Evaluation of Strategies for Reducing Vancomycin-Piperacillin/Tazobactam Incompatibility.

BACKGROUND: Drug incompatibility is defined as a physical-chemical reaction between two or more injectable drugs and that results mainly in precipitation or insolubility. Several strategies for reducing incompatibilities have been implemented empirically in intensive care units. However, these strategies have never been compared directly (and particularly in terms of the particulate load and drug mass flow rate) under standardized conditions. The objective of the present in vitro study was to evaluate the impact of various strategies for preventing incompatibility between simultaneously infused vancomycin and piperacillin/tazobactam. METHODS: An in-line filter, a dilute vancomycin solution (5 mg/mL), and an alternative saline administration line were evaluated separately. The infusion line outlet was connected to a dynamic particle counter. The antibiotic concentration was measured in an HPLC-UV assay. RESULT: The use of an in-line filter and an alternative saline administration route did not significantly reduce the particulate load caused by vancomycin-piperacillin/tazobactam incompatibility. Dilution of the vancomycin solution was associated with a significantly lower particulate load and maintenance of the vancomycin mass flow rate. DISCUSSION: It is important to systematically compare the efficacy of strategies for preventing drug incompatibility. The use of diluted vancomycin solution gave the best results in the case of vancomycin-piperacillin/tazobactam incompatibility.

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.

Factors influencing accuracy when preparing injectable drug concentrations in appliance with clinical practice: a norepinephrine case study.

Errors in injectable preparations with high-risk drugs can be fatal. This study aimed to identify the factors influencing the accuracy of high-risk injectable drug concentrations in appliances used for intensive care unit preparation practices. Norepinephrine (NE) was chosen as an example of a high-risk medication drug. The concentration (0.2 and 0.5 mg/mL), the diluent (sodium chloride 0.9% and 5% dextrose), and the container type (prefilled- and empty-infusion bag and syringe) were tested as potential variability factors. An ultraviolet spectrophotometric method was used for NE dosage. 108 NE solutions were prepared by five individuals (pharmacists or laboratory technicians) with clinical experience as well as experience in the aseptic preparation of solutions. The container type was found to be the only factor influencing the accuracy of NE concentration. NE solutions in syringes proved to be the most accurate while preparations in prefilled bags tended to underdose NE.

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

BACKGROUND: In neonatal intensive care units (NICUs), the simultaneous administration of drugs requires complex infusion methods. Such practices can increase the risk of drug incompatibilities resulting in the formation of a particulate load with possible clinical consequences. METHODS: This paper evaluates strategies to reduce the particulate load of a protocol commonly used in NICUs with a potential medical incompatibility (vancomycin/cefepime combination). The protocol was reproduced in the laboratory and the infusion line directly connected to a dynamic particle counter to evaluate the particulate matter administered during infusion. A spectrophotometry UV assay of cefepime evaluated the impact of filters on the concentration of cefepime administered. RESULTS: A significant difference was observed between the two infusion line configurations used in the NICU, with higher particulate load for cefepime infused via the emergency route. There was no change in particulate load in the absence of vancomycin. A filter on the emergency route significantly reduced this load without decreasing the cefepime concentration infused. Preparation of cefepime seemed to be a critical issue in the protocol as the solution initially contained a high level of particles. CONCLUSION: This study demonstrated the impact of a reconstitution method, drug dilution and choice of infusion line configuration on particulate load.

Strategies to prevent drug incompatibility during simultaneous multi-drug infusion in intensive care units: a literature review.

PURPOSE: Drug protocols in intensive care units may require the concomitant administration of many drugs as patients' venous accesses are often limited. A major challenge for clinicians is to limit the risk of simultaneously infusing incompatible drugs. Incompatibilities can lead to the formation of particles and inactivation of drugs, whose consequences on the body have already been indicated. Our objective was to assess current strategies to counter the risk of incompatible infusions and control the resulting clinical consequences. METHODS: This review was independently conducted by three investigators in respect of the PRISMA statement. Three online databases were consulted. Full-text articles, notes, or letters written in English or French, published or in press between the 1990s and the end of February 2020, with clinical study design, were eligible. Parameters of interest were mainly number and size of particles, and a number of observed/avoided incompatibilities. RESULTS: All in all, 382 articles were screened, 17 meeting all the acceptance criteria. The strategies outlined and assessed were filtration, the use of multi-lumen devices, the purging of infusion lines, incompatibility tables and databases, and the use of standard operating procedures. CONCLUSION: Although many strategies have been developed in recent years to address drug incompatibility risks, clinical data is still lacking. All studies with in vitro design were excluded although some current innovative strategies, like niosomes, should be considered and studied by means of clinical data in the future.