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Published on: October 12, 2012
The Physical Compatibility of Clinically Used Concentrations of Diltiazem Hydrochloride With Heparin Sodium
Sydney R Dobson1, Vincent F Mauro1, Sai H S Boddu2
1University of Toledo, Toledo, OH, USA.
Insights
Higher concentration diltiazem (5 mg/mL) is incompatible with heparin infusions. Lower concentration diltiazem (1 mg/mL) with heparin is physically compatible, but chemical stability requires further study.
Area of Science:
- Critical care medicine
- Cardiology
- Pharmacology
Background:
- Acute treatment of atrial fibrillation often necessitates concurrent intravenous infusions of unfractionated heparin and diltiazem.
- Co-infusion via a single IV line minimizes venipuncture sites.
- Previous compatibility studies had limitations in drug concentrations and dwell times.
Purpose of the Study:
- To assess the physical compatibility of diltiazem hydrochloride at 5 mg/mL and 1 mg/mL with heparin sodium at 100 units/mL.
- To determine compatibility through visual inspection, spectrophotometry, and pH monitoring.
Main Methods:
- Heparin sodium (100 units/mL) was mixed with equal volumes of diltiazem hydrochloride (5 mg/mL or 1 mg/mL) in PVC bags.
- Admixtures were analyzed in triplicate for visual precipitation, turbidity, absorbance, and pH at specified time points up to 24 hours.
- Physical incompatibility criteria included visual changes, increased absorbance, and significant pH shifts.
Main Results:
- Diltiazem 5 mg/mL admixtures showed haze and increased absorbance, indicating turbidity.
- No significant pH changes were observed with the 5 mg/mL diltiazem admixture.
- Diltiazem 1 mg/mL admixtures exhibited no visual precipitation or turbidity, with only one minor pH fluctuation.
Conclusions:
- Co-infusion of diltiazem hydrochloride 5 mg/mL with heparin sodium 100 units/mL is not recommended due to physical incompatibility.
- Diltiazem hydrochloride 1 mg/mL appears physically compatible with heparin sodium 100 units/mL, although chemical stability was not evaluated.
Abstract:
Background: Acute treatment of atrial fibrillation often requires concomitant intravenous (IV) continuous infusions of unfractionated heparin and diltiazem. Concomitantly infusing these medications through the same IV line minimizes multiple IV sites. Diltiazem and heparin visual compatibility have been previously investigated but with limited drug dwell times and differing drug concentrations leading to inconsistent published results. Objective: To investigate the physical compatibility of diltiazem hydrochloride at concentrations of 5 and 1 mg/mL combined with an equal volume of heparin sodium 100 units/mL. Methods: Using a 0.22-µm filter, 15 mL of heparin sodium were placed into a polyvinyl chloride infusion bag followed by 15 mL of either diltiazem hydrochloride 5 or 1 mg/mL. Admixtures were prepared in triplicate. Each admixture was investigated for visual precipitation, spectrophotometric absorbance, and pH change at baseline and 1, 5, 8, and 24 hours after mixing. Physical incompatibility was determined by visual observation, increased spectrophotometric absorbance, and demonstrative pH changes. Results: Each diltiazem 5 mg/mL admixture exhibited a slight haze and enhanced absorbance readings indicating turbidity while none revealed a demonstrative pH change. None of the diltiazem 1 mg/mL assessments revealed visual precipitation or suggested turbidity. Only one pH reading at 5 hours revealed a demonstrative change from baseline. Conclusions: Our findings indicate that infusing diltiazem hydrochloride 5 mg/mL with heparin sodium 100 units/mL in the same IV line cannot be advocated. In contrast, our findings suggest that heparin sodium 100 units/mL infused with diltiazem hydrochloride 1 mg/mL is physically compatible but chemical stability was not assessed.
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