Venous access is often limited in an emergent situation, such as in the critically ill COVID-19 patient. The National Institutes of Health recommend the use of balanced crystalloid solutions, such as lactated Ringer's solution, Plasma-Lyte, and Normosol-R, for acute resuscitation of adults with shock and COVID-19. These preparations may be associated with less renal impairment.
To facilitate the administration of life-saving medications, patients may require the concurrent administration of drugs via a Y-site. While there is information about the Y-site administration of medications for both lactated Ringer's solution and Plasma-Lyte, there is limited information on the compatibility of medications administered via a Y-site during Normosol-R infusion.
Researchers undertook the current study to determine the physical compatibility of selected ICU medications with Normosol-R. It is hypothesized that these physical compatibility studies may be extrapolated to indicate whether such medications can be concomitantly administered with NormosolR.
Physical compatibility studies included visual assessment with the Tyndall light assessment, turbidity measurements, and pH measurements that were performed immediately after mixing, and after 1 and 4 hours; the turbidity test was only conducted at 1 and 4 hours post mixing to allow sufficient time for equilibration for microbubbles to dissipate. Study medications, which included amiodarone, caspofungin, dexmedetomidine, dobutamine, dopamine, epinephrine, levofloxacin, norepinephrine, pantoprazole, phenylephrine, piperacicllin/tazobactam, vancomycin, and vasopressin, were diluted with either normal saline or 5% dextrose injection to one clinically used therapeutic concentration, except for epinephrine and norepinephrine; these medications were compounded in two different strengths to reflect use in clinical practice.
Using a 1:1 ratio, simulation of Y-site administration was performed by mixing 20 mL of Normosol-R with 20 mL of the test drug in a 50-mL, clear, colorless tube. Compatibility was checked twice with the order of mixing of the colloid and the drug reversed. A negative control was prepared using 40 mL of the test medication alone, and a positive control was utilized that consisted of acyclovir mixed with levofloxacin, which resulted in a precipitate formation. The solutions were stored in a dark, temperature-controlled (21oC) room.
For the Tyndall light visual assessment test, incompatibility was present if a haze, particulate, gas, or color change was observed. Turbidity measurements were conducted using a portable turbidity meter and were recorded in nephelometric turbidity units (NTU). If the turbidity of the negative control was <0.5 NTU, the test solution was deemed incompatible if the turbidity of the admixture was >0.3 NTU; 0.3 NTU is considered a more stringent threshold to determine incompatibility due to turbidity. Lastly, pH of the admixture was measured using a pH meter with incompatibility defined as an absolute change in pH >1.0. Incompatibility for the overall study was defined as failure of any of the tests at any time point.
The investigators found that there was no evidence of visual incompatibility for any of the admixtures based on Tyndall light visual assessment. However, turbidity was >0.5 NTU for 0.32 mcg/mL of norepinephrine (which was the highest strength), pantoprazole, and phenylephrine. Pantoprazole also failed the pH compatibility test with the range of pH values changing from 8.74 to 8.86 at baseline to 7.98 to 8/25 when mixed with Normosol-R. This crossed the reported pKa of 8.19 and was deemed incompatible.
The authors identified several limitations for this study, including definitions of incompatibility were not consistent or standardized and outcomes may be different in actual patients. Further, the compatibility studies were restricted to only one drug concentration for most medications. Nonetheless, this study helps guide pharmacist when they are advising on the management of critically ill patients who require Y-site administration of the above studied medications.
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