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ANNPLA-1232; No. of Pages 13

Annales de chirurgie plastique esthétique (2016) xxx, xxx—xxx

Available online at

ScienceDirect
www.sciencedirect.com

GENERAL REVIEW

Leech therapy in flap salvage: Systematic

review and practical recommendations
Utilisation des sangsues dans le sauvetage des lambeaux :
revue systématique, mise au point et recommandations d’usage

C. Herlin a,b,c,*, N. Bertheuil d, F. Bekara a,b,c, F. Boissiere a,b,c,

R. Sinna e, B. Chaput f

a
Service de chirurgie plastique et reconstructrice, centre des brûlés, CHRU Lapeyronie, 325, avenue du
doyen-Gaston-Giraud, 34295 Montpellier cedex 5, France
b
Service de chirurgie plastique et craniofaciale pédiatrique, CHRU Lapeyronie, 34295 Montpellier, France
c
Unité de plaies et cicatrisation, CHRU Lapeyronie, 34295 Montpellier, France
d
Service de chirurgie plastique, reconstructrice et esthétique, CHRU de Rennes, 35000 Rennes, France
e
Service de chirurgie plastique, reconstructrice et esthétique, CHRU de Picardie, 80080 Amiens, France
f
Service de chirurgie plastique, reconstructrice et esthétique, CHRU de Rangueil, 31400 Toulouse, France

Received 3 February 2016; accepted 12 June 2016

KEYWORDS Summary
Leeches; Introduction. — Medicinal leeches have been part of the therapeutic armamenterium of plastic
Flaps; surgeons for more than 50 years. While their use in hand surgery is a matter of course, their use in
Biotherapy; salvage of flaps with venous congestion remains facultative depending on teams.
Review Materials and methods. — We conducted a systematic review of leech therapy for flap salvage
between 1960 and 2015, analyzing 121 articles and subsequently taking into consideration 41
studies. In parallel, we collected data from 43 patients for whom leach therapy had recently
been applied in treatment of venous insufficiency in pedicled or free flaps after revision surgery
had failed to improve flap vascularization, or in cases where flap revision was not appropriate.
The data collected pertained to relevant indications, treatment procedure, efficacy, adjuvant
therapies, side effects and complications.
Results. — For this indication, the success rate of leech therapy ranged from 65 to 85% (83.7% in
our series) according to the situations encountered. Optimal frequency of application ranged
from 2 to 8 hours, while average overall duration ranged from 4 to 10 days. The number of

* Corresponding author at: Service de chirurgie plastique et reconstructrice, centre des brûlés, CHRU Lapeyronie, 325, avenue du doyen-
Gaston-Giraud, 34295 Montpellier cedex 5, France.
E-mail address: drchristianherlin@gmail.com (C. Herlin).

http://dx.doi.org/10.1016/j.anplas.2016.06.004
0294-1260/# 2016 Elsevier Masson SAS. All rights reserved.

Please cite this article in press as: Herlin C, et al. Leech therapy in flap salvage: Systematic review and practical recommendations. Ann Chir
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2 C. Herlin et al.

leeches to be applied can be determined depending on volume of the flap. In 50% of the cases
reported in the literature, the patients required transfusion. Antibiotic prophylaxis against
Aeromonas is highly advisable. A ciprofloxacin and trimethoprim-sulfametoxazole combination
currently appears as the most relevant prophylactic antibiotherapy.
Conclusion. — Hirudotherapy is a reliable treatment in cases of patent venous insufficiency of
pedicled or free flaps (or when revision surgery is not recommended). Even though the relevant
literature is highly heterogeneous, we have attempted to put forward a specific protocol bringing
together dosage, delivery route, frequency of administration and appropriate prophylactic
antibiotherapy. An algorithm for treatment and management of venous congestion and a
practical information sheet have been placed at the disposal of plastic surgery teams.
# 2016 Elsevier Masson SAS. All rights reserved.

Résumé
MOTS CLÉS Introduction. — Les sangsues font partie de l’arsenal thérapeutique des chirurgiens-plasticiens
Sangsues ; depuis plus de 50 ans. Si leur utilisation est largement protocolisée en chirurgie de la main, leur
Lambeaux ; utilisation pour le sauvetage des lambeaux en congestion veineuse reste une affaire d’école.
Biothérapie ; Matériels et méthodes. — Nous avons analysé 121 articles entre 1960 et 2015 puis retenu 41
Revue études. Parallèlement, nous avons colligé les données de 43 patients récemment traités. Les
données colligées portaient sur les indications, le mode d’administration, l’efficacité du
traitement, les traitements adjuvants, les effets indésirables et enfin, les complications.
Résultats. — Le taux d’efficacité des sangsues dans cette indication était de 65 à 85 % en
fonction des situations (83,7 % dans notre série). La fréquence d’application idéale, adaptée
individuellement, se situait entre 2 et 8 heures et la durée totale moyenne entre 4 et 10 jours. Le
nombre de sangsues à appliquer peut être défini en fonction de la taille et du volume du lambeau.
Les patients ont nécessité une transfusion dans 50 % des cas de la littérature analysée. Une
antibioprophylaxie dirigée contre Aeromonas est fortement conseillée. L’association trimétho-
prime—sulfamétoxazole et ciprofloxacine nous paraît la plus pertinente à l’heure actuelle.
Conclusion. — L’hirudothérapie est un traitement fiable en cas d’insuffisance veineuse patente
des lambeaux pédiculés ou libres lorsqu’une reprise chirurgicale n’est pas opportune. Malgré une
littérature hétérogène, nous nous sommes efforcés de proposer un protocole précis englobant la
posologie, le mode d’administration, le rythme et l’antibioprophylaxie adaptée. Un algorithme
de prise en charge des congestions veineuses et une fiche d’utilisation sont également mis à
disposition pour les équipes de chirurgie plastique.
# 2016 Elsevier Masson SAS. Tous droits réservés.

Introduction History

Notwithstanding substantial progress in reconstructive sur-
gery, particularly microsurgery, venous congestion in trans-
planted or reimplanted tissues has remained a frequent and
challenging complication [1,2]. While partial venous obstruc-
tion can be physiologically offset by neovascularization over a
period of 3 to 10 days [3,4], total obstruction by lumen collapse
or venous thrombosis leads in 3 hours to severe microcircula-
tory lesions and in 8 to 12 hours to irreversible microcircula-
tory lesions culminating first in the ‘‘no reflow phenomenon’’
inside the flap, and subsequently in tissulary necrosis [5].
While early revision surgery is most often of use, it does not
always suffice to reestablish physiological circulation in the
distressed tissue. In such cases, the use of leeches, otherwise
known as hirudotherapy, is a practical technique with which all
plastic surgeons are acquainted. Along with larvotherapy, it is
one of the rare biotherapies currently employing complex
living organisms. The most commonly used species in today’s
medicine is Hirudo medicinalis, which has been privileged due
to its efficacy. Currently, only the company called Ricarim-
pex1, located in the Arcachon basin, breeds leeches on an
industrial scale for medicinal purposes [6].
While the first written evidence of hirudotherapy, in Egypt, is
more than 3500 years old, actual proof of its therapeutic, by
the Greek, Roman and Indian civilizations, dates back to
approximately 2000 years ago [7]. Leeches were used mainly
for treatment of phlebitis and hemorrhoids, and only spor-
adically for bloodletting. In France, François-Joseph-Victor
Broussais, an early 19th-century ‘‘Napoleonic’’ physician
practicing at the military hospital of Val-de-Grâce, who
was considered as one of the most sanguinary physician in
history, intensively developed the use of leeches in treat-
ment of inflammatory diseases and as a method of ‘‘hyper-
stimulation’’ of the digestive organs. As a result of his
efforts, by 1830, France had become the world leader in
the field, with a hundred million leeches being put to work
year in and year out [7]. Over the following decades, how-
ever, a prolonged cholera epidemic and application of the
asepsis techniques advocated by Louis Pasteur prevailed over
the once-fashionable application of leeches.
The 20th century was marked by a crisscrossing of contra-
dictory tendencies. On the one hand, in 1974, reimburse-
ment of leech treatment by French social security was

Please cite this article in press as: Herlin C, et al. Leech therapy in flap salvage: Systematic review and practical recommendations. Ann Chir
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Leech therapy in flap salvage: Systematic review and practical recommendations
officially discontinued. On the other hand, inauguration of a
new chapter in leech use, particularly in plastic and recon-
structive surgery, was largely initiated by French surgeons. In
the 1960s, Derganc and Zdravic et al. [8] described the interest
of hirudotherapy in the treatment of venous congestion in
pedicled flaps. In the 1970s, Jacques Baudet highlighted its
interest with regard to venous congestion in free flaps [9], and
Foucher and Norris illustrated its relevance in digital reattach-
ments [10]. In the United States, however, only in 2004 was the
utilization of leeches authorized by the FDA [11].
At present, leeches are credited with multiple virtues,
particularly in the treatment of thromboembolic diseases
and their sequelae, arthritis, tendinitis, high blood pressure,
old hematomas, purpura fulminans and migraines, but it is in
plastic surgery that leeches are widely recognized as a
leading and difficultly replaceable means of treatment
[12]. Hirudotherapy has been described as contributing to
the salvaging of pedicled flap [8,13,14], nipple-areolar com-
plex [15,16], free flaps [17—20] and to the replantation of
fingers [10,21,22], ears [23,24], lips [25], noses [26], penises
[27] and other organs or organ fragments presenting with
forms of venous insufficiency that cannot be remedied by
revision surgery.
Even though the therapeutic efficacy of leeches has been
recognized [28], there exist no guidelines for their use,
particularly when they contribute to flap salvage. Through
a systematic review of the literature on the basis of our
multicentered experience, we wish to draw a synthesis of
current knowledge pertaining to the properties of medicinal
leeches, knowledge acquired under the same controlled and
reproducible conditions as those required with regard to
more conventional medicinal products. More specifically,
we wish to clarify their mechanisms of action, relevant
indications, modalities for treatment, possible complica-
tions, and means of preventing them. The synthesis could
be of major importance in attempts to optimize today’s
therapeutic use of medicinal leeches.
Presentation of leeches and their mechanism of
action
Hirudo medicinalis is a hematophagous, hermaphroditic
aquatic annelid worm measuring 3 to 5 cm and weighing 1
to 2 grams when fasting. Suction cups are found at the two
extremities of its body (Fig. 1). Of a finer texture than the
back end, the front end presents a suction cup with three
retractable jaws Y-shaped. When applied, a leech can ingest
from 5 to 20 mL of blood over a period lasting from 15 min-
utes to 2 hours, and then spontaneously detach itself. After
that, it is able to fast for a hundred days. For 6 to 8 hours,
blood will flow profusely from the site of the bite, and then
more slowly for another day or two [29].
In the leech’s natural state, during its feed intake, it is
necessary to keep the blood from the prey in an incoagulable
state so that it can be assimilated in its digestive tract. This
comes about by means of its saliva, which contains numerous
active ingredients such as anticoagulants, platelet aggrega-
tion inhibitors and proteinase inhibitors. In 1884, Haycraft
was the first scientist [30] to identify in leeches’ salivary
glands an anticoagulant substance he named hirudin. As a
powerful anticoagulant, it inactivates thrombin by taking
the place of fibrinogen, and it also affects the Xa factor that
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3
Figure 1 View from above of Hirudo medicinalis, the motor
extremity (see above) helps it simply to crawl and to find a
position. The anterior extremity (see below) contains the mand-
ibles with which a leech feeds itself.
catalyzes the conversion of prothrombin into thrombin. The
activity of hirudin renders possible the flow of blood while
the bite is taking place. Moreover, leech saliva contains
platelet function inhibitors (calin, apyrase, collagenase,
prostaglandin. . .) accounting for the persistence of bleeding
subsequent to biting. Leech saliva also contains proteinase
inhibitors such as bdellin and eglin with their anti-inflamma-
tory activity, and proteases such as hyaluronidase and pyr-
ase, which decrease the viscosity of the interstitial liquid and
improve the depth-wise penetration of the other substances.
Lastly, leech saliva possesses a histamine-like vasodilator
substance and a powerful anesthetizing substance rendering
the bite painless.
Review of the literature and multicentered
retrospective review
A systematic review of the literature dating from 1960 (initial
description) to December 2015 was conducted on the
Pubmed, Cochrane and EmBASE platforms. The following
keywords were researched: ‘‘Leeches’’ OR ‘‘Leeching’’ OR
‘‘Leech therapy’’ OR ‘‘Medicinal leech’’ AND ‘‘Flap’’ OR
‘‘Flaps’’. By applying this method, we preselected 121 arti-
cles. The sought-after data pertained to indications for local,
local-regional or free flaps, method of administration, treat-
ment efficacy, adjuvant therapies, side effects and compli-
cations. Duplicated data were excluded. The articles
analyzed were written in English or in French.
Out of the 121 articles, 41 had exclusively to do with the
use of leeches in flap salvage. We identified 25 case series
and 16 clinical cases representing 335 flaps. The studies
included had a low level of evidence (Jadad or Oxford score
from 0 to 1, level of evidence 4 or 5 according to the criteria
of the American Society of Plastic Surgeons).
In parallel, applying the same criteria, the authors col-
lected and studied their multicenter experiences over the
last five years on the utilization of leeches in flap salvage. We
recovered the data for 43 patients having undergone leech
therapy to salvage a pedicled or a free flap. The data were
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4 C. Herlin et al.
analyzed in view of drawing up and defending proposed
guidelines on good practice.
Indications for hirudotherapy in flap surgery:
venous insufficiency
Venous insufficiency often appears during first postoperative
hours as gradually aggravated congestion. Flaps with cuta-
neous skin island present accelerated capillary refill
(< 2 seconds), and in a few hours, dark pink coloration
becomes purpuric purple (Fig. 2). Quite frequently, dressings
are stained and the edges of the flap bleed spontaneously of a
dark red blood.
It is important to clearly identify early complete venous
insufficiencies, which affect a major proportion of free flaps
or propeller perforator flaps with skeletonized pedicle; in
these cases, hirudotherapy is not considered as first-line
treatment. Early venous insufficiencies should be painstak-
ingly distinguished from late venous insufficiencies, which
are often distally located, and preferentially affect local
‘‘random’’ flaps or local-regional pedicled flaps; in these
cases, the flap is initially pale and the congestion occurs
somewhat belatedly (often at H + 12).
While mixed (arterial and venous) circulatory insufficien-
cies present similar colorations, no congestion ensues, and
the needlestick causes an effusion of blood that is less
profuse and blackish than in venous insufficiency alone. In
Figure 2 Example of typical distal venous overloading of a
peroneal pedicled perforator flap. Leech therapy (6 days)
brought about full salvage without requiring an additional surgi-
cal intervention.
Please cite this article in press as: Herlin C, et al. Leech therapy in flap salvage: Systematic review and practical recommendations. Ann Chir
Plast Esthet (2016), http://dx.doi.org/10.1016/j.anplas.2016.06.004
these ‘‘mixed’’ cases, leech use is presumed deleterious
[31]. It should be noted that these cases most often occur
during the late stages of venous insufficiency, when capillary
venous pressure impedes arterial blood influx and thereby
leads to arterial thrombosis just prior to circulatory arrest
(no reflow phenomenon).
Finally, it is more difficult and of major importance to
clearly distinguish the pathological congestive venous
insufficiency from the rheological physiological adaptation
phenomena undergone by some free or pedicled perforator
flaps, of which the specificity consists in its exhibiting rapid
pinkish coloration during the first 6 to 12 hours following flap
harvesting (Fig. 3). In this particular case, the phenomenon is
rapidly reversible and is not associated with other signs
(congestion, bleeding of the edges). In the absence of quan-
tifiable monitoring (doppler, laser doppler, oxymetry, micro-
dialysis. . .), the needlestick may occasionally be useful to see
the blood color to which it leads.
Local ‘‘random’’ flaps
With random flaps, distal venous insufficiency is a frequent
occurrence; it is often ‘‘mixed’’ and difficult to improve by
surgical revision. However, prior to the introduction of
leeches, release of some points of tension on the edges or
at the bottom of the flap should be considered as an option,
as should be the return of the flap to its initial position
through a two-step procedure.
Pedicled local-regional flaps
Some distally-based flaps such as the reverse flow sural neu-
rocutaneous flaps are reputed to be frequently congested.
Indeed, congestion is often perceptible during or after the
intervention [32]; it appears over the first postoperative hours
as a distally delimited purplish area requiring immediate leech
therapy [13] when surgical revision appears pointless (Fig. 2).
However, when congestion affects the entire flap, as may be
the case with propeller perforator flaps of which the vein has
completely collapsed by ‘‘twisting’’, a revision remains the
Figure 3 False appearance of venous overloading in a helical
dorsal intercostal artery perforator flap (DICAP) during intro-
duction. After 3 hours of close monitoring, the flap had regained
normal cutaneous refill, and it never showed any sign of conges-
tion other than a phase of rapid capillary refill.
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Leech therapy in flap salvage: Systematic review and practical recommendations
treatment of choice, and it is aimed at decompressing or
‘‘untwisting’’ the pedicle by returning the flap to its initial
position. And then, within 48 hours, the decongested flap is
returned to an appropriate position. This delayed procedure
should always be considered as a possible option for large and/
or voluminous flaps, that is to say indications for which the
efficacy of leeches is limited. In our experience, hirudother-
apy has been used in 86% of the relevant cases (37/43) for
pedicled flaps.
Free flaps
Aside from replantation of fingers or small organs such as
auricle parts of the ear [33], leeches are not meant to
supplant a venous micro-anastomosis [34]. Leeches rather
tend to be used in flap microsurgery if surgical revision has
failed to improve local condition or is medically or techni-
cally impossible. With regard to free cutaneous flaps, parti-
cularly perforator flaps, leeches can be used in the event of
distal insufficiency, when the venous perforasome does not
coincide with the arterial perforasome. Distal insufficiency
often appears belatedly, and on voluminous flaps. Leeches
should then be applied rapidly at the affected area, and the
required number is greater than is the case for pedicled flaps.
In our experience, hirudotherapy has been used in 14% (6/43)
of our patients for free flaps.
We also perform hirudotherapy during the period between
the decision to undertake revision surgery and the onset of
the actual operation. Indeed, in the event of insufficiency
necessitating revision of anastomosis, the time elapsed
between decision and act is often greater than the time
between two monitoring sessions. In such cases hirudother-
apy may be considered as a logical option, especially inas-
much as it helps, when the operating theater is inaccessible,
to limit the formation of distal thromboses and to avoid
highly pejoratively termed circulatory collapse. The leeches
are removed in the operating theater just before surgery.
This technique may be associated with the protocols for in
situ thrombolysis applied by a number of teams [35—37],
which in our opinion present multiple advantages: no vessel
trauma caused by manipulation, no catheterization, disse-
mination of the anticoagulants on the thrombotic areas
Figure 4 Prone positioning and introduction of a ‘‘cage’’ for
secure installation of the leeches without setting up a device.
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5
where thrombolysis usually failed, monitoring of reperfusion
through the bite orifices. . .
Contraindications
Generally recognized contraindications include immunosup-
pression, advanced arterial insufficiency, hemophilia or any
other severe pathology affecting coagulation, hemopathies,
sepsis, hepatobiliary insufficiency, cachexis, refusal of trans-
fusion due to religious beliefs or psychological instability
[38,39].
Introduction of the leeches
Once the patient has been informed of the utilization of
leeches, of the concomitant treatments and of the hemor-
rhagic and infectious risks incurred, he should ideally be
placed in a position allowing the leeches to be kept on a
horizontal plane during the period of ingestion (Fig. 4). The
leeches are ordered from a pharmacy, where they are made
to fast for a hundred days prior to use, thereby rendering
them as hungry as possible. They are transported and con-
served until time of use in a plastic pot filled with pH neutral
mineral water at a temperature of 4 to 18 8C (Fig. 5). Placed
on the surface, the most mobile leeches are often the most
effective, and should be selected. Before introduction of the
leeches, it is necessary to eliminate all traces of antiseptics
on the flap by cleansing it with lukewarm serum. In our
experience, the leeches are manipulated with a gloved hand;
that said, some authors have proposed use of a 5 mL syringe
designed to force the leech to bite at a precise place [38];
this is of special interest for intraoral flaps. Faeces collectors
can also be used in large flaps. As a general rule, we build a
‘‘cage’’ around the insufficient flap; it consists in com-
presses rolled around the edges of the monitoring window
(Fig. 4). A compress, a hydrocolloid or a punctured trans-
parent adherent film can enhance precision of application.
More specifically, the compress-containing cage facilitates
blood harvest and helps to avoid soiling the dressing in its
entirety. The compresses are regularly changed. At times,
Figure 5 Placing the leeches in a plastic pot filled with pH
neutral mineral water. The most voluminous and most mobile of
the leeches are selected for the therapy.
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6 C. Herlin et al.

needle puncture can attract recalcitrant leeches by eliciting
a drop of blood. On the other hand, a leech may refuse
attachment if it is not hungry or in the event of advanced
arterial insufficiency [40]. Some authors have described the
deleterious effects of benzodiazepines and certain systemi-
cally given analgesics on the vitality and effectiveness of the
leeches [38]. In any case, following a suction period that can
last from 15 minutes to 2 hours, the leech will detach itself
spontaneously. It must then be sacrificed in acetone or in 70%
alcohol and incinerated; any reuse is strictly forbidden.
At what pace should leeches be introduced?
As leeches help to improve blood flow 6 to 8 hours after their
introduction, one may consider an equivalent time interval
to be optimally logical. However, some trams have proposed
pronouncedly shorter time intervals (2 h) [28]. In our opi-
nion, standardization of these intervals is to be avoided, the
reason being that the degree of venous overload is not
quantifiable without implementing sophisticated methods
such as oxymetry or microdialysis of which the effectiveness
in our context has yet to be demonstrated. The clinician and
the nurse must adapt to each situation by proposing first a
‘‘trial’’ interval of 2 to 6 hours according to congestion
severity during the first 12 hours, and then a ‘‘maintenance’’
interval of 4 to 8 hours according to congestion reduction and
blood color during bleeding. While measurement of the blood
gases on the flap may be helpful, in our experience blood
color and congestion should suffice. Moreover, once conges-
tion has occurred, skin color only gradually lightens, which
means that it is not a good criterion during the first hours.
How can the number of leeches to be introduced
during each cycle be estimated?
While we know that leeches are able to anticoagulate 100 mL
of blood in vitro [29], there exists no consensus on the
number of leeches to be introduced in cases of pedicled
flap or free flap insufficiency, whatever may be the composi-
tion and volume of the latter, the characteristics of the
receiving site, the degree of congestion, the time elapsed
prior to therapy, or the overall background. Indeed, our
review of the literature highlights the considerable hetero-
geneity of protocols from one team to the other; in equiva-
lent situations, therapy may involve less than 10 or more than
350 leeches per flap [19,28,34]. In their study, Nguyen et al.
[34] reported greater consumption of leeches in partial than
in full-scale flap salvage operations; this disparity is likely to
be explained by the variable degree of venous insufficiency
severity at the outset. As for salvage failures, they entail less
consumption; that is because therapy is often discontinued
at an early stage and also because the circulatory collapse
phenomenon reduces venous pressure and the quantity of
blood evacuated. In cases of flap insufficiency in the distal

Figure 6 Venous overloading by venous thrombosis of a DIEP flap (a). As revision surgery was not effective, hirudotherapy was
undertaken (b). It permitted effective decongestion (c), but after treatment was discontinued on D5, the flap was completely
necrotized in 48 hours.

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Leech therapy in flap salvage: Systematic review and practical recommendations 7

region, one or two leeches are generally used during each
cycle according to the size of the flap. As regards salvage in
cases of total congestion, it is estimated that a leech can be
put effectively to work on 10 cm2 of congested flap. How-
ever, the sizeable volume of reconstructions such as the DIEP
flap often renders them difficult to improve by hirudotherapy
(Fig. 6). It nonetheless seems logical to increase the number
of leeches according to flap thickness. More precisely, dou-
bling the number of leeches for every 2 additional centi-
meters of flap thickness is from our standpoint both
reasonable and representative of the different studies
described in the literature [34,41,42]. We have personally
experienced the advanced deterioration of cutaneous flap
due to leech misuse, as advanced ischemia was conjoined
with action of the proteases delivered by leech saliva.
the flap and the receiving site, which takes place, on the
average, between the 3rd and the 8th day [3,4]. For Nguyen
et al., in their series of 39 flaps, 7 days was the maximum
[34]. As is the case with regard to optimal time lapse
between two cycles, and keeping in mind the risk of blood
depletion, we are convinced that duration of treatment
should not be standardized. Daily photographic assessment,
always at the same time, of the ‘‘grey’’ or shadowed area, of
the cutaneous recoloration time lapse, of congestion and,
finally, of the color of the blood flowing from the bites should
help to determine the timing of treatment discontinuation
[19], which we carry out gradually over one day, dividing by
two the number of leeches present prior to cessation. In our
experience, average length of medicinal leech treatment is
6.3 days (4 to 10), and only exceptionally exceeds 7 days.

For how long should the therapy last? Effectiveness

As concerns duration of leech treatment, the data in the Numerous animal studies have facilitated identification of
literature are once again highly variable, with length of time the physiological role of leeches in flaps with venous over-
from one to 22 days [28]. Theoretically, average duration of load. Through their actions, leech bites increase oxygen
treatment should correspond to neovascularization between concentration in the blood by reducing capillary venous

Figure 7 Overall postoperative congestion of a peroneal artery perforator propeller flap (c) in spite of a reassuring early
postoperative aspect (b). Introduction of leeches over 5 days yielded complete flap salvage (d).

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8 C. Herlin et al.

pressure, and they also help to delay onset of circulatory

collapse [42]. The studies have also underlined the poten-
tially deleterious effects of hirudotherapy in cases of mixed
circulatory failure [31].
As regards for clinical practice, Whitaker et al. [28]
recently carried out a review of the literature of the last
50 years on the effectiveness of leeches in reconstructive
surgery. Out of 111 usable findings pertaining to flaps, 82.4%
(61/74) of the free flaps and 81.1% (30/37) of the pedicled
flaps treated by hirudotherapy were salvaged. As for Nguyen
et al. [34], they reported a salvage rate of 100% (5/5) for
random local flaps, 64.3% (9/14) for local and regional
pedicles, and 69.2% (9/13) for free flaps. As in the other
reported experiments, the very low number of cases in each
study (most often a single case or a number inferior to 10
patients per study) may be deplored. And while some studies,
for example Grobe et al. [43], have included a very high
number of cases (n = 148), they are lacking in data or details
allowing them to be productively used in relevant meta-
analysis. As a general rule, in studies involving more than five
cases the salvage rate has oscillated between 65 and 80%
[19,39,44] for free or pedicled flaps, without any appreciable
difference between the two techniques in terms of success,
even though their respective rheologies are difficult, if not
impossible to compare.
Out of the 43 patients included in our retrospective study,
leeches were used with total success in 60.5% (26/43) of the
cases and with partial success in 23.3% (10/43), while they Figure 9 Postoperative congestion of a distally-based medial
failed in 16% (7/43). The difference in size between the free plantar flap (a). Introduction of leeches over 5 days yielded
flap (n = 6) and the pedicled flap (n = 37), populations did not complete flap salvage (c).
allow us to draw any conclusions on possible differences in
effectiveness between the two (Figs. 7—10).

Adverse effects

Blood loss
Blood loss during leech use is constant. In their meta-ana-
lysis, Whitaker et al. [28] reported a transfusion rate of 50%.
The more voluminous the flap and the more pronounced its
insufficiency, the more it becomes necessary to endeavor to
avoid rapid deglobulizing, which would render the insuffi-
ciency of the flap more acute [34]. If possible, the blood
count should be monitored prior to therapy, and once ther-
apy starts, it should be monitored either every day or every
two days according to the number of leeches introduced by
day. Transfusion is indicated when the hemoglobin level is
lower than 8 g
dl 1 and/or in the event of poor clinical
tolerance. In the event of non-desired and prolonged bleed-
ing emanating from the bites, hemostatic dressings [45] or
suture [46] may be needed. In clinical practice, with use of
one leech every 2 hours, average blood loss will approximate
1 g
dl 1/24 h, necessitating blood transfusion when therapy
duration exceeds 5 days, and/or when the patient presents
with an initial hemoglobin level lower than 12 g
dl 1. Blood
transfusion is not a routine procedure, which is why leech use
and bleeding management must be considered taking into
account the effect on risk-benefit balance is comparison to
possible partial or total flap necrosis.

Figure 8 Overall postoperative congestion of a posterior tibial Scars from bites

artery perforator propeller flap (a). Introduction of leeches over While scars always initially appear, in more than 90% of cases
5 days yielded complete flap salvage (b). they later disappear [28] (Fig. 10). That said, potential

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Leech therapy in flap salvage: Systematic review and practical recommendations
Figure 10 Major venous congestion of a sural neuro-cutaneous
flap having necessitated intensive therapy (two leeches every
2 hours for 48 hours, and then two leeches every 4 hours for 5
days). In spite of the treatment, flap salvage was incomplete and
necessitated another means of covering (free anterolateral
thigh flap).
esthetic cost must be taken into account when the flap
site is located in a zone of esthetic interest. For improve-
ment in severe cases, recommendations include topical
application of non-steroidal anti-inflammatory drugs or
Figure 11 Algorithm proposed for management of postoperative venous congestion of pedicled flaps leading to hirudotherapy.
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9
dermocorticoids  associated with per os anti-histamine
drugs in cases of pronounced perilesional reaction [38].
Complications
Overall complication rates have been only rarely analyzed in
the literature. Whitaker et al. [28] have evoked a percentage
of 21.8%, of which about half have been related to infection.
Infection
Infection is frequently due to symbiotic bacteria residing in
the digestive tract of the leech; Aeromonas hydrophila is the
species most commonly responsible for localized or general-
ized infections. The other bacteria belong to the Aeromonas,
Serratia, Vibrio, Pseudomonas genus. . . In their meta-ana-
lysis, Whitaker et al. reported an infection rate following
hirudotherapy of 14%, whatever the mode of utilization [28].
Infectious manifestations include lymphangitis, dermo-
hyperdermitis, abscesses, severe sepsis and gas necrotizing
myositis due to synergistic infections [47]. The infections can
appear 24 hours after the leeches are introduced or up until a
month later [38]. In the event of infection, the flap salvage
rate declines drastically (88 to 37% for Whitaker et al. [28],
80 to 30% for De Chalain et al. [48]).
Prophylactic antibiotic treatment is recommended by
most of the authors and should be prolonged up to 24 hours
after the therapy ends [41,49]. The most widely reported
molecules in the literature are third-generation cephalos-
porins (3GC) [29,49,50], fluoroquinolones [51] and the tri-
methoprim-sulfametoxazole association [38,52]. Some
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ANNPLA-1232; No. of Pages 13
10
Figure 12 Algorithm proposed for management of postoperative venous congestion of free flaps leading to hirudotherapy.
authors have suggested a ‘‘feeding’’ treatment through the
ingestion of antibiotics directed against bacteria in a com-
mensal relationship with leeches; this treatment could yield
in situ eradication of the potentially pathogenic bacteria
species found in the digestive tract of the leeches [53]. Given
the elevated risk of inducing resistance in these species, we
consider this proposal to be dangerous. Cases of resistance to
fluoroquinolones have been repeatedly reported [50,54,55].
Nor does the use of 3GC appear indicated, given the exis-
tence in Aeromonas of an inducible cephalosporinase. To
conclude, we are convinced that a ciprofloxacin and tri-
methoprime-sulfametoxazole association (Ciflox1
1
500 mg  2/day and Bactrim Forte 1cp  2/day) could be
a satisfactory alternative.
Less frequently encountered complications
Cases of cutaneous reactions such as lymphangitis, persis-
tent painful adenopathies and even febricula have been
reported [38]. Some patients, 3% according to Whitaker
et al. [28], develop an inopportune stress reaction during
and after treatment. Some cases of pain, vasovagal response
and protracted hypotension have also been reported. Finally
and even more anecdotally, allergic and anaphylactic reac-
tions have been noted [38,56,57].
Recommendations for use and therapy
algorithms
Notwithstanding the heterogeneity of the literature, we can
confirm the essential role of leeches in the salvage of both
Please cite this article in press as: Herlin C, et al. Leech therapy in flap salvage: Systematic review and practical recommendations. Ann Chir
Plast Esthet (2016), http://dx.doi.org/10.1016/j.anplas.2016.06.004
C. Herlin et al.
free and pedicled flaps suffering from venous congestion
(Figs. 10—12). That said, while it is possible to apply quanti-
tative protocols for venous congestion in finger [58] or ear
[59] replantation, it is appreciably more complex to apply a
single protocol to all situations of venous insufficiency in
flaps. We are nonetheless putting forward an algorithm for
treatment of venous congestion in pedicled flaps (Fig. 11)
and free flaps (Fig. 12) in which leeches take on a clearly
determined role. Indeed, for cases where the decision to use
leeches has just been taken, we are proposing a common
protocol (Annexe A) providing guidance for practitioners and
a poster to be displayed in nursing care rooms (Fig. 13). The
number of leeches can be initially modulated according to
degree of congestion and time elapsed prior to treatment. As
for frequency of leech introduction, even though it has to be
modulated, mainly by monitoring treatment effectiveness, it
provides a way of successfully coping in difficult situations.
Indeed, a strict monitoring protocol not only facilitates rapid
action that limits ischemia, but also allows for optimal
adaptation of the number of leeches to be employed per
cycle.
This review of the literature provides corroboration of our
experience concerning the importance of prophylactic anti-
biotic treatment. It seems to us that the ciprofloxacin and
trimethoprim-sulfametoxazole association is currently the
best compromise solution, given the increasing number of
reported cases of resistance to fluoroquinolones. Screening
of resistances by a local pharmaceutical team seems logical,
especially insofar as it should help to avoid the appearance of
multiple drug resistance in the years to come. Means of
packaging and astutely applied methods of introduction
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Leech therapy in flap salvage: Systematic review and practical recommendations 11

Figure 13 Leech application protocol proposed in cases of flap salvage printable in the form of a poster that can be used by
paramedical staff.

can increase treatment effectiveness, ensuring enhanced area and/or volume, can likewise benefit from this thera-
comfort for the patient and the health care team. peutic approach when venous supercharging is not feasible.
The last recommendation pertains to the prevention of
congestion, as it takes into account the evident interest of Disclosure of interest
double venous anastomoses and the supercharging of the
pedicled flaps [1,32,60—64].
The authors declare that they have no competing interest.

Conclusion

Hirudotherapy currently represents the only validated treat- Annexe A. Leech application protocol
ment of patent venous insufficiencies in pedicled or free proposed in cases of flap salvage
flaps when surgical revision is not a suitable option. Its
success rate in salvage attempts is close to that of well- Information & Accord du patient
conducted corrective operations. Even though today’s lit- Antibioprophylaxie
erature is highly heterogeneous, it has enabled us to propose (en accord avec l’écologie locale, du début jusqu’à 24h
a precisely formulated protocol including dosage, means of après la fin du traitement)
administration, frequency and pace of delivery and appro- Sulfamethoxazole 800mg + trimethoprime 160mg (Bac-
priate prophylactic antibiotic treatment. Monitoring and trim Forte): 1cp x 2
dose adjustment are essential to success. While the antic- ou Ciprofloxacine 500mg x 2
oagulant and decongestant effects of hirudotherapy in treat- ou Ceftriaxone 1g x 2 (deuxième ligne)
ment of distal insufficiency in pedicled flaps is well-known, in Positionner le patient, surface du lambeau vers le haut
this paper we have confirmed the hypothesis that free flaps, Confection d’une cage ou mise en place d’une interface
particularly perforator-based cutaneous flaps with a large trouée

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Plast Esthet (2016), http://dx.doi.org/10.1016/j.anplas.2016.06.004
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12
Détersion au sérum physiologique
Choix des sangsues mobiles
Manipulation avec des gants/pinces atraumatiques
Application sur les zones congestives d’une sangsue tous
les 10cm2
Doubler le nombre de sangsues si lambeau> 2cm
d’épaisseur
Maximum 4 sangsues en même temps
Temps d’indigestion entre 25 et 45min (changer au
besoin)
Renouveler le traitement toutes les 2h si ischémie
veineuse ou toutes les 4 heures si congestion simple
Surveillance horaire du lambeau (TRC, congeston, cou-
leur du lambeau, couleur du sang)
Bilan clinique à H12 +/- Modification de la posologie ou
de la fréquence
Numération globulaire tous les jours du traitement
Transfusion si Hb<8g
dl-1 et/ou si mauvaise tolérance
Arret du traitement si amélioration entre J5 et J7
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