Simultaneous infusion of two incompatible antibiotics: Impact of the choice of infusion device and concomitant simulated fluid volume support on the particulate load and the drug mass flow rates.

Vancomycin and piperacillin/tazobactam are known to be incompatible. The objectives of the present study were to evaluate the impact of their simultaneous infusion on mass flow rates and particulate load and identify preventive strategies. We assessed both static conditions and a reproduction of an infusion line used in a hospital's critical care unit. A high-performance liquid chromatography/UV diode array system and static and dynamic laser diffraction particle counters were used. The mass flow rates were primarily influenced by the choice of the infusion device and the presence of simulated fluid volume support. Drug incompatibility also appeared to affect vancomycin's mass flow rate, and the dynamic particulate load increased during flow rate changes - especially in the infusion set with a large common volume line and no concomitant simulated fluid volume support. Only discontinuation of the piperacillin/tazobactam infusion was associated with a higher particulate load in the infusion set with a large common volume line and no concomitant simulated fluid volume support. A low common volume line and the use of simulated fluid volume support were associated with smaller fluctuations in the mass flow rate. The clinical risk associated with a higher particulate load must now be assessed.

Clinical implications of intravenous drug incompatibilities in critically ill patients.

OBJECTIVE: The aim of this review is to analyse the clinical consequences of intravenous drug incompatibilities in critically ill patients, especially the incidence of organ dysfunctions and mortality. METHODS: A review of literature was conducted according to the PRISMA statement in June 2017, using Medline, ISI Web of Science and Clinicaltrials.gov. DATA EXTRACTION: Eligible studies were case reports and randomised controlled trials (RCTs) that assessed the effects of drug incompatibilities in critically ill patients on morbidity or mortality as primary or secondary outcomes, or adverse events. Two investigators independently reviewed the eligibility of the study from abstracts or manuscript data. DATA SYNTHESIS: Twelve articles met the selection criteria. The six articles reporting RCTs concern only four RCTs. RCTs were single-centre studies comparing infusion with or without filter. One of them included adult patients. The others included paediatric and neonatal intensive care unit patients. Primary endpoints were SIRS, organ failure, overall complication rate, bacteraemia, sepsis, phlebitis and length of stay. The results are mixed with one RCT reporting a reduction in SIRS, organ failure and overall complication rate, two studies in disagreement over the occurrence of sepsis and one study reporting no impact on length of hospital stay. The six articles on case reports show different drug incompatibility situations. They report pulmonary toxicity. CONCLUSION: Little data is available on this topic. Infused particles may induce organ failure, in particular pulmonary toxicity and SIRS. Further studies are needed to establish a link between the level of exposure to drug incompatibilities and clinical implication.

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

BACKGROUND: In 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. METHODS: The 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). RESULTS: For 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. CONCLUSIONS: This 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.