RESUMO
Background: Hospital medication errors are frequent and may result in adverse events. Data on non-prescription of regular medications to emergency department short stay unit patients is lacking. In response to local reports of regular medication omissions, a multi-disciplinary team was tasked to introduce corrective emergency department (ED) process changes, but with no additional financing or resources. Aim: To reduce the rate of non-prescription of regular medications for patients admitted to the ED Short Stay Unit (SSU), through process change within existing resource constraints. Methods: A pre- and post-intervention observational study compared regular medication omission rates for patients admitted to the ED SSU. Included patients were those who usually took regular home medications at 08:00 or 20:00. Omissions were classified as clinically significant medications (CSMs) or non-clinically significant medications (non-CSMs). The intervention included reinforcement that the initially treating acute ED doctor was responsible for prescription completion, formal checking of prescription presence at SSU handover rounds, double-checking of prescription completeness by the overnight SSU lead nurse and junior doctor, and ED pharmacist medication reconciliation for those still identified as having regular medication non-prescription at 07:30. Results: For the 110 and 106 patients in the pre- and post-intervention periods, there was a non-significant reduction in the CSM omission rate of -11% (95% CI: -23 to 2), from 41% (95% CI: 32-50) to 30% (95% CI: 21-39). Conclusion: Non-prescription of regular CSMs for SSU patients was not significantly reduced by institution of work practice changes within existing resource constraints.
RESUMO
OBJECTIVES: Cisapride was compared with midazolam in vivo to determine its potential applicability as a cytochrome P450 (CYP) 3A4 "probe." As well, we evaluated whether cisapride was transported by P-glycoprotein. METHODS: Bidirectional transport assays were conducted in LLC-PK1 cells and the derivative cell line L-MDR1 to determine whether cisapride was a substrate for P-glycoprotein. A pharmacokinetic study was also conducted in 17 healthy adults (n = 8 women) who received intravenous midazolam (0.025 mg/kg), oral midazolam (0.15 mg/kg), and oral cisapride (0.07 mg/kg) in a randomized crossover design. Plasma concentrations were quantitated from repeated after-dosing blood samples by HPLC with ultraviolet detection for midazolam and HPLC with tandem mass spectrometry detection for cisapride and norcisapride. Pharmacokinetic parameters were determined by noncompartmental methods. Both linear and nonlinear regression analyses were used to examine the association between the apparent plasma clearance of midazolam and cisapride and the cisapride/norcisapride plasma concentration ratios. RESULTS: Although not a substrate for P-glycoprotein, cisapride inhibited P-glycoprotein with an apparent inhibition constant (K(i)) of 16.1 micromol/L. Linear correlations between cisapride clearance and both intravenous and oral midazolam clearance (P =.01, r(2) = 0.43 and P =.001, r(2) = 0.46, respectively) were found. Cisapride/norcisapride plasma concentration ratios at 8 hours (P =.001, r(2) = 0.90) and 12 hours (P =.001, r(2) = 0.96), as well as cisapride plasma concentrations at these time points, were shown to accurately predict the area under the plasma concentration versus time curve for cisapride. CONCLUSIONS: CYP3A4 activity reflected by the total body clearance after oral administration of cisapride should be independent of transport by P-glycoprotein. Concordance between the pharmacokinetics for cisapride and midazolam support the applicability of oral cisapride as a pharmacologic substrate to assess total CYP3A4 activity in vivo. Cisapride plasma concentration ratios at 8 or 12 hours after a single oral cisapride dose may prove useful as a single-point determination to reflect the area under the plasma concentration versus time curve and the plasma clearance of cisapride and, as well, total CYP3A4 activity in vivo.
