BACKGROUND AND OBJECTIVES: Propofol facilitates deep sedation without requiring intubation and is often used by infusion to maintain sedation. Variability in ordering and preparation strategies resulted in significant propofol volumes wasted at the conclusion of procedures in our clinic. With drug shortages now common, we designed a quality improvement initiative to reduce our propofol waste. METHODS: Data collection during the preintervention phase reflected current practice trends. Two propofol dosing tables ($50 or ,50 kg) were designed to estimate the volume of propofol infusion required for sedations spanning 15 to 180 minutes. Nurses prepared propofol infusions as directed by these tables. The primary outcome measure was reduction in waste when the infusion was prepared by standardized strategy versus usual practice. Balancing measures included occurrences of insufficient infusion volume and premature awakenings from deep sedation. Waste volumes were plotted and displayed chronologically in statistical process control charts for the clinic and individual providers. RESULTS: A total of 155 patients received a propofol infusion to maintain deep sedation. The preintervention phase included 77 patients, and the intervention phase included 78 patients. Special cause variation was achieved in the intervention phase. Median (interquartile range) propofol waste volume per procedure declined from 45.6 mL (24.3-71 mL) to 14.3 mL (9.6-19.4 mL), representing a 68% waste reduction. CONCLUSIONS: Using an internally derived systematic approach to ordering and preparing a propofol infusion, we reduced variability, reduced propofol waste, and created cost savings for our organization. This approach is tailorable to other infusions and clinical settings.
Doxifluridine (5'-deoxy-5-fluorouridine, 5'-dFUR) metabolism has been reported to be saturable and associated with a fall in clearance of the drug as the dose is increased. The aim of the present study was to determine the disposition of 5'-dFUR and 5-fluorouracil (5-FU) when 5'-dFUR was given as a 5-day infusion, with the infusion rate increased stepwise every 24 h. Measurement of plasma and urinary levels of 5'-dFUR and 5-FU at steady state for each infusion rate enabled the estimation of 5'-dFUR renal (ClR) and nonrenal (ClNR) clearance and 5-FU renal clearance. A total of 28 patients with histologically proven malignancy received 5-day courses of 5'-dFUR ranging in dose from 3.75 to 20 g/m2 per 120 h. The lowest dose given over 24 h was 0.25 g/m2, and the highest was 5 g/m2. Steady-state plasma levels of 5'-dFUR ranged from 167 to 6,519 ng/ml. At these plasma levels there was no evidence of significant saturation of 5'-dFUR metabolism; steady-state plasma levels of 5'-dFUR increased approximately linearly with dose, and nonrenal clearance did not change significantly with dose. There was also no evidence of nonlinearity in 5'-dFUR renal clearance. The mean (+/- SD) ClR of 5'-dFUR was 108.9 +/- 53.6 ml/min per m2 (range, 45.7-210 ml/min per m2), and the ClNR was 728 +/- 181 ml/min per m2 (range, 444-1,119 ml/min per m2). Renal clearance comprised 13% of the total 5'-dFUR clearance. The mean renal clearance of 5-FU was 100.8 +/- 48.6 ml/min per m2 (range, 23.5-198 ml/min per m2). There was considerable interpatient variability in 5'-dFUR renal and nonrenal clearance, even at the same dose level. We concluded that the administration of 5'-dFUR by the infusion method described avoided the saturation of nonrenal elimination processes reported to occur with shorter infusion schedules.
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