Analysis of particulate exposure during continuous drug infusion in critically ill adult patients: a preliminary proof-of-concept in vitro study

Abstract

BackgroundIn critically ill patients, drug incompatibilities frequently occur because of the number of drugs to be administered through a limited number of infusion lines. These are among the main causes of particulate contamination. However, little data is available to quantify particle exposure during simultaneous IV-drug infusion. The objective of this study was to evaluate the particulate matter potentially administered to critically ill patients.MethodsThe particulate matter (between 1 μm and 30 mm) of infused therapies used in ICUs for patients suffering from either septic shock or acute respiratory distress syndrome was measured in vitro over 6 h using a dynamic image analysis device, so that both overall particulate contamination and particle sizes could be determined. Data is presented according to the recommendations of the European Pharmacopoeia (≥ 10 and 25 μm).ResultsFor the six experimental procedures (continuous infusion of norepinephrine, midazolam, sufentanil, heparin, 5% glucose, binary parenteral nutrition and discontinuous administrations of omeprazole, piperacillin/tazobactam and fluconazole), the overall number of particles over the 6-h infusion period was 8256 [5013; 15,044]. The collected values for the number of particles ≥ 10 and 25 μm were 281 [118; 526] and 19 [7; 96] respectively. Our results showed that discontinuous administrations of drugs led to disturbances in particulate contamination.ConclusionsThis work indicates the amount of particulate matter potentially administered to critically ill adult patients. Particulate contamination appears lower than previous measurements performed during multidrug IV therapies in children.

<p>Pharmaceutical Quality of Selected Metronidazole and Ciprofloxacin Infusions Marketed in South Eastern Nigeria</p>

“…The particulate contaminants can be detectable particles that are visible on visual inspection with sizes ≥50 µm or sub-visible particles that are not detectable on visual inspection with sizes varying between 2 and 50 µm 36 . Both visible and sub-visible particulate contaminations in parenteral fluids or solutions are dangerous [36][37][38][39][40] as these fluids are meant to pass through the blood vessels. The present study showed that the drug products are free from both visible and sub-visible particulate contaminations and their use cannot lead to the deleterious effects of particulate contamination.…”

Optimising an Infusion Protocol Containing Cefepime to Limit Particulate Load to Newborns in a Neonatal Intensive Care Unit

“…Currently, no standard recommendations have been issued by the three main Pharmacopoeias (European, American and Japanese) for dynamic particle counting. This work has been carried out in our laboratory using a new technique for the dynamic counting of non-visible particles (<50 µm) which indicates the potential particulate load to which patients are exposed [ 16 , 17 , 22 , 32 , 33 , 34 ]. With the use of this appliance, different assembly lines used for infusion protocols in intensive care units (adult, paediatric and neonatal) can be reproduced and studied in vitro.…”

Update on the Use of Filters for Parenteral Nutrition: An ASPEN Position Paper

“…In recent years, the increasing complexity of intravenous therapy has brought renewed scrutiny to the presence of particulate matter in parenteral fluids. A number of in vitro studies have simulated multidrug protocols for neonatal, pediatric, and adult patients, many involving drug administration in conjunction with PN admixtures 47,48,52,60,67–70 . Variation exists in the lower range of particle sizes evaluated in these studies, which may reduce the ability to accurately determine the total number of particles in a given solution.…”

“…Given the high degree of patient‐specific customization required for each PN admixture, not all instances of incompatibility or admixture instability can be predicted 3,50 . Studies have documented sharp increases in particulate matter when medications are co‐infused with PN, underscoring the importance of using appropriate administration techniques, including filters, when infusing medications in conjunction with PN 52,67,70 . Strategies that limit contact time between drugs, such as avoiding the use of extension sets, reduces particulate contamination during multidrug therapies 50,66,68 .…”

“…Implementing recognized best practices for filtering PN admixtures and using specific techniques for priming filters can improve their function, particularly with low flow rates. Best practices for using filters for PN administration include the steps listed below: 2,38,67,70,73,76 Prior to compounding, a pharmacist must verify the stability and compatibility of the PN formulation. Perform visual inspection of the PN container for evidence of particulate matter or admixture instability, including emulsion cracking for TNAs. When administering the dextrose‐amino acid component of the PN and the ILE as separate infusions, the first infusion must be completely set up and the pump programmed for that fluid before setting up the second infusion. Avoid co‐administration of medications with PN admixtures. When no other option exists, use appropriate flushing techniques before and after the medication is administered. When co‐administration of medications with PN cannot be avoided, the medication tubing should be attached at a Y‐site above the filter.…”