The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes
Hypercortisolemia has been suggested as a primary hormonal mediator of whole-body catabolism following severe burn injury. Ketoconazole, an anti-fungal agent, inhibits cortisol synthesis. We, therefore, studied the effect of ketoconazole on post-burn cortisol levels and the hyper-catabolic response...
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| creator | Jeschke, Marc G Williams, Felicia N Finnerty, Celeste C Rodriguez, Noe A Kulp, Gabriela A Ferrando, Arny Norbury, William B Suman, Oscar E Kraft, Robert Branski, Ludwik K Al-mousawi, Ahmed M Herndon, David N |
| description | Hypercortisolemia has been suggested as a primary hormonal mediator of whole-body catabolism following severe burn injury. Ketoconazole, an anti-fungal agent, inhibits cortisol synthesis. We, therefore, studied the effect of ketoconazole on post-burn cortisol levels and the hyper-catabolic response in a prospective randomized trial (block randomization 2:1).
Fifty-five severely burned pediatric patients with >30% total body surface area (TBSA) burns were enrolled in this trial. Patients were randomized to receive standard care plus either placebo (controls, n = 38) or ketoconazole (n = 23). Demographics, clinical data, serum hormone levels, serum cytokine expression profiles, organ function, hypermetabolism measures, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout the acute hospital course. Statistical analysis was performed using Fisher's exact test, Student's t-test, and parametric and non-parametric two-way repeated measures analysis of variance where applicable. Patients were similar in demographics, age, and TBSA burned. Ketoconazole effectively blocked cortisol production, as indicated by normalization of the 8-fold elevation in urine cortisol levels [F(1, 376) = 85.34, p |
| doi_str_mv | 10.1371/journal.pone.0035465 |
| format | Article |
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Fifty-five severely burned pediatric patients with >30% total body surface area (TBSA) burns were enrolled in this trial. Patients were randomized to receive standard care plus either placebo (controls, n = 38) or ketoconazole (n = 23). Demographics, clinical data, serum hormone levels, serum cytokine expression profiles, organ function, hypermetabolism measures, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout the acute hospital course. Statistical analysis was performed using Fisher's exact test, Student's t-test, and parametric and non-parametric two-way repeated measures analysis of variance where applicable. Patients were similar in demographics, age, and TBSA burned. Ketoconazole effectively blocked cortisol production, as indicated by normalization of the 8-fold elevation in urine cortisol levels [F(1, 376) = 85.34, p<.001] with the initiation of treatment. However, there were no significant differences in the inflammatory response, acute-phase proteins, body composition, muscle protein breakdown or synthesis, or organ function between groups.
Both groups were markedly hypermetabolic and catabolic throughout the acute hospital stay. Normalization of hypercortisolemia with ketoconazole therapy had no effect on whole-body catabolism or the post-burn inflammatory or hypermetabolic response, suggesting that hypercortisolemia does not play a central role in the post-burn hypermetabolic catabolic response.
ClinicalTrials.gov NCT00675714; and NCT00673309.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0035465</identifier><identifier>PMID: 22606232</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>14-alpha Demethylase Inhibitors - therapeutic use ; Acute phase proteins ; Acute phase substances ; Acute-Phase Proteins - metabolism ; Antiandrogens ; Antifungal agents ; Antifungal Agents - therapeutic use ; Body composition ; Body composition (biology) ; Body Composition - drug effects ; Burns ; Burns - complications ; Burns - drug therapy ; Burns - metabolism ; Catabolism ; Child ; Child health ; Clinical outcomes ; Cytokines ; Cytokines - metabolism ; Demographics ; Demography ; Female ; Fungicides ; Gender ; Glucocorticoids ; Hormones ; Humans ; Hydrocortisone ; Hydrocortisone - biosynthesis ; Inflammation ; Inflammation - drug therapy ; Inflammation - etiology ; Inflammation - metabolism ; Inflammatory response ; Ketoconazole ; Ketoconazole - therapeutic use ; Liver ; Male ; Medicine ; Metabolism ; Metabolism - drug effects ; Muscle Proteins - metabolism ; Muscles ; Patient outcomes ; Patients ; Pediatrics ; Physiological aspects ; Prospective Studies ; Protein biosynthesis ; Protein composition ; Protein synthesis ; Proteins ; Randomization ; Respiratory distress syndrome ; Sepsis ; Statistical analysis ; Surface area ; Surgery ; Ultrasonic imaging ; Urine ; Variance analysis ; Wound infection</subject><ispartof>PloS one, 2012-05, Vol.7 (5), p.e35465-e35465</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Jeschke et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Jeschke et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-6dc3206ec2ee418b07382aeb897610864c0280c1e127eb8969b28a94a016f0bf3</citedby><cites>FETCH-LOGICAL-c758t-6dc3206ec2ee418b07382aeb897610864c0280c1e127eb8969b28a94a016f0bf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350497/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3350497/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22606232$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jeschke, Marc G</creatorcontrib><creatorcontrib>Williams, Felicia N</creatorcontrib><creatorcontrib>Finnerty, Celeste C</creatorcontrib><creatorcontrib>Rodriguez, Noe A</creatorcontrib><creatorcontrib>Kulp, Gabriela A</creatorcontrib><creatorcontrib>Ferrando, Arny</creatorcontrib><creatorcontrib>Norbury, William B</creatorcontrib><creatorcontrib>Suman, Oscar E</creatorcontrib><creatorcontrib>Kraft, Robert</creatorcontrib><creatorcontrib>Branski, Ludwik K</creatorcontrib><creatorcontrib>Al-mousawi, Ahmed M</creatorcontrib><creatorcontrib>Herndon, David N</creatorcontrib><title>The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Hypercortisolemia has been suggested as a primary hormonal mediator of whole-body catabolism following severe burn injury. Ketoconazole, an anti-fungal agent, inhibits cortisol synthesis. We, therefore, studied the effect of ketoconazole on post-burn cortisol levels and the hyper-catabolic response in a prospective randomized trial (block randomization 2:1).
Fifty-five severely burned pediatric patients with >30% total body surface area (TBSA) burns were enrolled in this trial. Patients were randomized to receive standard care plus either placebo (controls, n = 38) or ketoconazole (n = 23). Demographics, clinical data, serum hormone levels, serum cytokine expression profiles, organ function, hypermetabolism measures, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout the acute hospital course. Statistical analysis was performed using Fisher's exact test, Student's t-test, and parametric and non-parametric two-way repeated measures analysis of variance where applicable. Patients were similar in demographics, age, and TBSA burned. Ketoconazole effectively blocked cortisol production, as indicated by normalization of the 8-fold elevation in urine cortisol levels [F(1, 376) = 85.34, p<.001] with the initiation of treatment. However, there were no significant differences in the inflammatory response, acute-phase proteins, body composition, muscle protein breakdown or synthesis, or organ function between groups.
Both groups were markedly hypermetabolic and catabolic throughout the acute hospital stay. Normalization of hypercortisolemia with ketoconazole therapy had no effect on whole-body catabolism or the post-burn inflammatory or hypermetabolic response, suggesting that hypercortisolemia does not play a central role in the post-burn hypermetabolic catabolic response.
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biosynthesis</subject><subject>Inflammation</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - etiology</subject><subject>Inflammation - metabolism</subject><subject>Inflammatory response</subject><subject>Ketoconazole</subject><subject>Ketoconazole - therapeutic use</subject><subject>Liver</subject><subject>Male</subject><subject>Medicine</subject><subject>Metabolism</subject><subject>Metabolism - drug effects</subject><subject>Muscle Proteins - metabolism</subject><subject>Muscles</subject><subject>Patient outcomes</subject><subject>Patients</subject><subject>Pediatrics</subject><subject>Physiological aspects</subject><subject>Prospective Studies</subject><subject>Protein biosynthesis</subject><subject>Protein composition</subject><subject>Protein synthesis</subject><subject>Proteins</subject><subject>Randomization</subject><subject>Respiratory distress syndrome</subject><subject>Sepsis</subject><subject>Statistical analysis</subject><subject>Surface area</subject><subject>Surgery</subject><subject>Ultrasonic imaging</subject><subject>Urine</subject><subject>Variance analysis</subject><subject>Wound infection</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNk9-L1DAQx4so3nn6H4gWBFFw1_xq2r4Ix-GPhYMDPX3xIUzT6W7WtNlrUvH8603d3rGVe5A8JEw-853MTCZJnlKypDynb7du6Duwy53rcEkIz4TM7iXHtORsIRnh9w_OR8kj77eEZLyQ8mFyxJgkknF2nHy_3GCKTYM6pK5Jf2Bw2nXw21lMXZfunA-LKgZKTddYaFsIxnVv0s31DvsWA1TOGt-m0NWptqYzGmzqhqBdi_5x8qAB6_HJtJ8kXz-8vzz7tDi_-Lg6Oz1f6DwrwkLWmjMiUTNEQYuK5LxggFVR5pKSQgpNWEE0Rcry0SrLihVQCiBUNqRq-EnyfK-7s86rqS5eUc7EKJAVkVjtidrBVu1600J_rRwY9dfg-rWCPhhtURFZxwhNLnVOBRU5UABe17SuWSF4nUWtd1O0oWqx1tiFHuxMdH7TmY1au5-K84yIMo8CryaB3l0N6INqjddoLXTohvhuQjMmBGMioi_-Qe_ObqLWEBOIjXIxrh5F1anIc0pllo1ayzuouGpsTew5NibaZw6vZw6RCfgrrGHwXq2-fP5_9uLbnH15wG4QbNh4Z4fxZ_k5KPag7p33PTa3RaZEjTNwUw01zoCaZiC6PTts0K3TzafnfwCcGQCz</recordid><startdate>20120511</startdate><enddate>20120511</enddate><creator>Jeschke, Marc G</creator><creator>Williams, Felicia N</creator><creator>Finnerty, Celeste C</creator><creator>Rodriguez, Noe A</creator><creator>Kulp, Gabriela A</creator><creator>Ferrando, Arny</creator><creator>Norbury, William B</creator><creator>Suman, Oscar E</creator><creator>Kraft, Robert</creator><creator>Branski, Ludwik K</creator><creator>Al-mousawi, Ahmed M</creator><creator>Herndon, David N</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>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120511</creationdate><title>The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes</title><author>Jeschke, Marc G ; Williams, Felicia N ; Finnerty, Celeste C ; Rodriguez, Noe A ; Kulp, Gabriela A ; Ferrando, Arny ; Norbury, William B ; Suman, Oscar E ; Kraft, Robert ; Branski, Ludwik K ; Al-mousawi, Ahmed M ; Herndon, David N</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-6dc3206ec2ee418b07382aeb897610864c0280c1e127eb8969b28a94a016f0bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>14-alpha Demethylase Inhibitors - 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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>Jeschke, Marc G</au><au>Williams, Felicia N</au><au>Finnerty, Celeste C</au><au>Rodriguez, Noe A</au><au>Kulp, Gabriela A</au><au>Ferrando, Arny</au><au>Norbury, William B</au><au>Suman, Oscar E</au><au>Kraft, Robert</au><au>Branski, Ludwik K</au><au>Al-mousawi, Ahmed M</au><au>Herndon, David N</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-05-11</date><risdate>2012</risdate><volume>7</volume><issue>5</issue><spage>e35465</spage><epage>e35465</epage><pages>e35465-e35465</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Hypercortisolemia has been suggested as a primary hormonal mediator of whole-body catabolism following severe burn injury. Ketoconazole, an anti-fungal agent, inhibits cortisol synthesis. We, therefore, studied the effect of ketoconazole on post-burn cortisol levels and the hyper-catabolic response in a prospective randomized trial (block randomization 2:1).
Fifty-five severely burned pediatric patients with >30% total body surface area (TBSA) burns were enrolled in this trial. Patients were randomized to receive standard care plus either placebo (controls, n = 38) or ketoconazole (n = 23). Demographics, clinical data, serum hormone levels, serum cytokine expression profiles, organ function, hypermetabolism measures, muscle protein synthesis, incidence of wound infection sepsis, and body composition were obtained throughout the acute hospital course. Statistical analysis was performed using Fisher's exact test, Student's t-test, and parametric and non-parametric two-way repeated measures analysis of variance where applicable. Patients were similar in demographics, age, and TBSA burned. Ketoconazole effectively blocked cortisol production, as indicated by normalization of the 8-fold elevation in urine cortisol levels [F(1, 376) = 85.34, p<.001] with the initiation of treatment. However, there were no significant differences in the inflammatory response, acute-phase proteins, body composition, muscle protein breakdown or synthesis, or organ function between groups.
Both groups were markedly hypermetabolic and catabolic throughout the acute hospital stay. Normalization of hypercortisolemia with ketoconazole therapy had no effect on whole-body catabolism or the post-burn inflammatory or hypermetabolic response, suggesting that hypercortisolemia does not play a central role in the post-burn hypermetabolic catabolic response.
ClinicalTrials.gov NCT00675714; and NCT00673309.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22606232</pmid><doi>10.1371/journal.pone.0035465</doi><tpages>e35465</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-05, Vol.7 (5), p.e35465-e35465 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1324610858 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | 14-alpha Demethylase Inhibitors - therapeutic use Acute phase proteins Acute phase substances Acute-Phase Proteins - metabolism Antiandrogens Antifungal agents Antifungal Agents - therapeutic use Body composition Body composition (biology) Body Composition - drug effects Burns Burns - complications Burns - drug therapy Burns - metabolism Catabolism Child Child health Clinical outcomes Cytokines Cytokines - metabolism Demographics Demography Female Fungicides Gender Glucocorticoids Hormones Humans Hydrocortisone Hydrocortisone - biosynthesis Inflammation Inflammation - drug therapy Inflammation - etiology Inflammation - metabolism Inflammatory response Ketoconazole Ketoconazole - therapeutic use Liver Male Medicine Metabolism Metabolism - drug effects Muscle Proteins - metabolism Muscles Patient outcomes Patients Pediatrics Physiological aspects Prospective Studies Protein biosynthesis Protein composition Protein synthesis Proteins Randomization Respiratory distress syndrome Sepsis Statistical analysis Surface area Surgery Ultrasonic imaging Urine Variance analysis Wound infection |
| title | The effect of ketoconazole on post-burn inflammation, hypermetabolism and clinical outcomes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-06T03%3A54%3A34IST&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=The%20effect%20of%20ketoconazole%20on%20post-burn%20inflammation,%20hypermetabolism%20and%20clinical%20outcomes&rft.jtitle=PloS%20one&rft.au=Jeschke,%20Marc%20G&rft.date=2012-05-11&rft.volume=7&rft.issue=5&rft.spage=e35465&rft.epage=e35465&rft.pages=e35465-e35465&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0035465&rft_dat=%3Cgale_plos_%3EA477116554%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=1324610858&rft_id=info:pmid/22606232&rft_galeid=A477116554&rft_doaj_id=oai_doaj_org_article_06d969f76c714147a1aa3dd1dd2843d5&rfr_iscdi=true |