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. 2015 Nov 11:8:473-84.
doi: 10.2147/MDER.S91019. eCollection 2015.

Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance

Cecile Berteau  1 , Orchidée Filipe-Santos  1 , Tao Wang  2 , Humberto E Rojas  2 , Corinne Granger  1 , Florence Schwarzenbach  1
Affiliations

Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance

Cecile Berteau et al. Med Devices (Auckl). .

Abstract

Aim: The primary objective of this study was to evaluate the impact of fluid injection viscosity in combination with different injection volumes and flow rates on subcutaneous (SC) injection pain tolerance.

Methods: The study was a single-center, comparative, randomized, crossover, Phase I study in 24 healthy adults. Each participant received six injections in the abdomen area of either a 2 or 3 mL placebo solution, with three different fluid viscosities (1, 8-10, and 15-20 cP) combined with two different injection flow rates (0.02 and 0.3 mL/s). All injections were performed with 50 mL syringes and 27G, 6 mm needles. Perceived injection pain was assessed using a 100 mm visual analog scale (VAS) (0 mm/no pain, 100 mm/extreme pain). The location and depth of the injected fluid was assessed through 2D ultrasound echography images.

Results: Viscosity levels had significant impact on perceived injection pain (P=0.0003). Specifically, less pain was associated with high viscosity (VAS =12.6 mm) than medium (VAS =16.6 mm) or low (VAS =22.1 mm) viscosities, with a significant difference between high and low viscosities (P=0.0002). Target injection volume of 2 or 3 mL was demonstrated to have no significant impact on perceived injection pain (P=0.89). Slow (0.02 mL/s) or fast (0.30 mL/s) injection rates also showed no significant impact on perceived pain during SC injection (P=0.79). In 92% of injections, the injected fluid was located exclusively in SC tissue whereas the remaining injected fluids were found located in SC and/or intradermal layers.

Conclusion: The results of this study suggest that solutions of up to 3 mL and up to 15-20 cP injected into the abdomen within 10 seconds are well tolerated without pain. High viscosity injections were shown to be the most tolerated, whereas injection volume and flow rates did not impact perceived pain.

Keywords: injection speed; injection viscosity; injection volume; pain; subcutaneous.

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Figures

Figure 1
Figure 1
Study subjects enrollment. Notes: Viscosity: H, high (15–20 cP); M, medium (8–10 cP); L, low (1 cP). Speed: F, fast 0.30 mL/s; S, slow 0.20 mL/s.
Figure 2
Figure 2
Injection procedure and injection site location. Notes (A) Injection procedure. The delivery system was composed of plastic syringe 50 mL (BD Plastipak™) connected to one electric pump (Agilia® Fresenius) and linked to a 27G 6 mm needle (Mesalyse® Microinjection needle) through an extension line (BD Connecta™). The needle was introduced perpendicularly to the skin. A foam pad was used to maintain this position during the entire duration of the injection. (B) Injection site location. Each subject received six injections in the abdomen area, divided into two sessions, one in the morning (1, 3, 5), the other in the afternoon (2, 4, 6). Abbreviation: SC, subcutaneous.
Figure 3
Figure 3
Perceived injection pain for all 144 injections at needle insertion and after injection completion. Note: VAS was used to assess pain and goes from 0 mm/no pain to 100 mm/extreme pain; medians are indicated. Abbreviation: VAS, visual analog scale.
Figure 4
Figure 4
Perceived injection pain after the end of the 144 injections, per group of volume, speed of injection, and viscosity. Notes: VAS was used to assess pain and goes from 0 mm/no pain to 100 mm/extreme pain; medians are indicated. A significant difference is observed across viscosity injections (*P=0.0003). Abbreviation: VAS, visual analog scale.
Figure 5
Figure 5
Injected fluid location after injection (N=144). Notes: (A) Example of typical 2D-ultrasound B-mode echography of the injection site in the abdomen, before (left) and after (right) injection in the same subject. The white arrow measures the injection depth. (B) Fluid location evaluated by echography images, percentage of fluid located exclusively in SC tissue. Significant difference (*P=0.0213) between 2 and 3 mL injections: fluid located exclusively in SC tissue more frequently with 3 mL injections. Abbreviation: SC, subcutaneous; 2D, two-dimensional.
See this image and copyright information in PMC

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