ArticleBlood purification2024
The Clearance of Midazolam and Metabolites during Continuous Renal Replacement Therapy in Critically Ill Patients with COVID-19.
Article in Blood purification, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- Drug Monitoring of Therapy with Midazolam in Patients with ARDS: A Single-Center Prospective Study.Medicina (Kaunas, Lithuania) · 2026Article
- Analgesic and sedative drug dosing in critically ill patients with Acute Kidney Injury undergoing different modalities of Kidney Replacement Therapy.Journal of anesthesia, analgesia and critical care · 2025Review
- Investigating the Relationship Between Midazolam Serum Concentrations and Paediatric Delirium in Critically Ill Children.Pediatric reports · 2025Article
- Sedation for Patients with Sepsis: Towards a Personalised Approach.Journal of personalized medicine · 2023Review
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8 authors at 2 institutions in 1 country.
Funding
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Abstract
introductionMidazolam-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.
methodsPre-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]).
resultsThree 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 (0-6,700) μg/L, 153 (0-295) μg/L, and 27,297 (1,727-39,000) μg/L, respectively. The SD was 0.03 (0.02-0.03) for midazolam, 0.05 (0.05-0.06) for 1-OH-midazolam, and 0.33 (0.23-0.43) for 1-OH-midazolam-glucuronide. The delivered CRRT CL was 1.4 (0-1.7) mL/min for midazolam, 2.7 (0-3.5) mL/min for 1-OH-midazolam, and 15.7 (4.0-27.7) mL/min for 1-OH-midazolam-glucuronide.
conclusionsMidazolam 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.
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