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Local Anesthetics: Use and Effects in Autologous Fat Grafting

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Abstract

Autologous fat grafting has been used for over a century and is considered as a technique of choice for soft tissue filling in plastic and reconstructive surgery. However, the critical point of this technique is fat graft survival. In order to assure best efficiency of adipose grafts, new techniques and procedures have been optimized in order to avoid graft resorption and thus, to improve graft survival. Among the steps involved in lipofilling process, some researchers and surgeons have inter alia focused on the effects of local anaesthetics on adipose graft. After an overview on the different local anaesthetics commonly used and their mode of action, this review focuses on the effects of these drugs on non-neuronal cells with special emphasis on adipose tissue and adipose-derived stem cells. Moreover, while there is no consensus on the best way how to handle adipose tissue prior to its injection, this review describes how to get rid of the adverse effects of local anaesthetics.
Surgery: Current Research
Girard et al., Surgery Curr Res 2013, 3:4
http://dx.doi.org/10.4172/2161-1076.1000142
Review Article Open Access
Volume 3 • Issue 4 • 1000142
Surgery Curr Res
ISSN: 2161-1076 SCR, an open access journal
Local Anesthetics: Use and Effects in Autologous Fat Grafting
Girard AC*, Festy F and Roche R
ADIP’SCULPT, Platform CYROI, 2 rue Maxime Rivière, 97490 Sainte Clotilde, Reunion Island, France
*Corresponding author: Girard AC, ADIP’SCULPT, Platform CYROI, 2 rue
Maxime Rivière, 97490 Sainte Clotilde, Reunion Island, France, Tel: +262 262 938
840; Fax: +33 176 620 781; E-mail: ac.girard@adipsculpt.com
Received June 11, 2013; Accepted August 22, 2013; Published August 29, 2013
Citation: Girard AC, Festy F, Roche R (2013) Local Anesthetics: Use and Effects in
Autologous fat Grafting. Surgery Curr Res 3: 142. doi:10.4172/2161-1076.1000142
Copyright: © 2013 Girard AC, et al. This is an open-access article distributed under
the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and
source are credited.
Keywords: Autologous fat graing; Liposuction; Local anaesthetics;
Lidocaine; Adipose-derived stem cells
Abbreviations: AFG: Autologous Fat Graing; LA: Local
Anaesthetic; ADSC: Adipose-Derived Stem Cell
Introduction
Because of its easy access by liposuction and due to the fact that it
contains many progenitor cells, subcutaneous adipose tissue is a tissue
of choice for so tissue lling in cosmetic and reconstructive surgery.
Autologous Fat Graing (AFG), or lipolling, has been used for over
a century and represents a safe technique for so tissue lling [1-3].
However, although the technique has seen marked improvements
over time, surgeons are still facing gra resorption that oen requires
overcorrection of the treated area or other interventions so that the
aesthetic result is in line with expectations of the patient [2,4]. us,
new processes have been developed in order to increase the rate of
engrament by promoting cell survival within the gra [5]. Among
the critical points that may impair adipose gra retention and survival,
Local Anesthetics (LAs) have been investigated. Even under general
anesthesia, LAs are oen inltrated at the fat donor site (generally
through a tumescent solution with epinephrine for vasoconstriction)
and can also be delivered at the injection site to ensure patient comfort.
Further studies in the context of autologous fat graing in plastic
surgery have allowed to highlight LAs adverse eects but controversies
remain regarding their substantial impact on fat gra survival [6-
11]. Although this confusion remains among all LAs, lidocaine is the
most commonly used LA for liposuction procedure and is thereby the
best described in this context. However, this drug has also been so far
neglected in terms of recommendations for dosage.
us, through the literature, local anesthesia use and eects in AFG
are described herein.
From adipose tissue to so tissue lling
Adipose tissue is rst and foremost an organ of lipid storage. It
represents the main body’s energy reserve, involving lipids as the
main fuel for adult humans. Adipose tissue is also considered as a true
endocrine organ where the adipocyte lies at the heart of this system by
participating in the regulation of energy homeostasis in the body [12].
While mature adipocytes constitute the specialized cells of
adipose tissue, stocking triglycerides in a huge lipid droplet inside
their cytoplasm, other cell types are included in adipose environment
[13]. Beside mature adipocytes surrounded by conjunctive tissue
Abstract
Autologous fat grafting has been used for over a century and is considered as a technique of choice for soft tissue
lling in plastic and reconstructive surgery. However, the critical point of this technique is fat graft survival. In order to
assure best efciency of adipose grafts, new techniques and procedures have been optimized in order to avoid graft
resorption and thus, to improve graft survival. Among the steps involved in lipolling process, some researchers and
surgeons have inter alia focused on the effects of local anaesthetics on adipose graft.
After an overview on the different local anaesthetics commonly used and their mode of action, this review focuses
on the effects of these drugs on non-neuronal cells with special emphasis on adipose tissue and adipose-derived stem
cells. Moreover, while there is no consensus on the best way how to handle adipose tissue prior to its injection, this
review describes how to get rid of the adverse effects of local anaesthetics.
with collagene bers, the Stromal Vascular Fraction (SVF) includes
preadipocytes, endothelial cells, smooth muscle cells, blood cells (from
blood vessels) and Adipose-Derived Stem Cells (ADSCs), that have
been discovered not so far ago [14,15]. ese ADSCs share similar
properties with mesenchymal stem cells: quite similar phenotype,
ability to proliferate and to dierentiate into mesenchymal cell types
such as adipocytes [15-17], chondrocytes [18-22], osteoblasts [15,18,23-
26], tenocytes [27,28], myocytes [15,28,29]. But their dierentiation
potential is not restricted to mesodermal lineage: ADSCs have been
shown to trans dierentiate into other cell types, including endothelial
cells [28,30] and neuronal-type cells [28,31]. Besides dierentiation,
ADSCs can also secrete numerous paracrine factors (like cytokines,
growth factors, anti-apoptotic factors) that would strongly support
tissue regeneration [30,32].
Owing to their high potential for tissue regeneration and their easy
access by simple liposuction, ADSCs are subject to special attention
and are already used in regenerative medicine (many clinical trials
ongoing) [33]. Plastic surgeons also pay attention to these cells as
they exhibit special functions that may improve fat gra survival
and eciency [34-40]. Indeed, these ADSCs are known to be able to
dierentiate into mature adipocytes, which may contribute to face fat
gra resorption and maintain the desired volume for so tissue repair
or augmentation. Moreover, there is increasing evidence that ADSCs
contribute to vascularization of adipose gras, thus improving cell
survival inside the gras [38,41-43]. For all that considerations, the
technique of cell-assisted lipotransfer has emerged: it consists in ADSCs
enrichment of autologous fat prior to its injection [37,38]. However
regulations regarding the use of stem cells in plastic surgery dier
between countries and this practice is not legally approved everywhere.
Further clinical studies must be performed to assure patient safety and
eciency of such procedures [39].
us, containing many dierent types of cells (voluminous
Citation: Girard AC, Festy F, Roche R (2013) Local Anesthetics: Use and Effects in Autologous fat Grafting. Surgery Curr Res 3: 142. doi:10.4172/2161-
1076.1000142
Page 2 of 7
Volume 3 • Issue 4 • 1000142
Surgery Curr Res
ISSN: 2161-1076 SCR, an open access journal
adipocytes, stromal cells) and being easily accessible, adipose tissue
has been shown to be a great ller and is now commonly used to ll
so tissues and restore volume. Lipolling has now gained popularity,
especially with the development of liposuction technique and also
thanks to abundance and availability of subcutaneous fat in the human
body. Beside its role as a secretory and endocrine organ, adipose tissue
is used to correct so tissue defects as well as facial rejuvenation, body
contouring, or other numerous applications, both for aesthetic and
reconstructive purposes [32,34].
Autologous fat graing and the tumescent technique for
liposuction
Autologous fat transfer has been subject to great evolution over the
last century. Conceived by Fisher and Fisher, liposuction rst appeared
as a revolutionary technique in 1974 [44]. en, Klein invented the
tumescent liposuction which consists of inltrating at the sampling
zone a local anesthetic and a vasoconstrictor diluted in a large volume
of uid (saline type) [45]. Usually, the volume of tumescent solution
is almost equal to the volume of adipose tissue to be removed. is
technique allowed the patients to benet from liposuction totally by
local anesthesia, thus avoiding the risks of general anesthesia and
promoting a short recovery time. is also allowed the use of much
smaller cannulas and practice of supercial liposuction, only 3-4
mm deep subcutaneous [46]. Patients no longer had to fear excessive
bleeding and undesirable skin depressions. In addition, liposuction by
cannulation did not seem to damage the adipocytes. en in the mid-
80s, plastic surgeons began to inject the fat obtained by liposuction
[47,48].
With invention of the innovative technique of tumescent
liposuction by Klein, lidocaine systemic toxicity has been signicantly
reduced: dilution of lidocaine in a large volume of normal saline
signicantly decreased systemic absorption rate of the drug [45,49,50].
Tumescent anesthesia nally oers many advantages, among which:
decreased LA absorption at the inltrated donor site, increased patient
comfort aer surgery due to a longer lasting eect of LA, decreased
and delayed systemic absorption and lower peak blood plasma levels
(thus, avoiding toxic potential like cardiotoxicity or central nervous
system toxicity) [51]. Moreover, even if LA inltration at the fat
donor site can allow avoiding general anesthesia and its related risks,
tumescent liposuction with local anesthesia is currently mixed with
general anesthesia in order to assure post-operative patient comfort.
Despite recorded patient safety with tumescent anesthesia, questions
remain about LAs eect in AFG.
Local anesthetics: classes and mode of action
Local anesthetics act by blocking sodium ionic channels involved
in neural impulse conduction, thus avoiding peri- and post-operative
pain [52,53]. ese cocaine-derived substances have been discovered
more than a century ago, and are divided in two distinct chemical
families: amino esters (tetracaine, procaine…) and amino amides
(lidocaine, bupivacaine, ropivacaine) (Table 1). Compared to amino
esters, amino amides may cause rare allergies.
Lidocaine was the rst amino amide-type LA synthesized by
Löfgren [54]. is LA presents a rapid onset and an intermediate
duration of action. rough the years, other LAs have been discovered
in order to improve duration of action and decrease toxicity risk when
possible (Table 1). Although lidocaine is the oldest aminoamide LA,
this drug is widely used all over the world and seems to be the most
appropriate in the context of liposuction and autologous fat transfer
[45].
LA potency is partly due to their lipid solubility: LAs have a
lipophilic chemical group (comprising benzene ring or thiophene ring
for articaine) that allows them to diuse across plasma membrane and
Classication and
name
Date of
discovery
pKa
(25°C Metabolism Onset
(min)
Duration of action
(min)
Relative
potency
Maximal dose
(for adults)
Maximal
dose with
epinephrine
Dose for
tumescent
anesthesia
Relative
toxicity
Amino esters
Procaine 1905 9 Plasma
esterases
Slow
(10-20)
Short
(15-60) 1500 mg
(7 mg/kg) - - 1
Chloroprocaine 1952 9.3 Plasma
esterases
Fast
(5)
Short
(15-45) 1600 mg
(8 mg/kg) - - 9
Tetracaine 1928 8.6 Plasma
esterases
Slow
(15)
Intermediate
(60-200) > 4 100 mg
(1.5 mg/kg) - - 4.1
Amino amides
Lidocaine 1943 7.9 Liver Fast
(2-5)
Intermediate
(60-120) Longer with
epinephrine
4200-300 mg
(5 mg/kg)
500 mg
(7 mg/kg) 30-35 mg/kg 2
Prilocaine 1960 7.9
Lung
Kidney
Liver
Fast
(2-5)
Intermediate
(30-90) 4500 mg
(7 mg/kg)
600 mg
(8 mg/kg) 15 mg/kg 1.8
Articaine 1969 7.8
Liver
Serum
esterases
Fast
(2-3)
Intermediate
(60-180) 5 7 mg/kg 7 mg/kg 35 mg/kg 1.5
Mepivacaine 1956 7.9 Liver Fast
(3-5)
Intermediate
(45-90) 4300 mg
(5 mg/kg) (5 mg/kg) - 2.2
Bupivacaine 1963 8.1 Liver Slow
(10-15)
Long
(200 +) Longer with
epinephrine
16 175 mg
(2.5 mg/kg)
225 mg
(3 mg/kg) - 8
Levobupivacaine 1960’s 8.1 Liver Slow
(10-15)
Long
(200 +) 16 175 mg
(2.5 mg/kg) - - < 8
Ropivacaine 1950’s 8.1 Liver Slow
(5-15)
Long
(200 +) 16 188 mg
(2.5-3 mg/kg) - - 7
Data from [54,83,84]
Table 1: Key pharmacologic properties of principal LAs.
Citation: Girard AC, Festy F, Roche R (2013) Local Anesthetics: Use and Effects in Autologous fat Grafting. Surgery Curr Res 3: 142. doi:10.4172/2161-
1076.1000142
Page 3 of 7
enter neural cells to reach the inner part of voltage-dependent channels
and block them [53,54]. Due to their liposolubility potential, LAs
are also known to diuse in adipose tissue, in the case of tumescent
anesthesia for liposuction [55].
Moreover, the use of a vasoconstrictor as epinephrine (adrenaline)
provides potentialization of LAs, providing increased long-lasting
action [56]. Indeed, epinephrine is used to decrease bleeding and
also slows the passage of LAs in systemic circulation, thus ensuring
prolonged retention in the tissue.
Currently used LAs in AFG
Maximum recommended doses of LAs are confused. For lidocaine
injection, they are estimated at 200 mg [57]; for tumescent lidocaine,
estimation is 30 mg/kg for the French Society of Anesthesia and
Intensive Care (“Société française d’anesthésie et de réanimation”,
SFAR), and safe limit dose is estimated at 35 mg/kg by Klein [49] who
has also reached highest dose of 50 mg/kg in tumescent anesthesia [58].
LA dose for tumescent anesthesia (30-35 mg/kg) is nally much higher
than recommended dose for injection (5-7 mg/kg). is is explained by
the fact that 1) LAs are lipid soluble so they may preferentially diuse
into fat; 2) adipose tissue is not much vascularized; 3) supplementation
with vasoconstrictor delays plasma diusion [45,51].
For other LAs like ropivacaine, bupivacaine and levo‐bupivacaine,
and due to their higher relative potency and their potential higher
systemic toxicity (Table 1), doses could be 10 fold less compared to
lidocaine [59,60]. e use of long-acting LAs as bupivacaine may oer
interesting postoperative analgesia [61] but these drugs are poorly
referenced in the context of fat graing, in which appropriate doses and
eects are not well known. is is the same lack of knowledge regarding
prilocaine, which has also been used for tumescent anesthesia (maximal
dose of 15 mg/kg for safe liposuction) [62].
Ultimately, the most currently used LA for liposuction and AFG
is lidocaine and that’s on this molecule that literature is the most
abundant. Indeed, a survey from the American Society for Aesthetic
Plastic Surgery concluded that: for adipose tissue harvest, 40% of
surgeons use tumescent solution containing 50 mL of 1% xylocaine + 1
mL epinephrine 1:1000 in 1 L normal saline, which corresponds to 0.5
mg/mL of lidocaine. en, about 30% of them use a mixture of 0.5%
xylocaine with epinephrine and 22% use 1% xylocaine epinephrine
mixture. e remaining 8% of American physicians use epinephrine
alone or other solution [63].
Among other solutions, articaine, which is widely used in dentistry,
has also been reported to be an ecient LA for tumescent liposuction
[64,65]. With dose of 0.4 mg/mL articaine combined with 1 µg/mL
epinephrine, this tumescent solution presents high anesthetic potency
(due to high lipid solubility that improves cell membrane diusion),
and also presents low systemic toxicity (because of easy and rapid
metabolism by esterases) [64].
Moreover, regarding site of injection of adipose tissue, 80% of
plastic surgeons use either 0.5 or 1% xylocaine with epinephrine. Other
solutions may be used but nest fat injections in small areas also allow
to avoid the use of local anesthesia at the site of injection [63].
To some extent, regarding systemic toxicity and duration of action
in the context of liposuction and fat graing, there is no reason to
use another anesthetic as lidocaine [45,66]. Indeed, for this kind of
procedure, a tumescent solution containing lidocaine plus epinephrine
(at recommended doses) is sucient, ecient, and present almost no
risk of local anesthesia complication.
Cytotoxicity of LAs in non-neuronal cells
LA toxicity in neuronal cells has already been reported [67].
Furthermore, as described above and aside from patient allergies,
systemic toxicity of LAs is quite rare, particularly in the context of
tumescent liposuction. Even for face surgery, where areas are well
vascularized and highly innerved, this toxicity can be easily managed
by respecting the recommended doses for LA injection.
However, to a lesser extent in terms of serious medical risk, LAs
have been shown to exert cytotoxic eects in many non-neuronal
cells, including broblasts [68], chondrocytes [69] and myoblast cells
[70]. Considering LAs adverse eects in many cell types, their use
is therefore more cautious in some clinical applications. is is the
case of intra-articular injections following joint surgery, where LAs
(mostly lidocaine, bupivacaine or ropivacaine) exert cytotoxic eects
on chondrocytes and thus, may contribute to cartilage degeneration
[69,71]. Some studies now recommend to avoid intra-articular
administration of LA or to nd alternatives [72]. Publication of several
case reports about postoperative chondrolysis have nally alerted
orthopedic surgeons and anesthetists who now pay more attention on
these severe and disabling complications that can be partly due to LAs
[73].
By the same, it is now time to consider LAs eects in the context of
lipolling. Concerning LAs eects in adipose tissue cells, the debate is
still relevant. Overall related studies are reported in Table 2.
Finally, only few studies exist on LA eects in AFG and the
methods used are all dierent, which may explain the dierent and so-
called “controversial” results. Indeed, most of the studies are made in
vitro and include sometimes high doses, and other times minor doses
of LA. Moreover, as there is no standardized protocols, adipose tissue
harvest and processing are also involved in these dierences between
studies, as well as type of cells studied, in culture or not (Table 2). us,
it is dicult to really compare all these studies.
From our own studies, we have shown that clinical doses of
lidocaine (ranging from 0.4 to 1.6 mg/mL) could aect cultured ADSC
viability in a dose and time dependent manner [10]. However, this
cytotoxicity could be partially prevented by washing the cells aer
lidocaine incubation. us, depending on the dose, duration of action,
and also procedure of adipose tissue handling (like centrifugation and
washing that may remove LAs and avoid their deleterious eects) LAs
can cause more or less harmful eects on the cells within the gra.
Similarly, Keck et al. have shown that LAs impair preadipocyte viability
and their dierentiation into mature adipocyte [7,8]. Finally, our results
were conrmed in an in vivo study of fat transfer into immunodecient
mice (Table 2) [74,75].
Actually, the dierent conclusions made in all these studies are
dependent on the method used for adipose tissue handling prior to
injection, insofar as centrifuging and washing adipose tissue must
allow removing most of the drugs present from liposuction.
Moreover, regarding the use of epinephrine for vasoconstriction,
the low doses that are currently used (usually 1 µg/mL) seem to be safe
for the patient and do not inuence adipose-derived stem cell viability
[10]. erefore, epinephrine can be used in liposuction procedure for
AFG.
Knowing the importance of ADSCs for fat gra survival [38-
40,42,43], the potential impact of LAs on these cells has to be considered
in the context of AFG. Indeed, as mentioned here above, ADSCs
properties may be of great interest for fat gra retention and eciency,
Citation: Girard AC, Festy F, Roche R (2013) Local Anesthetics: Use and Effects in Autologous fat Grafting. Surgery Curr Res 3: 142. doi:10.4172/2161-
1076.1000142
Page 4 of 7
Reference LAs Type of
study
Tissue or cell type and
origin
LA effects on adipose tissue,
adipose-derived stem cells and fat
grafting
Comments
Moore et al.
1995 [85] Lidocaine In vitro
Adipocytes from human
suction lipectomy, after
collagenase digestion
Lidocaine potently inhibits glucose
transport and lipolysis in adipocytes
and their growth in culture
But adipocytes regain their function
after washing
This study introduces the impact of LAs in AFG
and proposes washing as an interesting method
to erase LA adverse effects
Large et al.
1997 [86] Lidocaine In vitro Subcutaneous fat cells
from obese patients
Compared to general anesthesia,
local anesthesia does not inuence
adrenergic regulation of lipolysis
This study is more related to obesity (adipose
tissue harvest during clinical studies)
Sommer
and Sattler
(2000) [11]
- Review
Comparative studies
(human, animal and in
vitro studies) on graft
survival and longevity
Review of literature shows similar
survival rates of fat grafts after either
general or local anesthesia
This review does not focus on LA effects in
AFG and authors draw conclusions from studies
that do not focus on the use and effects of LAs
Shoshani et
al. 2005 [6]
Lidocaine
Adrenaline
In vivo (nude
mice)
Adipose tissue from a
healthy human patient
undergoing elective
surgery, and grafted into
nude mice
Lidocaine and adrenaline do not
have any inuence on the take of
fat grafts or adipocyte viability after
lipotransfer in nude mice
This is the rst in vivo study related to lidocaine
and adrenaline effects
However, this interesting study includes a
centrifugation step that may be essential to
preserve the cells
Keck et al.
2009 [7]
- Lidocaine 1%
- Articaine 1% +
epinephrine 1:200,000
- Ropivacaine 0.75%
- Prilocaine 1%
- Tumescent solution
(sodium chloride 0.9%
+ 25 mL
Articaine 1% +
epinephrine 1:200,000 +
25 mL bicarbonate)
In vitro
Human preadipocytes in
culture (obtained after
collagenase digestion
of adipose tissue, from
abdominoplasties)
All the tested LAs exert cytotoxic
effects
The tumescent solution used (with
diluted articaine) appears to be safe
Incubation time of 30 min is less but very high
doses of LAs are directly applied on the isolated
cells, which explains the terrible cytotoxic effect
Keck et al.
2010 [8]
- Bupivacaine 1%
- Mepivacaine 1%
- Ropivacaine 0.5%
- Articaine 4% +
epinephrine 1:100,000
- Lidocaine 2%
In vitro Human preadipocytes in
culture
All LAs exert cytotoxic effects,
to various degrees (articaine +
epinephrine is the worst)
All LAs signicantly impaired
the ability of preadipocytes to
differentiate into adipocytes
Cells have been let in culture for 24 or 48
h before being trypsinized, centrifuged and
resuspended directly in the different high
concentrated LAs. This explains the high level
of cytotoxicity
Keck et al.
2012 [87] Lidocaine 2% In vitro Human preadipocytes in
culture
Lidocaine induces necrosis but
not apoptosis on preadipocytes.
Necrotic effect of lidocaine cannot be
prevented by coenzyme Q10.
The dose of lidocaine used is still very high
Sazaki 2011
[88]
Tumescent lidocaine
(10.5 – 20 mg/kg) Case report Human adipocytes
The amount of instilled tumescent
uid and lidocaine dosage seem to
be safe for water-assisted liposuction
This study focuses on water-assisted
liposuction and does not compare with and
without LA
Livaoglu et
al. 2012 [9]
Lidocaine + epinephrine
Prilocaine
In vivo (rat
model of
AFG with fat
from rat)
Adipose tissue from rat
grafted for 30 and 180
days
Lidocaine plus epinephrine or
prilocaine have no negative effect
on microangiogenesis and fat graft
survival
Fat was not from human lipoaspirates but was
excised from rats (from inguinal region)
Histologic ndings are questionable
Girard et al.
2013 [10]
Lidocaine (0.4 to 1.6
mg/mL)
± adrenaline (1:1000000)
In vitro
Human adipose-derived
stem cells (ADSCs) in
primary culture for few
days (4 days without any
passage)
Lidocaine affects ADSC viability (but
no apoptosis)
Adrenaline has no effect
Lidocaine cytotoxicity can be partly
avoided by washing
Lidocaine may have anti-
inammatory properties
First authors in vitro study regarding lidocaine
effects
In vivo effects have to be conrmed
Clinical doses of lidocaine have been used
Atlan et al.
(2012) [74]
Lidocaine (0.4 to 1.6
mg/mL)
Ropivacaine (0.4 to 1.6
mg/mL)
± adrenaline (1:1000000)
In vitro
Human adipose-derived
stem cells (ADSCs) in
primary culture for 4 days
(no passage)
Ropivacaine is more cytotoxic than
lidocaine
Ropivacaine and lidocaine have been tested
at equal doses, which represent high dose for
ropivacaine
Girard et al.
2013 [75]
Tumescent lidocaine (0.8
mg/mL)
+ adrenaline (1:1000000)
In vivo
(mouse
model with
fat from
human
patient)
Adipose tissue from
human patient (injected
into immunodecient
mice)
After 1 month of fat grafting,
histologic studies reveal that
lidocaine inltrated at the fat harvest
site gives worst results compared to
tumescent solution without lidocaine
Prior to adipose tissue injection, at
least 2 washes with soft and short
centrifugations allow to improve graft
quality (better organization, more
stromal cells)
This in vivo study completes the previous
in vitro studies from authors. Comparison is
done from a same patient: adipose tissue
was harvested on one side without lidocaine
(tumescent adrenaline), and on the other side
with a currently used tumescent solution with
lidocaine + adrenaline
Table 2: Studies reporting LA effects in AFG.
Citation: Girard AC, Festy F, Roche R (2013) Local Anesthetics: Use and Effects in Autologous fat Grafting. Surgery Curr Res 3: 142. doi:10.4172/2161-
1076.1000142
Page 5 of 7
by enabling vascularization of the gra (thus assuring cell survival) and
enabling adipose tissue regeneration within the gra (thus assuring
gra volume retention). ADSCs are also known to secrete growth
factors and exert trophic eects that may contribute to surrounding
tissue regeneration [34,38,43].
erefore, ADSC survival inside adipose gras may improve
considerably the quality of the gra, so it is of great importance to limit
LA adverse eects during AFG.
How to limit LA eects in AFG: Recommendations
First of all, when fat is used for lipolling, it is better not to use local
anesthesia for liposuction if the surgery is performed under general
anesthesia. Indeed, the use of a tumescent solution containing diluted
epinephrine is recommended but there is no need of LA administration
under general anesthesia. However, in order to ensure post-operative
patient comfort, tumescent LA inltration can be preformed aer
adipose tissue harvest for AFG.
en, under local anesthesia alone, simple techniques as
centrifugation and washing have been tested in order to get rid of LA
deleterious eect. But alike controversies about LA eects in AFG,
controversies also exist on centrifugation and washing eects.
Smith et al. did not nd any advantages using centrifugation and
washing and advised minimal manipulation of adipose tissue [76].
While positive aspect of washing have been highlighted in [77], the same
authors found that decantation was better than strong centrifugation
which could lead to loss of ADSCs, falling to the bottom of the tube as
a cell pellet [78].
From our own studies, concerning centrifugation, adipose cell
death is correlated to centrifugation speed and time, but cell death
remains low below 400 g [79]. Liquid removal (containing LA and
epinephrine) is also correlated to centrifugation speed and time, but
there is no statistical dierence between 400 g and 900 g. us, knowing
that strong centrifugation has already been reported as a cause of
adipose tissue and ADSC damage [78,80,81], so centrifugation at 400
g (1 min maximum) represents a good compromise.
About washing, Alexander described its eect on adipose tissue
by measuring lidocaine remnants [82]. He draws the conclusion that
washing allows to remove a part of lidocaine inltrated in adipose
tissue, and he advised at least 2 wash in order to remove most of the
drug. But washing steps alone are not sucient as he could still observe
some remnants of the drug. us, our combined studies [10,79]
allow to dene a protocol combining washing (at least 2) and so
centrifugations which clearly improve extraction of remnant liquids,
thus removing LA.
In addition, this protocol encourages the presence of stromal cells
and a large network of conjunctive tissue inside the gra. ese cells are
indeed capable of synthesizing collagen bers and could be involved in
neo vascularization of the gra, and therefore in its survival. Finally,
this procedure of adipose tissue/lipoaspirate handling enhances gra
survival by elimination of deleterious elements, among which local
anesthetics, by a non-traumatic protocol involving washings and so
centrifugations (100 g/1 sec, to 400 g/1 min) [74,75].
Actually, it is dicult to compare methods if they have not been
made in the same way. is can explain dierences observed between
studies. Results are mostly from in vitro studies in which too high speed
centrifugation is used. Moreover, we have to keep in mind that adipose
stem cells are essential for the survival of adipose tissue, and that LAs
have a negative eect on these stem cells. us, our results, combined
with those of other teams, tend to prove that it is necessary to wash the
tissue at least two times, with short centrifugation at low speed, in order
to obtain better results in fat graing.
Conclusion
Before imagining overly complex methods to improve AFG (such
as the use of bioscaolds, growth factors...), it is rst better to focus on
simple ways to maximize cell survival upstream. Since there is so far no
consensus on adipose tissue handling, it is still interesting to rene the
protocol for adipose tissue harvest and handling.
To summarize, here are the principle recommendations regarding
LA use in AFG:
- e use of LA should be avoided under general anesthesia
(tumescent solution with diluted epinephrine but without LA
is recommended)
- Under local anesthesia, inltration of a tumescent solution
containing diluted lidocaine and epinephrine is preferred
- Maximal dose of tumescent lidocaine is 35 mg/kg (or 30 mg/kg
in France) to avoid systemic toxicity
- But lidocaine concentration should be as low as possible (below
0.8 mg/mL and even less) to avoid excessive cytotoxicity inside
adipose gra
- So and short centrifugations with short washing steps should
be included in adipose tissue handling prior to its injection, in
order to get rid of inltrated drugs.
Obviously, these recommendations should also be considered in
the context of regenerative medicine when using ADSCs extracted
from lipoaspirates.
Acknowledgements
We are grateful to the plastic surgeons: Atlan M, Delarue P and Hulard O, who
took part in this study by giving advice and allowed the collection of subcutaneous
adipose tissue samples for our own experimental studies. We would also like to
thank the group Clinifutur from Reunion Island, and French Ministry of National
Education and Research nancial support.
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Citation: Girard AC, Festy F, Roche R (2013) Local Anesthetics: Use and
Effects in Autologous fat Grafting. Surgery Curr Res 3: 142. doi:10.4172/2161-
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The goal of this study is to evaluate an alternative to tissue grafts and cutaneous substitutes. Five hundred and seventeen burn patients were treated between February 2012 and June 2016: 381 of them benefited from cell therapy. 1 to 4 cm ² of autologous healthy total skin graft was dissected into epidermis, dermis and hypodermis, and then separately transformed into three cell-rich suspensions: some of these suspensions were eclectically chosen and associated first with platelet-rich plasma and thereafter with cryoprecipitate of plasma. Also, sequential seedings were performed every 2 days. The day after seeding, irrigation with antioxidants, protectors and healing stimulants was carried out twice daily. Deep 2 nd degree burns healed in 5 to 10 days, while for 3 rd degree burns results were achieved in 20 days for small areas and 50 days, on average, for larger areas. This reproducible technique could find its place in the therapeutic arsenal against burns. © 2018, Mediterranean Club for Burns and Fire Disasters. All rights reserved.
... 28 Lors du prélèvement cutané initial, quelle que soit l'anesthésie réalisée, il faut éviter d'infiltrer la zone par un anesthésique local ou de l'adrénaline, potentiellement cytotoxiques. 44,45 La partie dermo-épidermique du prélèvement ini-tial contient certes des CS, mais en quantité relativement limitée. 28,29 En revanche, l'hypoderme représente la source de CS mésenchymateuses adultes la plus accessible et la plus abondante de l'organisme. ...
Article
Full-text available
The goal of this study is to evaluate an alternative to tissue grafts and cutaneous substitutes. Five hundred and seventeen burn patients were treated between February 2012 and June 2016: 381 of them benefited from cell therapy. 1 to 4 cm2 of autologous healthy total skin graft was dissected into epidermis, dermis and hypodermis, and then separately transformed into three cell-rich suspensions: some of these suspensions were eclectically chosen and associated first with platelet-rich plasma and thereafter with cryoprecipitate of plasma. Also, sequential seedings were performed every 2 days. The day after seeding, irrigation with antioxidants, protectors and healing stimulants was carried out twice daily. Deep 2nd degree burns healed in 5 to 10 days, while for 3rd degree burns results were achieved in 20 days for small areas and 50 days, on average, for larger areas. This reproducible technique could find its place in the therapeutic arsenal against burns.
... Subcutaneous and intraperitoneal equine adipose tissue samples were taken from 4 horses with ages ranging from <1 to 6 years (Supplemental data 1). For subcutaneous adipose tissue extraction, the region was aseptically prepared (for example dock region = base tail) and skin incisions were made under the influence of an adequate anaesthetic [36]. Underlying tissues were harvested by a veterinary surgeon. ...
Article
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Osteoarthritis (OA) commonly causes lameness in the horse and has a great impact in performance animals. Due to the limitations of current medical therapies, allogenic mesenchymal stem cells (MSCs) may become an alternative method to control inflammation, reduce tissue damage and pain, and therefore improve lameness. We present the results of a regulatory clinical trial testing adipose derived MSCs (Horse Allo 20) in veterinary (Agencia Española del Medicamento y Productos Sanitarios, AEMPS, Spanish Medicines Agency, Reference number 325/ECV) involving a total number of 80 participants and with 90 days of follow-up period. The manufacturing process of Horse Allo 20 was robust with no influence of the adipose tissue donor (gender, age or breed), sample origin (intraperitoneal or subcutaneous) or storage conditions (fresh versus frozen product presentations) on the quality, safety and efficacy of the drug product. An in vivo safety study showed that local and systemic tolerance was safe even after repeated intra-articular (IA) administration (three injections). An in vivo efficacy study demonstrated the efficacy of the treatment after one or two injections by a reduction in lameness (P<0.05) for an extended period of time (90 days), decreasing the need for prolonged local and/or systemic anti-inflammatory therapies and their well-known deleterious effects and toxicities.
... Recently invented techniques such as the tissue liquefaction technology liposuction, which uses warm saline and low pressure for adipocyte harvesting, may have been shown to reduce donor-side morbidity; however, the regenerative potential of ASCs harvested via this approach remains uncertain [24]. In addition to harvesting methods, there are multiple other factors influencing the regenerative efficacy of ASCs, some known such as shear stress [25] and lidocaine exposure [26], and some yet to be determined. Ongoing research will help to identify which elements of fat harvesting, processing and application positively or negatively affect ASC functions. ...
Article
Background aims: Regenerative medicine employs human mesenchymal stromal cells (MSCs) for their multi-lineage plasticity and their pro-regenerative cytokine secretome. Adipose-derived mesenchymal stromal cells (ASCs) are concentrated in fat tissue, and the ease of harvest via liposuction makes them a particularly interesting cell source. However, there are various liposuction methods, and few have been assessed regarding their impact on ASC functionality. Here we study the impact of the two most popular ultrasound-assisted liposuction (UAL) devices currently in clinical use, VASER (Solta Medical) and Lysonix 3000 (Mentor) on ASCs. Methods: After lipoaspirate harvest and processing, we sorted for ASCs using fluorescent-assisted cell sorting based on an established surface marker profile (CD34(+)CD31(-)CD45(-)). ASC yield, viability, osteogenic and adipogenic differentiation capacity and in vivo regenerative performance were assessed. Results: Both UAL samples demonstrated equivalent ASC yield and viability. VASER UAL ASCs showed higher osteogenic and adipogenic marker expression, but a comparable differentiation capacity was observed. Soft tissue healing and neovascularization were significantly enhanced via both UAL-derived ASCs in vivo, and there was no significant difference between the cell therapy groups. Conclusions: Taken together, our data suggest that UAL allows safe and efficient harvesting of the mesenchymal stromal cellular fraction of adipose tissue and that cells harvested via this approach are suitable for cell therapy and tissue engineering applications.
Article
Background: Fat transplantation is becoming increasingly popular for off-face rejuvenation. Objective: To provide an update in the literature of current knowledge and emerging concepts in the use of fat transplantation for nonfacial applications. Materials and methods: This update includes the potential benefits and risks of using fat transfer techniques on the body. Results: The current literature and author experiences are provided to help understand this growing field of aesthetic procedures. Conclusions: The use of nonfacial fat transplantation is increasing and will become a larger part of aesthetic practices.
Article
Full-text available
The local anesthetic lidocaine, which has been used extensively during liposuction, has been reported to have cytotoxic effects and therefore would be unsuitable for use in autologous lipotransfer. We evaluated the effect of lidocaine on the distribution, number, and viability of adipose-derived stem cells (ASCs), preadipocytes, mature adipocytes, and leukocytes in the fatty and fluid portion of the lipoaspirate using antibody staining and flow cytometry analyses. Adipose tissue was harvested from 11 female patients who underwent liposuction. Abdominal subcutaneous fat tissue was infiltrated with tumescent local anesthesia, containing lidocaine on the left and lacking lidocaine on the right side of the abdomen, and harvested subsequently. Lidocaine had no influence on the relative distribution, cell number, or viability of ASCs, preadipocytes, mature adipocytes, or leukocytes in the stromal-vascular fraction. Assessing the fatty and fluid portions of the lipoaspirate, the fatty portions contained significantly more ASCs (p < 0.05), stem cells expressing the preadipocyte marker Pref-1 (p < 0.01 w/lidocaine, p < 0.05 w/o lidocaine), and mature adipocytes (p < 0.05 w/lidocaine, p < 0.01 w/o lidocaine) than the fluid portions. Only the fatty portion should be used for transplantation. This study found no evidence that would contraindicate the use of lidocaine in lipotransfer. Limitations of the study include the small sample size and the inclusion of only female patients.
Article
Die autologe Fetttransplantation gilt als sekundär rekonstruktives Verfahren und hat als Therapieziel eine Verbesserung der Lebensqualität. Beim Lipofilling wird autologes Fett in den Empfängersitus übertragen, um die Weichteilkontur der Empfängerregion zu optimieren. Brustkrebs ist die häufigste Krebserkrankung der Frau. Dank individualisierter Behandlungsmethoden steigen zwar die Heilungsraten, aber immer mehr Frauen müssen viele Jahre mit den Ergebnissen und Folgen der Operation leben. Auch wenn die Operationsverfahren immer differenzierter und an den individuellen Situs adaptiert sind, kommt es zu Narben, Defekten oder Einziehungen und Volumenverlust der Brust, durch eine nachfolgende Radiatio werden diese häufig verstärkt. Autologes Fett eignet sich zur Verstärkung des Weichteilmantels und zur Verbesserung der Kontur sowie auch der Hautperfusion und zum Volumenausgleich. Damit eignet Fett sich zur Rekonstruktion der Brust sowohl nach Mastektomie und Lappenplastik oder nach haut- und nippelsparender Mastektomie und Implantateinlage. Auch nach brusterhaltender Therapie eines Mammakarzinoms können Defekte, Asymmetrien und Narbenkonstriktionen mit Eigenfett kompensiert werden. Zu beachten ist, dass Fett ausschließlich in eine gesunde Brust transplantiert werden darf. Vor der autologen Fetttransplantation sollte ein Residualtumor oder ein Rezidiv sicher ausgeschlossen werden. Je länger die Karenzzeit zwischen der Onkochirurgie und dem Fetttransfer ist, desto höher ist die Sicherheit. Der Erfolg dieser Methode ist von profunden Kenntnissen der Methode, einer sorgfältigen Ausführung jedes einzelnen Behandlungsschrittes abhängig. Gemessen wird er an Parametern wie unbeeinträchtigte Beurteilbarkeit der Brust in der Bildgebung, Volumenstabilität und onkologische Sicherheit.
Chapter
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Transplantation of viable adipocytes and precursor cells for contour augmentation, enlargement, or filling of defects has become one of the most common clinical treatments in clinical practice. Based on evidence that lidocaine solution may alter the metabolic activity, evaluation on effects of multiple rinsings is presented. Statistically significant reduction of intracellular lidocaine was documented with such rinsings. It was concluded that a minimal of three rinses utilizing equal volume of saline to graft material achieved substantial reduction of the lipophilic lidocaine concentrations held intracellularly after harvest. Such rinsings did not result in complete removal of lidocaine levels, but did effectively reduce the potential influence of high intracellular lidocaine to the grafted cellular elements. It is believed that high concentrations of retained intracellular lidocaine may inhibit the return to metabolic activities and potentially impact survivability of autologous fat cells and precursor element in grafts. With the evolution of minimal traumatic harvesting equipment and techniques, there is continued growth of interest in the ability to successfully provide volume tis-sue augmentations of the face and body. Since the advent of superpolished cannulas and closed syringe systems, harvesting has become easier and graft acceptance more predictable (1– 6) . As the preferred equipment arma-mentarium has stabilized, attention has turned to recog-nition of factors that have signifi cant infl uence on the safety and effi cacy of adipose-derived grafts. Among those factors recognized as potentially important, the decision as to whether it is advanta-geous to provide harvested cells with rinsing prior to addition of additives or actual transfer (4– 6) . On the basis of evidence that lidocaine solution may infl uence metabolic activity within the graft or host tissues, eval-uation of effects of serial rinsing was carried out. Transplantation of autologous live adipocytes and precursor cells for purposes of contour augmentation, structural enhancement, or fi lling of defects has become one of the most common modalities and surgi-cal treatment options. With the understanding of tumescent infi ltration providing a vehicle in which the donor cellular matrix can become suspended, use of controlled, low pressure harvest with closed syringe techniques has become very important. It is clear, both from clinical and laboratory evidence that viability, in vitro, has been enhanced (1– 3) . Relatively little infor-mation has been available regarding concentration of the intracellular lidocaine solution following use of the standard tumescent concentrations of 0.05–0.1% lido-caine. The potential for metabolic alteration during early graft phases, and in the longer-term reactivation of storage activities seen in tissue culture, makes evaluation of the lidocaine elements a potentially important subject. Throughout existing literature and presentations, controversy still remains as to the cel-lular survival quantities, and even less understood fea-tures of use of additives to enhance the return to metabolic storage activities within the grafted cells. The wide ranges reported in the literature claim sur-vival rates of 40–60%, often not accounting for the fl uid medium volumes introduced during the actual grafting. It is clear that cells and matrix are "fl oated" out of selected donor sites, often compressed slightly with gentle centrifugation, and then transferred within a liquid carrier during placement. It is, therefore, very important to account for the volume of extracellular fl uid at the time of all graftings. This fl uid volume resorption should be anticipated and certainly not interpreted as loss of cellular volume resultant from the grafts themselves (6) . Tissue culture suggests very high cellular survival rates, often reported in the 90+ percentile (1) . Selection of the genetically driven fat deposits as potential donor sites has gradually been better recog-nized and understood (4– 19) . The surgeon's access should be given minor importance relative to the har-vest of prime storage cellular elements, often referred to as "primary fat deposits." Such sites are metaboli-cally relatively unavailable to diet and exercise. Further, it is believed that transplanted adipose tissues retain
Article
The current recommendations regarding maximum doses of local anesthetics presented in textbooks, or by the responsible pharmaceutical companies, are not evidence based (ie, determined by randomized and controlled studies). Rather, decisions on recommending certain maximum local anesthetic doses have been made in part by extrapolations from animal experiments, clinical experiences from the use of various doses and measurement of blood concentrations, case reports of local anesthetic toxicity, and pharmacokinetic results. The common occurrence of central nervous system toxicity symptoms when large lidocaine doses were used in infiltration anesthesia led to the recommendation of just 200 mg as the maximum dose, which has remained unchanged for more than 50 years. In most cases, there is no scientific justification for presenting exact milligram doses or mg/kg doses as maximum dose recommendations. Instead, only clinically adequate and safe doses (ranges) that are block specific are justified, taking into consideration the site of local anesthetic injection and patient-related factors such as age, organ dysfunctions, and pregnancy, which may influence the effect and the pharmacokinetics of the local anesthetic. Epinephrine in concentrations of 2.5 to 5 microg/mL should be added to the local anesthetic solution when large doses are administered, providing there are no contraindications for the use of epinephrine. As a rule, conditions (eg, end-stage pregnancy, high age in epidural, or spinal block) or diseases (uremia) that may increase the rate of the initial uptake of the local anesthetic are indications to reduce the dose in comparison to one normally used for young, healthy, and nonpregnant adults. On the other hand, the reduced clearance of local anesthetics associated with renal, hepatic, and cardiac diseases is the most important reason to reduce the dose for repeated or continuous administration. The magnitude of the reduction should be related to the expected influence of the pharmacodynamic or pharmacokinetic change.
Book
The book covers all aspects of autologous fat transfer including the history of fat transfer, the history of autologous fat survival, a variety of aesthetic and plastic procedures of the face and body, noncosmetic applications of fat transfer, preoperative care, complications, and medical-legal aspects. The contributors are international experts in the field of autologous fat transfer. The Table of Contents shows the variety of subjects.The book is intended for residents and fellows, practicing and highly experienced cosmetic surgeons, and surgeons in the fields of plastic surgery, general surgery, otolaryngology, ophthalmology, oral-maxillofacial surgery, neurosurgery, orthopedic surgery, and other surgical subspecialties.
Book
Liposuction began as a contouring procedure but has evolved into the treatment of obese patients, gynecomastia, ptosis, macromastia, and even patients who have complications from heart disease or diabetes. Other disorders such as axillary sweat hypersecretion, lipomas, and angiomas are also potential disorders that may be treated with liposuction. Physicians performing liposuction must be adequately trained and experienced in the potential and actual complications before attempting to perform liposuction. Patient safety is the most important aspect of all surgeries, but especially of cosmetic surgery, which is an elective procedure. New technology helps improve results but experience, care, and skill of the cosmetic surgeon is necessary to obtain optimal results that satisfy the patient. The contributors to this book have spent time and effort presenting the cosmetic and plastic surgeon as much information as possible on the techniques and uses of liposuction for cosmetic and non-cosmetic surgery purposes.
Chapter
The history of autologous fat augmentation gives insight into the development of fat transfer for both cosmetic and non cosmetic problems. Transplantation of pieces of fat and occasionally diced pieces of fat advanced to removal of small segments of fat by liposuction after the development of technique by Fischer and Fischer reported in 1975. The progression of techniques in fat transfer progressed because of this innovation and nor autologous fat transfer is a common technique in facial rejuvenation, repair of defects and deficits and more recently for non aesthetic purposes including neurosurgical and orthopedic.