Q U I N T E S S E N C E I N T E R N AT I O N A L
PROSTHODONTICS
Hemostatic gingival retraction agents
and their impact on prosthodontic treatment steps:
A narrative review
Christian Maischberger, med dent1/Bogna Stawarczyk, PD Dr rer biol hum Dipl-Ing (FH) MSc2/
Annette von Hajmasy, MDT3/Anja Liebermann, Dr med dent, MSc4
The purpose of this topic review is to give a general overview
of gingival retraction agents used during prosthodontic treat-
ment, and the possible difficulties connected to them that may
be faced by the dentist. Hemostatic agents are important for
successful gingival retraction and in achieving hemostasis.
However, these agents may show numerous negative effects
on the prosthodontic treatment and oral tissues of which the
practicing dentist must be aware, and which will be elucidated
in this review. PubMed and Google Scholar databases were
searched for publications up to and including 2017. The follow-
ing key words were used in different combinations: “hemostat-
ic agent,” “astringent,” “astringency,” “epinephrine,” “ferric
sulfate,” “aluminum chloride,” “hemorrhage control,” “soft
tissue,” “hard dental tissue,” “self-etch adhesive,” “total-etch
adhesive,” “bond strength,” “impression,” “gypsum,” “plaster
cast,” and “dental cast.” In the last three decades the hemostatic
Key words: adhesion, astringent, hemorrhage control, hemostatic agent, prosthodontics
1 Doctoral Student, Department of Prosthetic Dentistry, University Hospital, LMU
Munich, Munich, Germany.
2 Head of Material Science, Department of Prosthetic Dentistry, University Hospital,
LMU Munich, Munich, Germany.
3 Master Dental Technician, Annette v. Hajmasy Dental, Grabenstätt, Germany.
4 Assistant Professor, Department of Prosthetic Dentistry, University Hospital, LMU
Munich, Munich, Germany.
Correspondence: Dr med dent Anja Liebermann, Department of Prosthetic
Dentistry, University Hospital, LMU Munich, Goethestrasse 70, 80336 Munich,
Germany.
Email: Anja.Liebermann@med.uni-muenchen.de
VOLUME 49 • NUMBER 9 • OCTOBER 2018
Christian
Maischberger
agents used by practicing dentists have changed from epi-
nephrine towards astringents, with AlCl3 and Fe2(SO4)3 now the
most popular. All of the currently known hemostatic agents
cause some local, temporary gingival tissue damage, but only
epinephrine is known to elicit negative systemic effects.
Studies concerning the influence of hemostatic agents on
impression materials show highly contradictory results regard-
ing the possible polymerization-inhibiting properties of hemo-
static agents, probably due to the lack of standardization of
methodology. Hemostatic agents seem to alter the dentinal
surface properties making it more resistant to acid etching.
Therefore the relatively low acidity of self-etch adhesives when
compared to total-etch systems may not be strong enough to
sufficiently etch a more resistant dentinal surface, and conse-
quently may result in lower adhesive bond strengths.
(Quintessence Int 2018;49:719–732; doi: 10.3290/j.qi.a41010)
In the field of prosthodontic treatment one of the most
challenging phases is gingival tissue management,
exposing the gingival margin around the prepared
teeth to aid an accurate impression.1,2 In the long term,
to perform a precise and successful restoration, har-
mony between the restoration and the periodontal
tissue is essential. The key to achieving that goal is an
accurately made impression in case of indirect restor-
ations or a properly placed direct restoration into the
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Maischberg er et al
prepared cavity.3 Often caries or noncaries cervical
lesions are at or even extend below the free gingival
margin. Also, the preparation margins for fixed pros-
thodontics, such as crowns or inlays, are often placed
para- or subgingivally due to esthetic or functional
reasons. Particularly in such cases additional measure-
ments and techniques to retract/displace the gingival
tissues and to control gingival hemorrhage and sulcular
fluids are inevitable to provide access for preparation,
impressioning, and luting procedures.4,5
DATA SOURCES
A literature search was performed for articles that were
published in English and German language. The search
was performed by electronically searching PubMed and
Google Scholar databases for publications up to and
including 2017. The following key words were used in
different combinations: “hemostatic agent,” “astrin-
gent,” “astringency,” “epinephrine,” “ferric sulfate,” “alu-
minum chloride,” “hemorrhage control,” “soft tissue,”
“hard dental tissue,” “self-etch adhesive,” “total-etch
adhesive,” “bond strength,” “impression,” “gypsum,”
“plaster cast,” and “dental cast.”
RESOURCE SELECTION
A preselection by reviewing the abstracts of all results
was carried out to select only literature relevant to den-
tistry. All preselected articles were reviewed and con-
sidered as relevant or nonrelevant for the present nar-
rative review. Whether a paper was considered relevant
depended on its study design/methodology, clinical
significance, and contribution of knowledge about the
investigated subject. A total of 97 papers were consid-
ered to provide beneficial knowledge to the reader
about the reviewed topic. The authors further subdi-
vided the selected papers into two main groups, one
concerning gingival tissue management in pros-
thodontic dentistry in general with its relevant meth-
ods and applied materials, and one concerning the
adverse effects of commonly used hemostatic retrac-
tion agents to different prosthodontic treatment steps.
720
REVIEW
Gingival tissue management and hemostatic
procedures in general
Gingival tissue management generally consists of two
parts. The first is gingival margin retraction/displace-
ment, which is defined as the deflection of marginal
gingiva away from the tooth.5 This provides temporary
access to and beyond the abutment preparation mar-
gin by creating lateral and vertical space between the
tooth and the gingival tissue in order to allow the injec-
tion of an adequate bulk of impression material into
the expanded sulcus.5,6 The second part of gingival tis-
sue management is confined to moisture control in the
sulcus. Control of gingival hemorrhage, sulcular fluid
flow, and saliva contamination is especially important
when a hydrophobic impression material is used, as
moisture may lead to an unsatisfactory impression of
the critical finish line.5,7,8 The difficulty of the procedure
is further complicated by variations in sulcular depth,
ability of the gingival tissues to distend, degree of gin-
gival inflammation, level of margin placement, and tis-
sue laceration. Therefore, to obtain consistent predict-
able results, the dentist must alter the armamentarium
and technique to be able to meet the specific clinical
demand.2 Techniques of marginal soft tissue manage-
ment can be classified as mechanical, chemical, surgi-
cal, or any combination of those,2 and also broadly dif-
ferentiated as nonsurgical and surgical methods.5 The
most common method of gingival displacement is a
combination of mechanical and chemical displace-
ment. This includes the usage of gingival retraction
cords, representing the mechanical part, in combina-
tion with one or more chemical retraction agents.9,10
Hemostatic agents may be placed on plain retraction
cords prior to packing, or dry cords may be inserted
into the sulcus first and modified immediately after
packing by the addition of an agent. The purpose of the
cord is not only to physically displace the free gingival
tissue; it also plays an important role by keeping the
chemicals in close contact with the target tissues, and
confines them to the application site.11 Many manufac-
turers also offer pre-impregnated retraction cords. The
VOLUME 49 • NUMBER 9 • OCTOBER 2018

agents remain in place until satisfactory shrinkage and
retraction of gingival tissues away from tooth struc-
tures is achieved and hemostasis is obtained.12 This
preference of the mechanico-chemical method was
documented by surveys which stated that in 1985
66.67% and in 1999 81% of practicing dentists soaked
plain or impregnated cords with an additional retrac-
tion agent before packing them into the sulcus.13,14 To
the present authors’ knowledge, there are no further
published surveys about today’s preferences for gingi-
val tissue displacement methods. Another possibility is
to place the hemostatic agent first on the sulcular tis-
sue to achieve hemostasis, followed by packing the
sulcus with a plain or soaked retraction cord. For that
purpose the practitioner requires a special applicator or
infuser, with which it is possible to burnish the agent
into the tissues. An example for such a device is the
tissue management system provided by Ultradent in
form of a syringe with a small brush at the tip for the
application of the hemostatic agent, named Viscostat.15
Mechanical gingival displacement methods were
described as a method that physically moves the free
gingival tissue away from the tooth simply by the virtue
of the pressure it creates on the tissues in an outward
direction.10,11 Many materials have been suggested and
tested over the years; nevertheless, the most useful and
most popular method is the usage of gingival retrac-
tion cord.2,10,11,16 Which one to choose out of the large
variety of existing retraction cords has been shown to
be the dentist’s personal preference.4
Surgical methods of gingival retraction include
rotary gingival curettage/gingettage, conventional sur-
gery (gingivoplasty/gingivectomy/periodontal flap pro-
cedures), and electrosurgery and laser application (CO2/
diode/Nd:Yag).1,2,4,5,8 These procedures are rapid, but
also destructive as they involve the excision of gingival
tissues and therefore require soft tissue healing.4,17
Over time new materials emerged on the market,
and these can be summarized under the topic “cordless
retraction.” These materials are commonly based on a
kaolin matrix combined with a hemostatic agent in the
form of a paste (eg, Expasyl, Kerr)17 or even on a polyvi-
nyl siloxane base (eg, Magic Foam Cord, Coltène/
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Maischberg er et al
Whaledent).4 These cordless retraction techniques pro-
vide hemostasis and some gingival retraction. The
degree of displacement can be enhanced in some sys-
tems by using a compression cap. Furthermore these
materials may be used by themselves or in combina-
tion with any other tissue displacement method.4 Due
to the large variety of different clinical challenges faced
by dentists, several authors agreed that not only one
method of gingival tissue displacement is sufficient,
but that the approach should be individual, using a
combination of methods depending on the current
clinical situation.2,17 It is possible to conclude that there
is no consensus on the best gingival retraction tech-
nique.14 Figures 1 to 4 show the clinical application of a
hemostatic agent combined with a retraction cord
before impression taking.
Hemostatic retraction agents
The medicaments (hemostatic agents) that are used
alone or in conjunction with a retraction cord in any
gingival displacement procedure should fulfill three
basic criteria.13 First, the agent should be effective, result-
ing in sufficient lateral and vertical displacement of gin-
gival tissues, and at the same time should provide con-
trol of hemorrhage and sulcular fluid seepage. Second,
its usage should not cause any significant irreversible
tissue damage. Even though it was shown that all tech-
niques of finish line exposure may result in some minor
tissue injury, complete healing should be accomplished
within 2 weeks.13,18,19 Third, the used material should not
cause any potentially harmful systemic effects. The den-
tist always has to keep in mind that the medicament
may pass via the gingival tissues into the systemic circu-
lation and therefore might pose a risk for undesired,
harmful, systemic effects following overdosing.13
Numerous different chemical gingival retraction
agents have been used or suggested over the years.
Nowakowska20 chemically classified the retraction
agents according to their pharmacologic action into
two major classes: class 1 being adrenergics (vasocon-
strictors) with α- and β-adrenergics or α-adrenergics
only; and class 2 being astringents with chlorides or
sulfates (Table 1).20
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Fig 1 Tooth preparation with retraction Fig 2 Tooth preparation with retraction
cord inserted into the gingival sulcus (lat- cord inserted into the gingival sulcus
eral view). (occlusal view).
Fig 4 Lateral view of tooth preparation
with hemostatic agent.
Vasoconstrictors are agents that are able to stop
bleeding by the constriction of blood vessels.21,22 They
act on the sympathetic α-1, β-1, and β-2 adrenergic
receptors.21 Thereby the activation of α-1 receptors on
the smooth muscles of blood vessels causes the vessels
to constrict, leading to a reduced local blood flow result-
ing in a decrease of volume of the usually highly per-
fused gingival tissues and a decrease in bleeding.7,23,24
As already stated, the group of vasoconstrictive agents
was subdivided into α- and β-adrenergics and α-adren-
ergics only.20 Epinephrine acts on both α- and β-recep-
tors, and was the most commonly used adrenergic
agent for gingival retraction.5,7,21 Nevertheless, the pre-
ferred chemical retraction agents have changed over
the years. In a survey published in 1980, 73.3% of den-
tists chose epinephrine-impregnated cords;25 in 1985
these were preferred by 79%,13 in 1986 by 55%,26 in
1999 by 39%,14 and by 29% in 2015,27 showing a steady
decrease in its usage. As retraction agent, epinephrine
is used in the racemic form in concentrations of 0.1%
722
Fig 3 Application of hemostatic agent
around the tooth preparation onto the
retraction cord.
and 8%.5,21 In contrast to astringents, which only exert
their effects locally, epinephrine can be absorbed via
the gingival tissues into the systemic circulation and
affect several organ systems, especially the cardiovas-
cular system.8,13 Epinephrine stimulates the myocar-
dium which in turn leads to an increase in ventricular
contraction strength and heart rate (tachycardia), and
eventually results in a blood pressure rise. Symptoms of
an epinephrine overdose, also called “epinephrine syn-
drome” manifest via tachycardia, tachypnea, hyperten-
sion, anxiety, tremor, restlessness, headache, dizziness,
pallor, heavy sweating, and in the worst cases even
fainting or fatality.5,9,16,28,29 The systemically absorbed
amount depends on the administered epinephrine
concentration, duration of application, and severity of
gingival tissue laceration.13 Other factors related to the
total dose of epinephrine have to be kept in mind by
the dentist as there is the possibility of a cumulative
effect of epinephrine from sources other than retrac-
tion cords. These sources include not only epinephrine
administered via the local anesthetic solution, but also
endogenously produced epinephrine that may be
secreted as a reaction to stress during the dental pro-
cedure.30-33 All these above-mentioned undesired
effects may occur in any patient, but especially in
patients with predisposing diseases like cardiovascular
disease, hyperthyroidism, diabetes, and known hypersen-
sitivity to epinephrine. Also, in patients taking mono-
amine or tricyclic antidepressants, rauwolfia compounds,
ganglionic blockers, cocaine or other epinephrine-poten-
tiating drugs, the dentist has to substitute epinephrine for
VOLUME 49 • NUMBER 9 • OCTOBER 2018

another retraction agent.2,10,16,18,28,29 After considering the
significant number of above-mentioned contraindica-
tions, possible adverse effects, and the fact that epineph-
rine-containing cords have no clinical advantage in
terms of tissue displacement to other agents, nowa-
days there is a general consensus that epinephrine
should be avoided during tissue displacement.34-36 In
the second subgroup of vasoconstrictors (adrenergics),
agents are found to act solely on α-1 adrenergic recep-
tors: tetrahydrozoline HCl, 0.05% (Visine, Johnson and
Johnson); oxymetazoline HCl, 0.05% (Afrin, Bayer); and
phenylephrine HCl, 0.25% (Neo-synephrine, Founda-
tion Consumer Healthcare). All of these substances are
the active ingredients of different non-prescription
nasal or ophthalmic decongestants and are classified as
sympathomimetic amines acting as α-agonists. The
effectiveness of different conventional (alum, epineph-
rine) and new retraction agents (Afrin, Visine, Neo-syn-
ephrine) was compared by measuring the sulcular
width after 5 minutes of application time of a retraction
cord impregnated with the respective chemical retrac-
tion agent. It was concluded that Visine and Afrin pro-
duced significantly greater retraction than Neo-syneph-
rine and the conventional agents. Soft tissue evaluation
after 10 days did not show any permanent gingival
depression caused by the new experimental retraction
agents. Cardiovascular responses during the applica-
tion were monitored, and all three α-agonists caused
significantly lower pulse rates than epinephrine.9 Differ-
ent epinephrine concentrations (0.01%, 0.05%, 0.1%)
were compared with the different sympathomimetic
agents and all of them were more biocompatible than
any epinephrine-containing solution.37 This may also
stand in conjunction with their significantly higher pH
of 6 or more when compared to the other retraction
agents.38,39 Even though it was suggested that sym-
pathomimetic amines may provide a safer and also
more effective alternative to other retraction agents,9
sympathomimetics are still – even after two decades –
considered experimental retraction agents.37
Astringents are the second big group of gingival
retraction agents. There are still widely differing opin-
ions on the current state of knowledge concerning
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astringency, as its molecular and physiologic mechan-
isms are not yet fully understood.40 In 2004 the Ameri-
can Society for Testing and Materials (ASTM) defined
astringency as “the complex of sensations due to
shrinking, drawing or puckering of the epithelium as a
result of exposure to substances such as alums or tan-
nins.”41 According the Concise Medical Dictionary
(CMD), medically an astringent is considered as “a drug
that causes cells to shrink by precipitating proteins
from their surfaces.”42 Therefore, the current chemical
and pharmacologic definition of an astringent com-
pound as one that binds and precipitates proteins has
not deviated from its Latin root adstringere, meaning
“to bind.”40,43 The definition for astringent compounds
used in dental research articles from different
authors5,7,44 is based on definitions of Mohan et al44 and
Felpel.23 Mohan et al44 define astringents as “substances
that precipitate proteins, but do not penetrate cells,
thus affecting the superficial layer of mucosa only. They
toughen the surface by making it mechanically stron-
ger and decrease exudation. Examples are alum, alumi-
num chloride, zinc chloride (8% to 20%), and tannic
acid. Styptics are the concentrated form of astringents.
They cause superficial and local coagulation. Examples
are ferric chloride and ferric sulfate.” Felpel23 defines
astringents in a similar way, as “metal salts that cause
gingival retraction by precipitating protein or, in some
cases, by a desiccant effect. Precipitated protein physi-
cally obstructs hemorrhaging, thus making astringents
useful as hemostatics.” It was further stated: “Astrin-
gents produce hemostasis by causing tissue contrac-
tion followed by coagulation of blood in the vessels in
the local area. Styptics may be considered as a concen-
trated form of an astringent.”23 After reviewing these
different definitions, it is safe to say that there is still no
full understanding and no generally accepted defini-
tion of astringent compounds.
Retraction agents based on aluminum chloride, alu-
minum sulfate, ferric sulfate, zinc chloride, alum (alumi-
num potassium sulfate), tannic acid, ferric subsulfate
(Monsel’s solution), and Negatol solution are astrin-
gents.11,22,25,45 The predominance of astringents nowa-
days was demonstrated by several authors who showed
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Table 1 Overview of hemostatic agents (modified from Nowakowska20)

Class 1: Vasoconstrictors (adrenergics) Class 2: Astringents

Sulfur
α + β -Adrenergics α-Adrenergics Aluminum chloride Aluminum Iron
0.05% tetrahydrozoline HCl 10% AlCl3 (eg, Gingiva Liquid, 20% Al2(SO4)3 (eg, Rastringent, 15.5% Fe2(SO4)3
(eg, Visine, Johnson and Coltène/Whaledent) Pascal International) (eg, Astringedent, Ultradent)
Johnson)
0.05% oxymetazoline HCl 20% AlCl3 (eg, Orbat, Lege 25% Al2(SO4)3 20% Fe2(SO4)3
0.1/1.0/8.0%
(eg, Afrin, Bayer) Artis; Alustin, Chema) (eg, Orbat Sensitive, Lege Artis) (eg, ViscoStat, Ultradent)
epinephrine
0.25% phenylephrine HCl 25% AlCl3 (eg, Racestyptine 12.7% Fe2(SO4)3 +
(eg, Neo-synephrine, solution, Septodont; ViscoStat ferric subsulfate
Foundation Consumer Clear, Ultradent) (eg, Astringedent X, Ultradent)
Healthcare)

that aluminum chloride and ferric sulfate are the most
commonly used medicaments.13,14 Considering these
surveys showing a shift from epinephrine towards
astringents as gingival retraction agents already in 1985
and 1999, the increasing awareness of possible systemic
adverse effects caused by epinephrine, and after review-
ing the current dental market, it is possible to say that
aluminum chloride and ferric sulfate are nowadays the
most commonly used gingival retraction agents.
Each of the astringent agents shows different mech-
anisms of action and certain specific characteristics that
should be further explained.
Aluminum chloride (AlCl3) is, as stated above, one of
the most commonly used astringents.13,14 It is used in
concentrations from 5% to 25%. The mechanism of
action of aluminum chloride to stop bleeding is astrin-
gent by precipitation of proteins, but the literature
shows differences in the specific mechanism of alumi-
num chloride. The acidic property of aluminum chloride
causes a reaction with blood proteins, which in turn
creates a barrier by coagulated proteins and thereby
prevents the outflow of blood from vessels. This barrier
at the same time prevents aluminum chloride from
entering the blocked vessels and thereby does not
allow any systemic effects to happen.46 Others describe
that aluminum chloride acts by precipitating proteins
and inhibiting transcapillary movement of plasma pro-
teins.13 Ultradent Products USA in turn describes the
mechanism of their 25% AlCl3 gel ViscoStat Clear in the
following manner: tissues surrounding capillaries swell
and thereby squeeze the capillaries causing the bleed-
ing and sulcular fluid seepage to stop.47,48
Ferric sulfate (Fe2(SO4)3) is next to aluminum
chloride the most used gingival retraction agent.13,14
Generally it is provided in concentrations from 13% to
20%. Concentrations above 15.5% are highly acidic and
may cause gingival tissue irritations and postoperative
root sensitivity. The recommended application time is
1 to 3 minutes, resulting in a tissue displacement of up
to 30 minutes.11,15,44,49 A major adverse effect of ferric
sulfate is a temporary stain of soft tissues in a bluish to
brown/black color due to its iron content. Even though
the gingiva returns to its normal pink appearance after
1 to 2 days, it might be felt as disturbing by the
patient.11,45 A black staining of dentin under porcelain
crowns may occur in some situations.50 When used in
connection with epinephrine, a massive blue precipi-
tate develops and it should therefore be avoided.11 The
mechanism of action of ferric sulfate is mostly by blood
coagulation, but also astringent.15,49 The agglutination
of blood proteins is caused by the reaction of blood
with ferric and sulfate ions. Protein-plugs are formed
directly in the endings of the cut capillaries and physi-
cally occlude them, resulting in hemostasis.15,47-49,51-53
The intracapillary clots can be recognized as small dark
dots inside the gingival sulcus.49 Blood is coagulated in
such a quick manner that the application has to be
directly against the lacerated tissue, otherwise the fer-

724 VOLUME 49 • NUMBER 9 • OCTOBER 2018


ric sulfate would react immediately with the already
extravasated blood and flow away.11,22 Therefore the
best results are obtained when the agent is rubbed into
the bleeding gingival surface.47,48
Ferric subsulfate (Fe4H2O22S5), also called Monsel’s
solution, is rarely used nowadays as gingival retraction
agent. It is classified as a very strong astringent (styptic)
and more effective than epinephrine, but causes
sloughing of soft tissues and might even be corrosive
to teeth.1,11
Alum (KAl(SO4)2·12H2O), chemically aluminum
potassium sulfate, was suggested as gingival retraction
agent, but is not in use nowadays, even though it has
good hemostatic properties. There is no significant
difference in aspects of effectivity and local tissue
effects between 100% alum, 8% racemic epinephrine,
and aluminum chloride.9,16,36 There is also no indication
that alum might elicit any adverse systemic effect.9,13
Aluminum sulfate (Al2(SO4)3) shows almost the same
characteristics as alum, but differs chemically.11,45 It also
does not show any adverse systemic effects.13 It was
shown that dental professionals were not able to
detect any difference between the clinical retraction
results of racemic epinephrine and aluminum sulfate,
which is in concordance with other studies.35 Alumi-
num sulfate achieves hemostasis by a weak vasocon-
strictive effect in combination with precipitation of tis-
sue proteins, causing tissue contraction and inhibition
of transcapillary movement of plasma proteins result-
ing in subsequent hemostasis.35 Local adverse effects
may be seen as permanent recession and loss of alveo-
lar crest bone in case of an application time exceeding
20 minutes.54
Zinc chloride (ZnCl2) is not used as gingival retrac-
tion agent due to its inacceptable caustic effect on tis-
sues.16 It was used in concentrations of 8% and 40%.
Both concentrations cause severe injury to gingival tis-
sues, which do not show complete healing after
21 days, and therefore cannot be recommended as
gingival retraction agent.19 In a 100% solution it may
even cause damage to bone.10
Negatol solution, also called Negatan, is a 45% con-
densation product of metacresol sulfonic acid and
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formaldehyde.11,45 It is highly acidic and may decalcify
teeth in both 10% and 100% concentration solutions.
Soft tissue recovery was shown to be not satisfactory.16
Negatan is therefore contraindicated as gingival retrac-
tion agent.
Tannic acid (tannin) (C76H52O46) is a vegetable poly-
phenol and is the most common astringent source
found in foods and beverages.40 Its hemostatic efficacy
is less than epinephrine, but with very good tissue
recovery.16 It is found in tea and probably is most useful
in dentistry as a home remedy to control small tem-
porary intraoral bleedings (eg, after an extraction) by
biting on a tea bag.23
Adverse effects of hemostatic retraction
agents
Gingival retraction agents also cause adverse effects
that have to be taken into account and which were
reviewed in several studies.16 Of particular importance
is their behavior in relation to local tissues, potential
systemic effects, impression materials, and adhesive
materials and procedures.
As previously stated, there are no systemic effects
with any chemical retraction agent except for epineph-
rine, which causes elevated blood pressure and heart
rate with its subsequent symptoms.
Surrounding soft tissues and their reaction and
compatibility to hemostatic retraction agents were
addressed in several studies. Without exception these
studies revealed that all retraction agents, even plain
retraction cords, cause some degree of tissue damage
in the form of inflammation or desquamation of the
sulcular epithelium. In all cases the injury was of a tem-
porary nature and showed full recovery after 14
days.10,12,16,19,24,36,37,55,56 Only zinc chloride and Negatan
showed caustic characteristics resulting in severe per-
manent tissue damage, with Negatan even causing
decalcification of enamel.10,16,19 The cytotoxic potential
and its dependence on the agent’s concentration and
the duration of exposure was evaluated. All conducted
experiments showed that an increase in concentra-
tion12,37,55,57,58 and exposure time12,19,36 will result in an
increase in tissue damage. By far the least cytotoxic
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agents were sympathomimetics, which showed the
highest biocompatibility in terms of cell survival.24,37,58
Different authors evaluated how the concentration of a
retraction agent influences its pH-value and its effect
on the oral environment. In all studies pH-values of
astringents ranged between 0.7 and 3.0, except for
sympathomimetics, for which the highest values were
recorded, between 4.1 and 7.4. It is possible to con-
clude that a lower pH of agents and a longer exposure
time cause an increase in tissue damage and therefore
sympathomimetics should be considered more in the
future to preserve periodontal, gingival, and oral
health.38,39,59 Not only the concentration and the expo-
sure time, but also the form of the agent seem to have
a significant influence on cell survival, as gels showed
less cytotoxic damage than solutions; this might be
because of the more precise placement of gels on gin-
gival tissues, thereby reducing the exposure area.12
Contrary to general opinion, De Gennaro36 found great
differences in the degree of inflammation between
different individuals after application of the same agent
and the same application time, which led to the sug-
gestion that patient-specific factors may have a greater
effect on the severity of inflammation than the agent
itself.36
Compatibility with the used impression material is
another important aspect that has to be considered
when choosing a suitable retraction agent. It is well
known and documented that the polymerization of
polyvinyl siloxane (PVS) materials is inhibited by sulfur
compounds, which are present in various dental mater-
ials such as latex gloves, rubber dam, and also in several
retraction agents (aluminum sulfate, ferric sulfate,
etc).60,61 The inhibition may be caused by direct contact
or due to indirect contamination of intraoral soft and
hard tissues by contact with latex gloves.62-66 The inhibi-
tion of the PVS polymerization becomes evident as a
rippled surface on the set impression material which
will be slippery to touch in areas that were contami-
nated. In addition to an insufficient impression, the
gypsum cast produced from such a contaminated
impression shows flaws. The rippling is duplicated and
the cast often appears wet, wrinkled, poorly defined,
726
and part of the impression material may even still
adhere to the cast after removal, compromising the
cast.62 Multiple authors tested the influence of retrac-
tion agents on different parameters of PVS materials,
presenting contradictory results.
To test the interaction between the agents and the
PVS material, the authors of three studies used the
same standardized stainless dies (as describe in Amer-
ican Dental Association [ADA] specification no. 19),
which show three horizontal and two vertical grooves.
To determine any interactions the authors evaluated
the dimensional accuracy (after 24 hours, by measur-
ing the length of the horizontal lines) and the surface
detail reproduction (after 1 hour using a stereomicro-
scope with 10× magnification). With all the agents and
also within the control group, dimensional changes
occurred, but were within the ADA specification for
PVS materials (< 0.5%). Surface detail reproduction was
affected by all tested agents (epinephrine, aluminum
chloride, ferric sulfate), with epinephrine producing
the least surface changes. Aluminum chloride caused
the surface of the impression to be extremely rough
with a melted appearance. Ferric sulfate produced an
impression that appeared as the reproduction of a
contaminated die, but in general the adverse effect
was less severe than with aluminum chloride. The
authors concluded that it is of the highest importance
that the clinician makes effort to remove any residue of
the retraction medicaments prior to placing PVS
impression material.67-70 In another study the influence
of retraction agents on the polymerization time of PVS
materials was tested. Ten different agents of all classes
(vasoconstrictors, sympathomimetics, astringents)
were analyzed and all of them without exception
changed the setting time or even caused a total inhibi-
tion of polymerization. The worst results were
obtained with aluminum chloride. In general, adrener-
gics (epinephrine and sympathomimetics) showed
better results than astringents.71
In contrast to these findings, other authors did not
record any inhibitory effect of aluminum chloride, alu-
minum sulfate, alum, ferric sulfate, or epinephrine on
the polymerization of PVS materials.62,72-74
VOLUME 49 • NUMBER 9 • OCTOBER 2018

For polyether (PE) impression materials the study
results were less controversial and were in agreement
with each other, reporting that PE impression materials
are not compatible with gingival retraction agents.
Ferric sulfate showed the greatest disturbances in the
polymerization process and also 25% aluminum
chloride gave unsatisfactory impressions. Aluminum
chloride 10% did not show significant adverse effects
and therefore may be used prior to a polyether impres-
sion. It was also shown overall that adrenergics (epi-
nephrine and sympathomimetics) presented with bet-
ter results than astringents.69,72,74,75
There is a limited number of studies available on the
interaction of retraction chemicals with condensation
silicone and polysulfide impression materials. The ten-
sile strength of condensation silicone is affected neither
by aluminum chloride nor by sympathomimetic agents.
Its polymerization was inhibited by aluminum chloride.
Polysulfide shows significantly lower tensile strength
when in contact with aluminum chloride or Afrin during
polymerization, but not with Visine. None of the agents
caused an inhibition of polysulfide polymerization.72,74
Hemostatic agents come into contact not only with
impression materials and soft tissues; they are also in
direct contact with dental hard tissues and possibly
may exert adverse effects. The bond strength of adhe-
sive bonding systems depends on the incorporation of
resin into the demineralized dentin matrix formed by
acid etching.76 Some studies showed that the high
acidity of commonly used hemostatic agents causes
changes or even the complete removal of the dentinal
smear layer.59,77-79 Such significant alterations in the
morphology of the prepared dentin surfaces may
reduce the dentin’s susceptibility to acid etching.80 In
turn these properties affecting the dentin surfaces may
have an adverse effect on hybrid layer formation and
quality and therefore might result in a reduction of
bond strength.78 Due to such findings, the use of these
agents raised some doubts as to whether the bond
strength of adhesives to hemostatic-contaminated
dentin and enamel may be adversely affected.81 Sev-
eral studies (all of them in vitro) concerning the influ-
ence of hemostatic agents on various self-etch and
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Q U I N T E S S E N C E I N T E R N AT I O N A L
Maischberg er et al
etch-and-rinse adhesive bonding systems were con-
ducted. Experiments investigating the influence of
hemostatic agents, mostly aluminum chloride and
ferric sulfate, on total-etch (etch-and-rinse) adhesive
systems reported varying results. Currently there are
four studies reporting no significant differences
between the bond strength of total-etch adhesive sys-
tems to hemostatic-contaminated dentin and to nor-
mal dentin. After a 2-minute application of aluminum
chloride, the smear layer was partially removed with
smear plugs still occluding the dentinal tubules. After
phosphoric acid etching both the normal dentin sur-
face (no previous contamination) and the contami-
nated dentin surface did not show any difference in
their appearance. Also, no difference could be seen
between the bonding interfaces of the resin cement to
normal dentin and to contaminated dentin by using a
scanning electron microscope (SEM) with 5,000× mag-
nification. Due to their results, it was concluded that
the aggressive etching-pattern of 37% phosphoric acid
(pH 0.5) most probably redeemed all contaminant-in-
duced adverse effects on the dentin surface and there-
fore a bond strength comparable to normal dentin
could be achieved.78,79,82,83
In contrast, other authors claim a decrease in bond
strength when total-etch adhesives are used on con-
taminated dentin surfaces. Aluminum chloride and
ferric sulfate were tested in different studies with
widely varying application times and cleaning proto-
cols, resulting in significant lower shear bond strength
values than their uncontaminated control groups.84-86 In
two of these studies, a 0.2% chlorhexidine (CHX) rinse
was used to clean contaminated dentin surfaces and
resulted in contrasting outcomes. In one study the
cleaning protocol with CHX resulted in bond strengths
almost identical to those without any contamination.85
In contrast, in another study the CHX caused an even
more severe decrease in bond strength than the hemo-
static agents alone.84 Unfortunately the study models of
these two studies are too different (order of clinical
steps, application time, etc) for comparison, and it can-
not be concluded what led to such opposing outcomes
in relation to CHX usage as cleaning agent.
727
Q U I N T E S S E N C E I N T E R N AT I O N A L
Maischberg er et al
Studies concerning the influence of hemostatic
agents on the bond strength of self-etching adhesive
systems to dentin are less contrasting and show more
similar results, even though the lack of standardization
among different studies is also present and has to be
kept in mind. Most authors demonstrated a decrease in
bond strength.
In one study in 2007, the acidic primer of the self-
etch adhesive Clearfil SE Bond (Kuraray) was applied for
20 seconds in one test group and for 40 seconds in
another test group. Even though the bond strength of
the 40-second group was significantly higher than in
the 20-second group, both groups showed a decreased
value compared to the control. Normal dentin after
applying the primer for 20 seconds showed removal of
smear layer and open tubules with intact peritubular
dentin, whereas in contaminated dentin the tubules
were still occluded. The 40-second application opened
the dentinal tubules and removed peritubular dentin,
eventually resulting in a higher bond strength. There-
fore, the authors concluded that the extended primer
application might enhance its etching effect and even-
tually may result in a higher dentin bond strength of
such an adhesive system.79 In contrast to their findings
in 2007, the same authors conducted a study in 2009
using the self-etch adhesive system ED Primer II (Kur-
aray) in connection with a dual-cured resin cement
(Panavia F, Kuraray), and this did not show any
decrease in bond strength when applied on aluminum
chloride-contaminated dentin. The ED Primer II seems
to be acidic enough to cause a self-etching effect that is
sufficient to remove any contaminants left from hemo-
static agents. However, the authors reported the forma-
tion of small gaps at the interface between the hybrid
layer and the resin cement. Even though the bond
strength to contaminated dentin was satisfactory, the
gap formation might cause microleakage and should
be investigated in further studies.78 As in both of their
studies the same astringent (Racestyptine solution,
Septodont) with the same application time and cleans-
ing protocol was used, their opposing results might be
attributed to the properties of the different bonding
agents.
728
Clearfil SE Bond and its bond strength to dentin
previously contaminated with different hemostatic
agents was evaluated in two further studies. One con-
firmed the results of previous studies showing a
decrease in bond strength and a further worsening
when CHX was applied in an attempt to remove hemo-
static residues prior to bonding.84 Another evaluated
Clearfil SE Bond when used on dentin contaminated
with freshly drawn blood and one of four hemostatic
agents, 25% aluminum chloride (ViscoStat Clear, Ultra-
dent), 15.5% ferric sulfate (Astringedent, Ultradent),
12.7% ferric subsulfate (Astringedent X, Ultradent), and
a newly introduced agent from Turkey (Ankaferd Blood
Stopper [ABS], Ankaferd Health Products). In contrast to
other studies only a minimal decrease in bond strength
was reported for all agents, which was not considered
as significant. Only ABS caused an increase of bond
strength when compared to the control. Because ABS
consists only of vegetal components, the authors sug-
gested that the vegetal content may have a positive
impact on bond strength.87
AdheSE (Ivoclar Vivadent) and AdheSE One F (Ivo-
clar Vivadent) were compared in another experiment.
After a 1-minute contamination with ferric sulfate,
AdheSE showed significantly lower bond strength to
dentin. Surprisingly, AdheSE One F did not show
reduced bond strengths, which might be explained by
the moderate acidity (pH 1.5) of the agent, which
causes a better smear layer removal and therefore
might increase its dentinal diffusion depths.83 Despite
these results, several authors reported a common
decrease in bond strength between dentin and
self-etching adhesives after contamination with a
hemostatic agent.88-91
Two of these researchers additionally investigated
possible contamination removal methods.
A 5-minute water spray, 60 seconds’ application of
10% ethylenediaminetetraacetic acid (EDTA), and
15 seconds’ application of 35% phosphoric acid on
dentin surfaces previously contaminated with 15%
aluminum chloride all resulted in higher bond strength
when compared with contaminated dentin that didn’t
undergo any cleaning protocol. Both EDTA and phos-
VOLUME 49 • NUMBER 9 • OCTOBER 2018

phoric acid were able to remove aluminum chloride
contaminants, but between them only EDTA was able
to produce bond strengths that were only slightly
below the bond strength of uncontaminated dentin
and therefore clinically acceptable. This removal of the
aluminum contaminants from the dentin surface is due
to the aluminum chelating ability of EDTA.90 In another
study, cleaning methods included 20 seconds of water
spray, 15 seconds’ etching with 37% phosphoric acid,
and usage of aluminum oxide abrasion. After cleaning
of the contaminated dentin surfaces with phosphoric
acid and aluminum oxide abrasion, the bond strengths
were not significantly different from the uncontami-
nated control group. There was no difference noticed
in the interaction of cleaning methods and the different
types of hemostatic agents.91 In addition to these stud-
ies other authors evaluated the effect of hemostatic
agents on microleakage of class V composite resin res-
torations when either bonded with a self-etch or
bonded with a total-etch adhesive system. Four authors
evaluated self-etching adhesives and reported that
there was an increase in marginal microleakage when a
hemostatic agent was used.92-95 In two of these studies
the authors also evaluated total-etch adhesives and
demonstrated that there was no increase in microleak-
age.93,94 Therefore the results of studies conducted
about microleakage are in accordance with the major-
ity of studies concerning the bond strength of self-etch-
ing and total-etching adhesives.
DISCUSSION
In recent years there has been a shift in dentists’ prefer-
ences for chemical retraction agents. The predominance
of epinephrine steadily decreased, as was illustrated in
several studies showing that in a time period of 30 years
the number of dentists using epinephrine was reduced
from 79 to 29%.13,27 Such a drastic decrease may be
attributable to the possible systemic adverse effects on
the cardiovascular system seen with the use of epineph-
rine, which may be especially dangerous in patients
taking specific medications or suffering from predispos-
ing diseases. Furthermore, there were no studies that
VOLUME 49 • NUMBER 9 • OCTOBER 2018
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Maischberg er et al
were able to show a significant advantage of epineph-
rine compared to astringent agents or sympathomimet-
ics. Considering that there is no clinical advantage, and
there is the possibility of a medical emergency due to
systemic effects elicited by epinephrine, it is easily
understandable why many dentists prefer other hemo-
static agents nowadays. As stated before, all retraction
agents, even plain cords, may cause some degree of
reversible tissue damage, with sympathomimetic
amines being by far the most biocompatible. These
agents are not commonly used by dentists, for no obvi-
ous reason. Some authors have suggested that sym-
pathomimetic amines may provide a safer and even a
more effective alternative to other agents.9 For epineph-
rine and astringent agents, several studies investigating
their compatibility with several other materials used
during prosthodontic treatments are available but show
differing results. Studies concerning the inhibitory effect
of hemostatic agents on impression materials presented
contradictory results, especially in the case of polyvinyl
siloxanes. None of the studies, neither the ones showing
polymerization inhibition of PVS materials nor the ones
showing no detrimental effect at all, used any cleansing
protocol to remove the hemostatic agent prior to
impression taking, as is recommended by manufactur-
ers of hemostatic agents. In all of these studies the
impression material came in direct contact with the
tested hemostatic agent, which may have led to a
chemical reaction between different ingredients of the
materials resulting in the polymerization inhibition.
Contrary to this assumption, also in all studies that did
not show any inhibition of the polymerization process,
the tested hemostatic agent came in direct contact with
the polymerizing impression material.62,73,74 In all studies,
hemostatic agents of different manufacturers but with
the same active ingredients were tested with different
impression materials, and the reason for a possible
chemical reaction must be attributed to the combina-
tion of a specific hemostatic agent with a specific
impression material and cannot be attributed solely to
the active ingredient of the hemostatic agent. A further
uncertain variable is the amount of hemostatic agent
used in the different studies. Only one study71 provided
729
Q U I N T E S S E N C E I N T E R N AT I O N A L
Maischberg er et al
the reader with this information, and therefore high
variations of used amounts in different studies may be a
further cause that led to opposing outcomes. Possibly in
some experiments the used amount might have been
too little and therefore insufficient to trigger any inhibi-
tion. Also, in all presented studies that did not show any
inhibition, the testing specimens were only evaluated
by the naked eye of the operator or with 10× magnifica-
tion. Hence there is the possibility that in these studies
some degree of inhibition took place but to such a min-
imal extent that it did not produce any clinically relevant
effects and therefore was not evident to the operator.
Studies concerning the influence of hemostatic
agents on polyether materials did not show such con-
troversial results, stating that PE materials are not com-
patible with hemostatic agents.69,72,74,75 Only in one
study 10% aluminum chloride did not inhibit the poly-
merization process and therefore was declared as a
suitable agent prior to PE impression taking.74 But also
in all of these studies the hemostatic agent was in
direct contact with the setting impression material,
which opposes the manufacturer’s recommendations
and therefore it is questionable to what extent these
experiments may resemble a real clinical situation.
Other factors that may have an impact on an experi-
ment’s outcome are the same as already discussed for
PVS materials involving the combination of different
products, severity of contamination, and handling of
testing specimens during preparations.
Also for adhesives there is no general consensus as
to the manner in which and extent that different adhe-
sive systems are affected by the prior use of hemostatic
agents. After reviewing all the previously mentioned
articles concerning the bond strength of adhesives to
dentin contaminated with a hemostatic agent, it is not
possible to come to a definitive conclusion about the
presented results as they conflict greatly. Furthermore,
there is a lack of standardization regarding methodol-
ogy in different studies. Some investigators dropped
the hemostatic agents on the dentin surfaces, some
applied it by microbrushes, others even soaked the
dentin testing specimens in hemostatic solutions.
Some authors applied blood and saliva contamination
730
prior to application of the hemostatic agent while oth-
ers only placed the agent itself. The application times
show enormous ranges between 10 seconds and
48 hours. The order of clinical steps differs in several
studies. Another uncertain variable is the different den-
tin substrate condition, such as the age of the tooth or
the storage conditions.96,97 Differences in combination
and used amounts of materials may also contribute to
dissimilar results. Due to such varieties in methodologic
criteria between the studies it is not yet possible to
conclude definitive statements about the effect of
hemostatic agents on adhesive bonding and further,
more standardized studies are required. Nevertheless,
the available study findings do suggest some assump-
tions. Any residual particles of hemostatic agents that
are left on the dentinal surface may interfere with the
bond strength of adhesive systems.91 Small contami-
nant particles, for example in the form of unbound
aluminum particles if an aluminum chloride hemostatic
agent is used, may obliterate dentinal tubules or form a
layer of residues, therefore decreasing the monomer
infiltration of the bonding system and eventually
affecting the development of the hybrid layer.81,90 Due
to the high acidity of hemostatic agents, calcium in
hydroxyapatite may be replaced by aluminum, result-
ing in a hydroxyapatite form that seems to be more
resistant to acids and therefore a higher acidity of the
etching/primer agents is required to achieve sufficient
surface preparation.79,91 Given such dentinal surface
alterations, the relatively low acidity of self-etching
adhesive primers may not be strong enough to suffi-
ciently remove all contaminants or to sufficiently etch a
more acid-resistant dentinal surface.81,90 In contrast, in
total-etch adhesive systems the high acidity (pH 0.5) of
phosphoric acid seems to be strong enough to remove
all contaminants on the dentinal surface, therefore giv-
ing the adhesive the possibility to infiltrate dentinal
tubules to a sufficient depth, resulting in a thicker
hybrid layer and conclusively in no reduction of bond
strength.81 Therefore, self-etching adhesives, rather
than total-etch systems, might result in decreased
bond strength when a hemostatic agent came in con-
tact with the dentinal surface beforehand.3 Also, stud-
VOLUME 49 • NUMBER 9 • OCTOBER 2018

ies not directly concerning the tensile bond strength of
adhesive systems but investigating the effect of hemo-
static agents on microleakage of class V composite
restorations, showed an increase in microleakage when
self-etch adhesives were used and no increase when
total-etch adhesives were used.92-95 Nevertheless, fur-
ther studies with more standardized methodology are
required in the future to make definite conclusions.
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VOLUME 49 • NUMBER 9 • OCTOBER 2018