Therapeutic Whole-Body Hypothermia Reduces Death in Severe Traumatic Brain Injury if the Cooling Index Is Sufficiently High: Meta-Analyses of the Effect of Single Cooling Parameters and Their Integrated Measure
Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the deaths of adul...
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| Veröffentlicht in: | Journal of neurotrauma 2018-10, Vol.35 (20), p.2407-2417 |
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| creator | Olah, Emoke Poto, Laszlo Hegyi, Peter Szabo, Imre Hartmann, Petra Solymar, Margit Petervari, Erika Balasko, Marta Habon, Tamas Rumbus, Zoltan Tenk, Judit Rostas, Ildiko Weinberg, Jordan Romanovsky, Andrej A Garami, Andras |
| description | Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the deaths of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure interstudy homogeneity. We extracted data on TBI severity, body temperature, death, and cooling parameters; then we calculated the cooling index, an integrated measure of therapeutic hypothermia. Forest plot of all identified studies showed no difference in the outcome of TBI between cooled and not cooled patients, but interstudy heterogeneity was high. On the contrary, by meta-analysis of randomized clinical trials that were homogenous with regard to statistical, clinical designs, and precisely reported the cooling protocol, we showed decreased odds ratio for death in therapeutic hypothermia compared with no cooling. As independent factors, milder and longer cooling, and rewarming at |
| doi_str_mv | 10.1089/neu.2018.5649 |
| format | Article |
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We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the deaths of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure interstudy homogeneity. We extracted data on TBI severity, body temperature, death, and cooling parameters; then we calculated the cooling index, an integrated measure of therapeutic hypothermia. Forest plot of all identified studies showed no difference in the outcome of TBI between cooled and not cooled patients, but interstudy heterogeneity was high. On the contrary, by meta-analysis of randomized clinical trials that were homogenous with regard to statistical, clinical designs, and precisely reported the cooling protocol, we showed decreased odds ratio for death in therapeutic hypothermia compared with no cooling. As independent factors, milder and longer cooling, and rewarming at <0.25°C/h were associated with better outcome. Therapeutic hypothermia was beneficial only if the cooling index (measure of combination of cooling parameters) was sufficiently high. We conclude that high methodological and statistical interstudy heterogeneity could underlie the contradictory results obtained in previous studies. By analyzing methodologically homogenous studies, we show that cooling improves the outcome of severe TBI, and this beneficial effect depends on certain cooling parameters and on their integrated measure, the cooling index.</description><identifier>ISSN: 0897-7151</identifier><identifier>EISSN: 1557-9042</identifier><identifier>DOI: 10.1089/neu.2018.5649</identifier><identifier>PMID: 29681213</identifier><language>eng</language><publisher>United States: Mary Ann Liebert, Inc</publisher><subject>Body temperature ; Brain Injuries, Traumatic - mortality ; Brain Injuries, Traumatic - therapy ; Brain research ; Clinical trials ; Cooling ; Death ; Gastroenterology ; Head injuries ; Humans ; Hypothermia ; Hypothermia, Induced - methods ; Medical schools ; Meta-analysis ; Mortality ; Patients ; Statistics ; Studies ; Systematic review ; Traumatic brain injury</subject><ispartof>Journal of neurotrauma, 2018-10, Vol.35 (20), p.2407-2417</ispartof><rights>Copyright 2018, Mary Ann Liebert, Inc., publishers This Open Access article is distributed under the terms of the Creative Commons License ( http://creativecommons.org/licenses/by/4.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c360t-1d22fdc055b402665e937996fb2740840ae401ef9b2560156473df0abde892fc3</citedby><cites>FETCH-LOGICAL-c360t-1d22fdc055b402665e937996fb2740840ae401ef9b2560156473df0abde892fc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29681213$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Olah, Emoke</creatorcontrib><creatorcontrib>Poto, Laszlo</creatorcontrib><creatorcontrib>Hegyi, Peter</creatorcontrib><creatorcontrib>Szabo, Imre</creatorcontrib><creatorcontrib>Hartmann, Petra</creatorcontrib><creatorcontrib>Solymar, Margit</creatorcontrib><creatorcontrib>Petervari, Erika</creatorcontrib><creatorcontrib>Balasko, Marta</creatorcontrib><creatorcontrib>Habon, Tamas</creatorcontrib><creatorcontrib>Rumbus, Zoltan</creatorcontrib><creatorcontrib>Tenk, Judit</creatorcontrib><creatorcontrib>Rostas, Ildiko</creatorcontrib><creatorcontrib>Weinberg, Jordan</creatorcontrib><creatorcontrib>Romanovsky, Andrej A</creatorcontrib><creatorcontrib>Garami, Andras</creatorcontrib><title>Therapeutic Whole-Body Hypothermia Reduces Death in Severe Traumatic Brain Injury if the Cooling Index Is Sufficiently High: Meta-Analyses of the Effect of Single Cooling Parameters and Their Integrated Measure</title><title>Journal of neurotrauma</title><addtitle>J Neurotrauma</addtitle><description>Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the deaths of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure interstudy homogeneity. We extracted data on TBI severity, body temperature, death, and cooling parameters; then we calculated the cooling index, an integrated measure of therapeutic hypothermia. Forest plot of all identified studies showed no difference in the outcome of TBI between cooled and not cooled patients, but interstudy heterogeneity was high. On the contrary, by meta-analysis of randomized clinical trials that were homogenous with regard to statistical, clinical designs, and precisely reported the cooling protocol, we showed decreased odds ratio for death in therapeutic hypothermia compared with no cooling. As independent factors, milder and longer cooling, and rewarming at <0.25°C/h were associated with better outcome. Therapeutic hypothermia was beneficial only if the cooling index (measure of combination of cooling parameters) was sufficiently high. We conclude that high methodological and statistical interstudy heterogeneity could underlie the contradictory results obtained in previous studies. By analyzing methodologically homogenous studies, we show that cooling improves the outcome of severe TBI, and this beneficial effect depends on certain cooling parameters and on their integrated measure, the cooling index.</description><subject>Body temperature</subject><subject>Brain Injuries, Traumatic - mortality</subject><subject>Brain Injuries, Traumatic - therapy</subject><subject>Brain research</subject><subject>Clinical trials</subject><subject>Cooling</subject><subject>Death</subject><subject>Gastroenterology</subject><subject>Head injuries</subject><subject>Humans</subject><subject>Hypothermia</subject><subject>Hypothermia, Induced - methods</subject><subject>Medical schools</subject><subject>Meta-analysis</subject><subject>Mortality</subject><subject>Patients</subject><subject>Statistics</subject><subject>Studies</subject><subject>Systematic review</subject><subject>Traumatic brain injury</subject><issn>0897-7151</issn><issn>1557-9042</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</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><recordid>eNpdkUtvEzEURi0EoqGwZIsssWEzqR_zMrs2FBqpCESCWI484-vE0cw49QMxf5NfhEdpqdSV5XvPPbLvh9BbSpaU1OJihLhkhNbLoszFM7SgRVFlguTsOVqkfpVVtKBn6JX3B0IoL1n1Ep0xUdaUUb5Af7d7cPIIMZgO_9rbHrIrqyZ8Mx1tSK3BSPwDVOzA408gwx6bEW_gNzjAWyfjIOfBKydTeT0eopuw0ThN4pW1vRl3qargD157vIlam87AGPrkN7v9R_wVgswuR9lPPvntafBaa-jCfNuk-f7R9F06OUAA57EcFU4vNy7pA-ycDKCSTfro4DV6oWXv4c39eY5-fr7erm6y229f1qvL26zjJQkZVYxp1ZGiaHPCyrIAwSshSt2yKid1TiTkhIIWLStKQtN6K640ka2CWjDd8XP04eQ9OnsXwYdmML6Dvpcj2OgbRtKaeZWLOqHvn6AHG136d6IoLWrCc14mKjtRnbPeO9DN0ZlBuqmhpJnDblLYzRx2M4ed-Hf31tgOoP7TD-nyfyDvpxI</recordid><startdate>20181015</startdate><enddate>20181015</enddate><creator>Olah, Emoke</creator><creator>Poto, Laszlo</creator><creator>Hegyi, Peter</creator><creator>Szabo, Imre</creator><creator>Hartmann, Petra</creator><creator>Solymar, Margit</creator><creator>Petervari, Erika</creator><creator>Balasko, Marta</creator><creator>Habon, Tamas</creator><creator>Rumbus, Zoltan</creator><creator>Tenk, Judit</creator><creator>Rostas, Ildiko</creator><creator>Weinberg, Jordan</creator><creator>Romanovsky, Andrej A</creator><creator>Garami, Andras</creator><general>Mary Ann Liebert, Inc</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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88G</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>M2M</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PSYQQ</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>20181015</creationdate><title>Therapeutic Whole-Body Hypothermia Reduces Death in Severe Traumatic Brain Injury if the Cooling Index Is Sufficiently High: Meta-Analyses of the Effect of Single Cooling Parameters and Their Integrated Measure</title><author>Olah, Emoke ; Poto, Laszlo ; Hegyi, Peter ; Szabo, Imre ; Hartmann, Petra ; Solymar, Margit ; Petervari, Erika ; Balasko, Marta ; Habon, Tamas ; Rumbus, Zoltan ; Tenk, Judit ; Rostas, Ildiko ; Weinberg, Jordan ; Romanovsky, Andrej A ; Garami, Andras</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c360t-1d22fdc055b402665e937996fb2740840ae401ef9b2560156473df0abde892fc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Body temperature</topic><topic>Brain Injuries, Traumatic - 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Academic</collection><jtitle>Journal of neurotrauma</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Olah, Emoke</au><au>Poto, Laszlo</au><au>Hegyi, Peter</au><au>Szabo, Imre</au><au>Hartmann, Petra</au><au>Solymar, Margit</au><au>Petervari, Erika</au><au>Balasko, Marta</au><au>Habon, Tamas</au><au>Rumbus, Zoltan</au><au>Tenk, Judit</au><au>Rostas, Ildiko</au><au>Weinberg, Jordan</au><au>Romanovsky, Andrej A</au><au>Garami, Andras</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Therapeutic Whole-Body Hypothermia Reduces Death in Severe Traumatic Brain Injury if the Cooling Index Is Sufficiently High: Meta-Analyses of the Effect of Single Cooling Parameters and Their Integrated Measure</atitle><jtitle>Journal of neurotrauma</jtitle><addtitle>J Neurotrauma</addtitle><date>2018-10-15</date><risdate>2018</risdate><volume>35</volume><issue>20</issue><spage>2407</spage><epage>2417</epage><pages>2407-2417</pages><issn>0897-7151</issn><eissn>1557-9042</eissn><abstract>Therapeutic hypothermia was investigated repeatedly as a tool to improve the outcome of severe traumatic brain injury (TBI), but previous clinical trials and meta-analyses found contradictory results. We aimed to determine the effectiveness of therapeutic whole-body hypothermia on the deaths of adult patients with severe TBI by using a novel approach of meta-analysis. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to February 2017. The identified human studies were evaluated regarding statistical, clinical, and methodological designs to ensure interstudy homogeneity. We extracted data on TBI severity, body temperature, death, and cooling parameters; then we calculated the cooling index, an integrated measure of therapeutic hypothermia. Forest plot of all identified studies showed no difference in the outcome of TBI between cooled and not cooled patients, but interstudy heterogeneity was high. On the contrary, by meta-analysis of randomized clinical trials that were homogenous with regard to statistical, clinical designs, and precisely reported the cooling protocol, we showed decreased odds ratio for death in therapeutic hypothermia compared with no cooling. As independent factors, milder and longer cooling, and rewarming at <0.25°C/h were associated with better outcome. Therapeutic hypothermia was beneficial only if the cooling index (measure of combination of cooling parameters) was sufficiently high. We conclude that high methodological and statistical interstudy heterogeneity could underlie the contradictory results obtained in previous studies. By analyzing methodologically homogenous studies, we show that cooling improves the outcome of severe TBI, and this beneficial effect depends on certain cooling parameters and on their integrated measure, the cooling index.</abstract><cop>United States</cop><pub>Mary Ann Liebert, Inc</pub><pmid>29681213</pmid><doi>10.1089/neu.2018.5649</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Body temperature Brain Injuries, Traumatic - mortality Brain Injuries, Traumatic - therapy Brain research Clinical trials Cooling Death Gastroenterology Head injuries Humans Hypothermia Hypothermia, Induced - methods Medical schools Meta-analysis Mortality Patients Statistics Studies Systematic review Traumatic brain injury |
| title | Therapeutic Whole-Body Hypothermia Reduces Death in Severe Traumatic Brain Injury if the Cooling Index Is Sufficiently High: Meta-Analyses of the Effect of Single Cooling Parameters and Their Integrated Measure |
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