{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T20:09:16Z","timestamp":1792440556232,"version":"4.5.0"},"reference-count":20,"publisher":"S. Karger AG","issue":"2","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Blood Purif"],"published-print":{"date-parts":[[2024]]},"abstract":"<b><i>Introduction:<\/i><\/b> Midazolam-based continuous intravenous sedation in patients admitted to the intensive care unit (ICU) was a necessity during the COVID-19 pandemic. However, benzodiazepine-based sedation is associated with a high incidence of benzodiazepine-related delirium and additional days on mechanical ventilation. Due to the requirement of high midazolam doses in combination with the impaired renal clearance (CL) of the pharmacological active metabolite 1-OH-midazolam-glucuronide (10% compared to midazolam), ICU patients with COVID-19 and continuous renal replacement therapy (CRRT) were at risk of unintended prolonged sedation. Several CRRT-related factors may have influenced the delivered CL of midazolam and its metabolites. Therefore, the aim of the study was to identify and describe these CRRT-related factors. <b><i>Methods:<\/i><\/b> Pre-filter blood samples and ultrafiltrate samples were collected simultaneously. Midazolam, 1-OH-midazolam, and 1-OH-midazolam-glucuronide plasma samples were analyzed using an UPLC-MS\/MS method. The prescribed CRRT dose was corrected for downtime and filter integrity using the urea ratio (urea concentration in effluent\/urea concentration plasma). CL of midazolam and its metabolites were calculated with the delivered CRRT dose (corrected for downtime and saturation coefficient [SD]). <b><i>Results:<\/i><\/b> Three patients on continuous venovenous hemodialysis (CVVHD) and 2 patients on continuous venovenous hemodiafiltration (CVVHDF) were included. Midazolam, 1-OH-midazolam, and 1-OH-midazolam-glucuronide concentrations were 2,849 (0\u20136,700) \u03bcg\/L, 153 (0\u2013295) \u03bcg\/L, and 27,297 (1,727\u201339,000) \u03bcg\/L, respectively. The SD was 0.03 (0.02\u20130.03) for midazolam, 0.05 (0.05\u20130.06) for 1-OH-midazolam, and 0.33 (0.23\u20130.43) for 1-OH-midazolam-glucuronide. The delivered CRRT CL was 1.4 (0\u20131.7) mL\/min for midazolam, 2.7 (0\u20133.5) mL\/min for 1-OH-midazolam, and 15.7 (4.0\u201327.7) mL\/min for 1-OH-midazolam-glucuronide. <b><i>Conclusions:<\/i><\/b> Midazolam and 1-OH-midazolam were not removed during CVVHD and CVVHDF. However, 1-OH-midazolam-glucuronide was removed reasonably, approximately up to 43%. CRRT modality, filter integrity, and downtime affect this removal. These data imply a personalized titration of midazolam in critically ill patients with renal failure and awareness for the additional sedative effects of its active metabolites. <\/jats:p>","DOI":"10.1159\/000534538","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T22:00:51Z","timestamp":1699048851000},"page":"107-113","source":"Crossref","is-referenced-by-count":9,"title":["The Clearance of Midazolam and Metabolites during Continuous Renal Replacement Therapy in Critically Ill Patients with COVID-19"],"prefix":"10.1159","volume":"53","author":[{"given":"Tim J.L.","family":"Smeets","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilde R.H.","family":"de Geus","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham J.","family":"Valkenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Baidjoe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diederik A.M.P.J.","family":"Gommers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Birgit C.P.","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole G.M.","family":"Hunfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Endeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-06307-9"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1177\/10600280211021925"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-022-01122-5"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-2600(20)30552-x"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1992.84"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(95)91209-6"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2020.05.006"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-059046"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-020-02301-6"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/s0272-6386(99)70076-4"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1007\/BF01700172"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0b013e3181aab3d0"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.2005"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1177\/00912700122010933"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1007\/s001340100965"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2004.09.004"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.02500310"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-015-0818-8"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1592\/phco.27.3.389"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1186\/s40560-018-0331-7"}],"container-title":["Blood Purification"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/bpu\/article-pdf\/53\/2\/107\/4163989\/000534538.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/karger.com\/bpu\/article-pdf\/53\/2\/107\/4163989\/000534538.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T15:48:01Z","timestamp":1745423281000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000534538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,3]]},"references-count":20,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2,1]]},"published-print":{"date-parts":[[2024,1,31]]}},"URL":"https:\/\/doi.org\/10.1159\/000534538","archive":["Portico"],"relation":{},"ISSN":["0253-5068","1421-9735"],"issn-type":[{"value":"0253-5068","type":"print"},{"value":"1421-9735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,3]]}}}