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Stability of norepinephrine infusions prepared in dextrose and normal saline solutions

[La stabilité des perfusions de norépinéphrine préparées dans des solutions dextrosées ou salées]

Maryse Tremblay, MD FRCPC^*, Martin R. Lessard, MD FRCPC^*, Claude A. Trépanier, MD FRCPC^*, Pierre C. Nicole, MD FRCPC^*, Linda Nadeau, MD FRCPC and Gilles Turcotte, MD MSc

^* From the Departments of Anesthesiology, and
Medical Biology, Centre hospitalier affilié universitaire de Québec, Université Laval, Québec City, Québec, Canada.

Address correspondence to: Dr. Martin R. Lessard, Département d’anesthésie-réanimation, Hôpital de l’Enfant-Jésus du CHA, 1401, 18e rue, Québec City, Québec G1J 1Z4, Canada. Phone: 418-649-5807; Fax: 418-649-5918; E-mail: martin.lessard{at}anr.ulaval.ca

Purpose: Norepinephrine (NE) infusions are commonly used in the intensive care unit and in the operating room. Data on long term stability of NE solutions are lacking. This prospective study was designed to evaluate the stability of NE, in dextrose (5%) in water (D5W) and in normal saline (NS) solutions, for a period up to seven days.

Methods: We prepared norepinephrine solutions in quadruplicate, by aseptically diluting 1 mg NE in 250 mL of D5W or NS and 4 mg NE in 250 mL of D5W or NS (final concentrations, 4 µg·mL^–1 and 16 µg·mL^–1, respectively) and stored the solutions at room temperature under ambient light. We sampled the solutions, in duplicate, at times 0, 24, 48, 72, 120, and 168 hr and stored them at –80°C for later assay. Norepinephrine concentrations were measured by high-performance liquid chromatography with electrochemical detection (coefficient of variation 4.6%). Statistical analysis was done by nonparametric, repeated measures ANOVA (Friedman test).

Results: There was no significant decrease in NE concentration for either, NE 4 µg·mL^–1 in D5W or NS (P = 0.09 and 0.11, respectively) or for NE 16 µg·mL^–1 in D5W or NS (P = 0.18 and 0.40, respectively). The ratios of NE concentration at 168 hr, compared to baseline, were 95.7% and 96.4%, for NE 4 µg·mL^–1 in D5W and NS, respectively, and 104.5% and 96.4%, for NE 16 µg·mL^–1 in D5W and NS, respectively.

Conclusion: Norepinephrine solutions, in concentrations commonly used in the clinical setting, are chemically stable for seven days, at room temperature and under ambient light, when diluted either in D5W or NS.

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