Preparation of ready-to-use 5 µg/mL norepinephrine syringes to manage anesthesiainduced arterial hypotension

Norepinephrine (NE) is used to manage anesthesia-induced arterial hypotension
(intermittent IV bolus or continuous infusion). The objective of this study was to investigate the reconstitution of norepinephrine syringes at 5 µg/mL obtained by dilution at 1:400 in operating room, and then to propose compounding of hospital preparation by the pharmacy unit. NE concentration was assessed thanks to the development of a HPLC-DAD stability indicating method. Regarding the analytical method, linearity was demonstrated (r² > 0.999, residues < 5%) from 0 to 20 µg/mL and quality controls performed at 2.5, 5 and 20 µg/mL demonstrated the precision (CV < 5.54%) and accuracy (bias 6.25%) of the method. For syringes reconstituted in the operating room, observed mean was significantly different (p =
0.022) compared to theoretical mean (5 µg/mL) and 68% of the reconstituted syringes were outside the accepted limit (± 10%), while the concentration of all syringes prepared at the pharmacy were at 5 µg/mL ± 10%. Moreover, our study demonstrated the physico-chemical stability of NE syringes at 5 µg/mL over 28 days of storage at 5 ± 3°C. The reconstitution of NE syringes at the operating room shows high variability exposing the patient to inadequate dose leading, to potential health risk. Therefore we propose an alternative using NE syringes prepared at the pharmacy unit to ensure security and safety of patient treated for anesthesiainduced arterial hypotension.

Keywords: norepinephrine, bolus, assay validation, reconstitution, hospital preparation