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

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          Abstract

          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.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s00134-014-3470-x) contains supplementary material, which is available to authorized users.

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          Most cited references88

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          Primary outcomes for resuscitation science studies: a consensus statement from the American Heart Association.

          The guidelines presented in this consensus statement are intended to serve researchers, clinicians, reviewers, and regulators in the selection of the most appropriate primary outcome for a clinical trial of cardiac arrest therapies. The American Heart Association guidelines for the treatment of cardiac arrest depend on high-quality clinical trials, which depend on the selection of a meaningful primary outcome. Because this selection process has been the subject of much controversy, a consensus conference was convened with national and international experts, the National Institutes of Health, and the US Food and Drug Administration. The Research Working Group of the American Heart Association Emergency Cardiovascular Care Committee nominated subject leaders, conference attendees, and writing group members on the basis of their expertise in clinical trials and a diverse perspective of cardiovascular and neurological outcomes (see the online-only Data Supplement). Approval was obtained from the Emergency Cardiovascular Care Committee and the American Heart Association Manuscript Oversight Committee. Preconference position papers were circulated for review; the conference was held; and postconference consensus documents were circulated for review and comments were invited from experts, conference attendees, and writing group members. Discussions focused on (1) when after cardiac arrest the measurement time point should occur; (2) what cardiovascular, neurological, and other physiology should be assessed; and (3) the costs associated with various end points. The final document underwent extensive revision and peer review by the Emergency Cardiovascular Care Committee, the American Heart Association Science Advisory and Coordinating Committee, and oversight committees. There was consensus that no single primary outcome is appropriate for all studies of cardiac arrest. The best outcome measure is the pairing of a time point and physiological condition that will best answer the question under study. Conference participants were asked to assign an outcome to each of 4 hypothetical cases; however, there was not complete agreement on an ideal outcome measure even after extensive discussion and debate. There was general consensus that it is appropriate for earlier studies to enroll fewer patients and to use earlier time points such as return of spontaneous circulation, simple "alive versus dead," hospital mortality, or a hemodynamic parameter. For larger studies, a longer time point after arrest should be considered because neurological assessments fluctuate for at least 90 days after arrest. For large trials designed to have a major impact on public health policy, longer-term end points such as 90 days coupled with neurocognitive and quality-of-life assessments should be considered, as should the additional costs of this approach. For studies that will require regulatory oversight, early discussions with regulatory agencies are strongly advised. For neurological assessment of post-cardiac arrest patients, researchers may wish to use the Cerebral Performance Categories or modified Rankin Scale for global outcomes. Although there is no single recommended outcome measure for trials of cardiac arrest care, the simple Cerebral Performance Categories or modified Rankin Scale after 90 days provides a reasonable outcome parameter for many trials. The lack of an easy-to-administer neurological functional outcome measure that is well validated in post-cardiac arrest patients is a major limitation to the field and should be a high priority for future development.
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            Sedation confounds outcome prediction in cardiac arrest survivors treated with hypothermia.

            Therapeutic hypothermia is commonly used in comatose survivors' post-cardiopulmonary resuscitation (CPR). It is unknown whether outcome predictors perform accurately after hypothermia treatment. Post-CPR comatose survivors were prospectively enrolled. Six outcome predictors [pupillary and corneal reflexes, motor response to pain, and somatosensory-evoked potentials (SSEP) >72 h; status myoclonus, and serum neuron-specific enolase (NSE) levels 72 h, and absent pupillary reflexes >72 h predicted poor outcome with a 100% specificity both in hypothermia and normothermia patients. In contrast, absent corneal reflexes >72 h, motor response extensor or absent >72 h, and peak NSE >33 ng/ml <72 h predicted poor outcome with 100% specificity only in non-sedated patients, irrespective of prior treatment with hypothermia. Sedative medications are commonly used in proximity of the 72-h neurological examination in comatose CPR survivors and are an important prognostication confounder. Patients treated with hypothermia are more likely to receive sedation than those who are not treated with hypothermia.
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              Neurological examination of critically ill patients: a pragmatic approach. Report of an ESICM expert panel.

              Many patients admitted to the intensive care unit (ICU) have pre-existing or acquired neurological disorders which significantly affect their short-term and long-term outcomes. The ESICM Neuro Intensive Care Section convened an expert panel to establish a pragmatic approach to neurological examination (NE) of the critically ill patient.
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                Author and article information

                Contributors
                sandroni@rm.unicatt.it
                Journal
                Intensive Care Med
                Intensive Care Med
                Intensive Care Medicine
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0342-4642
                1432-1238
                15 November 2014
                15 November 2014
                2014
                : 40
                : 12
                : 1816-1831
                Affiliations
                [ ]Department of Anaesthesiology and Intensive Care, Catholic University School of Medicine, Largo Gemelli 8, 00168 Rome, Italy
                [ ]Medical ICU, Cochin Hospital (APHP), Paris Descartes University, Paris, France
                [ ] Department of Clinical Sciences, Division of Neurology, Lund University, Lund, Sweden
                [ ]Anaesthesiology and Intensive Care Medicine, Skåne University Hospital, Lund University, Lund, Sweden
                [ ]Intensive Care, Radboud University, Nijmegen Medical Centre, Nijmegen, The Netherlands
                [ ]Intensive Care, Academic Medical Center, Amsterdam, The Netherlands
                [ ]Department of Anaesthesia and Intensive Care Medicine, Royal United Hospital, Bath, UK
                [ ]Department of Clinical Neurosciences, CHUV and University of Lausanne, Lausanne, Switzerland
                [ ]Department of Anaesthesia and Intensive Care Medicine, Southmead Hospital, Bristol, UK
                Article
                3470
                10.1007/s00134-014-3470-x
                4239787
                25398304
                9bddd8d9-797a-4594-8c53-0884621a5b5b
                © The Author(s) 2014

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution NonCommercial NoDerivatives 4.0 International License which permits re-use and distribution of the article (in whole or in part) for non-commercial purposes in any medium or format provided that inter alia the original author(s) and the source are credited. The license does neither allow the use of the article for commercial purposes (for example the distribution of the article via commercial channels) nor the distribution of modified versions of the article.

                History
                : 20 August 2014
                : 22 August 2014
                Categories
                Conference Reports and Expert Panel
                Custom metadata
                © Springer-Verlag Berlin Heidelberg and ESICM 2014

                Emergency medicine & Trauma
                heart arrest,coma,prognosis,clinical examination,somatosensory evoked potentials,neuron specific enolase,ct scan,magnetic resonance

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