize studies and the principal tools presently available for outcome prediction and to describe a practical approach to the multimodal prognostication of coma after CA, with a particular focus on neuromonitoring tools. We also propose an algorithm for the optimal use of such multimodal tools during the early ICU phase of post-CA coma.

Prognostication in comatose survivors of cardiac arrest: An advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine.

OBJECTIVES: To review and update the evidence on predictors of poor outcome (death, persistent vegetative state or severe neurological disability) in adult comatose survivors of cardiac arrest, either treated or not treated with controlled temperature, to identify knowledge gaps and to suggest a reliable prognostication strategy. METHODS: GRADE-based systematic review followed by expert consensus achieved using Web-based Delphi methodology, conference calls and face-to-face meetings. Predictors based on clinical examination, electrophysiology, biomarkers and imaging were included. RESULTS AND CONCLUSIONS: Evidence from a total of 73 studies was reviewed. The quality of evidence was low or very low for almost all studies. In patients who are comatose with absent or extensor motor response at ?72h from arrest, either treated or not treated with controlled temperature, bilateral absence of either pupillary and corneal reflexes or N20 wave of short-latency somatosensory evoked potentials were identified as the most robust predictors. Early status myoclonus, elevated values of neuron specific enolase at 48-72h from arrest, unreactive malignant EEG patterns after rewarming, and presence of diffuse signs of postanoxic injury on either computed tomography or magnetic resonance imaging were identified as useful but less robust predictors. Prolonged observation and repeated assessments should be considered when results of initial assessment are inconclusive. Although no specific combination of predictors is sufficiently supported by available evidence, a multimodal prognostication approach is recommended in all patients.

From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest.

OBJECTIVES: Therapeutic hypothermia has been recommended for postcardiac arrest coma due to ventricular fibrillation. However, no studies have evaluated whether therapeutic hypothermia could be effectively implemented in intensive care practice and whether it would improve the outcome of all comatose patients with cardiac arrest, including those with shock or with cardiac arrest due to nonventricular fibrillation rhythms. DESIGN: Retrospective study. SETTING: Fourteen-bed medical intensive care unit in a university hospital. PATIENTS: Patients were 109 comatose patients with out-of-hospital cardiac arrest due to ventricular fibrillation and nonventricular fibrillation rhythms (asystole/pulseless electrical activity). INTERVENTIONS: We analyzed 55 consecutive patients (June 2002 to December 2004) treated with therapeutic hypothermia (to a central target temperature of 33 degrees C, using external cooling). Fifty-four consecutive patients (June 1999 to May 2002) treated with standard resuscitation served as controls. Efficacy, safety, and outcome at hospital discharge were assessed. Good outcome was defined as Glasgow-Pittsburgh Cerebral Performance category 1 or 2. MEASUREMENTS AND MAIN RESULTS: In patients treated with therapeutic hypothermia, the median time to reach the target temperature was 5 hrs, with a progressive reduction over the 18 months of data collection. Therapeutic hypothermia had a major positive impact on the outcome of patients with cardiac arrest due to ventricular fibrillation (good outcome in 24 of 43 patients [55.8%] of the therapeutic hypothermia group vs. 11 of 43 patients [25.6%] of the standard resuscitation group, p = .004). The benefit of therapeutic hypothermia was also maintained in patients with shock (good outcome in five of 17 patients of the therapeutic hypothermia group vs. zero of 14 of the standard resuscitation group, p = .027). The outcome after cardiac arrest due to nonventricular fibrillation rhythms was poor and did not differ significantly between the two groups. Therapeutic hypothermia was of particular benefit in patients with short duration of cardiac arrest (<30 mins). CONCLUSIONS: Therapeutic hypothermia for the treatment of postcardiac arrest coma can be successfully implemented in intensive care practice with a major benefit on patient outcome, which appeared to be related to the type and the duration of initial cardiac arrest and seemed maintained in patients with shock.

Cardiovascular Pathology. 004. Pathomorphological and CT-angiographical characteristics of coronary atherosclerotic plaques in cases of sudden cardiac death

Objective. The goal of this study was to present the pathological and radiological patterns of "vulnerable" atherosclerotic plaques in cases of sudden cardiac death. Method. This retrospective study was performed on forensic cases for which the cause of death was attributed to coronary artery disease. A complete autopsy was performed in all cases, along with either post-mortem CT-angiography, toxicological analyses and/or biochemistry. Results. 89 cases were selected (mean age 55±11.6 years; 75 men and 14 women). In 96.6% of cases a CT-angiography was performed. Acute coronary lesions were found in 60 cases (mean age 53±11.1 years), which included plaque erosion in 26 cases (mean age 47±8.3 years) and ruptures or intraplaque hemorrhage in 33 cases (mean age 58±10.4 years). Erosions were most frequently found in the left ascending artery (61.5 %), while only 36% of ruptures were observed in this artery. Chronic coronary pathology was described in 30 cases (mean age 58±10.4 years). CT-angiographies performed prior to the autopsy enabled an initial evaluation of coronary artery perfusion. Conclusion. In the face of decreasing clinical autopsy rates, postmortem studies on forensic autopsies, including modern radiological examinations, allow for a more thorough understanding of the clinical picture of disease which can result in sudden cardiac death.