{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:55:29Z","timestamp":1792788929608,"version":"4.5.0"},"reference-count":304,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","funder":[{"name":"Verdun Research Fund"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2022,4]]},"abstract":"\n Methotrexate is used in the treatment of many malignancies, rheumatological diseases, and inflammatory bowel disease. Toxicity from use is associated with severe morbidity and mortality. Rescue treatments include intravenous hydration, folinic acid, and, in some centers, glucarpidase. We conducted systematic reviews of the literature following published EXtracorporeal TReatments In Poisoning (EXTRIP) methods to determine the utility of extracorporeal treatments in the management of methotrexate toxicity. The quality of the evidence and the strength of recommendations (either \u201cstrong\u201d or \u201cweak\/conditional\u201d) were graded according to the GRADE approach. A formal voting process using a modified Delphi method assessed the level of agreement between panelists on the final recommendations. A total of 92 articles met inclusion criteria. Toxicokinetic data were available on 90 patients (89 with impaired kidney function). Methotrexate was considered to be moderately dialyzable by intermittent hemodialysis. Data were available for clinical analysis on 109 patients (high-dose methotrexate [>0.5 g\/m\n 2<\/jats:sup>\n ]: 91 patients; low-dose [\u22640.5 g\/m\n 2<\/jats:sup>\n ]: 18). Overall mortality in these publications was 19.5% and 26.7% in those with high-dose and low-dose methotrexate\u2013related toxicity, respectively. Although one observational study reported lower mortality in patients treated with glucarpidase compared with those treated with hemodialysis, there were important limitations in the study. For patients with severe methotrexate toxicity receiving standard care, the EXTRIP workgroup: (\n 1<\/jats:italic>\n ) suggested against extracorporeal treatments when glucarpidase is not administered; (\n 2<\/jats:italic>\n ) recommended against extracorporeal treatments when glucarpidase is administered; and (\n 3<\/jats:italic>\n ) recommended against extracorporeal treatments instead of administering glucarpidase. The quality of evidence for these recommendations was very low. Rationales for these recommendations included: (\n 1<\/jats:italic>\n ) extracorporeal treatments mainly remove drugs in the intravascular compartment, whereas methotrexate rapidly distributes into cells; (\n 2<\/jats:italic>\n ) extracorporeal treatments remove folinic acid; (\n 3<\/jats:italic>\n ) in rare cases where fast removal of methotrexate is required, glucarpidase will outperform any extracorporeal treatment; and (\n 4<\/jats:italic>\n ) extracorporeal treatments do not appear to reduce the incidence and magnitude of methotrexate toxicity.\n <\/jats:p>","DOI":"10.2215\/cjn.08030621","type":"journal-article","created":{"date-parts":[[2022,3,2]],"date-time":"2022-03-02T14:05:11Z","timestamp":1646229911000},"page":"602-622","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":39,"title":["Extracorporeal Treatment for Methotrexate Poisoning"],"prefix":"10.2215","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4794-4127","authenticated-orcid":false,"given":"Marc","family":"Ghannoum","sequence":"first","affiliation":[{"name":"Research Center, CIUSSS du Nord-de-l'\u00eele-de-Montr\u00e9al, University of Montreal, Montreal, Quebec, Canada"},{"name":"Department of Nephrology and Hypertension, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9101-7577","authenticated-orcid":false,"given":"Darren M.","family":"Roberts","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Toxicology, St Vincent\u2019s Hospital, Sydney, New South Wales, Australia; and St Vincent\u2019s Clinical School, University of New South Wales, Sydney, New South Wales, Australia; and Drug Health Services, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S.","family":"Goldfarb","sequence":"additional","affiliation":[{"name":"Nephrology Division, NYU Langone Health and NYU Grossman School of Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6211-1967","authenticated-orcid":false,"given":"Jesper","family":"Heldrup","sequence":"additional","affiliation":[{"name":"Childhood Cancer and Research Unit, University Children\u2019s Hospital, Lund, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Anseeuw","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, ZNA Stuivenberg, Antwerp, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tais F.","family":"Galvao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, University of Campinas, Campinas, Sao Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4339-1382","authenticated-orcid":false,"given":"Thomas D.","family":"Nolin","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Therapeutics, and Department of Medicine Renal-Electrolyte Division, University of Pittsburgh Schools of Pharmacy and Medicine, Pittsburgh, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert S.","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Division of Medical Toxicology, Ronald O. Perelman Department of Emergency Medicine, NYU Grossman School of Medicine, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valery","family":"Lavergne","sequence":"additional","affiliation":[{"name":"Research Center, CIUSSS du Nord-de-l'\u00eele-de-Montr\u00e9al, University of Montreal, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Meyers","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Gosselin","sequence":"additional","affiliation":[{"name":"Centre Int\u00e9gr\u00e9 de Sant\u00e9 et de Services Sociaux (CISSS) de la Mont\u00e9r\u00e9gie-Centre Emergency Department, H\u00f4pital Charles-Lemoyne, Greenfield Park, Quebec, McGill University Emergency Department, Montreal, Quebec and Centre Antipoison du Qu\u00e9bec, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tudor","family":"Botnaru","sequence":"additional","affiliation":[{"name":"Emergency Department, Lakeshore General Hospital, CIUSSS de l'Ouest-de-l'lle-de-Montreal, McGill University, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Mardini","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Verdun Hospital, CIUSSS du Sud-Ouest-de-l\u2019\u00efle-de-Montr\u00e9al, University of Montreal, Montreal, Quebec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-7237","authenticated-orcid":false,"given":"David M.","family":"Wood","sequence":"additional","affiliation":[{"name":"Clinical Toxicology, Guy\u2019s and St Thomas\u2019 NHS Foundation Trust and King\u2019s Health Partners, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,4]]},"reference":[{"key":"B1-20241015","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1053\/j.ackd.2011.01.008","article-title":"Blood purification in toxicology: Nephrology's ugly duckling","volume":"18","author":"Ghannoum","year":"2011","journal-title":"Adv Chronic Kidney Dis"},{"key":"B2-20241015","doi-asserted-by":"crossref","first-page":"403","DOI":"10.3109\/15563650.2012.683436","article-title":"The EXTRIP (EXtracorporeal TReatments In Poisoning) workgroup: Guideline methodology","volume":"50","author":"Lavergne","year":"2012","journal-title":"Clin Toxicol (Phila)"},{"key":"B3-20241015","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/sdi.12251","article-title":"Guidelines for reporting case studies on extracorporeal treatments in poisonings: Methodology","volume":"27","author":"Lavergne","year":"2014","journal-title":"Semin Dial"},{"key":"B4-20241015","doi-asserted-by":"crossref","first-page":"2475","DOI":"10.1681\/ASN.2020050564","article-title":"Extracorporeal treatment for chloroquine, hydroxychloroquine, and quinine poisoning: Systematic review and recommendations from the EXTRIP workgroup","volume":"31","author":"Berling","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"B5-20241015","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1080\/15563650.2020.1870123","article-title":"Extracorporeal treatment for calcium channel blocker poisoning: Systematic review and recommendations from the EXTRIP workgroup","volume":"59","author":"Wong","year":"2021","journal-title":"Clin Toxicol (Phila)"},{"key":"B6-20241015","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1002\/phar.2519","article-title":"Extracorporeal treatments for isoniazid poisoning: Systematic review and recommendations from the EXTRIP workgroup","volume":"41","author":"Mowry","year":"2021","journal-title":"Pharmacotherapy"},{"key":"B7-20241015","first-page":"1018","article-title":"The metabolic fate of tritiated methotrexate. 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