title: Benzodiazepine Use During Hospitalization: Automated Identification of Potential Medication Errors and Systematic Assessment of Preventable Adverse Events.
abstract: OBJECTIVE
  Benzodiazepines and "Z-drug" GABA-receptor modulators (BDZ) are among the most frequently used drugs in hospitals. Adverse drug events (ADE) associated with BDZ can be the result of preventable medication errors (ME) related to dosing, drug interactions and comorbidities. The present study evaluated inpatient use of BDZ and related ME and ADE.
  
  
  METHODS
  We conducted an observational study within a pharmacoepidemiological database derived from the clinical information system of a tertiary care hospital. We developed algorithms that identified dosing errors and interacting comedication for all administered BDZ. Associated ADE and risk factors were validated in medical records.
  
  
  RESULTS
  Among 53,081 patients contributing 495,813 patient-days BDZ were administered to 25,626 patients (48.3%) on 115,150 patient-days (23.2%). We identified 3,372 patient-days (2.9%) with comedication that inhibits BDZ metabolism, and 1,197 (1.0%) with lorazepam administration in severe renal impairment. After validation we classified 134, 56, 12, and 3 cases involving lorazepam, zolpidem, midazolam and triazolam, respectively, as clinically relevant ME. Among those there were 23 cases with associated adverse drug events, including severe CNS-depression, falls with subsequent injuries and severe dyspnea. Causality for BDZ was formally assessed as 'possible' or 'probable' in 20 of those cases. Four cases with ME and associated severe ADE required administration of the BDZ antagonist flumazenil.
  
  
  CONCLUSIONS
  BDZ use was remarkably high in the studied setting, frequently involved potential ME related to dosing, co-medication and comorbidities, and rarely cases with associated ADE. We propose the implementation of automated ME screening and validation for the prevention of BDZ-related ADE.
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich ZH, Switzerland.|Swiss Federal Institute of Technology Zurich (ETHZ), Zurich, ZH Switzerland.
authors.forename: David Franklin
authors.initials: DF
authors.lastname: Niedrig
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich ZH, Switzerland.
authors.forename: Liesa
authors.initials: L
authors.lastname: Hoppe
authors.affiliation: drugsafety.ch, Küsnacht ZH, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mächler
authors.affiliation: Neurologie am See, Küsnacht ZH, Switzerland.
authors.forename: Heike
authors.initials: H
authors.lastname: Russmann
authors.affiliation: Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, Zurich ZH, Switzerland.|Swiss Federal Institute of Technology Zurich (ETHZ), Zurich, ZH Switzerland.|drugsafety.ch, Küsnacht ZH, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Russmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001331:Automation; D001569:Benzodiazepines / Q000009:adverse effects* / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006760:Hospitalization; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D008508:Medication Errors / Q000517:prevention & control / Q000706:statistics & numerical data*; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D001569:Benzodiazepines