{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T11:13:17Z","timestamp":1791976397348,"version":"4.4.0"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background\/objectives<\/jats:title>\n                    <jats:p>Metamizole (dipyrone) is a non-opioid analgesic and antipyretic widely used in Germany, with prescriptions having increased more than tenfold since 1997. Despite its popularity, metamizole remains controversial due to the risk of agranulocytosis\u2013a potentially life-threatening adverse reaction that can occur independently of dose or duration of therapy. This study aimed to describe severe cases of metamizole-induced agranulocytosis requiring intensive care treatment and to contextualize them within current consumption data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective analysis was conducted of all patients admitted to the interdisciplinary medical intensive care units of a tertiary university hospital in southern Germany between April 2022 and April 2025 due to metamizole-associated agranulocytosis. Demographic, clinical, and laboratory data were collected. Bone marrow examinations, microbiological findings, treatment regimens, and outcomes were analyzed descriptively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seven patients required intensive care for metamizole-induced agranulocytosis. All presented with profound neutropenia and severe infections. Two patients died from multiorgan failure despite maximal supportive care. The five survivors experienced prolonged ICU stays (11\u201360 days) with complications including septic shock, acute respiratory distress syndrome, and renal failure requiring dialysis. None of the patients had pre-existing hematologic disorders or immunosuppression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Metamizole-induced agranulocytosis is a rare but potentially severe adverse reaction. Even though its absolute incidence is low relative to the widespread use of metamizole, affected patients may experience life-threatening complications. Awareness of this risk, combined with careful benefit\u2013risk assessment and consideration of alternative analgesics, remains essential for safe and rational use of metamizole in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1765803","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:39:21Z","timestamp":1775021961000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Metamizole-induced agranulocytosis from a German intensive care perspective"],"prefix":"10.3389","volume":"13","author":[{"given":"Laura","family":"Hille","sequence":"first","affiliation":[{"name":"Interdisciplinary Medical Intensive Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]},{"name":"Pharmacy, Medical Center - University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Hug","sequence":"additional","affiliation":[{"name":"Pharmacy, Medical Center - University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Wengenmayer","sequence":"additional","affiliation":[{"name":"Interdisciplinary Medical Intensive Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Hilger","sequence":"additional","affiliation":[{"name":"Interdisciplinary Medical Intensive Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul Marc","family":"Biever","sequence":"additional","affiliation":[{"name":"Interdisciplinary Medical Intensive Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg","place":["Freiburg, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"B1","volume-title":"Arzneiverordnungs-Report 2024.","author":"Ludwig","year":"2024"},{"key":"B2","unstructured":"Metamizol: Agranulozytose.\n          \n          2022"},{"key":"B3","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1111\/bcpt.13310","article-title":"Agranulocytosis attributed to metamizole: an analysis of spontaneous reports in EudraVigilance 1985-2017.","volume":"126","author":"Hoffmann","year":"2020","journal-title":"Basic Clin Pharmacol Toxicol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/s00228-002-0465-2","article-title":"Agranulocytosis and other blood dyscrasias associated with dipyrone (metamizole).","volume":"58","author":"Hedenmalm","year":"2002","journal-title":"Eur J Clin Pharmacol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1007\/s00210-019-01774-4","article-title":"Metamizole and the risk of drug-induced agranulocytosis and neutropenia in statutory health insurance data.","volume":"393","author":"Klose","year":"2020","journal-title":"Naunyn Schmiedebergs Arch Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s00228-014-1777-8","article-title":"Metamizole-induced agranulocytosis revisited: results from the prospective Berlin Case-Control Surveillance Study.","volume":"71","author":"Huber","year":"2015","journal-title":"Eur J Clin Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1186\/s40348-023-00160-8","article-title":"Metamizole-induced agranulocytosis (MIA): a mini review.","volume":"10","author":"Tomidis Chatzimanouil","year":"2023","journal-title":"Mol Cell Pediatr."},{"key":"B8","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.bcp.2019.01.011","article-title":"Non-immunological toxicological mechanisms of metamizole-associated neutropenia in HL60 cells.","volume":"163","author":"Rudin","year":"2019","journal-title":"Biochem Pharmacol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1624044","DOI":"10.3389\/fphar.2025.1624044","article-title":"Pharmacogenetics of metamizole-induced agranulocytosis: a systematic review and drug regulation implications.","volume":"16","author":"Fidelis","year":"2025","journal-title":"Front Pharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"210","DOI":"10.3238\/arztebl.m2024.0245","article-title":"Metamizole-Induced Agranulocytosis.","volume":"122","author":"Kohn","year":"2025","journal-title":"Dtsch Arztebl Int."},{"key":"B11","volume-title":"Metamizole-containing Medicinal Products \u2013 Article 107i Referral: Scientific Background.","year":"2024"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1438","DOI":"10.1016\/S0140-6736(02)11489-9","article-title":"Dipyrone and agranulocytosis: what is the risk?","volume":"360","author":"Edwards","year":"2002","journal-title":"Lancet."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.1002\/cpt.2258","article-title":"The uncertainties of metamizole use.","volume":"109","author":"Cascorbi","year":"2021","journal-title":"Clin Pharmacol Ther."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1765803\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:39:23Z","timestamp":1775021963000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1765803\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":13,"alternative-id":["10.3389\/fmed.2026.1765803"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1765803","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]},"article-number":"1765803"}}