{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:53:09Z","timestamp":1790805189711,"version":"4.1.0"},"reference-count":17,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Pharmacother"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Midazolam (MZ) is commonly used in critically ill neurosurgical patients. Neuro-penetration of MZ and its metabolite, 1-hydroxy-midazolam (1-OH-MZ), is not well characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>This study evaluated correlations between serum and cerebrospinal fluid (CSF) concentrations of MZ and 1-OH-MZ and assessed implications on patient sedation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Adults in the neurosurgical intensive care unit (ICU) with external ventricular drains receiving MZ via continuous infusion were prospectively studied. Serum and CSF samples were obtained 12-24 h and 72-96 h after initiation, and concentrations were determined in duplicate by high-performance liquid chromatography with tandem mass spectrometry. Bivariate correlation analyses used Pearson coefficient.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A total of 31 serum and CSF samples were obtained from 18 subjects. At sampling, mean MZ infusion rate was 3.9 \u00b1 4.4 mg\/h, and previous 12-h cumulative dose was 51.4 \u00b1 78.2 mg. Mean concentrations of MZ and 1-OH-MZ in serum and CSF were similar between timepoints. Similarly, ratios of 1-OH-MZ to MZ in serum and CSF remained stable over time. Serum MZ (126.2 \u00b1 89.3 ng\/mL) showed moderate correlation (r\n                      <jats:sup>2<\/jats:sup>\n                      = 0.68, P &lt; 0.001) with serum 1-OH-MZ (17.7 \u00b1 17.6 ng\/mL) but not CSF MZ (3.9 \u00b1 2.5 ng\/mL; r\n                      <jats:sup>2<\/jats:sup>\n                      = 0.24, P = 0.005) or CSF 1-OH-MZ (2.5 \u00b1 0.6 ng\/mL; r\n                      <jats:sup>2<\/jats:sup>\n                      = 0.47, P = 0.30). CSF MZ did not correlate with CSF 1-OH-MZ (r\n                      <jats:sup>2<\/jats:sup>\n                      = 0.003, P &lt; 0.001). Mean serum ratio of 1-OH-MZ to MZ (0.14 \u00b1 0.2 ng\/mL) did not correlate with CSF ratio (1.06 \u00b1 0.83 ng\/mL; r\n                      <jats:sup>2<\/jats:sup>\n                      = 0.06, P = 0.19). Concentrations and ratios were unrelated to MZ infusion rate or 12-h cumulative dose. Sedation was weakly correlated with CSF 1-OH-MZ, but not with serum MZ, serum 1-OH-MZ, or CSF MZ.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Relevance:<\/jats:title>\n                    <jats:p>Continuous infusions of MZ result in measurable concentrations of MZ and 1-OH-MZ in CSF; however, CSF concentrations of MZ and 1-OH-MZ poorly represent serum concentrations or dosages. Accumulation of MZ and 1-OH-MZ in serum or CSF over time was not evident. Concentrations of MZ and 1-OH-MZ do not predict sedation levels, reinforcing that pharmacodynamic assessments are warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/10600280241271130","type":"journal-article","created":{"date-parts":[[2024,8,21]],"date-time":"2024-08-21T20:09:35Z","timestamp":1724270975000},"page":"244-249","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Correlation Between Serum and CSF Concentrations of Midazolam and 1-Hydroxy-Midazolam in Critically Ill Neurosurgical Patients"],"prefix":"10.1177","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1144-4806","authenticated-orcid":false,"given":"Julie E.","family":"Farrar","sequence":"first","affiliation":[{"name":"College of Pharmacy, The University of Tennessee, Memphis, TN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia S.","family":"Stefanos","sequence":"additional","affiliation":[{"name":"Houston Methodist Hospital, Houston, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Cava","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Colorado, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyree H.","family":"Kiser","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott W.","family":"Mueller","sequence":"additional","affiliation":[{"name":"University of Colorado Hospital, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Neumann","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Colorado, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Rocky Mountain Regional VA Medical Center, Denver, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deb S.","family":"Sherman","sequence":"additional","affiliation":[{"name":"University of Colorado Hospital, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3569-5506","authenticated-orcid":false,"given":"Robert","family":"MacLaren","sequence":"additional","affiliation":[{"name":"Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,8,20]]},"reference":[{"key":"bibr1-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000003299"},{"key":"bibr2-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1007\/BF03189348"},{"key":"bibr3-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2021.114289"},{"key":"bibr4-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1007\/BF00543799"},{"key":"bibr5-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1016\/j.resuscitation.2023.109867"},{"key":"bibr6-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-200412000-00010"},{"key":"bibr7-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1186\/s40560-018-0331-7"},{"key":"bibr8-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinthera.2018.07.021"},{"key":"bibr9-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.22.2983"},{"key":"bibr10-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1992.84"},{"key":"bibr11-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1988.31"},{"key":"bibr12-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1093\/bja\/59.5.548"},{"key":"bibr13-10600280241271130","doi-asserted-by":"publisher","DOI":"10.2174\/138920008783331077"},{"key":"bibr14-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01481-w"},{"key":"bibr15-10600280241271130","doi-asserted-by":"publisher","DOI":"10.2174\/1381612822666151221150733"},{"key":"bibr16-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1990.tb03633.x"},{"key":"bibr17-10600280241271130","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2044.1987.tb03086.x"}],"container-title":["Annals 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