SKIN 
 

March 2019     Volume 3  Issue 2 
 

Copyright 2018 The National Society for Cutaneous Medicine 132 

RISING DERM STARS® 
 

 
In-Vitro Evaluation of Pre-Injection Aspiration as Safety Checkpoint for 
Hyaluronic Fillers 
 
Aaron S. Farberg, MD1, Richard L Torbeck, MD, Ezra Hazan, MD, Jordan V Wang, MD, MBE, 
Hooman Khorasani, MD 
 
1Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY 
 

 
 
Background/Objectives: In 2017, about 2.1 
million procedures using hyaluronic acid (HA) 
fillers were performed in the United States. 
While complications are rare, knowledge 
regarding their prevention and management 
are crucial. Intra-arterial injection can cause 
visual impairment and local skin damage, 
including necrosis. The use of pre-injection 
aspiration has become controversial 
regarding its usefulness as some clinicians 
believe aspiration of blood is not possible. 
However, no study on pre-injection aspiration 
has thoroughly examined physiochemical 
and rheological properties, which can help 
predict behavior of HA fillers. Our study 
investigated the utility of pre-injection 
aspiration as a safety checkpoint for HA 
fillers. 
 
Methods: An in-vitro model consisted of 
fresh whole blood collected in EDTA-coated 
vacutainers that were pressure equalized. 
Syringes containing HA filler were inserted, 
and plungers were each pulled back at 0.2cc 
and 0.5cc volumes to mimic pre-injection 
aspiration. The plunger was held at this 
distance until flashback was visualized or 
until 30 seconds had passed. Syringes of 10 
commonly used HA fillers were evaluated: 
Allergan (Pringy, France) Juvederm Ultra 
Plus XC, Juvederm Ultra XC, Juvederm 
Volbella, Juvederm Vollure, and Juvederm 

Voluma; Galderma (Uppsala, Sweden) 
Restylane Defyne, Restylane Lyft, Restylane 
Refyne, and Restlyane Silk; and Merz 
(Raleigh, N.C.) Belotero Balance. Product 
original syringes and their package provided 
needles were utilized. Values for 
physiochemical and rheological properties at 
0.1 Hz were gathered. 
 
Results: For the 10 HA fillers, the values for 
HA concentration, G’, G’’, and G* varied. 
Using a multivariable regression model 
(R2=.8324; F=12.42; p<.0001), HA 
concentration (p=.0016) and G* (p=.0017) 
were shown to positively affect time to flash, 
while G’ (p=.0017) and G’’ (p=.0029) were 
shown to negatively affect time to flash. 
Needle gauge (p=.1641) and pullback 
distance (p=.3263) did not show any 
significant effect in this model. However, 
when comparing pullback distance using a 
paired analysis for each HA filler, 0.5cc 
pullback distance had a significantly 
decreased mean time to flash than 0.2cc 
(8.86 vs 10.86; p=.0389). All HA fillers, 
except for Restylane Defyne, showed a 
decreased time to flash with 0.5cc vs 0.2cc 
pullback distance. A significantly greater 
decrease in time to flash between 0.5cc and 
0.2cc pullback distance was associated with 
HA concentration >21mg/ml (4.5 vs 0.57; 
p=.0166), G’ <153Pa (4.4 vs 0; p=.0024), and 



SKIN 
 

March 2019     Volume 3  Issue 2 
 

Copyright 2018 The National Society for Cutaneous Medicine 133 

G* <155Pa (4.4 vs 0; p=.0024), while G’’ 
showed no significant difference. 
 
Conclusion: Pre-injection aspiration may 
have utility as a safety checkpoint for HA 
fillers. Practitioners may have to adjust 
pullback distance of the plunger and waiting 
time to visualize the flashback based on 
physiochemical and rheological properties.