Retraction of the Plunger on a Syringe of Hyaluronic Acid

Before Injection: Are We Safe?

Wayne Carey, MD, FRCP(c), FAAD,* and Susan Weinkle, MD, FAAD†

BACKGROUND Controversy exists concerning the need for aspiration before injection with hyaluronic acid
(HA) fillers.

OBJECTIVE The authors undertook a study of HA products to determine if blood could be aspirated back into
a syringe of HA when the needle has been primed or filled with HA.

METHODS AND MATERIALS Two studies were set up to determine if or when blood could be withdrawn
from a heparinized fresh tube of blood into the HA syringe. Two different techniques were tested; one using
a slow-pull retraction of the plunger and up to a 5-second waiting time before release versus a rapid pullback
and quick release.

RESULTS Review of these data demonstrates that the usual clinical method, which involves quick withdrawal
and instant release of the syringe plunger does not allow for sufficient removal of the filler found intraluminal
in the needle and may give rise to false negative results in vitro and likely in vivo with the exception being the
Galderma/Medicis products.

CONCLUSION In summary, withdrawal of the syringe plunger with no visible blood in the syringe does not
eliminate the possibility of intravascular placement of the syringe needle.

Dr. W. Carey is a consultant and speaker for Teoxane, Merz and Galderma. Dr S. Weinkle is a consultant and
speaker for Merz, Galderma and Allergan.

C ontroversy exists concerning the need for

aspiration before injection with hyaluronic acid
(HA) fillers. Traditionally, before any injection into
the body, 2 principles regularly taught are removal of
air from the syringe by priming or filling the needle
with the solution and withdrawing the plunger in vivo
before injection to ensure that the needle is not
intravascular.1 Typically, the injected material is an
aqueous type of solution with similar characteristics
and flow comparable with blood. Withdrawal of
the plunger would easily draw back the solution into
the syringe and allow blood to enter the syringe if the
needle was located in the lumen of a vessel. However,
HA fillers used for cosmetic procedures have a gel-like
consistency which do not have the same flow
parameters of a liquid, and may impede the flow of
blood back into the syringe. A negative pull test by
*Department of Dermatology, McGill University, Montreal, Canada; †Department of Dermatology, University of South
Florida, Bradenton, Florida
retraction of the plunger before injection using these
products may give a false sense of security that the
needle is extravascular.
The authors undertook a study of HA products
obtained from 4 of the major manufacturers to
determine if blood could be aspirated back into
a syringe of HA when the needle has been filled with
HA. The authors examined all available HA products
of each company to study these findings.
The authors used a series of different gauge needles of
the same length on all products except for 2 companies
where additionally the authors used their supplied
29 G 1$ needle and 25 G 1$ needle. Two different
techniques were tested; one using a slow-pull retrac-
tion of the plunger and up to a 5 seconds waiting time

© 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.
· ·
ISSN: 1076-0512 Dermatol Surg 2015;41:S340–S346 DOI: 10.1097/DSS.0000000000000557

S340

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versus a rapid pullback and quick release, which rep-
resents more accurately the technique used in clinical
practice. This was performed on each product using
needles with increasing diameter until blood was
aspirated.
Overall their findings suggest that for the majority of
the products particularly with a high G prime and high
cohesivity that retraction of the plunger when using
primed smaller gauge needles or needles presupplied
with product do not allow for clearing of gel in the
needle lumen or hub. Subsequently, entry of blood into
the syringe is blocked, particularly when using a rapid-
pull release method. Therefore, the concept of being
extravascular while injecting HA cannot be deter-
mined in most cases by aspiration before injection. The
importance of these findings is applicable mainly for
bolus injections where the needle is held in a stationary
position.
Also with the increased use of motorized injectable
devices that do not allow for the retraction of the
plunger before injection, these results are relevant in
determining their safety compared with the manual
method.
Methods
In vivo and in vitro experiments were done to deter-
mine the smallest needle caliber through which blood
could be aspirated into an empty syringe without HA
present either in the needle or in the syringe.
Next, an in vitro study was performed to determine
where the potential blockage to aspiration of blood
could occur. Initially syringes of filler with the needle
loaded with HA were used in an attempt to obtain
blood from a heparinized tube of blood. If the authors
were unable to withdraw blood, the primed needle was
removed from that particular syringe and an empty
needle of the same caliber devoid of HA was attached
and reinserted into the tube to determine if blood could
be withdrawn into the syringe.
Subsequently, 2 studies were set up to determine if or
when blood could be withdrawn from a heparinized
fresh tube of blood into the HA syringe. The authors
© 2015 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
CAREY AND WEINKLE
used a series of increasing diameter needles until blood
was obtained. The authors studied the complete
product lines of 4 HA manufacturers, Teoxane, Merz,
Galderma/Medicis, and Allergan. Some lines were not
available in the United States and were studied only by
the lead author.
All needles were primed with HA before withdrawing.
A series of needles were used starting with the
company-supplied 30 G, 29 G(Medicis only), 27 G,
company-supplied 27 G (larger lumen), and finally
25 G and 25 G(Teoxane supplied). The product-
specific needle supplied in the box was always used for
the tested material and is indicated in the chart (Tables
1 and 2 indicated in red).
For the first technique, the slow pullback and hold
method (Table 1), 0.6 mL of material was initially
extruded and discarded from the 1 mL syringes or 1.6
mL in the 2 mL syringes. This was to allow sufficient
space to pullback the plunger to a maximum of 0.8
mL (0.4 mL of product and 0.4 of empty space) to
create a significant negative pressure estimated to be
0.5 atm.
With 0.4 mL of HA material left in the syringe, initially
a 30 G needle was primed with the tested HA before
insertion of the needle through the rubber stopper of
the tube containing heparinized blood. The tube was
held at approximately a 20° incline.
First, the authors determined what the smallest caliber
of needle was through which blood could be aspirated
into the tested syringe. If no blood was withdrawn, the
needle was changed up to the next larger diameter and
a small amount of material was extruded again to
prime or fill the needle. The systematic increase in the
needle caliber was continued until blood was with-
drawn into the syringe.
For the first technique of slow pullback, the plunger
was retracted very slowly using approximately 10
seconds to reach the 0.8 mL marking of the syringe if
needed representing a negative pressure of 0.4 mL.
The plunger was also retained in place up to a maxi-
mum of 5 seconds before release. The negative pres-
sure was noted in mL if blood entered the syringe
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 SAFETY OF PLUNGER RETRACTION

TABLE 1. Slow-pull Test

Needle Gauge

Product 30 G 29 G (R Only) 27 reg 27 G Company 25 G 25 1$ Company

Perlane 0.3 mL 0.2 mL N/A N/A N/A
Restylane 0.3 mL 0.2 mL N/A N/A N/A
Fine Lines 0.05 mL 0.1 mL N/A N/A N/A

Fortelis FE neg N/A neg neg neg

Modelis Lido MS neg N/A neg neg neg
Esthelis Basic Lido EB neg N/A neg 0.1 mL N/A Two needles supplied in box
Esthelis Soft Lido 0.1 mL N/A N/A N/A N/A

Juvederm Ultra 30g neg N/A 0.2 mL N/A N/A

Ultra Plus 27g neg N/A neg 0.2 mL N/A Plunger came off
Ultra XC 30g neg N/A neg 0.4 mL/hold N/A
Ultra XC Plus 27g neg N/A neg 0.2 mL N/A
Forma 27g neg N/A neg neg neg Plunger came off
Voluma 27g 0.3 mL N/A N/A N/A N/A
Volift 30g 0.2 mL N/A N/A N/A N/A
Refine 30g neg N/A neg 0.2 mL 0.3 mL

Ultimate neg N/A 0.4 mL 0.4 mL/hold N/A

Ultra Deep neg N/A N/A neg neg neg
Deep Lines neg N/A neg 0.4 mL/hold 0.1 mL
Global 0.4 mL N/A N/A N/A N/A

Kiss neg N/A 0.3 mL 0.3 mL N/A

First Lines 0.3 mL N/A N/A N/A N/A
Redensity 1 0.3 mL N/A N/A N/A N/A
Redensity 2 0.4 mL N/A N/A N/A N/A
RHA4 neg N/A neg neg neg
RHA3 neg N/A neg 0.4 mL/hold N/A
RHA2 neg N/A neg neg neg
RHA1 0.1 mL N/A N/A N/A N/A

Bold lettering indicates company supplied needle.

The 0.4 mL and hold indicates that during the 5 seconds hold period at 0.4 mL retraction that blood was obtained (0.4 mL of product and
0.4 mL empty space).
The mL indicates, for example that the plunger went from the initial 0.4 mL to 0.6 mL marking before blood was seen in the syringe (i.e.,
marked 0.2 mL).
N/A—the material was not tested with the needle; neg signifies that no blood was obtained in the syringe after retracting plunger another
0.4 mL and holding for 5 seconds before releasing the plunger. If blood was observed in the syringe no further testing was done on larger
diameter needles unless the company supplied needle had not been tested.

during the retraction period before reaching the 0.8
mL mark.
The second technique was used to replicate the usual
clinical technique used by many of the injectors who
perform a rapid pullback before injection (Table 2).
The plunger was pulled back promptly and then
released using the thumb of the injecting hand, as often
the nondominant hand is used to hold the skin tight
and may not be available to withdraw on the plunger.
The syringes were loaded in the same manner as in the
slow pullback technique and the needles were similarly
systematically exchanged using larger calibers until
blood was obtained.

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 CAREY AND WEINKLE

TABLE 2. Snap Test

Needle Gauge

Product 30 G 29 G 27 G Reg 27 G 25 G 25 G 1$
Perlane neg neg neg neg N/A
Restylane neg 0.3 mL N/A N/A N/A
Fine Lines neg 0.1 mL N/A N/A N/A

Fortelis FE neg N/A neg neg neg

Modelis Lido MS neg N/A neg neg neg
Esthelis Basic Lido EB neg N/A neg neg neg Two needles supplied
in box 30 and 27g
Esthelis Soft Lido neg N/A 0.4 mL 0.1 mL 0.1 mL

Juvederm Ultra neg N/A neg neg neg

Ultra Plus neg N/A neg neg neg
Ultra XC neg N/A neg neg neg
Ultra XC Plus neg N/A neg 0.3 mL N/A
Forma neg N/A neg neg neg
Voluma neg N/A neg 0.2 mL N/A
Volift 0.3 mL N/A N/A N/A N/A
Refine neg N/A neg neg neg

Ultimate neg N/A neg neg neg

Ultra Deep neg N/A neg neg neg neg
Deep Lines neg N/A 0.3 mL N/A N/A
Global neg N/A 0.2 mL N/A N/A
Kiss neg N/A neg neg neg
First Lines 0.2 mL N/A N/A N/A N/A
Redensity 1 neg N/A 0.2 mL N/A N/A
Redensity 2 neg N/A 0.2 mL N/A N/A
RHA4 neg N/A neg neg neg
RHA3 neg N/A neg neg neg
RHA2 neg N/A neg neg neg
RHA1 0.2 mL N/A N/A N/A N/A

Bold lettering indicates company supplied needle.

N/A—the material was not tested with the needle. Neg signifies that no blood was obtained in the syringe after retracting the plunger
rapidly 0.4 ml and releasing immediately the plunger. The mL signifies the amount of retraction before blood was obtained in the
syringe.

Results blood. This phenomenon is less likely to occur in an

Using an empty syringe and a needle free of HA it is
easy to withdraw blood in vivo from a vein or in vitro
from a tube containing heparinized blood, even with
a 32 G needle. As the gauge increases so does the flow
rate into the syringe.
In vivo, too strong of a negative pressure created by
rapid or excessive pulling back of the plunger can
collapse a small vein preventing withdrawal of
artery.
Because a greater pressure gradient is required for
gels compared with water (saline) (oral communi-
cation, M Lupin MD, FRCP, PhD[Physics], May
2015), there is a tendency to pullback the plunger
with a quick accelerated movement, which may col-
lapse the vessel and give a false negative result of
intravascular placement. Therefore a slow, gentle,

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 SAFETY OF PLUNGER RETRACTION
but firm withdrawal of the plunger in a linear non-
accelerated manner is essential if the practitioner is
attempting to check for intravascular placement of
the needle.
In vitro, when withdrawal test brings back no blood
from the test tube, by replacing the HA-loaded needle
with a HA-free needle of the same gauge or even
smaller, one can then readily withdraw blood into the
HA-containing syringe in all cases. This clearly dem-
onstrates that the ability to withdraw blood into the
syringe requires the needle lumen or hub to be cleared
of HA. The viscosity of blood or the material in the
syringe itself plays no role.
Factors affecting the removal of HA from the needle
will be the consistency and cohesivity of the material,
length of the needle, force of suction applied, and the
time under negative pressure during withdrawal.
Theoretically, products that are less cohesive and or
having a low G prime would likely be released from the
needle more easily as seen in this study.2,3
Review of these data also demonstrates that the usual
clinical technique, which involves pulling back quickly
with a short wait time before release, in most cases
does not allow for sufficient removal of the intra-
luminal filler, leading to false negative results in vitro
and likely in vivo.
Using a slower withdrawal rate then holding the
syringe under a negative pressure for up to 5 seconds
demonstrates that there is variability between different
product lines and different companies. There were also
more positive results when comparing the same
product and needle size from this technique with the
rapid pull and release method. The products that are
cleared intraluminally consistently on the slow-pull
test are the products from Galderma/Medicis when
using only their supplied needles. Despite having
a high G prime, this product also has a low cohesive
value.2 On the rapid pull test, it was negative only for
Perlane.
Using a manual retraction method, certain varia-
bles could not be controlled such as a uniform
retraction pressure on each syringe but the findings
S344 DERMATOLOGIC SURGERY
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suggest that for the majority of the products par-
ticularly with a high G prime and cohesivity,
retraction of the plunger when using smaller gauge
needles or those supplied with the particular prod-
uct do not allow for cleansing of the needle lumen or
hub and thus subsequent entry of blood into the
syringe, particularly when using a rapid pull release
method.
Discussion
Intraarterial or intravenous injection of HA is an
undesirable side effect with the former having more
serious consequences. Although not frequent, the
results of vascular occlusion also known as Nicolau
syndrome can result in necrosis, scarring and mor-
bidity, blindness, or less commonly ischemic cerebral
accidents.4 A number of procedures and treatments
have been described previously to deal with this
medical emergency.4,5 This may occur more com-
monly in areas having had previous surgery because
the vessels are less mobile and more susceptible to
puncture.
There are conflicting reports on preventing intravas-
cular injections. Many authors have recommended
withdrawal of the plunger before injection, the use of
cannulas only, using small bore needles, using large
bore needles, concomitant use or the absence of lido-
caine containing epinephrine, injecting a small bolus at
multiple sites, injecting slowly, pinching the tissue
before injection, compression, or limitation of vol-
ume.4–6 Despite the technique used, from the experi-
ence of the injector or precautions taken, an
intravascular injection may occur.
The authors took a particular interest in studying the
dynamics of plunger withdrawal before injection.
Both authors prefer using needles and do not aspirate
before injecting HA syringes. This method is done or
recommended routinely but it is not evidence based
but rather on an historic adage, it is important to
withdraw the plunger before injecting.
The studies performed demonstrated clearly that to be
100% certain that blood is pulled back successfully if
the needle or cannula was intravascular would be to

Figure 1. Motorized delivery equipment.
change the needle each time one injected a bolus
with a HA-free nonprimed needle. This method,
however, would be impractical, create a significant
loss of product in the dead space of the discarded
needle with each injection, with also the potential
risk of an air embolus because the empty needle
contains air.
The results show that withdrawal in most cases fails to
clear the needle lumen of material allowing return of
blood, particularly with the rapid pull–release
method. Whether material remains in the narrow
lumen or congests the needle hub or both is not certain.
The more efficacious technique of the 2 methods to
withdraw blood is to maintain a maximum negative
pressure with a prolonged waiting period, which may
release the material. However, this would be imprac-
tical, and not always a certainty. Certain product lines
and certain companies have products, which are more
likely to block the needle. The Galderma/Medicis
products routinely are cleared from the needle using
the slow-pull technique.
The rapid pull and release technique is significantly
less effective in demonstrating blood withdrawal,
especially with cohesive HA materials. Company
supplied needles, which are usually of a smaller caliber
will impede blood return. Another factor complicating
this maneuver is that with a full syringe of HA less
negative pressure can be achieved with retraction of
the plunger. Not all companies have their plungers
screwed into the mobile rubber tip and the plunger can
be easily pulled off this on retraction of the plunger.
The other point to be made is that it is unlikely with the
maneuvers required to pullback and release a viscous
gel that the needle remains absolutely in the exact same
cutaneous position during the withdrawal and release
of the syringe plunger.
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CAREY AND WEINKLE
Certain areas may be more prone to inadvertent
intravascular injections or more susceptible to dam-
age due to lack of collateral circulation.6 The cuta-
neous tissue in the region of the superior nasolabial
line lateral to the nose at the site of the lateral nasal
branch of the angular artery is extremely fibrous and
adherent possibly preventing vessels to be pushed out
of the way with an advancing needle or small can-
nulas, as may occur in scar tissue. In contrast, certain
areas sometimes labeled as dangerous such as the
infraorbital artery/vein location7 are relatively com-
paratively safe due to an extensive collateral
circulation.8
It has been postulated that certain types of HA may
elicit more damage than others depending on their
rheological properties.4 The quantity of material
will likely affect the outcome. Usually more than
0.1 mL needs to be injected intraarterially to cause
significant injury likely due to collateral vessels
except in a few specific areas such as the retina.
Therefore a slow, prudent “stop and go” technique
should limit damage. In most cases an embolization
can be recognized immediately, by an immediate
whitening of the skin, and subsequent bluish hue.
Therefore, injecting rapidly under high pressure
may result in larger amounts delivered intravascu-
larly before action can be taken to stop the
injection.
From these data, the controversy surrounding the
safety of motorized delivery equipment such as the
Teosyal Pen, AIS, and The Artist (Figure 1), which do
not allow for retraction of the plunger, is negated.
Because they have as a feature, a controllable flow
rate, and continuous low pressure that can be even
delivered in drops, there may be reduction in injection
risks.
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 SAFETY OF PLUNGER RETRACTION
Motorized devices may also offer some advantages
whereby multiple controlled micro boluses can be
delivered, particularly in danger zones such as the
nose. It may allow the physician to maintain their
concentration on observing the patient without
having to concentrate on the injecting hand and
the volume delivered. 9 Many of the cases of
embolism recorded were in situations where the
material was being injected under high pressure. 4
More case studies will be required to document
this decreased risk using motorized injectable
devices.
In summary, one cannot document negative intra-
vascular position with a negative pullback of the
plunger. Certain maneuvers such as compressing,
tenting, pinching, and slow injections may diminish
the risk or the degree of damage if it occurs. One
author suggests limiting the injection flow to 0.3 mL/
min.7 The authors agree and suggest an even longer
injection duration of 2 minutes per 0.3 mL, particu-
larly when injecting in susceptible areas. For physi-
cians who wish to continue using a pullback
technique before injection, the authors can only rec-
ommend using a large bore needle, maximum nega-
tive pressure, fixation of the syringe position, and
extended waiting time while the syringe is under
negative pressure.
S346 DERMATOLOGIC SURGERY
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Acknowledgments The authors gratefully
acknowledge the editorial contributions of Dr. Beatrice
Wang.
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Address correspondence and reprint requests to: Wayne
Carey, MD, FRCP(c), FAAD, Suite 100, 4 Westmount
Square, Montreal, Quebec, Canada H3Z 2S6, or e-mail:
wayne.carey@mcgill.ca