title: Evaluation of the impact of viscosity, injection volume, and injection flow rate on subcutaneous injection tolerance.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Becton-Dickinson Medical Pharmaceutical Systems, Le Pont de Claix, France.
authors.forename: Cecile
authors.initials: C
authors.lastname: Berteau
authors.affiliation: Becton-Dickinson Medical Pharmaceutical Systems, Le Pont de Claix, France.
authors.forename: Orchidée
authors.initials: O
authors.lastname: Filipe-Santos
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Eli Lilly and Company, Indianapolis, IN, USA.
authors.forename: Humberto E
authors.initials: HE
authors.lastname: Rojas
authors.affiliation: Becton-Dickinson Medical Pharmaceutical Systems, Le Pont de Claix, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Granger
authors.affiliation: Becton-Dickinson Medical Pharmaceutical Systems, Le Pont de Claix, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Schwarzenbach
keywords: injection speed; injection viscosity; injection volume; pain; subcutaneous