Neuromarkers and neurological outcome in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia-experience from the HAnnover COoling REgistry (HACORE)
Neuron-specific enolase (NSE) and S-100b have been used to assess neurological damage following out-of-hospital cardiac arrest (OHCA). Cut-offs were derived from small normothermic cohorts. Whether similar cut-offs apply to patients treated with hypothermia remained undetermined. We investigated 251...
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| creator | Akin, Muharrem Garcheva, Vera Sieweke, Jan-Thorben Adel, John Flierl, Ulrike Bauersachs, Johann Schäfer, Andreas |
| description | Neuron-specific enolase (NSE) and S-100b have been used to assess neurological damage following out-of-hospital cardiac arrest (OHCA). Cut-offs were derived from small normothermic cohorts. Whether similar cut-offs apply to patients treated with hypothermia remained undetermined.
We investigated 251 patients with OHCA treated with hypothermia but without routine prognostication. Neuromarkers were determined at day 3, neurological outcome was assessed after hospital discharge by cerebral performance category (CPC).
Good neurological outcome (CPC≤2) was achieved in 41%. Elevated neuromarkers, older age and absence of ST-segment elevation after ROSC were associated with increased mortality. Poor neurological outcome in survivors was additionally associated with history of cerebrovascular events, sepsis and higher admission lactate. Mean NSE was 33μg/l [16-94] vs. 119μg/l [25-406]; p |
| doi_str_mv | 10.1371/journal.pone.0245210 |
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We investigated 251 patients with OHCA treated with hypothermia but without routine prognostication. Neuromarkers were determined at day 3, neurological outcome was assessed after hospital discharge by cerebral performance category (CPC).
Good neurological outcome (CPC≤2) was achieved in 41%. Elevated neuromarkers, older age and absence of ST-segment elevation after ROSC were associated with increased mortality. Poor neurological outcome in survivors was additionally associated with history of cerebrovascular events, sepsis and higher admission lactate. Mean NSE was 33μg/l [16-94] vs. 119μg/l [25-406]; p<0.001, for survivors vs. non-survivors, and 21μg/l [16-29] vs. 40μg/l [23-98], p<0.001 for good vs. poor neurological outcome. S-100b was 0.127μg/l [0.063-0.360] vs. 0.772μg/l [0.121-2.710], p<0.001 and 0.086μg/l [0.061-0.122] vs. 0.138μg/l [0.090-0.271], p = 0.009, respectively. For mortality, thresholds of 36μg/l for NSE and 0.128μg/l for S-100b could be determined; for poor neurological outcome 33μg/l (NSE) and 0.123μg/l (S-100b), respectively. Positive predictive value for NSE was 81% (74-88) and 79% (71-85) for S-100b.
Thresholds for NSE and S-100b predicting mortality and poor neurological outcome are similar in OHCA patients receiving therapeutic hypothermia as in those reported before the era of hypothermia. However, both biomarkers do not have enough specificity to predict mortality or poor neurological outcome on their own and should only be additively used in clinical decision making.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0245210</identifier><identifier>PMID: 33411836</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Aged ; Biology and Life Sciences ; Biomarkers ; Biomarkers - blood ; Cardiac arrest ; Cardiology ; Care and treatment ; Clinical decision making ; Cooling ; Damage assessment ; Decision making ; Disease-Free Survival ; Emergency medical care ; Ethics ; Female ; Follow-Up Studies ; Heart ; Humans ; Hypothermia ; Hypothermia, Induced ; Intensive care ; Lactic acid ; Male ; Medical schools ; Medicine and Health Sciences ; Middle Aged ; Mortality ; Nervous system diseases ; Nervous System Diseases - blood ; Nervous System Diseases - mortality ; Out-of-Hospital Cardiac Arrest - blood ; Out-of-Hospital Cardiac Arrest - mortality ; Out-of-Hospital Cardiac Arrest - therapy ; Patient outcomes ; Patients ; Phosphopyruvate hydratase ; Phosphopyruvate Hydratase - blood ; Physical Sciences ; Prospective Studies ; Registries ; Regression analysis ; Rehabilitation ; Research and Analysis Methods ; Risk factors ; S100 Calcium Binding Protein beta Subunit - blood ; S100b protein ; Sepsis ; Survival ; Survival Rate ; Thresholds</subject><ispartof>PloS one, 2021-01, Vol.16 (1), p.e0245210-e0245210</ispartof><rights>COPYRIGHT 2021 Public Library of Science</rights><rights>2021 Akin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 Akin et al 2021 Akin et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-bb179fff44297ed6e3bf09b79637024fb87c0fc039009f2dfa947d1c3b8745243</citedby><cites>FETCH-LOGICAL-c692t-bb179fff44297ed6e3bf09b79637024fb87c0fc039009f2dfa947d1c3b8745243</cites><orcidid>0000-0002-0936-8755</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790428/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790428/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2101,2927,23865,27923,27924,53790,53792,79471,79472</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33411836$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Brunner-La Rocca, Hans-Peter</contributor><creatorcontrib>Akin, Muharrem</creatorcontrib><creatorcontrib>Garcheva, Vera</creatorcontrib><creatorcontrib>Sieweke, Jan-Thorben</creatorcontrib><creatorcontrib>Adel, John</creatorcontrib><creatorcontrib>Flierl, Ulrike</creatorcontrib><creatorcontrib>Bauersachs, Johann</creatorcontrib><creatorcontrib>Schäfer, Andreas</creatorcontrib><title>Neuromarkers and neurological outcome in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia-experience from the HAnnover COoling REgistry (HACORE)</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Neuron-specific enolase (NSE) and S-100b have been used to assess neurological damage following out-of-hospital cardiac arrest (OHCA). Cut-offs were derived from small normothermic cohorts. Whether similar cut-offs apply to patients treated with hypothermia remained undetermined.
We investigated 251 patients with OHCA treated with hypothermia but without routine prognostication. Neuromarkers were determined at day 3, neurological outcome was assessed after hospital discharge by cerebral performance category (CPC).
Good neurological outcome (CPC≤2) was achieved in 41%. Elevated neuromarkers, older age and absence of ST-segment elevation after ROSC were associated with increased mortality. Poor neurological outcome in survivors was additionally associated with history of cerebrovascular events, sepsis and higher admission lactate. Mean NSE was 33μg/l [16-94] vs. 119μg/l [25-406]; p<0.001, for survivors vs. non-survivors, and 21μg/l [16-29] vs. 40μg/l [23-98], p<0.001 for good vs. poor neurological outcome. S-100b was 0.127μg/l [0.063-0.360] vs. 0.772μg/l [0.121-2.710], p<0.001 and 0.086μg/l [0.061-0.122] vs. 0.138μg/l [0.090-0.271], p = 0.009, respectively. For mortality, thresholds of 36μg/l for NSE and 0.128μg/l for S-100b could be determined; for poor neurological outcome 33μg/l (NSE) and 0.123μg/l (S-100b), respectively. Positive predictive value for NSE was 81% (74-88) and 79% (71-85) for S-100b.
Thresholds for NSE and S-100b predicting mortality and poor neurological outcome are similar in OHCA patients receiving therapeutic hypothermia as in those reported before the era of hypothermia. However, both biomarkers do not have enough specificity to predict mortality or poor neurological outcome on their own and should only be additively used in clinical decision making.</description><subject>Aged</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Cardiac arrest</subject><subject>Cardiology</subject><subject>Care and treatment</subject><subject>Clinical decision making</subject><subject>Cooling</subject><subject>Damage assessment</subject><subject>Decision making</subject><subject>Disease-Free Survival</subject><subject>Emergency medical care</subject><subject>Ethics</subject><subject>Female</subject><subject>Follow-Up Studies</subject><subject>Heart</subject><subject>Humans</subject><subject>Hypothermia</subject><subject>Hypothermia, Induced</subject><subject>Intensive care</subject><subject>Lactic acid</subject><subject>Male</subject><subject>Medical schools</subject><subject>Medicine and Health Sciences</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Nervous system diseases</subject><subject>Nervous System Diseases - blood</subject><subject>Nervous System Diseases - mortality</subject><subject>Out-of-Hospital Cardiac Arrest - blood</subject><subject>Out-of-Hospital Cardiac Arrest - mortality</subject><subject>Out-of-Hospital Cardiac Arrest - therapy</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Phosphopyruvate hydratase</subject><subject>Phosphopyruvate Hydratase - blood</subject><subject>Physical Sciences</subject><subject>Prospective Studies</subject><subject>Registries</subject><subject>Regression analysis</subject><subject>Rehabilitation</subject><subject>Research and Analysis Methods</subject><subject>Risk factors</subject><subject>S100 Calcium Binding Protein beta Subunit - blood</subject><subject>S100b protein</subject><subject>Sepsis</subject><subject>Survival</subject><subject>Survival Rate</subject><subject>Thresholds</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk89u1DAQxiMEolB4AwSWkFB7yOLYSRxfkFarQitVrFT-XC3HGScu2TjYTmnfiYfEYbdVF_WAcogz_s03mc-eJHmV4UVGWfb-0k5ukP1itAMsMMkLkuFHybOMU5KWBNPH99YHyXPvLzEuaFWWT5MDSvMsq2j5LPn9GSZnN9L9AOeRHBo0zIHetkbJHtkpKLsBZIZ5mVqddtaPJsQtJV1jpELSOfABjTIYGIJHwYEM0KBfJnQodODkCFMwCnU3o52_N0amcD2Ci7wCpGP5mUOny2GwV-DQam17M7To4qQ1PrgbdHS6XK0vTo5fJE-07D283L0Pk28fT76uTtPz9aez1fI8VSUnIa3rjHGtdZ4TzqApgdYa85rxkrJolK4rprBWmHKMuSaNljxnTaZo3Ig25vQwebPVHXvrxc5oL0jOSpLxgs7E2ZZorLwUozPRwRthpRF_A9a1QrrYdA-ClYxhKEsoFMllwetYmVeaUEbqkuUQtT7sqk31BhoVXXSy3xPd3xlMJ1p7JRjjOCdVFDjaCTj7c4qHITbGK-h7OYCdtv9dlFVGSETf_oM-3N2OamVswAzaxrpqFhXLssBVVmA-U4sHqPg0sDEq3kptYnwv4XgvITIBrkMrJ-_F2ZeL_2fX3_fZd_fYDmQfOm_7eOns4PfBfAsqZ713oO9MzrCYh-rWDTEPldgNVUx7ff-A7pJup4j-AdrQHww</recordid><startdate>20210107</startdate><enddate>20210107</enddate><creator>Akin, Muharrem</creator><creator>Garcheva, Vera</creator><creator>Sieweke, Jan-Thorben</creator><creator>Adel, John</creator><creator>Flierl, Ulrike</creator><creator>Bauersachs, Johann</creator><creator>Schäfer, Andreas</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-0936-8755</orcidid></search><sort><creationdate>20210107</creationdate><title>Neuromarkers and neurological outcome in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia-experience from the HAnnover COoling REgistry (HACORE)</title><author>Akin, Muharrem ; Garcheva, Vera ; Sieweke, Jan-Thorben ; Adel, John ; Flierl, Ulrike ; Bauersachs, Johann ; Schäfer, Andreas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-bb179fff44297ed6e3bf09b79637024fb87c0fc039009f2dfa947d1c3b8745243</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aged</topic><topic>Biology and Life Sciences</topic><topic>Biomarkers</topic><topic>Biomarkers - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Akin, Muharrem</au><au>Garcheva, Vera</au><au>Sieweke, Jan-Thorben</au><au>Adel, John</au><au>Flierl, Ulrike</au><au>Bauersachs, Johann</au><au>Schäfer, Andreas</au><au>Brunner-La Rocca, Hans-Peter</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuromarkers and neurological outcome in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia-experience from the HAnnover COoling REgistry (HACORE)</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2021-01-07</date><risdate>2021</risdate><volume>16</volume><issue>1</issue><spage>e0245210</spage><epage>e0245210</epage><pages>e0245210-e0245210</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Neuron-specific enolase (NSE) and S-100b have been used to assess neurological damage following out-of-hospital cardiac arrest (OHCA). Cut-offs were derived from small normothermic cohorts. Whether similar cut-offs apply to patients treated with hypothermia remained undetermined.
We investigated 251 patients with OHCA treated with hypothermia but without routine prognostication. Neuromarkers were determined at day 3, neurological outcome was assessed after hospital discharge by cerebral performance category (CPC).
Good neurological outcome (CPC≤2) was achieved in 41%. Elevated neuromarkers, older age and absence of ST-segment elevation after ROSC were associated with increased mortality. Poor neurological outcome in survivors was additionally associated with history of cerebrovascular events, sepsis and higher admission lactate. Mean NSE was 33μg/l [16-94] vs. 119μg/l [25-406]; p<0.001, for survivors vs. non-survivors, and 21μg/l [16-29] vs. 40μg/l [23-98], p<0.001 for good vs. poor neurological outcome. S-100b was 0.127μg/l [0.063-0.360] vs. 0.772μg/l [0.121-2.710], p<0.001 and 0.086μg/l [0.061-0.122] vs. 0.138μg/l [0.090-0.271], p = 0.009, respectively. For mortality, thresholds of 36μg/l for NSE and 0.128μg/l for S-100b could be determined; for poor neurological outcome 33μg/l (NSE) and 0.123μg/l (S-100b), respectively. Positive predictive value for NSE was 81% (74-88) and 79% (71-85) for S-100b.
Thresholds for NSE and S-100b predicting mortality and poor neurological outcome are similar in OHCA patients receiving therapeutic hypothermia as in those reported before the era of hypothermia. However, both biomarkers do not have enough specificity to predict mortality or poor neurological outcome on their own and should only be additively used in clinical decision making.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33411836</pmid><doi>10.1371/journal.pone.0245210</doi><tpages>e0245210</tpages><orcidid>https://orcid.org/0000-0002-0936-8755</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2021-01, Vol.16 (1), p.e0245210-e0245210 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_2476219534 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Aged Biology and Life Sciences Biomarkers Biomarkers - blood Cardiac arrest Cardiology Care and treatment Clinical decision making Cooling Damage assessment Decision making Disease-Free Survival Emergency medical care Ethics Female Follow-Up Studies Heart Humans Hypothermia Hypothermia, Induced Intensive care Lactic acid Male Medical schools Medicine and Health Sciences Middle Aged Mortality Nervous system diseases Nervous System Diseases - blood Nervous System Diseases - mortality Out-of-Hospital Cardiac Arrest - blood Out-of-Hospital Cardiac Arrest - mortality Out-of-Hospital Cardiac Arrest - therapy Patient outcomes Patients Phosphopyruvate hydratase Phosphopyruvate Hydratase - blood Physical Sciences Prospective Studies Registries Regression analysis Rehabilitation Research and Analysis Methods Risk factors S100 Calcium Binding Protein beta Subunit - blood S100b protein Sepsis Survival Survival Rate Thresholds |
| title | Neuromarkers and neurological outcome in out-of-hospital cardiac arrest patients treated with therapeutic hypothermia-experience from the HAnnover COoling REgistry (HACORE) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T07%3A22%3A48IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Neuromarkers%20and%20neurological%20outcome%20in%20out-of-hospital%20cardiac%20arrest%20patients%20treated%20with%20therapeutic%20hypothermia-experience%20from%20the%20HAnnover%20COoling%20REgistry%20(HACORE)&rft.jtitle=PloS%20one&rft.au=Akin,%20Muharrem&rft.date=2021-01-07&rft.volume=16&rft.issue=1&rft.spage=e0245210&rft.epage=e0245210&rft.pages=e0245210-e0245210&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0245210&rft_dat=%3Cgale_plos_%3EA650815094%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2476219534&rft_id=info:pmid/33411836&rft_galeid=A650815094&rft_doaj_id=oai_doaj_org_article_76770e66e5c24a59bfc098f2372b674e&rfr_iscdi=true |