Systematic review of physical and chemical compatibility of commonly used medications administered by continuous infusion in intensive care units

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To quantify the physical and chemical stability data published for commonly used continuously infused medications in the intensive care unit and to evaluate the quality of the studies providing these data.

Data Sources and Study Selection:

We conducted a systematic electronic literature search of MEDLINE, EMBASE, and International Pharmaceutical Abstracts as well as the references of electronic drug compatibility textbooks for all English and French language research publications evaluating the physical compatibility or chemical stability of the 820 possible two-drug combinations of 41 commonly used drugs in an adult intensive care unit.

Data Extraction and Synthesis:

A total of 93 studies comprised of 86 (92%) studies evaluating physical compatibility and 35 (38%) studies evaluating chemical compatibility of at least one drug combination of interest were included. Physical and/or chemical compatibility data exist for only 441 of the possible 820 two-drug combinations (54%), whereas chemical compatibility data exist for only 75 (9%) of the possible combinations. Of the 441 combinations for which compatibility data are available, 67 (15%) represent incompatible combinations and 39 (9%) had conflicting data in which both compatible and incompatible data were identified.


Physical compatibility studies that provide the basis for y-site compatibility are lacking for commonly used medications in intensive care unit patients and may contribute to unsafe medication practices. Furthermore, the heterogeneity in the methodology of these studies likely contributes to the common finding of conflicting data for specific combinations of drugs. Future studies should apply similar methodologic and reporting principles to be able to reproduce and compare outcomes both clinically and in the laboratory.

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