Spiros^® and small administration volume: gravimetric control helps limit waste

Objective
Connected to a syringe, the Spiros^® permits to administer a cytotoxic agent while reducing the risk of exposure to the nurse. Its volume of approximately 0.1 mL requires a larger quantity of cytotoxic agent wich is not administered (Dead Volume (DV)). Our production is gravimetrically controlled with a weight +/- 5%. This DV may not be negligible regarding the small volume of cytotoxic agent to be administered. The aim of this study is to compensate for this DV with the help of gravimetry.

Material and Method
Several series of weighing using Water for Injection preparation (WFIP) as a template were performed with a target volume of 2 mL and weight of 1.964 g. All samples were taken with a Spiros^®.
The DV of the connected Spiros^® and syringe was determined. A Student’s t test (risk α = 5%) was performed for the following 4 tests: a) target volume = target mass, b) target volume + 5% of target mass, c) target mass = 1.964 g, d) target mass + mass of DV.

Results
The mass of WFIP is obtained by series of weighings for volumes of 0.1 and 0.2 mL using a micropipette.
The DV is 0.18 mL (n = 40 σ = 0.010 mL). For situations a), b), c) and d), the "injected" masses (simulating the injection) are 1.984 g (p-value = 1.97.10^-6 σ = 0.029g), 2.081g (p-value = 1.66.10^-9 σ= 0.015g), 1.802g (p-value= 2.64.10^-8 σ= 0.029g) and 1.967g (p-value = 0.65 σ = 0.019g) respectively.
Situations a), b), c) and d) have a deviation of the "injected" mass of 1.01%, 5.94%, 8.25%, and 0.77% respectively from our target weight.

Discussion and Conclusion
The DV has a non-negligible impact for 2 mL preparations (e.g. azacitidine). This will have a greater impact regarding to the lower the cytotoxic mass and lesser or negligible impact for higher cytotoxic masses.
All situations lead to inject significantly different masses from our target weight, except situation d). Situations a) and d) are within the tolerance of +/- 5%. As we use gravimetry exclusively for the control of our preparations, situation d) is the one we shall use for our preparations.
The target weight +/- 5% is automatically calculated by Chimio^® software on our production sheets. We shall therefore have to make the calculations ourselves to lead to situation d). An automated calculation transcribed on a label via Excel^® will be made. Situation a) requires at least a double visual check. This method is less accurate than situation d) and does not guarantee the accuracy of the cytotoxic agent used. Gravimetry is one of the most accurate control methods for preparing a cytotoxic.

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