Norepinephrine syringes in the operating room: accuracy of preparation and pharmacy supply
23 November 2020M. Delamotte1, L. Serreau2, N. Gillier2, G. Binson1, A. Dupuis1 1 Pharmacy Department, 2 rue de la milétrie, 86000 Poitiers, France
2 Poitiers, Anesthesia – reanimation Department, 2 rue de la milétrie, 86000 Poitiers, France
Norepinephrine (NE) is used in anesthesia for the emergency treatment of cardiovascular collapse.
Daily, syringes of NE at 5 µg/mL are prepared by nurses from glass vial at 2 mg/mL, using a double dilution 1:20 to obtain the required concentration. We found differences in practice and the objective of this study was to verify the concentration of NE syringes after dilution.
Material and Method
This is a monocentric, retrospective study and the collection of syringes was done over two weeks. An HPLC-DAD of NE assay method was developed and validated according to ICH criteria. NE syringes after the first dilution (100 µg/mL) and after the second dilution (5 µg/mL) were collected daily and immediately sent to the pharmacy for testing (n = 50 for each concentration). For each concentration, we evaluated the distribution of the results and compared the observed means to the theoretical means (Z-test).
Regarding the assay method, linearity was demonstrated (r²> 0.999, residue < 10%) from 0 to 20 µg/mL and quality controls at 2.5; 5 and 20 µg/mL demonstrated the precision (CV < 5.54%) and accuracy (6.24%) of the method. The forced degradation study did not show any degradation products interfering with the NE peak. For 100 µg/mL syringes: the mean (± standard deviation) concentration obtained was 99.45 (± 14.42) µg/mL and the median was 96.48 µg/mL. The difference between the observed mean and the theoretical mean is not significantly different (p = 0.78). 32% of the values are outside the accepted bias (+/- 10%).
For 5 µg/mL syringes: the mean concentration (± standard deviation) obtained is 5.81 (± 2.51) µg/mL and the median is 5.09 µg/mL. The difference between the observed mean and the theoretical mean is significantly different (p = 0.025). 68% of the values are outside the accepted bias (+/- 10%).
Discussion and Conclusion
Practices of NE used in anesthesia show a high variability in the preparation of NE syringes at 5 µg/mL. This may expose the patient to overdose or inadequate management of collapse. An alternative would be to ensure the production of these syringes at the pharmacy, in order to homogenize the manufacturing process and ensure a releasable analytical control. This requires the performance of physicochemical and microbiological stability studies that are currently underway.