Physical compatibility of Normosol-R with critical care medications used in patients with COVID-19 during simulated Y-site administration.

PURPOSE: Guidelines from the National Institutes of Health support the use of balanced crystalloid solutions such as Normosol-R (Hospira, Lake Forest, IL) for patients with coronavirus disease 2019 (COVID-19). However, their clinical utility is hindered by a lack of Y-site compatibility data that is essential for use in patients with limited intravenous access. The objective of this study was to determine the physical compatibility of selected intensive care unit medications with Normosol-R. METHODS: The study involved laboratory simulation of Y-site compatibility. Medications tested included amiodarone, caspofungin, dexmedetomidine, dobutamine, dopamine, epinephrine, levofloxacin, norepinephrine, pantoprazole, phenylephrine, piperacillin/tazobactam, vancomycin, and vasopressin. Tests performed were visual assessment with Tyndall light, turbidity measurement, and pH assessment. Tests were performed immediately after mixing (with the exception of turbidity testing) and after 1 hour and 4 hours. RESULTS: Incompatibility was defined as observation of haze, gas, particulate, or color change or admixture turbidity above 0.3 or above 0.5 nephelometric turbidity unit (NTU), depending on whether the baseline turbidity was less than or greater than 0.5 NTU, respectively. Analysis of solubility and compatibility based on change from baseline to admixture pH in relation to the reported -log of the acid dissociation constant (pKa) was performed. There was no evidence of visual incompatibility for any of the admixtures when mixed with Normosol-R. Turbidity exceeded the defined threshold with pantoprazole, phenylephrine, and highly concentrated norepinephrine. Pantoprazole was the only test medication with a significant pH change when compared to its pKa. CONCLUSION: Normosol-R is compatible for Y-site administration with all tested medications except for pantoprazole, phenylephrine, and highly concentrated norepinephrine, allowing for potential increased use in patients with COVID-19.

Structure-activity relationships among random nylon-3 copolymers that mimic antibacterial host-defense peptides.

Host-defense peptides are natural antibiotics produced by multicellular organisms to ward off bacterial infection. Since the discovery of these molecules in the 1980s, a great deal of effort has been devoted to elucidating their mechanisms of action and to developing analogues with improved properties for possible therapeutic use. The vast majority of this effort has focused on materials composed of a single type of molecule, most commonly a peptide with a specific sequence of alpha-amino acid residues. We have recently shown that sequence-random nylon-3 copolymers can mimic favorable properties of host-defense peptides, and here we document structure-activity relationships in this polymer family. Although the polymers are heterogeneous in terms of subunit order and stereochemistry, these materials display structure-activity relationships comparable to those that have been documented among host-defense peptides and analogous synthetic peptides. Previously such relationships have been interpreted in terms of a specific and regular folding pattern (usually an alpha-helix), but our findings show that these correlations between covalent structure and biological activity do not require the adoption of a specific or regular conformation. In some cases our observations suggest alternative interpretations of results obtained with discrete peptides.