Endodontics
Strategies to Treat Infected Root Canals
José F. Siqueira, Jr., DDS, MSc, PhD
Copyright 2001 Journal of the California Dental Association.
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Periradicular lesions are diseases either primarily or secondarily
caused by microorganisms and therefore they must be prevented or treated
accordingly. If the professional is well-versed in both preventing
and eliminating the root canal infection, the success rate of endodontic
therapy may exceed 90 percent. The present paper discusses theoretical
and practical aspects of effective antimicrobial endodontic therapy
and delineates strategies to effectively control root canal infections.
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Periradicular lesions are diseases either primarily or secondarily caused
by microorganisms.1-3 Microorganisms of probable pathogenic
significance in endodontic infections include Porphyromonas species,
Prevotella species, Fusobacterium nucleatum, species of the
Streptococcus anginosus group, Bacteroides forsythus, Treponema
denticola, Peptostreptococcus species, Eubacterium species,
and Actinomyces species.2,4-6 In addition, enterococci,
pseudomonas, yeasts, and some enteric rods may be involved in persistent
or secondary root canal infections7-9 (Figure 1).
Because of the critical role played by microorganisms in the pathogenesis
of periradicular lesions, endodontic therapy should be considered for
the clinical management of a microbial disease. Thus, it is extremely
important that clinicians understand the role of microorganisms in the
pathogenesis of periradicular lesions and be aware that they are treating
and/or preventing an infectious disease. Nonsurgical and surgical endodontic
techniques are unique tools to treat and/or prevent root canal infections.
Antimicrobial endodontic therapy is based on the premise that periradicular
diseases are infectious disorders. At a minimum, antimicrobial intracanal
procedures must be able to eradicate pathogenic microorganisms effectively.
As knowledge of the microorganisms implicated in the pathogenesis of periradicular
diseases and of the structure of the root canal microbiota increases,
clinicians will be able to incorporate more-effective antimicrobial strategies
as part of their armamentarium for optimum treatment. To date, from a
treatment point of view, root canal infections should be considered polymicrobial
and treated accordingly.
This paper outlines basic and current concepts of and practical approaches
to antimicrobial root canal therapy and attempts to relate current knowledge
to clinical protocol.
Root Canal Infection
As are all connective tissues, the dental pulp is a sterile tissue.
Contact with oral microorganisms is prevented by a barrier that consists
of enamel at the crown of the tooth and cementum at the root. In certain
conditions, such as caries, the pulp may come into contact with microorganisms
from the oral cavity and therefore be injured and become inflamed. If
pulp necrosis occurs as a consequence of injury, the pulp then loses its
defense capability. As a result, microorganisms colonize the root canal
system.
Most pulpal and periradicular pathoses are inflammatory diseases
of microbial etiology. Microorganisms and their products play an essential
role in the induction, progression, and perpetuation of such diseases.1-3
More than 150 microbial species have been isolated from infected root
canals, usually in mixed infections consisting of four to seven different
species and with predominance of obligate anaerobic bacteria.10
Whereas most of the endodontic microbiota remains suspended in the
fluid phase of the root canal,11 dense bacterial aggregates
also commonly adhere to the root canal walls, sometimes forming multilayered
bacterial condensations (Figure 2). In addition, particularly in
teeth associated with periradicular lesions, infection can propagate to
dentinal tubules and anatomic variables, which are more common in the
apical third of the root canal.
Given the importance of bacteria in the development of periradicular
lesions, the eradication of the root canal infection is paramount in endodontic
therapy. Studies have revealed that the success rate of the endodontic
treatment is significantly increased when the endodontic infection is
effectively eradicated before filling.12-14 In addition to
the eradication of the root canal infection, maintenance of the aseptic
chain also assumes special importance in root canal therapy. Treatment
must be undertaken in a sterile environment, thereby precluding the possibility
of new microorganisms entering the root canal system and establishing
a secondary infection. A rubber dam must be used, and it should not leak.
Efforts should also be made to effectively remove plaque and all vestiges
of caries, to decontaminate the operative field, to avoid touching with
fingers the parts of the sterilized endodontic instruments that will enter
the root canal, and always to use sterilized or self-sterilizing irrigant
solutions.10
Treating Infected Root Canals
Root canal infections possess some peculiarities that differentiate
them from infections in other human sites. Once established, a root canal
infection cannot be eliminated by the host defense mechanisms nor by systemic
antibiotic therapy. This is explained by the fact that microorganisms
present in root canal infections are in a privileged sanctuary, where
the absence of a blood supply in a necrotic pulp impedes the transport
of defense cells and molecules as well as systemically administrated antibiotics
to the infected site. On the other hand, although host defense mechanisms
and systemic antibiotics are ineffective against microorganisms within
the root canal system, if microorganisms gain access to the highly vascularized
periradicular tissues, they are usually effectively eliminated and thereby
prevented from spreading to other sites. Due to the anatomical localization
of the endodontic infection, it only can be treated through professional
intervention using both chemical and mechanical procedures. Thus, the
endodontic treatment involves three important steps to control of the
root canal infection: the chemomechanical preparation; the intracanal
medication; and the root canal obturation.10
Role of the Chemomechanical Preparation
The main root canal makes up the largest area of the root canal system.
Because most of the intracanal microorganisms and their products are located
in the main root canal, the chemomechanical preparation may be considered
an essential step in the root canal disinfection, once significant amounts
of irritants are removed during this phase.15-21 The removal
of irritants from the root canal is carried out through mechanical action
of instruments and the flow and backflow of the irrigant solution.15-18
In addition, antibacterial irrigants may be of significant help in eliminating
bacterial cells from the root canal system.19-21
Mechanical Action
Studies in which no antibacterial irrigants were used have reported
that the mechanical action of instrumentation and irrigation was effective
in significantly reducing the number of bacterial cells in the root canal.17,18
However, total elimination of bacteria was not observed in most of the
cases. Ingle and Zeldow22 have observed that immediately after
instrumentation, using sterile water as an irrigant, 80 percent of the
initially infected root canals yielded positive cultures. At the beginning
of the second appointment, 48 hours later, this number increased to 95.4
percent. Byström and Sundqvist,17 using physiologic saline
solution during instrumentation, found that bacteria persisted in about
half of the cases despite treatment on five successive occasions. Infection
persisted in those teeth with a high number of bacteria in the initial
sample. Siqueira et al.18 evaluated the reduction of the bacterial
population within root canals experimentally infected with E. faecalis
by the mechanical action of instrumentation using hand Nitiflex files
in alternate rotary motions, GT files, and Profile 0.06 taper Series 29
rotary instruments. Irrigation was performed using sterile saline solution.
All the techniques and instruments tested significantly reduced the number
of bacterial cells in the root canal. Instrumentation with a Nitiflex
#30 was significantly more effective than GT files. There were no significant
differences when comparing the effects of the Profile instrument #5 with
either the GT files or the Nitiflex #30. Enlargement to a Nitiflex #40
was significantly more effective in eliminating bacteria when compared
with the other techniques and instruments tested. The larger the apical
preparation, the higher the percentage of bacteria eliminated from the
root canal.
In clinical practice, the extent of instrumentation will depend on
the root dimension, the presence of curvatures, and the type of endodontic
instruments used. Hand and rotary nickel-titanium instruments can predictably
enlarge curved root canals, while maintaining the original path, to sizes
not routinely attainable with stainless steel files. Sufficient large
preparations can incorporate more anatomic irregularities and allow the
removal of a substantial amount of bacterial cells from the root canal.
In addition, instrumentation with larger file sizes can also result in
better irrigant exchange in the apical third of the root canal. Since
larger preparations remove more bacterial cells, a higher rate of treatment
success can be expected.
A higher success rate for endodontic treatment has been reported
for teeth instrumented with hand NiTi files when compared with teeth prepared
with hand stainless steel files.23 The authors observed that
NiTi file utilization was five times more likely to achieve success than
utilization of stainless-steel files.23 This probably occurred
because of the greater capability of NiTi files in maintaining the original
canal shape during instrumentation.
Thus, it appears that regardless of whether hand or rotary instruments
are used, it is more important how much the root canal is enlarged. NiTi
instruments allow the attainment of larger preparations in curved root
canals with reduced risks of procedural accidents. Because of this, they
should be the instruments of choice to prepare curved root canals. One
should bear in mind that enlargement must be restricted up to 1 mm short
of the root terminus. Although the apical foramen ideally should be cleaned,
disinfected, and maintained patent, it must not be enlarged, The clinician
should be aware of the risks in using large instruments at the patency
length, as this procedure can result in severe periradicular injury, cause
lack of an apical stop, and extrude a large amount of infected debris,
which can predispose the tooth to postoperative discomfort and/or jeopardize
the outcome of the endodontic therapy.10,13,24,25
Chemical Action
Although considerable bacterial reduction can be achieved by the
mechanical action of instruments and irrigants, microorganisms are rarely
completely eliminated from the root canals regardless of the instrumentation
technique and file sizes employed. Remaining pathogens may survive in
sufficient numbers to jeopardize the outcome of the root canal treatment.9,14,24,25
Therefore, it becomes evident that antibacterial irrigants must be used
to maximize bacterial elimination from the root canal. Stewart26
and Auerbach,27 in clinical investigations, reported negative
cultures in more than 70 percent of the initially infected root canals
after chemomechanical preparation using antibacterial irrigants. Siqueira
et al.21,28 found that irrigation with antibacterial irrigants
was significantly more effective than saline solution in rendering canals
free of bacteria.
During World War I, Dakin introduced the widespread use of a 0.5
percent to 0.6 percent sodium hypochlorite solution for antisepsis of
open and infected wounds.29 NaOCl was recommended as an endodontic
irrigant by Coolidge in 1919;30 and, in 1936, Walker introduced
the use of double-strength chlorinated soda (5 percent NaOCl) solution
as a root canal irrigant.31 NaOCl use as an irrigant in endodontic
practice has continued worldwide, and no study has hitherto definitively
shown any other substance to be more effective. NaOCl has tissue-dissolving
ability and a broad-spectrum antimicrobial activity; it can rapidly kill
vegetative bacteria, spore-forming bacteria, fungi, protozoa, viruses,
and bacterial spores.32-35
Siqueira et al.35 compared the antibacterial activity
of several irrigants against four black-pigmented anaerobic bacteria and
four facultative bacteria through the agar diffusion test. The antibacterial
effectiveness was ranked as follows, in decreasing order: 4 percent NaOCl;
2.5 percent NaOCl; 2 percent chlorhexidine; 0.2 percent chlorhexidine;
EDTA; citric acid; and 0.5 percent NaOCl. These laboratory findings also
confirmed that the antimicrobial effectiveness of NaOCl is directly dependent
on the concentration of the solution.
In another study, Siqueira et al.28 investigated the ability
of a 4 percent NaOCl solution used in different irrigation methods in
eliminating E. faecalis from the root canal. Regardless of the
irrigation method used, more than half of the teeth yielded negative cultures.
Conversely, all specimens irrigated with saline solution yielded positive
cultures. Although the mechanical effects of irrigation can significantly
contribute to the elimination of root canal bacteria, this finding confirmed
the need to use antimicrobial substances to maximize the root canal disinfection.
Siqueira et al.21 evaluated the in vitro intracanal bacterial
reduction produced by instrumentation and irrigation with 1 percent, 2.5
percent, or 5.25 percent NaOCl or saline solution. All test solutions
significantly reduced the number of bacterial cells in the root canal.
There was no significant difference between the three NaOCl solutions
tested. Nonetheless, all NaOCl solutions were significantly more effective
than saline solution in reducing the number of bacterial cells within
the root canal. This emphasized the importance of the chemical effects
together with the mechanical effects in eliminating intracanal bacteria.
Regular exchange and the use of large amounts of irrigant should maintain
the antibacterial effectiveness of the NaOCl solution, compensating for
the effects of concentration. The same observation was done by Baumgartner
and Cuenin36 when evaluating the tissue-dissolving ability
of NaOCl solutions.
Therefore, the use of an antimicrobial irrigant significantly contributes
to the elimination of microorganisms from the root canal. NaOCl remains
as the irrigant of choice in root canal therapy. Regardless of the concentration,
high volumes and frequent exchange are required for optimum antimicrobial
and tissue-dissolving capabilities.
Role of the Intracanal Medication
Although a considerable reduction in bacterial cell numbers within
the root canal can be achieved by the chemical and mechanical effects
of instrumentation and irrigation, viable bacteria can still be found
in at least half of the cases.17,19-21,28 Whilst minor anatomical
irregularities are usually incorporated into preparation, other areas
such as isthmuses, culs-de-sac, branches, and dentinal tubules can harbor
microorganisms. These areas are not commonly affected by the chemomechanical
preparation because of inherent physical limitations of instruments and
the short time the irrigants are present within the root canal (Figure
3).
In situ investigations have revealed that bacteria can infect dentinal
tubules to an extent ranging from 10 to 300
μm37-38 (Figure 4).
Bacterial cells penetrating up to approximately 200 to 300 μm are
unlikely to be eliminated by chemomechanical procedures. In such areas
of dentin infection, the root canal should be theoretically enlarged to
a diameter approximately 0.4 to 0.6 mm larger than the initial
diameter of the root canal in order to remove bacteria inside tubules.
This is practically impossible to accomplish in most cases, particularly
in the apical third of the root canal. In vitro studies have evaluated
the capacity of irrigants in eliminating bacterial cells within tubules
during varying periods.39,40 However, depths of disinfected
zones in dentin have been rarely reported. It is unknown to what extent
irrigants can reach antimicrobial effectiveness within dentin in in vivo
conditions.
In most cases, surviving bacteria within tubules are entombed by
the root canal filling and may have a drastically reduced substrate. In
such anatomical regions, bacteria entombed by the root filling usually
die or are prevented from gaining access to the periradicular tissues.
Even interred, some bacterial species are likely to survive for relatively
long periods, deriving residues of nutrients from tissue remnants and
dead cells.25 If the root canal filling fails in promoting
a fluid-tight seal, seepage of tissue fluids into the canal can provide
substrate for bacterial growth. If growing bacteria reach a significant
number and gain access to the periradicular tissues, they can perpetuate
inflammation.25 Thus, one might assume that persistent dentinal
infection has the potential to jeopardize the outcome of the endodontic
therapy and ideally should be eradicated before filling.
Histologic studies have shown that some root canal walls remain untouched
after chemomechanical preparation, regardless of the instrument type,
the instrumentation technique, and the irrigant used.16,41-43
Untouched areas may contain bacteria and necrotic tissue substrate even
though the root canal filling appears to be radiographically adequate.
If infected areas are not effectively isolated from the periradicular
tissues by a three-dimensional seal provided by the root canal filling,
microorganisms may maintain periradicular inflammation. The fact that
studies have reported the occurrence of viable microbial cells in treated
teeth with a persistent periradicular lesion indicates that microorganisms
derive nutrition from tissue fluid, which can seep into the root canal
space.9
Studies have revealed that the success rate of endodontic treatment
is increased if the root canal is free from microorganisms at the time
of obturation.12-14 Since microorganisms are the major etiological
agents of periradicular diseases, their presence in the root canal system
at the time of root canal filling jeopardizes the outcome of the treatment.
Therefore, all efforts should be directed toward the thorough elimination
of microorganisms.
Inherent physical limitations impede action of the instruments in
areas beyond the main root canal. Irrigants remain for a short time in
the root canal to eliminate microorganisms located in such areas, and
the faster the instrumentation technique the lesser the time of irrigant
presence within the root canal. Thus, the effects of the chemomechanical
preparation are restricted to the main root canal. By remaining for a
longer time in the canal than irrigants, antimicrobial intracanal medicaments
have a higher probability to reach microorganisms located in areas unaffected
by the chemomechanical preparation and thereby help in disinfection of
the entire root canal system.
One-Visit Versus Two-Visit Treatment
One-visit endodontic treatment offers some potential advantages to
both the dentist and patient. In addition to being faster and well-accepted
by patients, it prevents the contamination or recontamination of the root
canal system between appointments. In cases of vital pulp, treatment ideally
should be finished in one session provided that the time available, operator’s
skills and anatomical conditions are all favorable. On the other hand,
treatment in one session of necrotic pulps whether associated with a periradicular
lesion or not is still a controversial issue in endodontics.
Despite anecdotal evidence supporting endodontic therapy in a single
visit, two factors must be taken into account before deciding upon a one-visit
treatment of teeth with necrotic pulp: the incidence of postoperative
pain and the long-term outcome of the treatment. Studies have found no
difference in the incidence of postoperative pain between one- and multiple-visit
endodontics.44-46 As consequence, the outcome of the endodontic
treatment should be the major factor taken into account when deciding
the number of therapy sessions.
There is a paucity of studies comparing the success rate of the endodontic
therapy performed in one or more sessions. Most of these few studies have
been based on poorly defined criteria of evaluation. The most common flaws
include short-term follow-up, no differentiation between pathological
conditions (vital or necrotic pulps, presence of periradicular bone destruction,
etc.), nonstandardized intracanal procedures, multiple operators with
obvious divergent skills, retrospective evaluation, and loose criteria
in determining success and failure.
Pekruhn46 published one of the largest studies on single-visit
treatment results. His study used a one-year follow-up period, and the
inclusion criteria was undefined. Many cases were treated in two visits.
There were significantly fewer failures in the two-visit treatment group
than in the one-visit treatment group, regardless of the pretreatment
diagnosis.
A few studies have presented clearly defined criteria. In a very
well-controlled clinical study, Sjögren et al.14 investigated
the role of infection in the outcome of one-visit treatment after a follow-up
period of five years. All followed-up teeth (n = 53) showed infected
pulps before treatment. The irrigant solution used was 0.5 percent NaOCl.
Although it is considered a weak solution, it has not been demonstrated
to be clinically less effective than 5 percent NaOCl in eliminating intracanal
microorganisms.19,20 Forty-four cases were successful (83 percent).
Of the nine failed root canals, seven yielded positive culture before
filling. Slight overfilling appeared to have no influence on the outcome
because all 10 overfilled teeth were successful. The remaining 43 cases
were obturated within 2 mm of the apex. These findings can be directly
compared to others of the same research group.13 Success was
reported for 94 percent of the infected root canals associated with periradicular
lesions treated in multiple visits when the root canals were filled within
2 mm from the root apex (the same conditions of the one-visit study).
Thus, a difference of 11 percent could be detected between single- and
multivisit treatment.
In another well-controlled clinical study, Trope et al.47
evaluated radiographic healing of teeth with periradicular lesions treated
in one or two visits. All patients were treated by the same operator.
Instrumentation was standardized with 2.5 percent NaOCl used as irrigant.
All teeth were obturated with lateral condensation of gutta-percha and
Roth 801 sealer. In the two-visit group, root canals were medicated with
calcium hydroxide for at least one week. After a one-year follow-up evaluation,
the additional disinfecting action of calcium hydroxide resulted in a
10 percent increase in healing rates. This difference should be considered
clinically important.47
Katebzadeh et al.48,49 radiographically and histologically
compared periradicular repair after endodontic treatment of infected root
canals of dogs performed in one or two sessions. They reported better
results for the two-visit treatment in which calcium hydroxide was used
as an intracanal disinfecting medicament for one week.
Microorganisms can survive the effects of chemomechanical preparation
in 40 percent to 70 percent of the cases.17,19-21,28 Most of
the surviving microorganisms die either by the antimicrobial action of
root canal filling material or by the absence of available nutrients in
a filled root canal. Nonetheless, in certain cases, microorganisms can
survive even in a well-filled root canal, acquiring nutrients and reaching
sufficient numbers to perpetuate a periradicular lesion.
Perpetuation of a periradicular lesion caused by a persistent root
canal infection will depend on (a) the access of remaining microorganisms
to the periradicular tissues; (b) the ability of residual microorganisms
to survive in an environment with low nutrient availability; (c) the virulence;
(d) the number of the surviving microorganisms; and e) the host resistance.10
Therefore, overwhelming scientific evidence indicates that microorganisms
can survive the effects of chemomechanical preparation in at least a half
of the cases; and microorganisms are the major causative factors of the
endodontic failure, even in well-treated cases. Because remaining microorganisms
jeopardize the long-term outcome of the endodontic treatment, additional
measures should be taken to predictably eradicate the root canal infection.
To date, the support of an interappointment antimicrobial dressing is
necessary to accomplish such an objective.
In cases of vital pulp, a single-visit treatment should be used whenever
possible. This is based on the fact that the pulp is only superficially
infected and the root canal is free of bacteria, provided the aseptic
chain is maintained during the intracanal procedures. Therefore, there
is no apparent reason not to treat vital pulps in a single visit.
On the other hand, if the pulp is necrotic and associated with a
periradicular disease, there is ample evidence that the root canal system
is infected. In these cases, the root canal ideally should be cleaned
and shaped, an intracanal medication placed, and the canal filled in a
second appointment. These procedures, as previously mentioned, are based
on scientific evidence and not merely suppositions.
It is obvious that in the future, the single-visit treatment will
become a suitable choice for treating infected teeth also. Ongoing research
has the potential to discover measures that will enable dentists to treat
infected root canals in one session predictably. However, the current
treatment that offers a significantly higher success rate is accomplished
in two or more sessions and, for this reason, should be the only choice
for the treatment of infected root canals at this time.
Intracanal Medicaments
Since its introduction by B.W. Hermann,50 a German dentist,
in 1920, calcium hydroxide has been widely used in endodontics. It is
a strong alkaline substance with a pH of approximately 12.5. Currently,
this chemical substance is acknowledged as one of the most important antimicrobial
dressings used during endodontic therapy.
Most endodontopathogens are unable to survive in a highly alkaline
environment such as that of calcium hydroxide, therefore several bacterial
species commonly found in infected root canals are eliminated after a
short period when in direct contact with this substance.51
The antimicrobial activity of calcium hydroxide is related to the
release of hydroxyl ions in an aqueous environment. Hydroxyl ions are
highly oxidant free radicals that show extreme reactivity, reacting with
several biomolecules. This reactivity is high and indiscriminate, so this
free radical rarely diffuses away from sites of generation. Their lethal
effects on bacterial cells are probably due to the following mechanisms:
Damage to the bacterial cytoplasmic membrane. Hydroxyl ions
from calcium hydroxide can induce lipid peroxidation, resulting in the
destruction of phospholipids, structural components of the cellular membrane.
Hydroxyl ions remove hydrogen atoms from unsaturated fatty acids, generating
a free lipidic radical. This free lipidic radical reacts with oxygen,
resulting in the formation of a lipidic peroxide radical, which removes
another hydrogen atom from a second fatty acid, generating another lipidic
peroxide. Thus, peroxides themselves act as free radicals, initiating
an autocatalytic chain reaction, and resulting in further loss of unsaturated
fatty acids and extensive membrane damage.52
Protein denaturation. Alkalinization provided by calcium hydroxide
can induce the breakdown of ionic bonds that maintain the tertiary structure
of proteins. As a consequence, the enzyme maintains its covalent structure;
but the polypeptide chain is randomly unraveled in variable and irregular
spatial conformation. These changes frequently result in the loss of biological
activity of the enzyme and disruption of the cellular metabolism. Structural
proteins may also be damaged by hydroxyl ions.
Damage to the DNA. Hydroxyl ions react with the bacterial
DNA and induce the splitting of the strands. Genes are then lost.53
Consequently, DNA replication is inhibited, and the cellular activity
is disarranged. Free radicals may also induce lethal mutations.
Several studies have demonstrated that calcium hydroxide exerts lethal
effects on bacterial cells.51,54,55 Optimum effects were observed
when the substance was in direct contact with bacteria in solution. In
such conditions, the concentration of hydroxyl ions is very high, reaching
incompatible levels to bacterial survival. Clinically, this direct contact
is not always possible.
Although hydroxyl ions possess antibacterial effects, rather high
pH values are required to destroy microorganisms. Killing of bacteria
by calcium hydroxide will depend on the availability of hydroxyl ions
in solution, which is higher where the paste is applied (the main root
canal). Calcium hydroxide exerts antibacterial effects in the root canal
as long as they retain a very high pH. If calcium hydroxide needs to diffuse
to tissues and the hydroxyl concentration is decreased as result of the
action of buffering systems (bicarbonate and phosphate), acids, proteins,
and carbon dioxide, its antibacterial effectiveness may be reduced or
impeded.56
Bacteria inside dentinal tubules may constitute an important reservoir
from which root canal infection or reinfection may occur during and after
endodontic treatment. As previously mentioned, remaining microorganisms
may cause a persistent infection that puts the outcome of the endodontic
therapy at risk. Bacteria inside dentinal tubules are protected from the
effects of host defense cells and molecules, systemically administered
antibiotics, and chemomechanical preparation. Therefore, treatment strategies
that are directed toward the elimination of tubule infection are necessary
and must include medicaments that penetrate dentinal tubules and kill
microorganisms.
After a short-term intracanal dressing with calcium hydroxide, pH
levels reached in dentine may still allow the survival or growth of some
microbial strains. Microorganisms vary in their pH tolerance ranges, and
most human pathogens grow well within a range of 5 to 9 pH.57
Some strains of Escherichia coli, Proteus vulgaris, Enterobacter aerogenes
and Pseudomonas aeruginosa can survive in pH 8 or 9.58
These bacterial species have occasionally been isolated from infected
root canals, usually causing secondary infections.7 Certain
bacteria, such as some enterococci, tolerate very high pH values, varying
from 9 to 11. Fungi generally also exhibit a wide pH range, growing within
a range of 5 to 9 pH.58 It has been demonstrated that enterococci
and fungi are highly resistant to calcium hydroxide.51,59 Since
these microorganisms are commonly found in cases of endodontic failure,
the routine use of calcium hydroxide should be questioned.
The ability of a medicament to dissolve and diffuse in the root canal
system would seem essential for its successful action. A saturated aqueous
suspension of calcium hydroxide possesses a high pH, which has a great
cytotoxic potential. Nevertheless, this substance owes its biocompatibility
to its low water solubility and diffusibility. Because of these properties,
cytotoxicity is limited to the tissue area in direct contact with calcium
hydroxide. On the other hand, the low solubility and diffusibility of
calcium hydroxide may make it difficult to reach a rapid and significant
increase in the pH to eliminate bacteria within dentinal tubules and enclosed
in anatomical variations. Likewise, the tissue buffering ability controls
pH changes. Because of these factors, calcium hydroxide is a slowly working
antiseptic. Prolonged exposure may allow for saturation of the dentine
and tissue remnants. The long-term use of calcium hydroxide may be necessary
to obtain a bacteria-free root canal system.56 However, in
most instances, the routine use of an intracanal medication for a long
period does not seem to be an acceptable practice in modern endodontics.
Although clinical studies have revealed that the treatment using
calcium hydroxide as intracanal dressing showed higher success rates when
compared with single-visit treatment, the search for more-effective medicaments
or combinations should not necessarily stop. This statement is based on
the following facts: Living microorganisms still remain in approximately
20 percent of the previously infected canals after one week of medication
with calcium hydroxide;60-62 and some microorganisms associated
with endodontic failures are intrinsically resistant to calcium hydroxide.
Endodontic infections are polymicrobial, and no known medicament is effective
against all the bacteria found in infected root canals. In addition, the
medicament should ideally reach microorganisms located in distant areas
of the root canal system in lethal concentrations. Combination of two
medicaments may produce additive or synergistic effects. Recently, renewed
interest has been generated regarding the association of calcium hydroxide
with other antimicrobial substances, such as camphorated paramonochlorophenol
(CPMC), chlorhexidine, or iodine potassium iodide (IPI). Laboratory studies
have shown that these substances significantly increase the antimicrobial
spectrum of calcium hydroxide.63-66
Evidence suggests that the association of calcium hydroxide with
CPMC has a broader antibacterial spectrum, has a higher radius of antibacterial
action, and kill bacteria faster than mixtures of calcium hydroxide with
inert vehicles (water, saline, glycerin).56,63-65,67 Although
CPMC has strong cytotoxic activities,68 studies have reported
a favorable tissue response to calcium hydroxide/CPMC mixture.69,70
This association probably owes its biocompatibility to:
* The small concentration of released paramonochlorophenol (PMC).
Calcium hydroxide plus CPMC yields calcium paramonochlorophenolate, which
is a weak salt that progressively releases PMC and hydroxyl ions to the
surrounding medium.71 It is well-known that a substance may
have either beneficial or deleterious effects, depending on its concentration.
The low release of PMC from the paste might not be sufficient to have
cytotoxic effects;
* The denaturing effect of calcium hydroxide on connective tissue,
which may prevent the tissue penetration of PMC, reducing its toxicity;56
* The fact that the effect on periradicular tissues is probably associated
with the antimicrobial effect of the paste, which allows natural healing
to occur without persistent infectious irritation. If the wound area is
free of bacteria when the transitory chemical irritation occurs, there
is no reason to believe that tissue repair would not take place as the
initial chemical irritant decreases in intensity.56
Therefore, the use of an antimicrobial intracanal dressing can significantly
contribute to the eradication of the root canal infection. Logically,
not all antimicrobial substances used as intracanal medication exert such
desirable effects. Calcium hydroxide has yet to be tried by time and scientific
assessment. It is not a panacea. Besides not being effective against all
microorganisms present in the root canal infection, after a short exposure
calcium hydroxide may not reach microorganisms located beyond the main
root canal in lethal concentrations. Association of calcium hydroxide
with other antimicrobial substances, such as CPMC, IPI, and chlorhexidine,
has the potential to optimize the antimicrobial effectiveness of the intracanal
medication.
Role of the Root Canal Obturation
Most endodontic sealers show antimicrobial activity before setting,
but most of them also lose this ability after setting. Because antimicrobial
activity of most sealers is not pronounced and is usually ephemeral,72-74
it is highly unlikely that sealers will be of significant assistance in
killing microorganisms that survived the effects of the chemomechanical
preparation and the intracanal medicament (if used).
In reality, cleaned and shaped root canals must be three-dimensionally
filled, eliminating the empty space, which has the potential to be infected
or reinfected. In addition, by creating a fluid-tight apical, lateral,
and coronal seal, root canal fillings may confine residual irritants within
the root canal system, impeding their egress to the periradicular tissues.
A fluid-tight seal of the root canal system also prevents both the coronal
recontamination by saliva and the seeping of periradicular tissue fluids
into the root canal, denying nutrient supply to remaining microorganisms.
Therefore, the critical function of the root canal obturation is preventive,
essentially acting as a barrier to infection or reinfection of both the
root canal system and the periradicular tissues.
The root canal system often possesses a complex anatomy, including
fins, culs-de-sac, isthmi, ramifications, and other irregularities. It
has been claimed that many of these areas are difficult to fill using
conventional techniques, such as the lateral condensation technique. Thermoplasticized
gutta-percha techniques have been advocated for root canal obturation
as they can provide a more homogenous mass of obturation and a better
filling of root canal intricacies when compared with the traditional lateral
condensation technique.75,76 Theoretically, such properties
might favor the attainment of an impervious coronal and apical seal of
the root canal system.
Nonetheless, numerous studies have shown that neither contemporary
root canal obturation techniques nor available filling materials can provide
an impervious seal to leakage.77-80 To date, no well-controlled
clinical study has demonstrated that thermoplasticized gutta-percha techniques
provide more favorable treatment outcomes than traditional lateral condensation
technique. Further, one should bear in mind that apparently moving gutta-percha
or sealer or both into all anatomic variations does not necessarily mean
that the root canal system was appropriately cleaned, disinfected, and
sealed.
Antibiotics
The purpose of antibiotic therapy is to aid the host defenses in
controlling and eliminating microorganisms that have temporarily overwhelmed
the host defense mechanisms.81 The most important decision
in antibiotic therapy is not so much which antibiotic should be employed
but whether antibiotics should be used at all.
The vast majority of infections of endodontic origin can be treated
without antibiotics. Due to the absence of blood circulation within a
necrotic and infected pulp, antibiotics cannot reach and eliminate microorganisms
present in the root canal system. Thus, the source of infection is unaffected
by systemic antibiotic therapy. On the other hand, antibiotics can help
impede the spread of the infection and the development of secondary infections
in compromised patients. Therefore, antibiotic therapy can be a valuable
adjunct for the management of some cases of endodontic infection. The
rare occasions in which antibiotics are indicated in endodontics include:
* Acute periradicular abscesses associated with systemic involvement,
such as fever, malaise, and lymphadenopathy;
* Spreading infections resulting in cellulitis, progressive diffuse
swelling and/or unexplained trismus (Figure 5);
* Acute periradicular abscesses (even with localized swelling) in
medically compromised patients who are at increased risk of a secondary
infection at a distant site following a bacteremia;
* Prophylaxis for medically compromised patients during routine endodontic
therapy;
* Some cases of persistent exudation not resolved after revision
of intracanal procedures; and
* Replantation of avulsed teeth.
Acute periradicular abscesses in healthy patients without systemic
involvement and characterized by localized swelling do not require antibiotic
therapy.
Patients under antibiotic therapy must be monitored daily. The best
practical guide for determining the duration of antibiotic therapy is
clinical improvement of the patient. When clinical evidence indicates
that the infection is certain to resolve or is resolved, antibiotics should
be administrated for no longer than one or two additional days.
Antibiotic treatment of infections of endodontic origins is initiated
based on the knowledge of the most likely pathogens. Amoxicillin, a broad-spectrum
semisynthetic penicillin, is the antibiotic of first choice for such infections.
Most of the root canal microbiota is susceptible to amoxicillin.82
In patients allergic to penicillins or in cases resistant to amoxicillin
therapy, clindamycin is indicated. The risk/benefit ratio should be always
considered before administration of systemic antibiotic therapy.
Laser Irradiation of Infected Root Canals
A laser that transforms light of various frequencies into a chromatic
radiation in the visible, infrared, and ultraviolet regions with all the
waves in phase capable of mobilizing immense heat and power when focused
at close range.83 Many kinds of laser devices have been used
in dentistry. Among potential applications in endodontics, lasers have
been tested for efficacy in disinfecting root canals. All lasers have
an antimicrobial effect at high power that varies with the type of laser.
The Nd-YAG laser has been studied the most because its laser energy and
laser fiber can be easily controlled. Although promising results have
been reported in vitro,84,85 root canal disinfection
can be problematical in narrow curved canals and because of the possible
thermal injury to periodontal tissues. In addition, laser devices are
still relatively costly. Future research will help to define optimal laser
parameters for safe and effective disinfection of root canals.
Clinical Protocol Based on an Antimicrobial Strategy
Diligent antimicrobial therapy should focus upon employing well-tolerated
antimicrobial agents exhibiting effectiveness against the most prevalent
microorganisms involved in primary and persistent root canal infections.
Moreover, the antimicrobial endodontic therapy should be able to eliminate
microorganisms present not only in the main root canal, but also in all
variations of the root canal system. The following protocol to routinely
treat infected root canals is based on both scientific evidence and clinical
experience (Figures 6 and 7):
1. The tooth to be treated must be free of plaque and calculus.
2. Preparation of the access cavity can be initiated before the application
of a rubber dam but cannot be concluded until after its placement. All
carious tissue must be removed.
3. After rubber dam placement, the operative field must be cleaned
with hydrogen peroxide and disinfected with iodine solution, chlorhexidine,
or sodium hypochlorite solution.
4. After completion of access preparations, the pulp chamber must
be copiously irrigated with a 2.5 percent NaOCl solution.
5. Chemomechanical preparation should be performed using a crown-down
technique, with hand and/or rotary instruments and at least 1 to 2 ml
of 2.5 percent NaOCl after each file size. NiTi instruments should be
used in curved root canals. The root canal should be enlarged to 1 mm
short of the apex. Overinstrumentation is undesirable as it can predispose
the tooth to both postoperative symptomatology and treatment failure.
However, the 1 mm apical segment ideally should be cleaned and maintained
free of debris by using small size patency files.
6. After smear layer removal, the root canal is medicated with a
calcium hydroxide/CPMC/glycerin paste. The paste is prepared on a glass
slab, using equal proportions of CPMC and glycerin (1:1, v:v). The two
liquids are mixed and then calcium hydroxide is slowly added until a creamy
consistency is reached. The paste ideally is applied in the canal using
lentulo spirals.
7. The tooth is radiographed to check the proper placement of the
intracanal medication, and a temporarily coronal material is applied.
8. In the second appointment, three to seven days later, the paste
is removed using files under copious irrigation with 2.5 percent NaOCl
and the root canal obturated.
Outline of Strategies to Treat Root Canal Infections
1. Periradicular lesions are diseases of infectious origin and therefore
must be prevented or treated accordingly;
2. Maintenance of the aseptic chain is as important as disinfection
of the root canal for the outcome of root canal therapy. In other words,
from a microbiological point of view, what one removes from the root canal
is as important as what one places into it.
3. Root canal therapy in vital pulp cases ideally should be concluded
in a single visit.
4. It is essential to disrupt the microbial communities within root
canals by mechanical means (root canal instrumentation) with sodium hypochlorite
irrigation.
5. Antimicrobial dressings are valuable adjuncts to predictably eliminate
microorganisms from the root canal system. The smear layer should be removed
to facilitate diffusion of the medicaments into dentinal tubules.
6. Two-visit endodontic treatment using calcium hydroxide dressing
results in a higher success rate than a single-visit treatment. The success
rate of treatment may even be increased if an intracanal medicament or
a combination of medicaments (such as calcium hydroxide plus CPMC) with
a broader antimicrobial spectrum and a higher radius of action is used.
7. Root canal obturation assumes a special relevance in perpetuating
the status of root canal disinfection obtained after both chemomechanical
preparation and intracanal medication.
8. Antibiotics are never a substitute for either drainage procedures
or proper endodontic therapy. Thus, antibiotics are not used to treat
root canal infections, but mainly to prevent their spreading. Clinicians
should be aware of the risk/benefit ratio before indicating systemic antibiotic
therapy.
Acknowledgments
The author is very grateful to Drs. Isabela N. Rôças,
Hélio P. Lopes and Milton de Uzeda, and Mr. Fernando A. C. Magalhães
for their valuable support in the preparation of this manuscript.
This study was supported in part by grants from CNPq, a Brazilian
Governmental Institution.
Author
José F. Siqueira, Jr., DDS, MSc, PhD, is a professor and chairman
of the Department of Endodontics at the School of Dentistry, Estácio
de Sá University, Rio de Janeiro, RJ, Brazil.
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To request a printed copy of this article, please contact/José
F. Siqueira, Jr., Rua Herotides de Oliveira 61/601, Icaraí, Niterói,
RJ, CEP: 24230-230, or siqueira@estacio.br.
Legends

Figure 1. Fungi cells colonizing the dentinal walls in the middle
third of the root canal (original magnification 2,100x). Although fungi
are occasionally found in primary root canal infections, they have been
associated with several cases of persistent infections.
Figure 2. Dense mixed bacterial population colonizing the root
canal walls (original magnification 3,300x).

Figure 3. Tissue remnants in root canal irregularities after chemomechanical
preparation using 5.25 percent NaOCl as irrigant.
Figure 4. Bacterial cells invading dentinal tubules (original
magnification 1,900x). Efforts should be also directed toward their elimination.

Figure 5. Spreading root canal infection resulting in cellulitis.
Systemic antibiotic therapy is indicated in cases such as this (courtesy
of Dr. Henrique Martins).
Figure 6. Treatment in two sessions of a tooth associated with
periradicular lesion and showing apical root resorption. A. Preoperative,
and B. follow-up radiograph after seven months showing repair of
the lesion and stopping of the root resorption process.
Figure 7. Treatment in two sessions of a tooth associated with
extensive periradicular bone destruction. A. Preoperative, and
B. follow-up radiograph showing bone repair of the lesion (courtesy
of Dr. Luis Paulo Mussi).
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