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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EAdministration of acetaminophen to patients with severe sepsis and detectable plasma levels of cell-free hemoglobin (CFH) improved kidney function but did not appear to reduce oxidative injury. This article presents data from the Phase 2a randomized controlled trial of Acetaminophen for the Reduction of Oxidative Stress in Severe Sepsis trial [ACROSS; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01739361\u0026amp;atom=%2Fspmdc%2F14%2F11%2F20.atom\u0022\u003ENCT01739361\u003C\/a\u003E; Janz DR et al. \u003Cem\u003EAm J Respir Care Med\u003C\/em\u003E 2014.]\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EBacterial Infections\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPulmonary Clinical Trials\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EInfectious Diseases\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPulmonary \u0026amp; Respiratory Medicine\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EAdministration of acetaminophen to patients with severe sepsis and detectable plasma levels of cell-free hemoglobin (CFH) improved kidney function but did not appear to reduce oxidative injury. David R. Janz, MD, Vanderbilt University, Nashville, Tennessee, USA, presented data from the Phase 2a randomized controlled trial of Acetaminophen for the Reduction of Oxidative Stress in Severe Sepsis trial [ACROSS; \u003Ca class=\u0022external-ref external-ref-type-clintrialgov\u0022 href=\u0022\/lookup\/external-ref?link_type=CLINTRIALGOV\u0026amp;access_num=NCT01739361\u0026amp;atom=%2Fspmdc%2F14%2F11%2F20.atom\u0022\u003ENCT01739361\u003C\/a\u003E; Janz DR et al. \u003Cem\u003EAm J Respir Care Med\u003C\/em\u003E 2014.]\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003ESepsis is associated with increased plasma levels of CFH, which causes oxidative injury to the kidney [Janz DR et al. \u003Cem\u003ECrit Care Med\u003C\/em\u003E 2013]. Previous observational studies have suggested that acetaminophen can decrease detectable CFH plasma levels, reduce oxidative damage caused by CHF, and improve outcomes in patients with severe sepsis and detectable plasma CFH [Janz DR et al. \u003Cem\u003ECrit Care Med\u003C\/em\u003E 2013]. The hypothesis of the ACROSS trial was that oxidative injury would decrease and renal function would improve by treatment with acetaminophen in patients with severe sepsis and detectable CFH.\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EIn the Phase 2a trial, 45 patients with severe sepsis were randomly assigned to receive enteral acetaminophen (1 g every 6 hours for 3 days) or placebo within 24 hours of admittance to the intensive care unit. Patients were ineligible if they had taken acetaminophen within the past 48 hours, had no enteral access, had acute or chronic liver disease, were pregnant, or if death was imminent. Before randomization, blood was collected at baseline and Days 1, 2, and 3 and analyzed for CFH, F\u003Csub\u003E2\u003C\/sub\u003E-isoprostanes, F\u003Csub\u003E2\u003C\/sub\u003E-isofurans, and acetaminophen levels. Forty patients completed the trial (acetaminophen, n=18; placebo, n=22).\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThe primary outcome of the ACROSS trial was the concentration of F\u003Csub\u003E2\u003C\/sub\u003E-isoprostanes on Day 3, a measure of oxidative injury. Secondary outcomes included F\u003Csub\u003E2\u003C\/sub\u003E-isoprostanes levels on Day 2, F\u003Csub\u003E2\u003C\/sub\u003E-isofuran levels on Day 3, and serum creatinine levels on Day 3.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe results were negative for the primary end point, with no significant decrease in F\u003Csub\u003E2\u003C\/sub\u003E-isoprostanes levels on Day 3 (p=0.353) for patients who received acetaminophen compared to placebo (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E). F\u003Csub\u003E2\u003C\/sub\u003E-isofurans tended to decrease with acetaminophen treatment compared with placebo. Creatinine levels were significantly lower in the acetaminophen arm compared with the placebo arm beginning on Day 3 (p=0.039) and continuing to discharge or death (p=0.03; \u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/11\/20\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effect of Acetaminophen on F2-isoprostanes Levels in Patients With Severe Sepsis\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1431803550\u0022 data-figure-caption=\u0022\u0026amp;lt;div xmlns=\u0026amp;quot;http:\/\/www.w3.org\/1999\/xhtml\u0026amp;quot;\u0026amp;gt;Effect of Acetaminophen on F\u0026amp;lt;sub\u0026amp;gt;2\u0026amp;lt;\/sub\u0026amp;gt;-isoprostanes Levels in Patients With Severe Sepsis\u0026amp;lt;\/div\u0026amp;gt;\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/11\/20\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/11\/20\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/11\/20\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14349\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003EEffect of Acetaminophen on F\u003Csub\u003E2\u003C\/sub\u003E-isoprostanes Levels in Patients With Severe Sepsis\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ESquare\/circle=median; Upper and lower caps=interquartile range.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced with permission from DR Janz, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/11\/20\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Effect of Acetaminophen on Kidney Function in Patients With Severe Sepsis\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-1431803550\u0022 data-figure-caption=\u0022Effect of Acetaminophen on Kidney Function in Patients With Severe Sepsis\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/11\/20\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/11\/20\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/11\/20\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14351\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-8\u0022 class=\u0022first-child\u0022\u003EEffect of Acetaminophen on Kidney Function in Patients With Severe Sepsis\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003ESquare\/circle=median; Upper and lower caps=interquartile range.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-4\u0022\u003EReproduced with permission from DR Janz, MD.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-9\u0022\u003EAdverse events included elevation of aspartate and alanine aminotransferase above 400 units\/L in 6.8% of the study population, with 9.5% occurring in the acetaminophen arm and 4.3% occurring in the placebo arm. Aspartate aminotransferase levels were greatest on Day 1 of the study, whereas alanine aminotransferase levels were highest on Day 2 of the study.\u003C\/p\u003E\u003Cp id=\u0022p-10\u0022\u003EIn conclusion, Dr. Janz stated that the results from the ACROSS trial suggest that treatment of patients with severe sepsis and detectable CFH levels with acetaminophen did not result in a reduction in oxidative injury, the primary outcome; however, renal function was improved, as measured by serum creatinine. Overall, acetaminophen was well tolerated. Although further studies are needed to confirm the findings of the ACROSS trial, Dr. Janz stated that acetaminophen may improve renal outcomes of patients with severe sepsis and detectable CFH plasma levels.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/11\/20.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzp203\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzp203\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}