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Sensitivity of Aspiration As A Safety Test Before Injection of Soft Tissue Fillers
Sensitivity of Aspiration As A Safety Test Before Injection of Soft Tissue Fillers
DOI: 10.1111/jocd.12437
BACK TO BASICS
MD | Job Thuis MD
Jani AJ Van Loghem MD | James J Fouche
KEYWORDS
aspiration, complications, embolism, prevention, soft tissue fillers
under applied pressure are known as G prime (G’).10 The higher the the needle hub. When STF product packages contained needles with
G’ of a STF, the less it will deform under pressure and the more dimensions other than our selected needle dimensions, these needles
stored energy it retains. Thickness, or viscosity of a STF in its fluid were also tested with the STF’s with which they were supplied.
form (g*), refers to the measure of its resistance to gradual reforma- The aspiration test was then repeated using the same protocol,
tion by shear stress and how it flows from the needle while being but replacing the dyed ringer’s lactate solution with blood drawn
injected. Therefore, elasticity and viscosity will also determine how a from two of the authors (JvL and JF). Prior to use, the blood was
STF product behaves in the lumen of the needle when aspiration is anticoagulated using tubes containing ethylenediaminetetraacetic
applied. The higher the G’ and g*, the more force is needed to acid (EDTA) with a concentration of 1.8 mg/mL of blood.
obtain a positive aspiration result by emptying a needle filled with
STF material. Most commercial STF products have a viscosity
derm Ultraâ, Allergan Inc.,
between 7.307 centipoises (cP) (Juve 3 | RESULTS
â
Irvine, CA, USA) and 349 830 cP (Radiesse , Merz Pharmaceuticals
GmbH, Frankfurt, Germany).11 When comparing these values to The aspiration results are shown in Table 3. All needles tested in the
water (0.890 cP at 25°C) and blood (between 3.000 and 4.000 cP at 12 saline control tests yielded positive results within 1 s of aspira-
37°C), it becomes clear that the results of an aspiration test may not tion. In total, 340 tests with 24 STFs were performed; 112 tests
always be reliable as the high viscosity of STFs would mean that a yielded true-positive results (within 1 s), 101 tests yielded positive
very high suction pressure must be applied in order to obtain a posi- results between 1 and 10 s after aspiration, and 128 tests yielded
tive aspiration test result.12 negative results beyond 10 s of aspiration.
Our aim of this study was to investigate the value and reliability The reliability of aspiration as a safety test when a true-positive
of aspiration as a medical test to prevent mistakenly placing a pro- result was defined as being positive up to 10 s after the start of
duct in a vascular structure leading to possible complications, while aspiration was 63%. When this time limit was decreased to 1 s after
comparing different STFs and needle dimensions. the start of aspiration, the reliability and amount of true-positive
results dropped to 33%.
When only considering the needles supplied within the packages
2 | METHODS of the different STF products, the reliability of aspiration was 37%
(positive within 1 s) and 74% (positive up to 10 s of aspiration), as
To create an environment where we could be certain of mimicking an seen in Table 4.
intravascular positioning of a needle tip, we first used a 500 mL bag of
Ringer’s Lactateâ (RL) (Baxter Healthcare Corporation, Deerfield, IL,
USA) solution pressurized to 150 mm Hg by means of a Metpakâ 4 | DISCUSSION
pressure infusor (Riester GmbH, Jungingen, Germany) to which was
added 2 mL Bonnie’s Blueâ (Delasco, Council Bluffs, IA, USA) skin Aspiration before injection is in essence a clinical test, to determine
marking ink. The appearance of a blue color in the needle hub was whether the needle tip is inside a blood vessel, and therefore, it is a
considered as a positive aspiration test result (Figure 1). Eleven differ- safety test to reduce the risk of intravascular injection. The speci-
ent sharp point needle sizes were tested on all products as well as the ficity of an aspiration test is high, as blood in the needle hub indi-
needles that were supplied with the products by the manufacturer cates a very high probability of intravascular placement (Table 5).
(Table 1). The syringes and STF products tested are listed in Table 2. However, the sensitivity of aspiration as a diagnostic test is low (de-
All products except the control were produced and supplied by pending on the product and needle tested) as absence of blood in
the respective pharmaceutical companies in the Netherlands. the needle hub does not exclude the possibility of intravascular
Beloteroâ, Radiesseâ, and Etermisâ products were supplied by Merz placement of the needle tip, as can be seen from the false-negative
Pharmaceuticals, Restylaneâ products were supplied by Galderma, test results illustrated in Table 3. As a cutoff time of 1 s after aspira-
â
and Juvederm products were supplied by Allergan. Every product tion revealed fewer true-positive results, one could argue that these
except the control was tested with its originally supplied syringes, all tests are less reliable compared with those with a cutoff time of
of which were 1-mL syringes, with the exception of Radiesseâ which 10 s. However, in clinical practice, physicians usually do not aspirate
was supplied with 1.5 and 0.8-mL syringes. Each product was aspi- for more than 1 s. In this case, the orange cells in Table 3 could also
rated twice with every needle size to determine whether any of the be classified as false-negative test results, making aspiration a highly
blue-dyed Ringer’s lactate could be aspirated. Before testing, the unreliable test for many STFs when no blood is seen in the needle
needles were primed and the syringes emptied of half of their STF hub during aspiration.
contents to allow for sufficient aspiration with the plunger. A mini- Our results may also be slightly more conservative than those
mum of 0.5 mL vacuum was visible in the syringe when the plunger experienced in routine clinical practice in that we used a relatively
was pulled during aspiration, which correlates to a negative pressure high pressure (150 mm Hg) compared with the world population’s
of 50 mm Hg or 6666.118 Pa.13 A timer was used to measure the mean systolic blood pressure of 124 mm Hg as stated by the World
time between start of aspiration and the appearance of blue color in Health Organization.14
VAN LOGHEM ET AL. | 3
T A B L E 1 Sharp point needle gauge and length of needles tested A number of other factors can also influence the effectiveness of
in the study aspiration as a safety test. Blood vessels may collapse at negative
Manufacturer (products pressure during aspiration, which could prevent blood from entering
with manufacturer-supplied the syringe. During a preperiosteal injection, there is a chance that
Needle size needles are indicated in brackets) the needle may strike an artery and, instead of piercing through, the
33G, 13 mm TSK Laboratory, Japan needle tip may push the elastic artery to the periosteum. During
30G, 13 mm TSK Laboratory, Japan aspiration, one would see no blood, but an embolism could still arise
30G, 12 mm Terumo Europe N.V. Belgium after injection, while the bevel of the needle may be intra-arterial
(Etermis) even though the needle tip is located on the bone.16
29G, 12 mm Terumo Europe N.V. Belgium In a recent study, where the reliability of the aspiration study
(Restylane)
was examined in a rabbit ear model, results were positive for four
28G, 19 mm Exelint International, USA STF products tested with five different needle sizes.17 However,
(Radiesse)
with in vivo experiments, one can never be certain that the needle
27G, 12 mm Terumo Europe N.V. Belgium
lumen is indeed intra-arterial at the moment of aspiration as hand
(Etermis)
tremors can rapidly effect needle tip position. This can lead to a
27G, 13 mm TSK Laboratory, Japan
true-negative result under the assumption that the needle is placed
27G, 20 mm Terumo Europe N.V. Belgium
intravascularly.
(Radiesse Plus, Etermis)
Technically, aspiration before injection can be challenging. When
25G, 13 mm TSK Laboratory, Japan
one aspirates, the plunger needs to be pulled. After verifying that
25G, 25 mm Terumo Europe N.V. Belgium
there is no blood in the syringe, the fingers are repositioned on the
(Etermis)
plunger so that the STF can be injected. During this repositioning,
23G, 13 mm TSK Laboratory, Japan
the needle tip may change position. As one or two millimeters can
make the difference between intra- and extravascular injection, the
Although blood viscosity is marginally reduced by EDTA, the value of the aspiration test is further reduced. Furthermore, when
shape of the viscosity curve is relatively unchanged when evaluated aspirating with a full syringe, a maximum of 0.1 mL negative pres-
at different shear rates.15 Blood viscosity is a variable in the reliabil- sure can be created due to the limitations of the syringe. Our study
ity of the aspiration test. The higher viscosity of blood (3-4 cP) com- was performed with a minimum of 0.5 mL negative pressure per
pared with Ringer’s lactate solution (0.7-1 cP) slows down the product, indicating that in practice false-negative test results could
intraluminar movement of liquids, as can be seen in the greater time be more likely than in this experimental setup.
interval in the blood assay between aspiration and a positive test When considering bevel length, larger gauge needles have
result. greater bevel lengths compared to smaller gauge needles. When an
4 | VAN LOGHEM ET AL.
elastic artery is hit and pushed to the periosteum, and then pene- affected, and the chances of alternative oxygenation are reduced.
trated, the chance of the bevel being in the lumen of the artery is This is especially true in high-risk areas such as the nose or the
greater when a larger gauge needle is used, compared to smaller glabellar region where high amounts of end arterioles are present. A
gauge needles with shorter bevel lengths. This is especially relevant recent cadaver study, which sought to determine the amount of filler
in anatomic areas where arteries run very close to the periosteum, necessary to embolize the retina from the supratrochlear artery,
as seen in cadaver dissections at the temporal hollows, the perior- found that while the average volume required was 0.08 mL,
bital, and the frontal area.18 While this may argue in favor of using embolization was possible with amounts as small as 0.04 mL.19 In
small needles, our study has demonstrated that thinner gauge nee- the periorbital area, the maximum injected volume should therefore
dles lead to more false-negative test results and should not be not exceed 0.04 mL per bolus when injecting with a needle, consid-
considered safer on the basis of bevel length. ering the possibility that even though the needle tip might be placed
In the face, the different anatomic regions often have alternative on the periosteum, the lumen might still be intravascular due to the
blood supplies, in case an obstruction arises at one of the arterial bevelled needle tip.
sources. It is the authors’ belief that in practice, many patients are In the current study, the 28-G needle (19 mm) was associated
injected intra-arterially. However, because a retrograde injection with more false-negative results than the 30-G needle (13 mm) in a
technique is generally used, the extent of the embolism is limited number of tests, for example Belotero Balance. The same was true
and an alternative blood supply is sufficient for oxygenation of the for the 23-G (19 mm) vs the 25-G (13 mm) needle tests. When con-
affected capillary bed. When the embolus becomes more voluminous sidering the physics of fluid dynamics, pipe resistance (in this case
due to static injection inside an artery, a larger capillary bed will be needle lumen) is determined by diameter and length and possibly
VAN LOGHEM ET AL. | 5
(Continues)
6 | VAN LOGHEM ET AL.
TABLE 3 (Continued)
Needle gauge (G), length
Green: positive (within 1 s), orange: positive (between 1 and 10 s), red: false-negative test result (when still negative after 10 s).
RL, Ringer’s lactate; EDTA, ethylenediaminetetraacetic acid.
surface roughness of the needle lumen. When comparing the dimen- of the tests were false negative, which is comparable to our
sions of these two needles, the 28-G (or 23-G) needle with its longer results.17
length results in a higher flow resistance during STF aspiration or For optimal results and accurate product placement, anatomic
extrusion than the 30-G (or 25-G) needle, which is in accordance knowledge is a key. In addition, the risk of intra-arterial embolisms
with our results. Test results will therefore be influenced by filler can be reduced by adhering to the following advice:
rheology. For example, the rheology of Belotero Balance differs from
that of Restylane Lidocaine in terms of cohesivity (measured in kPa), • Take caution when practicing aspiration as a negative test result
and the 28-G (19 mm) needle showed positive test results with (no blood in needle hub) might be false negative and give the
Restylane Lidocaine but negative with Belotero Balance, while the injector a false sense of security;
30-G (13 mm) needle showed negative test results with Restylane • When injecting with a sharp point needle, a retrograde technique
Lidocaine and positive for Belotero Balance. should be used when the product is released. In the event that
A few papers have examined the value of aspiration before injec- the needle penetrates an artery, only a limited amount of product
tion. In one study which focused on Radiesse, the authors trans- would then be released intra-arterially;
ferred diluted Radiesse to a 1-mL luer lock syringe and used a 27-G • Avoid large-volume bolus injections with the needle in a static
needle.20 This syringe has different dimensions and therefore differ- position to avoid occlusion of a large area of the arterial system;
ent resistance characteristics compared to the syringe supplied by • Avoid high-pressure injections as these may lead to retrograde
the manufacturer. As seen in our results, both needle and syringe flow against the arterial blood flow into a proximal arterial system
dimensions may contribute to the reliability of an aspiration test. (like the ophthalmic artery);
In another recent publication, where the reliability of aspiration • Although nontraumatic cannulas can penetrate arterial walls,21
as a safety test with different STF materials was also examined, 60% we recommend using cannulas over needles, and with diameters
VAN LOGHEM ET AL. | 7
Green: positive (within 1 s), orange: positive (between 1 and 10 s), red: false-negative test result (when still negative after 10 s).
RL, Ringer’s lactate; EDTA, Ethylenediaminetetraacetic acid.
T A B L E 5 Aspiration a clinical diagnostic test 10. Sundaram H, Cassuto D. Biophysical characteristics of hyaluronic
acid soft-tissue fillers and their relevance to aesthetic applications.
The truth
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Aspiration as a diagnostic test Intravascular Extravascular 11. Sundaram H, Voigts B, Beer K, Meland M. Comparison of the rheo-
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13. Haseler L, Sibbitt RR, Sibbitt Jr WL, Michael AA, Gasparovic CM,
tion as a diagnostic test. Green: true positive test result, dark orange: false
Bankhurst AD. Syringe and needle size, syringe type, vacuum gener-
negative test result (analogue to red and orange in Tables 3,4).
ation, and needle control in aspiration procedures. Cardiovasc Inter-
vent Radiol. 2011;34:590-600.
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www.who.int/gho/ncd/risk_factors/blood_pressure_prevalence/en/.
to rely on the validity of a negative test result (no blood in the
Accessed April, 19, 2015.
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tem. In: Peker SM, Helvaci SS, eds. Solid liquid two-phase flow, 1st
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None.
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