The FUSION Study: compatibility of antibiotics with commonly used medication infusions in a paediatric intensive care unit

Abstract

OBJECTIVES: Beta-lactams and vancomycin often require extended or continuous infusion strategies for antibiotic optimisation in the paediatric intensive care unit (PICU). Simultaneous administration of multiple drugs through a single lumen via a Y-site connector is utilised with uncertainty due to limited intravenous access and the common need for sedative-analgesic infusions in critical illness. The compatibility data supporting antibiotics and sedative-analgesics co-administration is lacking. This study describes the physicochemical compatibility between antibiotics and sedative-analgesics commonly prescribed in the PICU. METHODS: Admixtures of cefotaxime, meropenem, piperacillin-tazobactam and vancomycin with fentanyl, midazolam and morphine were examined for physicochemical compatibility at 6 hours after mixing. Fifty drug combinations at different nominal concentrations and two mixing ratios were analysed in triplicates against standards set out by the UK National Health Service Yellow Cover Document and the European Pharmacopoeia. Physical compatibility was assessed by visual inspection and subvisible particle counting, and chemical compatibility using pH measurements and content by ultra-high-performance liquid chromatography. Deviation of drug concentrations after mixing (assayed vs nominal) within 10% was defined as chemically compatible. Overall compatibility was described as 'compatible' when all criteria were met, and as 'incompatible' when at least one criterion was not met. RESULTS: Y-site compatibility was demonstrated across all concentrations of fentanyl (10 to 50 μg/mL) and morphine (0.1 to 1 mg/mL) with the study antibiotics. Concentration-dependent compatibility of midazolam with cefotaxime, meropenem and piperacillin-tazobactam was observed. Compatibility was exhibited at a midazolam concentration of 0.2 mg/mL but not at concentrations of 1 and 2.5 mg/L. Vancomycin was compatible across the midazolam concentration range. CONCLUSIONS: This study describes the favourable compatibility of fentanyl, morphine and vancomycin admixtures with the study drugs. It highlights the incompatibility of midazolam when co-infused with beta-lactam antibiotics. Clinicians must exercise caution when co-administering prolonged infusions of antibiotics to minimise the risk of antibiotic ineffectiveness.