One of the steps involved in preparing IV medications is the mixing of the drug and the IV solution. Failure to completely mix a drug can be considered a type of error, but does this affect the drug concentration being administered?

To help answer this question, an experimental study was conducted to examine the importance of the mixing step after medication addition to the infusion bag. This was achieved by comparing the concentrations of four unmixed antibiotic infusions (i.e., cefuroxime, flucloxacillin [not available in the United States], meropenem, and vancomycin) at regular intervals during a test infusion.

Standardized parameters included doses per injection vial (cefuroxime 1,500 mg and 1,000 mg each of flucloxacillin, meropenem, and vancomycin); volumes after reconstitution (cefuroxime 16 mL and 20 mL each of flucloxacillin, meropenem, and vancomycin); infusion fluid (normal saline 50 mL for cefuroxime, flucloxacillin, and meropenem and 250 mL for vancomycin); and the declared concentrations (1,500 mg/66 mL for cefuroxime, 1,000 mg/70 mL for flucloxacillin and meropenem, and 1,000 mg/270 mL for vancomycin).

Pharmacy technicians prepared two sets of the four antibiotics—one set under the laminar air flow cabinet in the hospital pharmacy cleanroom and the second set in the medication room on the clinical unit. This was performed to determine the effect of normal handling of the IV solution and the impact that transportation may have on the drug concentration if the admixture is not mixed following compounding.

For the antibiotics compounded in the pharmacy, cefuroxime and meropenem were stored at 2 to 8 degrees Celsius and flucloxacillin and vancomycin were stored at room temperature prior to transport to the unit. However, all antibiotic infusions were stored at room temperature for 30 minutes prior to the simulated administration.

The antibiotics were administered via an electronic infusion pump. Cefuroxime, flucloxacillin, and meropenem were infused over 30 minutes, while vancomycin was administered over 120 minutes. Drug samples were collected three times during the infusion to minimize handling, which could affect the degree of mixing. These times were at 1 minute, 15 minutes, and 20 minutes following the start of the administration of cefuroxime, flucloxacillin, and meropenem.

Samples were collected for vancomycin at 1 minute, 60 minutes, and 110 minutes. While the first two samples were collected directly from the infusion line, the third sample was taken directly from the infusion bag to prevent the infusion pump from malfunctioning at the end of the administration period. All samples were stored at -80 degrees Celsius until they were analyzed.

The researchers found that the median concentrations for all four antibiotics were comparable to the declared concentrations at all time points (beginning, middle, and end of administration). All but one of the solutions' concentrations deviated less than 20% from the declared concentration; the 15-minute median concentration of cefuroxime deviated by 30.8% of the declared concentration. There were no statistically significant differences in drug concentrations whether the drug was prepared in the hospital pharmacy cleanroom or in the medication room on the unit.

The authors concluded that spontaneous mixing of the four antibiotics studied occurred even if the mixing step in the compounding process was omitted. The authors cautioned that the concentrations were measured by a method that is standardized for assessing blood levels—not the matrix used—and that overfill of infusion bags was not accounted for. These findings may be specific for these four drugs studied and under the conditions described.

Nonetheless, this study offers pharmacists some reassurance that failure to mix an infusion upon compounding may not adversely affect drug concentrations.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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