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Endodontic Topics 2005, 10, 123–147 Copyright r Blackwell Munksgaard

All rights reserved ENDODONTIC TOPICS 2005


1601-1538

Reaction of periradicular tissues


to root canal treatment: benefits
and drawbacks
JOSÉ F. SIQUEIRA JR

Tissue injury induced by intra-canal procedures and substances extruded through the apical foramen may influence
the development of post-operative pain as well as the outcome of root canal treatment. While the development of
pain is related to the intensity of tissue damage, treatment outcome is more dependent on the persistence of the
source of injury. Procedural errors are the main causative agents of either post-operative pain or persistent
periradicular lesions. However, even when the treatment has followed the highest standards, post-operative pain
can occur and periradicular disease can persist, albeit at a lower incidence when compared to teeth treated to a poor
technical standard. This paper critically reviews the effects of intra-canal procedures on the periradicular tissues,
with special emphasis on the occurrence of post-operative pain and the outcome of the root canal treatment. The
possible systemic effects stemming from root canal procedures are also discussed in the light of current knowledge.

The overwhelming scientific evidence demonstrates damage to the periradicular tissues. Because tissue
that periradicular lesions are diseases of infectious injury induced by intra-canal procedures may result in
origin (1–4), and that endodontic procedures should unfavorable responses to treatment, the practitioner’s
be directed towards the prevention and/or the choice on procedures to be used during root canal
elimination of the pulpal and periradicular microor- treatment should rely on those that are known to cause
ganisms. The prevention or healing of periradicular as little damage as possible. This review paper focuses
disease will depend on how effective the clinician is in on the reaction of the periradicular tissues to root canal
achieving these goals (5–7). Root canal treatment of procedures with special emphasis to the influence of
teeth containing irreversibly inflamed pulps is essen- those procedures on the development of post-opera-
tially a prophylactic treatment, since the radicular vital tive pain and the outcome of the root canal treatment.
pulp is usually free of infection and the rationale is to
prevent further infection of the root canal system (8).
On the other hand, in cases of infected necrotic pulps Post-operative pain and post-
or in root filled teeth associated with periradicular
treatment disease
disease, an intra-radicular infection is established and,
as a consequence, endodontic procedures should focus The worst-case scenario for periradicular tissue re-
not only on prevention of the introduction of new sponse to intracanal procedures is represented mainly
microorganisms in the root canal system, but also on by post-operative pain and/or the emergence/persis-
the elimination of those located therein (9, 10). tence of disease. While the development of pain is
Root canal procedures involve the use of instruments conceivably more dependent on the intensity of tissue
and substances to clean, shape and disinfect the root damage, the outcome of the root canal treatment is
canal system, as well as materials to fill the root canal more influenced by the persistence of the source of
space. These procedures inevitably cause some level of injury. This can be explained by the fact that post-

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operative pain is usually a result of an acute inflamma- periradicular tissues is low. Only a small volume of
tory response in the tissues, whilst post-treatment tissue will be injured and even then in a transient way.
disease is usually characterized by the emergence or On the other hand, when root canal procedures or
persistence of chronic inflammation. The intensity of substances are intentionally or accidentally extended
acute inflammation is directly proportional to the beyond the boundaries of the apical foramen, undesir-
extent of the injury (11); chronic inflammation is able events can ensue (28–33).
usually a result of a persistent low-grade injury (12). Examples of mechanical irritation to the periradicular
It is well established that microorganisms are the tissues include over-instrumentation and over-exten-
most common aetiologic agents of post-operative pain sion of filling materials. In the event of over-instru-
and post-treatment disease, and their participation in mentation, there is a risk of post-operative pain
these events will obviously depend on the intensity or developing, the intensity of which is usually propor-
the persistence of the injury caused to the periradicular tional to the extent of tissue damage (18): The larger
tissues, respectively. In some way, root canal procedures the instrument size, the larger the area of periradicular
can allow or precipitate the involvement of micro- tissue destruction. Moreover, in infected cases, over-
organisms in these events. instrumentation can be coupled with extrusion of
Microorganisms persisting in the root canal system infected debris, which may not only induce pain (18)
after treatment are the major causative agents of but also impair healing (21, 34). Over-extended filling
therapy-resistant periradicular lesions (13–16), inas- materials can induce pain by mechanical compression of
much as they usually represent a persistent source of the periradicular tissues (18).
irritation to periradicular tissues. In addition, micro- Examples of chemical irritation include apical extru-
organisms are usually regarded as the most common sion of irrigants, intra-canal medicaments and filling
cause of post-operative pain (17, 18); a clear indication materials. Most irrigants and medicaments are cyto-
of this relationship is that flare-ups are more likely to toxic to host tissues (35, 36), and as a consequence
occur in necrotic cases (infected) than in vital cases their use should be restricted to the root canal. In spite
(non-infected) (19). Apical extrusion of infected of being cytotoxic, clinical trials have shown that
debris and perturbations in the endodontic micro- substances used for irrigation or intra-canal medication
biota induced by intracanal procedures are the main have no influence on the occurrence of post-operative
situations in which microorganisms are involved with symptoms (37–40). There is no proven benefit in
the development of inter-appointment pain (18, 20). intentionally extruding irrigants or medicaments. In
The involvement of microorganisms with post-opera- fact, severe reactions have been reported after extrusion
tive pain and post-treatment disease has been reviewed of some commonly used substances into the periradi-
recently (18, 20–23). cular tissues (28–33). Overextended filling materials
Non-microbial factors can also induce periradicular also represent chemical irritation to the periradicular
inflammation, but since the source of non-microbial tissues, as virtually all endodontic sealers have a certain
irritation is usually transient the reaction is not degree of cytotoxicity, at least before setting (41–43).
maintained. As a consequence, although some authors Furthermore their irritating effects conceivably in-
suggest an exclusive involvement of intrinsic or crease as the material/tissue contact surface area
extrinsic non-microbial factors in causation of persis- increases. Thus, the larger the volume of over-extended
tent periradicular lesions (24–27), it remains to be material, the larger the surface of contact between the
proved and confirmed by studies using microbiological filling material and the tissue and the greater the
techniques more sensitive and specific than microscopy. intensity of chemical damage to the periradicular
However, in spite of being transient, inflammation tissues. Therefore, large overfillings are likely to
generated by non-microbial factors can be of enough increase the risk of pain. However, because tissue
intensity to cause pain. irritation induced by over-extended filling materials is
Non-microbial factors are represented by chemical or arguably transient (provided that there is no damage to
mechanical injury generated by intracanal procedures. anatomical structures such as the mandibular nerve or
When the use of instruments, irrigants, medications, the maxillary sinus), the impact on the outcome of the
and filling materials is restricted to the confines of the treatment without concomitant infection is question-
root canal system, the intensity of the reaction in the able. This issue will be addressed later in this paper.

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Reaction of periradicular tissues

The working length debate conditions that require professional intervention – vital
pulps, necrotic pulps and retreatment cases (Fig. 1).
One of the most controversial issues in root canal The recognition of the differences between these
treatment is related to the point where the chemome- conditions and the reliance of the clinical decision-
chanical and filling procedures terminate. This is an making on these differences represents the basis on
important discussion, since the response of the which the outcome of root canal treatment is founded.
periradicular tissues to intra-canal procedures is ob- The major difference between these conditions resides
viously influenced by the length at which they are in the fact that while in vital pulps infection is absent,
restricted. While the termination point of root canal necrotic pulps and retreatment cases present a micro-
procedures appears to have no significant influence on biological challenge that should be treated appropri-
the development of post-operative pain (except in cases ately. A diseased vital pulp, although irreversibly
of over-instrumentation), the same is apparently not inflamed, is free of microorganisms colonizing the root
true for the outcome of the root canal treatment, and canal. Infection is for the most part restricted to the
here resides the main reason for controversy. surface of the pulp exposed to the oral cavity. The
In addition to the fact that the anatomy of each root radicular pulp, as long as it remains vital, usually
canal system is unique, which makes any standardiza- succeeds in protecting itself against microbial invasion
tion prone to error, the pathological conditions of the and colonization. On the other hand, necrotic pulps
root canal should also be taken into consideration in lack the essential defense apparatus against infection,
any discussion on working length. In daily practice, and are therefore characterized by the presence of
clinicians usually face three diagnostic endodontic microorganisms colonizing the root canal system.

Fig. 1. Diagnostic endodontic conditions commonly faced by clinicians. The major difference between them resides in
the microbiological conditions of the root canal. Prevention of infection is paramount for a favorable outcome of vital
cases (asepsis). Because necrotic cases and retreatment cases are characterized by an intra-radicular infection, treatment
success will also rely on effective eradication of intracanal microorganisms (anti-sepsis).

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The fact that a periradicular radiolucency may not be


visible on a radiograph does not necessarily mean that
an inflammatory periradicular lesion is absent (44).
Therefore, regardless of the presence of radiographi-
cally detected periradicular pathosis, root canals con-
taining necrotic pulp tissue should be treated as
infected canals. Retreatment cases are usually associated
with a persistent or secondary root canal infection by
therapy-resistant microorganisms, which may be more
difficult to eradicate when compared to primary
infections (21–23). Several studies have reported on a
role of infection on the outcome of the root canal
treatment, and demonstrated that various factors
associated with the presence of microorganisms have
Fig. 2. Closure of the apical foramen by newly formed
a substantial influence on the outcome, including the
hard tissue has been considered as the ideal histological
preoperative pulpal status (5, 45–48), presence of a outcome of the endodontic treatment (courtesy of
periradicular lesion (5, 45, 46, 49–52), and retreatment Francisco Souza-Filho).
cases (5, 47, 48, 53).
The difference between these clinical conditions is
obvious and now accepted within the endodontic graphically detectable periradicular lesion accompanied
community. As a consequence it is also recognized by absence of signs and symptoms of infection, such as
that treatment techniques should be customized to pain, swelling or draining sinus tract (5, 61, 62).
meet the specific challenges they present in terms Clinical healing does not necessarily correlate well with
of infection control. Thus, the presence of infection histological healing, as many teeth classified as clinically
should be the most important factor that should healed can show inflammation in the periradicular
be taken into account when deciding whether the tissues adjacent to the apical foramen (63). However,
root canal should be treated in one or more visits, the implications of residual inflammation in the period-
what intracanal medicaments should be applied to the ontal ligament without any clinical or radiographic
canal or at what level the apical canal preparation manifestation remain to be elucidated, as well as for
should terminate. how much longer the inflammation persist in the
absence of microbial challenge.
In teeth with vital pulps, some authors recommend
Vital cases (Non-Infected) that canals should be instrumented up to 1 mm short
of the canal terminus in an attempt to preserve the
It has been claimed that the ideal outcome of root canal vitality of the apical pulp tissue (‘pulp stump’),
treatment is closure of the apical foramen by newly which might play a role in periradicular tissue repair.
formed hard tissue (54) (Fig. 2). Animal studies have Studies have shown that the procedure of preserving
described some procedures and materials that may the health of the ‘pulp stump’ in vital pulps allows
predictably favor the occurrence of periradicular natural healing processes to occur, most often with
tissue repair associated with deposition of cementum- apical closure by hard tissue formation, even when
like tissue sealing the apical foramen (55–58). dentinal chips have been packed against the ‘pulp
However, apical sealing by hard tissue formation is stump’ (56, 64, 65).
not always complete and predictable (59, 60) and it Nonetheless, it must be appreciated that maintain-
remains questionable as to whether it can be attained in ing such a small tissue fragment in a healthy condition
most cases. is not predictable, particularly during the instrumen-
Absence of inflammation in the periradicular tissues is tation of curved narrow root canals. Moreover,
arguably the major histological picture to be achieved irrigation with sodium hypochlorite solution in differ-
in successfully treated teeth. From a clinical standpoint, ent concentrations may lead to severe inflammation or
success is better characterized by absence of a radio- necrosis of the ‘pulp stump’ (66), as a result of its

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Reaction of periradicular tissues

cytotoxicity (67). Considering that asepsis is the major (the prevailing cells), osteoblasts and osteoclasts (lining
decisive factor in preventing the development of disease the bone surface of the ligament), cementoblasts
in the treatment of vital pulps, it could be argued (lining the cementum surface of the ligament),
that sodium hypochlorite irrigation should not be epithelial cells, macrophages and undifferentiated
used in order to reduce the potential of damaging the mesenchymal cells. The extracellular matrix is com-
‘pulp stump’. Admittedly, keeping the root canal posed principally of collagen fibre bundles embedded
flooded with sodium hypochlorite during chemome- in a ground substance consisting of glycosaminogly-
chanical preparation can help maintain asepsis during cans, glycoproteins and glycolipids. In vivo, period-
treatment. Furthermore, irritation to the periradicular ontal ligament constituents are constantly being
tissues caused by sodium hypochlorite is usually synthesized, removed and replaced. Fibroblasts are
transient and restricted to a small tissue area, which the major cells responsible for the matrix turnover,
will result in no substantial adverse effect, provided being able to simultaneously synthesize and degrade
the irrigant is prevented from extruding through the collagen, which is continuously remodeled (68). The
apical foramen. high turnover is not exclusive to the extracellular
It is important to point out that the repair of the matrix, as cells are frequently being renewed as well.
periradicular tissues after the treatment of vital pulps is The periodontal ligament is exceptionally well vascu-
accomplished by cells and molecules of the periodontal larized, which reflects the high rate of turnover of its
ligament. This is a soft specialized connective tissue, cellular and extracellular constituents. Its main blood
which ranges in width from 0.15 to 0.38 mm, with its supply comes from the superior and inferior alveolar
thinnest portion around the middle third of the root arteries. The ligament also possesses an efficient lymph
(68). As with any other connective tissue, the period- drainage system. Because the periodontal ligament has
ontal ligament consists of cells, extracellular matrix, a high turnover rate, it can easily adapt to changing
vessels and nerves. The major cells found are fibroblasts local conditions (69). All these features point to an

Fig. 3. Periradicular tissue response after overinstrumentation in vital teeth of dogs. (A) Radiograph taken at the time of
instrumentation beyond the apical foramen. (B and C) Histological picture after 180 days showing tissue ingrowth into
the canal and hard tissue deposition along the canal walls and closing the apical foramen. (D) Higher magnification of
the specimen showed in C (courtesy of Francisco Souza-Filho).

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excellent ability of the periodontal ligament to repair responsible for the periradicular tissue repair is the
itself after injury. apical periodontal ligament.
Maintenance of the vitality of the ‘pulp stump’ is
unpredictable during chemomechanical procedures Necrotic pulp and retreatment cases
(70, 71) and evidence indicates that it is not paramount (Infected)
for periradicular tissue repair to take place. Studies
have demonstrated that even after the mechanical Root canals containing necrotic pulp tissue associated
removal of the ‘pulp stump’ by instrumentation at or or not with a periradicular lesion as well as root-
beyond the apical foramen, repair by hard tissue filled teeth with recalcitrant lesions are a different
formation is not precluded, particularly when calcium matter because of the presence of infection. In these
hydroxide is used as intra-canal medication or it is cases, microorganisms may reach the apical part of the
present in formulations of root canal sealers (55, 57– canal and be near or at the apical foramen and accessory
60). In addition, studies in dogs (72–74) revealed that foramina, in close contact with the periradicular tissues
enlargement of the apical foramen with consequent (14, 75–77) (Fig. 4). Thus, the length of instrumenta-
removal of the ‘pulp stump’ was followed by periradi- tion in infected cases is critical (78) and it is reasonable
cular tissue ingrowth into the root canals, sometimes to assume that it would be preferable to clean the canal
associated with deposition of cementum-like tissue to its terminus. Nevertheless, the risks of instrumenting
over the canal walls (Fig. 3). This confirms the healing the canal to this position includes the possibility of
potential of the periodontal ligament, which is con- over-instrumentation, which can force infected debris
ceivably a consequence of its intense metabolic activity. and filling materials into the periradicular tissues.
However, although some studies have shown that even
under extreme conditions the periodontal ligament can
be repaired in the absence of concomitant infection,
one should be aware that, in clinical situations,
enlargement of the apical foramen is undesirable and
unnecessary, as it can result in lack of apical control and
severe post-operative pain.
The outcome of treatment of teeth with vital pulps
does not appear to be substantially affected by the
apical limit of the root canal procedures, provided
microorganisms are prevented from gaining entry into
the root canal before filling (8). Obviously, over-
extension should be avoided as it can predispose to
post-operative pain. The recommended working
length in teeth with vital pulps is 1–2 mm short of the
radiographic apex. The use of apical patency files has
been advocated to clean the apical foramen and to keep
it free of debris, without enlarging it. The price paid by
using patency files in such cases may be the removal of
the ‘pulp stump’. The reasons to maintain the apical
foramen patent in teeth with vital pulps are almost
exclusively based on mechanical factors, i.e., to pre-
vent apical blockage with dentinal debris that
could lead to loss of apical control and give rise to
procedural errors during chemomechanical prepara-
tion, particularly of curved and narrow root canals. Fig. 4. (A) Scanning electron micrograph showing
extensive bacterial colonization in the very apical part of
However, from a biological perspective, it seems that it the canal, near and at the apical foramen. (B) Higher
does not matter whether the ‘pulp stump’ is removed magnification of the inset in A. Modified with permission
by the use of small patency files, since the main entity from Siqueira and Lopes (77).

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Reaction of periradicular tissues

One of the requisites for microorganisms to partici-


pate in the pathogenesis of periradicular diseases is that
they should be spatially located in the root canal system
in such a way that they or their virulence factors can
gain access to the periradicular tissues (79). A region
that fulfills this requisite is the apical third of the root
canal, since microorganisms colonizing this region are
in intimate contact with the host tissues through the
apical foramen and accessory foramina, which have
been demonstrated to be more frequently found in the
apical third of the root (80).
Microorganisms infecting the apical region of necro-
tic pulps are predominantly anaerobic and the time of
Fig. 5. Bacterial prevalence in the apical portion of
infection can influence such a dominance. A study in infected root canals as evaluated by a molecular method.
monkeys (81) investigated the distribution of different Data according to Siqueira et al. (84).
microbial species in root canal samples after different
periods of time and in different parts of the root canal of infected root canals can be indicative of their role in
system. The numbers of anaerobic bacterial cells the pathogenesis of periradicular lesions.
significantly increased with time and outnumbered The apical part of the root canal can be regarded as a
facultative bacterial cells after 90 days. After 90 or 180 ‘critical territory’ for the pathogenic bacteria, for the
days of infection, 85–98% of the bacterial cells infecting host, and for the clinician (84). It is critical for
the apical root canal were anaerobic. Baumgartner and pathogenic bacteria, because in this region they are in
Falkler (82) cultured the apical 5 mm of root canals of close contact with the periradicular tissues from which
10 teeth with carious exposures and reported that the they can obtain nutrients and to which they can induce
most prevalent species were Prevotella intermedia/ damage. It is also critical to the host, because the host
nigrescens, Prevotella buccae, Peptostreptococcus anaero- defense must concentrate in this area and wall off the
bius and Veillonella parvula, all of them being isolated microbes in an attempt to prevent spreading of the
from one-half of the examined cases. Of a total of 50 infection. It is finally critical for the clinician, because
bacterial isolates, 68% were strict anaerobes. All cases the outcome of the treatment will depend on how
harbored anaerobes. The number of colony forming effective s/he is in eradicating the infection and in
units in the apical 5 mm of root canals ranged from promoting both fluid-tight and bacteria-tight seal in
5.6  104 to 4.3  106. this area.
Dougherty et al. (83) investigated the occurrence of Given its strategic anatomic position as well as its
black-pigmented anaerobic bacteria in the apical and complex anatomy, the apical portion of the root canal
coronal segments of infected root canals and found system can be considered as the most critical element of
these bacteria in 12 of 18 cases (67%). Prevotella the whole system with regard to the need for cleaning,
nigrescens was isolated from 9/12 apical segments, disinfection and sealing (85). Because it is not known
Prevotella melaninogenica from 3/12, P. intermedia how many microbial cells remaining in the apical
from 1/12, and Porphyromonas gingivalis from 1/12. portion can be managed by the host defenses, the
Siqueira et al. (84) surveyed samples taken from the length of the chemomechanical procedures should
apical third of infected root canals associated with presumably not be shorter than the apical level of the
periradicular lesions for the presence of 11 anaerobic infection. Thus, the apical limit of chemomechanical
bacterial species using the polymerase chain reaction preparation should ideally reach the full extent of the
method. All cases were positive for the presence of apical root canal up to the canal terminus, in an attempt
bacteria. Of the 23 teeth, Pseudoramibacter alactolyti- to remove or at least significantly reduce the microbial
cus was detected in 10, Treponema denticola in 6, counts before the filling is placed. In fact, the need for
Fusobacterium nucleatum in 6, Porphyromonas endo- control of apical preparation within infected canals has
dontalis in 4, and Filifactor alocis in 2 (Fig. 5). been demonstrated by clinical studies of treatment
Occurrence of these bacterial species in the apical third outcomes (5, 86).

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During instrumentation of infected root canals, blockage of the apical root canal, with consequent loss
dentinal debris containing microorganisms is produced of the working length.
and may be packed in the apical region or extruded into Attempts to regain working length should it be lost
the periradicular tissues. When packed in the canal, may result in other accidents, such as file breakage,
dentine debris may reduce the working length and may ledge formation and perforation (Fig. 6). In this
hinder repair because of the presence of residual regard, the principle is also applicable to non-infected
microorganisms (87). Infected dentine debris, which cases, as alluded to earlier. However, from a biological
is extruded into the periradicular tissues may also be point of view, the use of patency files arguably enhances
responsible for persistent periradicular inflammation cleaning and disinfection of the entire extension of the
and consequent treatment failure (34). root canal up to the canal terminus, eliminating
To effectively clean and disinfect the most apical part microorganisms and preventing accumulation of in-
of root canals, the use of patency files that reach or even fected debris in this area, which could jeopardize the
pass through the apical foramen have been proposed. outcome of the endodontic treatment (Fig. 7). Even if
The apical patency concept is based on the placement of instruments and irrigants do not succeed in completely
a small file (size 10 or 15) to 1 mm longer than the canal eliminating microorganisms in the apical segment of
terminus in an attempt to remove dentinal debris from the canal, they can conceivably disturb the environment
the apical portion of the canal (88). It is recommended and promote an imbalance that may be conducive to
that this small file should be passively moved through the successful action of host defense mechanisms.
the apical constricture without widening it. This To restrict apical cleaning and shaping procedures to
concept is currently taught in 50% of the United States 1–2 mm short of the apical foramen may leave behind
dental schools (89). sufficient numbers of microorganisms to maintain
Clinical experience demonstrates that patency with periradicular disease. Theoretically, the use of patency
small files can be of great value in maintaining control files may assist in elimination of bacteria located near or
of the working length. This is because the use of even at the apical foramen. A study (45) compared the
patency files ensures that the apical foramen remains outcome of root canal treatment performed by an
unblocked and patent, and when used repeatedly, tends endodontist using different protocols and evaluated
to prevent accumulation of pulpal and dentinal debris the influence of factors affecting outcome. A relatively
that can cause blockages that often lead to ledges and high rate of complete healing was observed for different
perforations, which, particularly in infected cases, put protocols. Although patency files were used, they were
the outcome at risk. Moreover, it has been suggested,
but remains to be proved, that keeping the foramen
patent allows penetration of irrigants deeper into the
apical portions of the root canal system (90). Also,
irrigant exchange is supposed to occur, when irrigation
fluids are displaced by patency files (90). However,
although patency files can actually prevent the blockage
of the apical foramen by dentinal debris, it also remains
to be clarified as to whether the use of patency files can
remove a significant amount of dentinal debris packed
in the apical canal.
In essence, the reasons proposed for the establish-
ment and maintenance of apical patency during
preparation of infected cases are based on biological
and mechanical factors. From a mechanical point of
view, when the instrument prepares a root canal to its
terminus and is repeatedly taken to that point, the risks Fig. 6. Blockage of the root canal during chemo-
mechanical procedures and consequent attempts to regain
of procedural accidents are theoretically reduced. This the initial working length may result in procedural
is because the accumulation of debris in this area is accidents, such as perforations, which can jeopardize the
prevented or reduced. Such accumulation may lead to outcome of the treatment of infected cases.

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Reaction of periradicular tissues

Fig. 7. The use of patency files can be justified by mechanical (non-infected and infected cases) and biological (infected
cases) reasons. (A) Instrumentation short of the apical foramen without reaching it can result in blockage of debris and
loss of the working length, particularly in curved canals. (B) The use of small patency files can prevent accumulation of
debris in the most apical segment of root canals. It can also help eliminate microorganisms located in this region. (C and
D) Radiographs showing establishment of the patency length.

not included as a variable. Therefore, the impact of the in preventing inoculation of periradicular tissues
patency concept on the bacterial elimination and on the with contaminated patency files and concluded
outcome of the endodontic treatment remains elusive. that the NaOCl present in the canal after irrigation
Ideally, there is no apparent reason to extend the use was sufficient to kill the test bacteria used to
of patency files beyond the confines of the canal. contaminate files.
Reaching the canal terminus would appear to be Because patency files can dislodge debris accumulated
sufficient to perform the effects expected for a patency in the apical part of the canal, it is possible that infected
file. Even so, because of the inherent difficulties in dentinal debris is pushed into the periradicular tissues.
establishing the precise location of the canal terminus Apically extruded infected dentinal debris can play a
clinically, patency files are likely to pass through the role in induction of post-operative pain and can cause
apical foramen in many cases. It is entirely unlikely that persistence of periradicular lesions after root canal
they can cause significant mechanical damage to the treatment. However, the participation of infected
periradicular lesions, provided small instruments are dentinal debris in these processes will depend on the
used. On the other hand, in infected canal systems, amount of debris as well as on the virulence and/or
instruments can become contaminated by microorgan- numbers of bacteria present. The fact that there is no
isms on their passage to the patency length. Thus, apparent influence on the development of post-
patency files could theoretically carry bacteria from the operative pain when using patency files (39, 92)
canal to the periradicular tissues. However, an ex vivo suggests that apical extrusion of debris during patency
study (91) analyzed the effectiveness of 5.25% NaOCI filing may not be important, provided small files are

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Siqueira

used gently and passively. The impact of apically


extruded debris during the use of patency files on the
outcome of root canal treatment remains elusive.
As mentioned previously, retreatment cases should
also be regarded as infected. Persistent infection in the
most apical portion of the root canal is the major
cause of the persistence of post-treatment disease
(14, 76). Remaining microorganisms may be locat-
ed in uninstrumented areas of the main root canal,
in dentinal debris, in ramifications, in apical deltas,
in dentinal tubules, and in voids of the root canal filling.
If those microorganisms contact the periradicular
tissues and they are in sufficient numbers to be
pathogenic, an inflammatory lesion can develop or be
maintained. Using light and transmission electron
microscopy, Nair et al. (14) reported that microorgan- Fig. 8. Ideal apical limit of root canal procedures.
isms may sometimes persist in the filled root canal and
survive beyond the apical constriction. Fukushima et al.
(76) examined root-filled teeth with periradicular
lesions by means of scanning electron microscopy
and bacteriological methods. In over 60% of the
cases, bacterial aggregates were visualized between
the terminus of the root canal filling and the apical
foramen. Those bacteria were likely to be members of a
persistent or secondary infection. These findings
indicated that bacteria can persist in the apical portion
of the root canal and can be responsible for recalcitrant
periradicular lesions. Therefore, the same principles
applied to the length of the chemomechanical proce-
Fig. 9. For instrumentation to touch all root canal walls
dures in cases of necrotic pulps should also be applied to
and to remove substantial amounts of pulp tissue and
retreatment cases. bacteria, the size of preparation should ideally
Therefore, it appears but has not been proven that incorporate anatomic irregularities, which can be
small patency files can help clean up to the canal difficult and sometimes impossible to carry out in canals
that are not round in cross-section.
terminus during chemomechanical procedures, with-
out enlarging it. Short of the canal terminus (0.5–
1 mm), the root canal should then be sufficiently exchange in the apical third of the root canal (98, 99).
enlarged to maximize cleaning and disinfection, as Although there are contradictory findings in the
well as to accommodate the filling material (Fig. 8). literature regarding the effects of apical enlargement
Studies have demonstrated that the larger the apical on the outcome of the treatment (45, 46, 51, 52, 86),
preparation of infected root canals, the greater the it is fair to assume that if increased elimination of
reduction of the bacterial numbers within the canal microorganisms is achieved, so are the chances for a
(93–97). Debris is also more effectively removed when better outcome of the treatment.
the apical preparation size is relatively large (98). Obviously, enlargement of infected canals should be
Sufficiently large preparations can incorporate more compatible with the tooth anatomy to avoid weakening
anatomic irregularities and allow the removal of a of the root and procedural errors, such as ledges and
substantial volume of bacterial cells and debris from the perforations. NiTi instruments allow the attainment of
root canal (Fig. 9). In addition, instrumentation to larger preparations in curved root canals with reduced
larger file sizes can also result in increased penetration risks of procedural accidents (100–103). Because of
of the irrigating needle and facilitate better irrigant this, they should be the instruments of choice to

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Reaction of periradicular tissues

prepare curved root canals. Less post-treatment disease


has been reported for teeth instrumented with hand
NiTi files when compared with teeth prepared with
hand stainless-steel files (104). NiTi file utilization was
five times more likely to achieve healing than using
stainless-steel files (104). This probably occurred
because of the improved ability of NiTi files in
maintaining the original canal path during instrumen-
tation and so facilitate removal of microorganisms.
One should be mindful that enlargement must be
restricted to the root canal without reaching the canal
terminus. As discussed above, the latter should be
cleaned, disinfected and maintained patent, but it must
not be enlarged. The clinician should be aware of the
risks when using large instruments beyond the canal Fig. 10. Scanning electron micrograph of the apical
terminus, as this procedure can result in severe foramen. Note the apical constriction (courtesy of Hélio
Lopes).
periradicular injury, lack of an apical stop, and extrusion
of a large amount of infected debris, which predispose
to the occurrence of post-operative discomfort and present. Alternatively, the apical foramen could be a
poses a potential threat to the long-term outcome of more useful landmark, but it is also difficult and many
the treatment. times impossible to locate clinically and radiographi-
cally. This is because the position of the apical foramen
in most cases does not coincide with the root apex
Establishing the working length
(105). To complicate matters further, when the apical
In his classic study, Kuttler (105) found that the root foramen exits to the side of the root in a buccal or
canal usually narrows toward the apex and then expands lingual direction it is virtually impossible to identify on
to form the apical foramen. The narrowest part of the a radiograph. Consequently, the exact determination of
canal formed the apical constriction, which is located where the root canal ends is a difficult if not impossible
just short of the apical foramen. This area is generally task (112). In addition to the anatomical variability, the
believed to be located at the cementum–dentinal apical root canal can be sclerosed or the apical
junction (CDJ) and its distance to the apical foramen constriction can have been modified or lost due apical
varies from 0.5 to 1 mm for teeth of different ages root resorption, as a result of an inflammatory
(105–107). In more than 60% of root canals, the apical periradicular lesion (113). In many cases, the very
foramen is not located at the apex, and the distance apical part of the root canal may contain an extension of
between the apical foramen and the radiographic apex inflammatory tissue (75), which can be derived from an
ranges from 0 to 3 mm (105, 108). Kuttler (105) ingrowth of inflamed periradicular tissues into the canal
reported that the mean apex to foramen distance was or it can be due to the fact that in some cases a
0.48 mm for young individuals and 0.6 mm for older periradicular lesion develops even before the entire
ones. Dummer et al. (106) reported the mean apex to pulp tissue is necrotic (114). Although this inflamma-
foramen distance in anterior teeth to be 0.36 mm. tory tissue may temporarily prevent microorganisms
Traditionally, the apical constriction has been con- from reaching the most apical part of the root canal, its
sidered as the ideal termination for root canal presence is unpredictable and virtually impossible to
procedures (109, 110) (Fig. 10). However, the greatest determine in the clinical situation.
problem to accept this area as a landmark, to which Because the root apex is usually visible radiographi-
endodontic procedures should be limited, is that the cally, it has been widely used as a reference for
CDJ is very often impossible to detect clinically, even by determination of the working length. However, even
experienced practitioners (111). This is because the though 0.5–1 mm short of the radiographic apex is
CDJ does not always represent the most constricted commonly used and recommended as the termination
area of the root canal and/or because it is not always point, this remains only an estimate. It can be argued

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that instrumenting and filling to an arbitrary measure-


ment short of the apex is not treating the root canal
system in its entirety. But if infection is absent (e.g.,
vital cases), this may not be necessary. On the other
hand, the entire infected root canal should ideally be
instrumented, and the clinician should take advantage
of the available methods to assess where the root
canal terminates.
Radiographs have been used widely for working
length determination. Other methods have also been
proposed, such as tactile sensation and the paper point
technique (90), but they are imprecise, unreliable,
empirical and fraught with limitations. In recent years,
electronic length measurement devices have been used
for determination of the root canal terminus with a
satisfactory degree of accuracy and reliability (115–
117). A long-term retrospective study used an electro-
nic apex locator to determine the working length in
infected root canals associated with periradicular
lesions and reported a high rate of healing (118).
Commercially available electronic apex locators direc-
ted to the analysis of several impedance values at
different frequencies concurrently have been reported
to be accurate to within 0.5 mm from the apical
foramen in more than 90% of cases, irrespective of the
pulpal diagnosis (117, 119–123). The working length Fig. 11. Blockage of the very apical part of the canal by
can then be established by subtracting 0.5 mm from dentin chips after instrumentation. In non-infected cases,
this may not affect the outcome of the treatment. On the
measurements of electronic devices, which would result
other hand, in infected cases, microorganisms embedded
in theory in the corrected working length being 1 mm in debris may pose a threat to the treatment outcome
short of the apical foramen. Afterwards, a radiograph (courtesy of Hélio Lopes).
should be taken to confirm measurements. As a matter
of fact, the combined use of electronic apex locators
and radiographs of a trial file has been shown to be (a) The apical segment can be blocked by dentinal
more accurate than the use of radiographs alone (124, debris (Fig. 11). In non-infected vital pulps, this
125). Because of their accuracy, apex locators allow for usually does not represent a problem as dentinal
a reduction in the number of radiographs necessary to chips can function as a nidus for calcification and
determine the working length particularly in teeth closure of the apical foramen (56, 65). On the other
where the apex is difficult to visualize on the radio- hand, in infected necrotic pulps and retreatment
graph. Even though electronic apex locators appear to cases, dentinal debris can contain microorganisms
be excellent tools for the determination of the working and their products. In these cases, the outcome of
length, they should be used as an adjunct not as a root canal treatment will depend on the virulence
substitute for radiographs. and numbers of remaining microorganisms as well as
on the host ability to cope with them (21, 22).
(b) The apical segment may remain filled with pulp
What happens in the apical region of tissue. In non-infected pulps, if microorganisms
were not introduced in the canal during treatment,
the canal after filling?
tissue repair will be uneventful. In infected pulps,
Different events can occur in the most apical segment microorganisms can remain in the necrotic tissue
of the root canal after filling. The most common are: and dentinal debris in the most apical portion of the

134
Reaction of periradicular tissues

canal. Again, the outcome of treatment will depend


on the virulence and numbers of remaining micro-
organisms as well as on the host resistance (21, 22).
(c) The apical segment of the root canal cleaned by
patency files can remain unfilled. In this situation, if
the apical segment is free of microorganisms, the
periodontal ligament can ingrow and occupy this
space (72, 74). If microorganisms remain, the
inflamed tissue can ingrow and the persistence of
inflammation will depend on the number and
virulence of microbial species and the host capability
to reach and eliminate remaining microorganisms.
(d) The apical portion can remain filled with the intra-
canal medicament, such as a calcium hydroxide
paste. As time goes by, calcium hydroxide paste can
be solubilized or phagocytosed, and then be
replaced by ingrowing periodontal ligament (126).
(e) The apical portion can be filled, which is the most
common situation observed when patency is
established. In this case, a biocompatible sealer
can occupy and seal this space. Theoretically, if the
filling material has antimicrobial properties, it may
help eliminate remaining microorganisms. Most
endodontic sealers have some antimicrobial activity
during setting, although this property is not as
pronounced as intracanal irrigants and medica-
ments (127–135). If the sealer is solubilized or Fig. 12. Formation of sealer ‘puffs’ gives a good ‘esthetic’
phagocytized, it can be replaced by tissue ingrowth. appearance on radiographs and has been regarded as
indicative that proper treatment has been accomplished.
However, even though a tiny extrusion of sealer is
There is a belief that the extrusion of sealer beyond unlikely to cause discomfort and may not compromise
the radiographic terminus confirms that the apical the outcome of the treatment, sealer ‘puffs’ does not
foramen is patent and has been sealed (136) (Fig. 12). necessarily guarantee that the root canal is properly sealed
or that the case will result in success.
Although minor extrusion of sealer is unlikely to cause
discomfort and may not compromise the outcome of
treatment, the presence of sealer in the apical part of the on opinion rather than on facts, which is in clear
canal does not necessarily guarantee that the root canal contrast with the current trend of evidence-based
is properly sealed or that success will ensue. Bacterial endodontic treatment. There is no evidence supporting
colonies can remain unaffected in the apical root canal this belief.
in spite of overfilling and can lead to treatment failure
(14, 137). In fact, the radiographic quality of the root Influence of overfilling on treatment
filling is in no way indicative that the root canal was well
outcome
sealed, particularly when canals are oval or ribbon-
shaped in transverse section (138) (Fig. 13). In It has been demonstrated that a better outcome for the
addition, disinfection of the root canal system cannot root canal treatment is observed when the intracanal
be determined from radiographs and, as a consequence, procedures terminate within the confines of the root
even apparently well-filled canals can remain infected canal system. A histological study (54) reported that
(14, 21). Therefore, the belief that the quality of root the most favorable response of the periradicular tissues
canal treatment is determined by the presence of sealer occurred when both instrumentation and filling
‘puffs’ visible on a post-obturation radiograph is based remained short of the apical constriction. A clinical

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Fig. 13. The quality of the root canal obturation as


visualized on a buccal–lingual radiograph is in no way
indicative that the root canal was well sealed, particularly
Fig. 14. Apical percolation as a result of overfilling can be
when canals are oval or ribbon-shaped in transverse
the main responsible for failures in the treatment of
section. Note the discrepancy of the image taken in a
previously infected teeth. Note the space between the
buccal–lingual direction as compared to that taken in
gutta-percha filling and the root canal walls clearly visible
a mesio-distal direction.
on radiographs.

study showed that an optimal treatment outcome in


infected teeth with periradicular lesions was achieved success rate of the treatment of teeth without
when the apical terminus was 0–2 mm short of the periradicular lesions even in cases of overfilling (6,
radiographic apex (5). The same study revealed that the 13). In addition, one should bear in mind that when
prognosis was markedly decreased with significant the apical terminus of the root canal filling is at the
underfill and with overfill. These findings corroborated radiographic apex, it actually is in many cases passing
earlier reports (61, 139). through the apical foramen, but the rate of healing
The toxicity of the root filling materials has been in those cases is rather high (5).
considered to play an important role in failures Obviously, overfilling should be prevented since post-
associated with overfillings (140). However, it has operative complications, such as post-filling pain, can
been reported that the apical extent of root fillings develop, particularly when a substantial amount of
seems to have no correlation with treatment failure, filling material extrudes through the apical foramen.
provided infection is absent (6, 7, 13, 141). Apart from Sealers are cytotoxic before setting and thereby have
the paraformaldehyde-containing materials, most of the ability to induce tissue damage and consequent
the materials used in root fillings are either biocompa- inflammation. Gross overfillings allow the introduction
tible or show cytotoxicity only prior to setting (41–43, of a large volume of sealer (and its cytotoxic compo-
142, 143). Therefore, it is highly unlikely that most of nents) into the periradicular tissues with a consequent
the contemporary endodontic materials by themselves large area of contact with them, maximizing damage
are able to sustain a periradicular inflammation when and inflammation. The risk of pain in those cases is
overfilled in the absence of a concomitant endodontic consequently high (20).
infection. This is because tissue injury caused by However, disease associated with overfilled root
extruded sealers is usually only transient but not canals is usually caused by concomitant infections and
persistent. This statement is reinforced by the high may occur mainly due to:

136
Reaction of periradicular tissues

Apical percolation which, unlike the acute abscess, is usually characterized


by absence of overt symptoms. This condition en-
In most cases, the apical seal is inadequate in overfilled
compasses the establishment of microorganisms in the
root canals (Fig. 14). Percolation of tissue fluids rich in
periradicular tissues, either by adherence to the apical
proteins and glycoproteins into the root canal system
external root surface in the form of biofilm-like
can supply substrate to residual microorganisms, which
structures (145) or by formation of cohesive colonies
can proliferate and reach sufficient numbers to
within the body of the inflammatory lesion (146, 147).
induce or perpetuate a periradicular lesion. If fluid
Extra-radicular microorganisms have been discussed as
penetrating into a previously non-infected canal or in a
one of the etiologies of persistence of periradicular
properly disinfected one finds no residual microorgan-
lesions in spite of a well-performed root canal treatment
isms, a periradicular lesion will not be induced or
(21, 148).
maintained.
Conceivably, the extra-radicular infection can be
dependent on, or independent of the root canal
Previous overinstrumentation infection (144). For instance, the acute periradicular
Another phenomenon is likely to occur in most of the abscess is for the most part clearly dependent on the
overfilled teeth. It is well known that over-instrumen- intra-radicular infection – once the intra-radicular
tation usually precedes over-filling. In infected cases, infection is properly eradicated by root canal treatment
over-instrumentation carries the risk of contamination or tooth extraction and drainage of pus is achieved, the
of the periradicular tissues by displacement of infected extra-radicular infection usually subsides. However, it
debris into the periradicular tissues. Embedded in should be appreciated that in some cases, bacteria that
debris, microorganisms can be physically protected have participated in acute periradicular abscesses may
from the host defense mechanisms and thereby can persist in the periradicular tissues following resolution
survive within the periradicular tissues and induce or of the acute response and establish a persistent extra-
maintain periradicular inflammation. The presence of radicular infection associated with a chronic periradi-
infected dentine or cementum chips in the periradicular cular inflammation. This would then characterize an
lesion has been associated with impaired healing (34). extra-radicular infection independent of the intra-
Theoretically, this can be regarded as a type of extra- radicular infection.
radicular infection. In fact, this may be one of the ways Studies using cultivation (147, 149, 150) or mole-
Actinomyces species and Propionibacterium propioni- cular methods (151–153) for microbial identification
cum reach the periradicular tissues to induce periradi- have reported the extra-radicular occurrence of a
cular actinomycosis (144). complex microbiota associated with periradicular le-
sions that not respond favorably to the root canal
Extra-radicular infection – clinical treatment. Anaerobic bacteria have been reported to be
the dominant microorganisms in several of those
implications
lesions (151, 152). Because those studies did not
Periradicular lesions are formed in response to intra- evaluate the bacteriological conditions of the apical part
radicular infection and comprise an effective barrier of the root canal, it is difficult to ascertain whether
against spreading of the infection to the alveolar bone those extra-radicular infections were dependent on or
and to other body sites. In most situations, inflamma- independent of an intra-radicular infection.
tory periradicular lesions succeed in preventing micro- In the light of recent evidence brought about by
organisms from gaining access to the periradicular culture and molecular studies (147, 150–153), the fact
tissues. Nevertheless, in some specific circumstances, that bacteria can be located outside the root canal and
microorganisms can overcome this barrier and establish within the inflamed periradicular tissues cannot be
an extra-radicular infection. The most common form of denied. However, the clinical implications of such
extra-radicular infection is the acute periradicular findings are far from clear. An important question is:
abscess, characterized by purulent inflammation in what is the fate of extra-radicular bacteria after proper
the periradicular tissues in response to the egress of chemomechanical and intracanal medication procedures?
virulent bacteria from the root canal (144). There is, The presence of bacterial colonies outside the root
however, another form of extra-radicular infection canal usually characterizes a borderline between the

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intra-radicular infection and the inflamed periradicular There are some situations that permit intra-radicular
tissues. Even so, their presence outside the canal bacteria to reach the periradicular tissues and establish
indicates an extra-radicular infection, which may be an extra-radicular infection. This may be a result of
dependent on the intra-radicular infection in the sense direct advance of some bacterial species that are able to
that if the latter is eradicated the, the former can be overcome host defenses concentrated near the apical
eliminated by the host. foramen or that manage to penetrate into the lumen of
In fact, most oral microorganisms are opportunistic pocket (bay) cysts (169, 170), which is in direct
pathogens and only a few species have the ability to communication with the apical foramen. This may
challenge and overcome the host defenses, to acquire also be due to bacterial persistence in the periradi-
nutrients and to thrive in the inflamed periradicular cular lesion after remission of acute abscesses. Finally,
tissues and, then, to establish an extra-radicular root canal procedures can also in some way favor
infection. Several species of putative oral pathogens the establishment of an extra-radicular infection, in
have been detected in recalcitrant periradicular lesions the event of apical extrusion of debris during root
(147, 151–157). Some of them are recognized to canal instrumentation (particularly after overinstru-
possess an apparatus of virulence that theoretically can mentation).
allow them to invade and to survive in a hostile As discussed above, bacteria embedded in dentinal
environment, such as the inflamed periradicular lesion. chips can be physically protected from the host defense
For instance, it is currently recognized that some cells and therefore can persist in the periradicular tissues
Actinomyces species and P. propionicum are able to and sustain periradicular inflammation. The virulence
participate in extra-radicular infections and to cause a and the quantity of the involved bacteria as well as the
pathological entity called periradicular actinomycosis, host ability to deal with infection will be the decisive
which is successfully treated only by periradicular factors dictating whether an extra-radicular infection
surgery (144). Some other putative oral pathogens, will develop or not. Because there is a potential risk of
such as Treponema species, Porphyromonas endodonta- treatment failure in the event of apical extrusion of
lis, Porphyromonas gingivalis, Tannerella forsythia, infected debris (not to mention the recognized risk of
Prevotella species and Fusobacterium nucleatum, have post-operative pain), the clinician’s choice of instru-
also been detected in chronic periradicular diseases by mentation techniques should ideally rely on those that
culture, immunological or molecular studies (149, allow minimal extrusion. In addition, accurate estab-
151–153, 155). Most of these species possess virulence lishment of the working length is paramount in
traits that can allow them to avoid or overcome the host prevention of debris extrusion.
defenses in the periradicular tissues (158–166).
The incidence of extra-radicular infections in un- Possible systemic effects stemming
treated teeth is rather low (75, 77), which is congruent
from endodontic infections
with the high success rate of non-surgical root canal
treatment. Even in root filled teeth with recalcitrant A revived interest in the focal infection theory has been
lesions, in which a higher incidence of extra-radicular generated in the last few decades due to reports from
bacteria has been reported, a high rate of healing epidemiological studies suggesting the involvement of
following retreatment (5) indicates that the major cause oral microorganisms in systemic diseases (171, 172). A
of endodontic disease is located within the root canal focal infection is a localized or generalized infection
system, characterizing a persistent or secondary intra- caused by the dissemination of microorganisms or their
radicular infection. This has been confirmed by studies products from a focus of infection, which is a confined
investigating the microbiological conditions of root area that contains pathogenic microorganisms (173).
canals associated with post-treatment disease (15, 16, Although there is a plethora of focal infections having
141, 167, 168). Based on this, one may assume that the oral cavity as suspected focus, the most documen-
most of the extra-radicular infections observed in root ted examples are bacterial endocarditis (174), brain
filled teeth could have been fostered by the intra- abscess (175) and orthopedic joint infections (173).
radicular infection. Thus, the usual origin of bacteria Oral bacteria have also been implicated in aspiration
involved with extra-radicular infections is the intra- pneumonia (176), preterm low birth weight (177), and
radicular infection. coronary heart disease (178). Infected root canals and

138
Reaction of periradicular tissues

periradicular lesions have been considered as potential now are how frequently and at what magnitude
foci of infection (173). (number of bacterial cells in the blood) bacteremia
There is no evidence showing that bacteremia occurs, how long it persists and whether endodontic
spontaneously arises from infected root canals asso- bacteria are able to cause disease at distant sites. It is
ciated with a chronic periradicular lesion. On the other difficult to prove that a given oral microorganism is the
hand, bacteremia can occur in cases of acute periradi- causative agent of a focal infection, unless it is of the
cular abscesses and during the treatment of infected same clonal type as that present in the oral cavity.
root canals or periradicular surgery (179–185). Studies Although it has been demonstrated that the microbial
revealed that it was far more probable that a bacteremia species present in the blood of patients undergoing
occurs if root canal procedures were performed beyond root canal treatment are of the same clonal types as
the apical foramen than when maintained within the those present in their root canals (191), such findings
confines of the root canal system (182, 183). Bender only mean that root canal treatment can cause
et al. (182) reported that the incidence of bacteremia bacteremia, but not that microorganisms from the
was none if the instrumentation remained within the root canal cause disease in remote sites of the body. For
canal and 15% if it extended beyond the apical foramen. bacteria present in the bloodstream to reach other body
Even so, the bacteremia following endodontic proce- sites and induce disease, they have to survive the host
dures was shown to last no longer than 10 min (182) defenses in the blood vessels as well as in the distant
due to clearance of microorganisms from within the body site, they have to encounter predisposing condi-
circulation. Using improved anaerobic cultivation tions in the distant body site for their attachment and
methods, Baumgartner et al. (184, 185) revealed that further colonization, and they have to be in sufficient
non-surgical root canal treatment resulted in a lower numbers to induce disease.
incidence of bacteremia (3%, as a result of over- It is apparent from well-conducted studies that oral
instrumentation) than surgical flap reflection (83%), bacteria are rarely a cause of systemic disease (173). For
periradicular curettage (33%) or tooth extraction instance, periodontal pathogens are very rarely a cause
(100%). In a study that performed intentional instru- of endocarditis, with 102 reported cases due to
mentation beyond the apex, a 34–54% incidence of Actinobacillus actinomycetemcomitans, two due to
bacteremia was detected (186). Prevotella oralis, one due to Prevotella bivia, one due
However, it has been recently demonstrated that to black-pigmented anaerobic bacteria, and five due to
bacteremia can occur even if instrumentation is Veillonella species (192, 193). Except for A. actinomy-
maintained within the root canal system. Debelian cetemcomitans, which has been infrequently found in
et al. (187) investigated the incidence of bacteremia endodontic infections (194, 195), the other species
following endodontic treatment of teeth with perira- have been isolated from infected root canals or
dicular lesions. In the treatment of one-half of the periradicular abscesses. As a matter of fact, obligate
patients, the first three reamers (sizes 15, 20 and 25) anaerobic bacteria from the oral cavity do not appear to
were used to a level 2 mm beyond the root apex, while survive well in other body locations and viridans group
in the other half, instrumentation ended inside the root streptococci, considered the principal oral culprits in
canal, 1 mm short of the apex. They found no statistical endocarditis, are not primary pathogens but rather
difference when the frequency of bacteremias in the opportunistic bacteria that usually require altered
two groups was compared. The most common micro- biologic tissue to induce disease (173).
organisms present within the associated bacteremia Cultivation-independent procedures for bacterial
were anaerobic bacteria. This can be explained by the identification have revealed previously unsuspected
fact that all instrumentation techniques induce apical degrees of diversity in the microbiota present in
extrusion of debris, some more than others, even when environmental and human-associated sites (196–
instrumentation is confined to the interior of the canal 200). Studies using sophisticated molecular methods
(188–190). If debris is infected, bacteria are launched have demonstrated that about 40–50% of the oral
into the periradicular tissues and then can gain entry microbiota is composed of as-yet uncultivable bacteria
into the circulation. (201–203). A similar picture has been demonstrated
Therefore, there is no doubt that root canal for the root canal microbiota of teeth associated with
procedures can induce bacteremia. The questions periradicular lesions (204, 205). Since many bacteria

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are still uncultivable, their pathogenicity and involve- tion (207). Because of the 1000–8000 times greater
ment in causation of disease remain unknown. A study chance of any bacteremia originating from normal daily
using molecular technology revealed a large amount of activities, it is equally impossible to determine if the
bacterial DNA in blood specimens from healthy bacteremia emanated from the endodontic interven-
individuals (206) and many of the DNA sequences tion or a time before or after it (173). Whatever the
detected were from unknown bacteria. The presence of origin, bacteremias are usually transient. Even so, in the
bacterial DNA in the blood has important implications absence of clear evidence regarding the effects of
for a possible, previously uncharacterized role of some bacteremia in some compromised patients and before
bacterial species in some diseases, sometimes distant elucidation of the speculative involvement of unculti-
from the focus of infection. It would appear that to date vable bacteria, empirical consensus indicates that
no molecular study has been performed to detect the antibiotic prophylaxis should be performed in patients
occurrence of uncultivable bacterial phylotypes from at risk to develop infective endocarditis. In addition,
the oral cavity in bacteremias following endodontic antibiotic prophylaxis should also be considered for
procedures. In addition, no study has evaluated the immunosuppressed patients, individuals with indwel-
presence of those phylotypes in remote diseases in the ling catheters or patients with orthopoedic prosthetic
body. Therefore, future research is warranted to devices (208).
ascertain whether uncultivable bacteria from the oral
cavity can be involved in focal diseases.
Concluding remarks
Although there is no definitive evidence that bacteria
from infected root canals can cause systemic diseases Some of the problems that dentists face in their clinical
after bacteremia, there is a potential risk in some special practice are caused or facilitated by improper (but
patients. Consequently, it would be prudent to avoid sometimes even proper) treatment of the root canal
certain situations that could predispose to bacteremias, system. In an attempt to accomplish the major goals of
such as over-instrumentation. Over-instrumentation root canal treatment, namely to prevent and/or to
induces damage to the periradicular tissues, affecting control endodontic infections, clinicians use proce-
cells, extracellular matrix and vessels. When over- dures, substances and materials that may induce some
instrumentation occurs during preparation of infected degree of injury to the periradicular tissues. Invariably,
root canals, large numbers of bacteria can also be periradicular tissue healing will occur uneventfully in
carried into the periradicular tissues. Bacteria intro- cases where microorganisms were successfully elimi-
duced in the periradicular tissues can then enter injured nated from and/or prevented from gaining entry into
vessels and a bacteremia ensues. It has been postulated the root canal system and minimal or no damage was
that lymphatics, and not blood vessels (where the inflicted on the periradicular tissues during therapy.
pressure gradient is outward and not inward after The worst-case scenario for periradicular tissue re-
trauma), may be the primary means of entry of oral sponse to intra-canal procedures is reflected largely in
bacteria into the blood (173). In addition to a higher post-operative pain and persistence of periradicular
risk of bacteremia, as alluded to earlier, bacteria present disease despite treatment. While the development of
in the periradicular tissues may cause postoperative pain post-operative pain is largely a short-term response
or even the failure of root canal treatment due to an related to the extent of tissue injury, post-treatment
extra-radicular infection. For all these reasons, over- disease is a long-term response influenced by the
instrumentation should be avoided. persistence of the source of injury. Even though
The focal infection theory has remained controversial chemical and mechanical factors can be involved with
due to the lack of indisputable evidence regarding the unfavorable responses of the periradicular tissues to
causal relationship between oral infections and other intracanal procedures, microorganisms are the major
medical conditions. In fact, non-surgical endodontics is causative agents of post-operative pain and post-
perhaps the least likely of dental treatment procedures treatment disease. In this regard, microorganisms can
to produce a significant bacteremia in either incidence be favoured when intra-canal procedures are carried
or magnitude (173). One should bear in mind that out ineffectively. For example, over-instrumentation
bacteremia can occur naturally as a result of normal during treatment of infected root canals can create
daily activities, including toothbrushing and mastica- conditions for both post-operative pain and post-

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Reaction of periradicular tissues

treatment disease. In addition, there is a higher risk of 11. Trowbridge HO, Emling RC. Inflammation. A Review
bacteremia after over-instrumentation; the systemic of the Process, 5th edn. Chicago: Quintessence, 1997.
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