{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:18:06Z","timestamp":1787318286444,"version":"build-2736575974"},"reference-count":39,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Critically ill patients who receive circulatory or respiratory assist using extracorporeal membrane oxygenation (ECMO) may develop hemolysis, which can complicate the delivery of supportive care and be a potential risk factor for increased morbidity and mortality. Clinically, hemolysis is often identified using laboratory markers such as cell-free hemoglobin (CFH) and haptoglobin (Hp). However, such measurements require photometry or enzyme-linked immunosorbent assay (ELISA) and are labor intensive. In contrast, metabolic downstream products of CFH, such as carboxyhemoglobin (CO-Hb) and methemoglobin (Met-Hb), can be regularly monitored via arterial blood gas analyses in the intensive care unit (ICU). We hypothesized that CO-Hb and Met-Hb values measured during ECMO would correlate with the presence of hemolytic events as measured by CFH values exceeding 50mg\/dl. We further hypothesized that CO-Hb and Met-Hb levels would correlate with peri-ECMO mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Retrospective analysis of 435 patients with acute respiratory distress syndrome (ARDS) and veno-venous ECMO admitted to a tertiary ARDS referral center. Plasma concentrations of CO-Hb and Met-Hb were correlated with hemolytic events. Cutoff values of mean CO-Hb (mCO-Hb) and mean Met-Hb (mMet-Hb) associated with increased ICU mortality were calculated with recursive binary partitioning. Single and multivariable regression models for HE and ICU mortality were trained and compared.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Simple and multivariable models including potential confounders identified associations between Met-Hb and hemolytic events (adj. odds ratio [OR] 2.99 [95% confidence interval {CI}, 2.19\u20134.10],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001). A cutoff value with 90% specificity of a hemolytic event was estimated for Met-Hb (1.55%). Both, mean CO-Hb (OR 2.03 [95% CI, 1.60\u20132.61],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001) and Met-Hb (2.78 [1.59\u20135.09],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001) were associated with ICU mortality. Cutoff values for mortality were 2% for mean CO-Hb and 1.25% for mean Met-Hb. The multivariable regression model for mortality including the continuous markers mCO-Hb and mMet-Hb produced an area under the curve (AUC) of 0.803.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In patients with ARDS and ECMO, Met-Hb plasma concentrations were independently associated with hemolytic events. Both, mean CO-Hb and Met-Hb levels were associated with ICU mortality. These markers and their associated cutoff values might serve as a risk indicator in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1213\/ane.0000000000007495","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T19:07:00Z","timestamp":1743448020000},"page":"1346-1354","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":2,"title":["Carboxyhemoglobin and Methemoglobin as Biomarkers of Hemolysis and Mortality in Acute Respiratory Distress Syndrome Treated by Veno-Venous Extracorporeal Membrane Oxygenation"],"prefix":"10.1213","volume":"141","author":[{"given":"Victoria","family":"B\u00fcnger","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, CCM\/CVK, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Menk","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, CCM\/CVK, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"Department of Anesthesiology and Intensive Care Medicine, University Hospital \u201cCarl Gustav Carus,\u201d Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"Hunsicker","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, CCM\/CVK, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Krannich","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center (ECRC), Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin, Berlin, Germany"},{"name":"BioStats GmbH, Nauen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Balzer","sequence":"additional","affiliation":[{"name":"Institute of Medical Informatics, Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia D.","family":"Spies","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, CCM\/CVK, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang M.","family":"Kuebler","sequence":"additional","affiliation":[{"name":"Institute of Physiology, Charite\u0301 \u2013 Universita\u0308tsmedizin Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Weber-Carstens","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, CCM\/CVK, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan A.","family":"Graw","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care Medicine, CCM\/CVK, Charit\u00e9 \u2013 Universit\u00e4tsmedizin Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Berlin, Germany"},{"name":"Department of Anesthesiology and Intensive Care Medicine, 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