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

Abstract

Disclaimer In an effort to expedite the publication of articles , AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. 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 reported 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.

Physical and Chemical Compatibility of Medications Commonly Used in Critically Ill Patients With Balanced Crystalloids: A Systematic Review

“…A total of 2961 publications via search of databases and 35 publications from additional sources were assessed, and 35 manuscripts were identified for inclusion (Figure 1). Six studies were adjudicated as high risk of bias 20-25 and excluded from further analysis, for a final inclusion of 29 studies 26-54 (Supplementary Figures 1 and 2). Full characteristics of all included studies can be found in Supplementary Table 3.…”

“…Some of the medications included in this review have only one unique assessment evaluated, which significantly limits generalizability. 46,48,50 Other medications were assessed in multiple different combinations but by only one study, which again limits external validity. 33,39,48 Recently the importance of utilizing balanced crystalloids instead of normal saline for resuscitation in critically ill patients has been emphasized to decrease the risk of hyperchloremic AKI, metabolic acidosis, and potentially mortality.…”

“…46,48,50 Other medications were assessed in multiple different combinations but by only one study, which again limits external validity. 33,39,48 Recently the importance of utilizing balanced crystalloids instead of normal saline for resuscitation in critically ill patients has been emphasized to decrease the risk of hyperchloremic AKI, metabolic acidosis, and potentially mortality. [8][9][10][11]14 This may suggest that even outside of the resuscitative period, patients receiving large loads of normal saline from IV medication use (either via admixture or fluid vehicle) could be at similar risk.…”

“…Some of the medications included in this review have only one unique assessment evaluated, which significantly limits generalizability. 46,48,50 Other medications were assessed in multiple different combinations but by only one study, which again limits external validity. 33,39,48…”

“…46,48,50 Other medications were assessed in multiple different combinations but by only one study, which again limits external validity. 33,39,48…”