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      Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review

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          Abstract

          Purpose

          To assess the ability of clinical examination, blood biomarkers, electrophysiology, or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict poor neurological outcome, defined as death, vegetative state, or severe disability (CPC 3–5) at hospital discharge/1 month or later, in comatose adult survivors from cardiac arrest (CA).

          Methods

          PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews (January 2013–April 2020) were searched. Sensitivity and false-positive rate (FPR) for each predictor were calculated. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed.

          Results

          Ninety-four studies (30,200 patients) were included. Bilaterally absent pupillary or corneal reflexes after day 4 from ROSC, high blood values of neuron-specific enolase from 24 h after ROSC, absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) or unequivocal seizures on electroencephalogram (EEG) from the day of ROSC, EEG background suppression or burst-suppression from 24 h after ROSC, diffuse cerebral oedema on brain CT from 2 h after ROSC, or reduced diffusion on brain MRI at 2–5 days after ROSC had 0% FPR for poor outcome in most studies. Risk of bias assessed using the QUIPS tool was high for all predictors.

          Conclusion

          In comatose resuscitated patients, clinical, biochemical, neurophysiological, and radiological tests have a potential to predict poor neurological outcome with no false-positive predictions within the first week after CA. Guidelines should consider the methodological concerns and limited sensitivity for individual modalities. (PROSPERO CRD42019141169)

          Electronic supplementary material

          The online version of this article (10.1007/s00134-020-06198-w) contains supplementary material, which is available to authorized users.

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          Most cited references171

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          Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies

          Systematic reviews of diagnostic test accuracy synthesize data from primary diagnostic studies that have evaluated the accuracy of 1 or more index tests against a reference standard, provide estimates of test performance, allow comparisons of the accuracy of different tests, and facilitate the identification of sources of variability in test accuracy.
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            Assessing bias in studies of prognostic factors.

            Previous work has identified 6 important areas to consider when evaluating validity and bias in studies of prognostic factors: participation, attrition, prognostic factor measurement, confounding measurement and account, outcome measurement, and analysis and reporting. This article describes the Quality In Prognosis Studies tool, which includes questions related to these areas that can inform judgments of risk of bias in prognostic research.A working group comprising epidemiologists, statisticians, and clinicians developed the tool as they considered prognosis studies of low back pain. Forty-three groups reviewing studies addressing prognosis in other topic areas used the tool and provided feedback. Most reviewers (74%) reported that reaching consensus on judgments was easy. Median completion time per study was 20 minutes; interrater agreement (κ statistic) reported by 9 review teams varied from 0.56 to 0.82 (median, 0.75). Some reviewers reported challenges making judgments across prompting items, which were addressed by providing comprehensive guidance and examples. The refined Quality In Prognosis Studies tool may be useful to assess the risk of bias in studies of prognostic factors.
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              Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

              Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.).
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                Author and article information

                Contributors
                sonia.darrigo@policlinicogemelli.it
                Journal
                Intensive Care Med
                Intensive Care Med
                Intensive Care Medicine
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0342-4642
                1432-1238
                11 September 2020
                11 September 2020
                2020
                : 46
                : 10
                : 1803-1851
                Affiliations
                [1 ]GRID grid.411075.6, ISNI 0000 0004 1760 4193, Department of Intensive Care, Emergency Medicine and Anesthesiology, , Fondazione Policlinico Universitario “Agostino Gemelli”- IRCCS, ; Largo Francesco Vito, 1, 00168 Rome, Italy
                [2 ]GRID grid.8142.f, ISNI 0000 0001 0941 3192, Institute of Anesthesiology and Intensive Care Medicine, , Università Cattolica del Sacro Cuore, ; Rome, Italy
                [3 ]GRID grid.10417.33, ISNI 0000 0004 0444 9382, Department of Intensive Care, , Radboud University Nijmegen Medical Centre, ; Nijmegen, The Netherlands
                [4 ]GRID grid.413532.2, ISNI 0000 0004 0398 8384, Intensive Care Catharina Hospital Eindhoven, ; Eindhoven, The Netherlands
                [5 ]GRID grid.9851.5, ISNI 0000 0001 2165 4204, Department of Intensive Care Medicine, , University Hospital and University of Lausanne, ; Lausanne, Switzerland
                [6 ]GRID grid.4989.c, ISNI 0000 0001 2348 0746, Department of Intensive Care, Erasme Hospital, , Université Libre de Bruxelles, ; Brussels, Belgium
                [7 ]GRID grid.7841.a, Department of Public Health and Infectious Disease, , Sapienza University, ; Rome, Italy
                [8 ]GRID grid.10417.33, ISNI 0000 0004 0444 9382, Department of Radiology and Nuclear Medicine, , Radboud University Nijmegen Medical Center, ; Nijmegen, The Netherlands
                [9 ]Department of ClinicalSciences, Clinical Neurophysiology, Lund University, Skane University Hospital, Lund, Sweden
                [10 ]GRID grid.418484.5, ISNI 0000 0004 0380 7221, Critical Care Unit, Southmead Hospital, , North Bristol NHS Trust, ; Bristol, UK
                [11 ]GRID grid.416091.b, ISNI 0000 0004 0417 0728, Department of Anaesthesia and Intensive Care Medicine, , Royal United Hospital, ; Bath, UK
                [12 ]Department of Clinical Sciences Lund, Neurology, Lund University, Skane University Hospital, Lund, Sweden
                Author information
                http://orcid.org/0000-0001-6740-3195
                Article
                6198
                10.1007/s00134-020-06198-w
                7527362
                32915254
                95b84f65-91b0-443a-a0a5-4fcc57f5fc2e
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 29 April 2020
                : 15 July 2020
                Categories
                Systematic Review
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                Emergency medicine & Trauma
                cardiac arrest,coma,prognosis,clinical examination,somatosensory-evoked potentials,neuron-specific enolase,computed tomography,diffusion magnetic resonance imaging

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