Impact of physical incompatibility on drug mass flow rates: example of furosemide-midazolam incompatibility

Abstract

BackgroundPatients in intensive care units receive many drugs simultaneously but through limited venous accesses. Several intravenous therapies have to be administered through the same catheter, thus increasing the risk of physicochemical incompatibility. The purpose of this work was to assess and to quantify the impact of physical incompatibility on the mass flow rates of drugs infused simultaneously to the patient, through an in vitro study.MethodsFurosemide-midazolam incompatibility was used to assess the impact of physical incompatibility on drug mass flow rates. Furosemide, midazolam, and saline were simultaneously infused. A filter was added at the end of the infusion line to retain visible particles. Two infusion conditions were tested with and without visible particles. A partial least square method on UV spectra was used to determine simultaneously the concentrations of the two drugs at the egress of the terminal extension line. The drug mass flow rate (expressed as mg/h) was calculated as the product of drug concentration versus total flow rate. Observed/theoretical mass flow rate ratios for each drug (%) were determined per infusion condition.ResultsEven in the absence of visible particles, precipitation of furosemide led to a drug loss estimated at between 10% and 15%. Furosemide is more impacted by interaction because the pH of the mixture is acid and this form is poorly soluble in an aqueous solution.ConclusionsPhysical incompatibility between furosemide and midazolam leads to a significant reduction in drug delivered to the patient and may result in treatment failure.

Analytical method for calculation of deviations from intended dosages during multi-infusion

“…However, in recent years, ample evidence has been found [1–4], including a number of clinical cases and in vivo studies [5–9], indicating that physical effects related to the infusion hardware are equally important to understand [10, 11]. Especially in critical care, on the ICU and the OR, where multiple medications are typically delivered through one single lumen of a thin catheter, these physical effects may cause ambiguous and counter-intuitive discrepancies between the intended dose and the dose that has been actually delivered.…”

Photochemical Mechanism of Riboflavin-Induced Degradation of Famotidine and a Suggested Pharmaceutical Strategy for Improving Photostability

“…1,2 Incompatibility sometimes induces various undesirable reactions, including precipitation, color change, drug degradation, and yield of toxic products upon covalent binding. 3 These factors might jeopardize the safety and effectiveness of intravenous drug therapies. 4 According to the clinical case, famotidine (FMT; Fig.…”

Incompatibilidade de medicamentos intravenosos e fatores de risco em pacientes críticos: coorte histórica

“…As mais escassas, como já mencionadas, são as que investigam sua frequência no âmbito hospitalar (6,7,(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) . Entretanto, testes laboratoriais entre medicamentos e pesquisas que visam à segurança do paciente também foram desenvolvidos (30)(31)(32)(33)(34)(35)(36)(37)(38)(39) .…”

“…Ações voltadas para o uso racional de medicamentos e a padronização de infusões são também incorporadas com o objetivo de garantir o sucesso da terapêutica (56,57) . O desenvolvimento de dispositivos, como os adaptadores multilúmens, filtros de linhas, cateteres com maiores distância entre os lúmens ou com mais vias (de três a cinco vias) é importante aliado na prevenção de incompatibilidades (37,38,43) .…”

“…A incompatibilidade química, também denominada não visível, pode levar à diminuição da dose, à degradação do medicamento e à formação de produtos inativos ou tóxicos. Ela ocorre devido a alterações moleculares ou reagrupamentos químicos das substâncias que são reações irreversíveis e incessantes (15,38) .…”