Medicaments: Aids to success in endodontics.

Part 1
A review of the literature
Paul V. Abbott, BDSc(WA), MDS(Adel), FRACDS(Endo)*

Key words: Endodontics, medicaments. The role of bacteria

The role of bacteria in pulpal and periapical
Abstract disease has been well researched in animals. Kake-
Bacteria play a major role in pulpal and periapical hashi and co-workers demonstrated in two studies',z
disease. They are capable of surviving in dentinal that pulps which were exposed to the oral environ-
tubules and other canal ramifications that are inac- ment in germ-free rats were capable of healing
cessible to mechanical instrumentation and whereas bacterially-contaminated pulps displayed
irrigation. In order to predictably achieve bacteria- degeneration. A recent series of report^^-^ (also on
free root canal systems, especially in pulpless teeth, germ-free rat pulps) confirmed the ability of pulps
it is necessary to use intra-canal medicaments. to heal if there was no contamination from bacteria.
These medicaments must be capable of destroying In general, there was a lack of inflammation and
bacteria, reducing inflammation and stimulating dentine bridges formed. However in the contamin-
hard tissue formation whilst not being toxic to the ated animals the responses included inflammation,
host tissues. Consideration of a material's pulp necrosis and lack of dentine bridge formation.
therapeutic action must be made when selecting a Inflammation in the periapical tisses of rats has also
medicament for any pathologicalcondition. Many of been shown to be directly related to bacterial inva-
the commercial preparations do not satisfy the sion of the root canal.'
requirements for the ideal root canal medicament.
In 1976, a comprehensive study of necrotic
(Received for publication March 1989. Revised
human dental pulps by Sundqvist' demonstrated
December 7989.Accepted January 1990.)
that all cases with a periapical radiolucent lesion
had microbes in the root canal system and there
Introduction were always between two and twelve strains of
bacteria present. A correlation was shown to exist
Endodontic treatment is most commonly between the number of strains present and cases
performed on teeth because the pulp or the peri- with acute periapical inflammation. In addition,
apical tissues or both are either inflamed and/or patients with pain had more than six strains and
infected. The most common cause of pulpal and those with large periapical lesions had more strains
periapical inflammation is infection. One of the than cases with smaller lesions. 'Flare-up' cases
primary goals of endodontic therapy must be to showed a correlation with the presence of a specific
eliminate bacteria from the root canal system. This organism, Bacteroides melaninogenicus.
can be achieved by a combination of mechanical
debridement and chemotherapy. The role of bacteria in periapical disease was
further demonstrated in monkeys by Moller et al.9
and Fabricius et a1." In these experiments teeth
were aseptically devitalized by pulp amputation one
Based on a lecture presented at the Australian Dental Association to two millimetres from the apex with a Hedstrom
25th Congress, Sydney, 15-20 May 1988.
*Visiting Lecturer in Endodontics, The University of Western
file. Some teeth were immediately closed and others
Australia; Visiting Consultant Endodontist, Perth Dental were left open to the oral cavity for seven days and
Hospital, Western Australia. then sealed. Histological analysis revealed that no

438 Australian Dental Journal 1990;35(5):438-48.

 Fig. la, b.-The complex nature of root canal systems is demonstrated by these two lower second molar teeth. Both specimens
show numerous transverse anastomoses, fins, accessory canals and apical deltas. (Photo courtesy of Dr Stephen Manning).
Fig. 2.-a, Periapical radiograph of a completed root canal filling on a lower left first molar. The root canal sealer has penetrated
several areas of canal irregularities including a large fin in the distal root and some smaller fins in both roots. b, Periapical
radiograph of a lower right first molar tooth taken with a slight mesial tube shift demonstrates root canal sealer in an interconnecting
area (fin) between the two mesial canals.

inflammatory reactions occurred in the periapical Bacteria can exist within the root canal itself or
regions of the control teeth with negative cultures within the dentinal t u b u l e ~ . ' ~Other
- ' ~ areas of the
except in two cases where the canals had been over- tooth root that may harbour bacteria include acces-
instrumented. All of the infected teeth had inflam- sory canals, canal ramifications, apical deltas, fins
mation in the periapical regions consisting mainly and transverse anastomoses - these entities have
of acute reactions with polymorphonuclear leuco- been demonstrated by several investigators.
cytes, lymphocytes and plasma cells. Bone and root Figure 1 demonstrates some of the complex canal
anatomy found in mandibular second molars and
resorption were also common in the infected cases.
Fig. 2 shows some canal irregularities observed
Many types of bacteria have been reported as radiographically after placing root canal fillings.
being involved in pulpal and periapical diseases. Of Such irregularities appear to be more common in
particular note is the high incidence of anaerobic the middle third of the r00t.l~
bacteria - reports range from 80 per cent" to 93
per centa2of the cultured bacteria. A review of the Effect of irrigation and instrumentation
types of bacteria implicated in pulpal and periapical Although thorough mechanical debridement is of
diseases has been presented re~ent1y.l~ the utmost importance to endodontic therapy, mech-

Australian Dental Journal 1990;35:5. 439

anical instrumentation alone is unable to remove 3 . Induce healing of calcified tissues.
all of the bacteria from within a root canal system.z2 4. Help eliminate apical exudate.
Bystrom and SundqvistZ3 demonstrated that 5. Control inflammatory root resorption.
mechanical instrumentation reduced bacterial
numbers in human root canals from an initial count 6. Prevent contamination between appointments.
of 104-106cells to a count of 10z-103cells. These Several studies have shown that when intra-canal
authors concluded that, in order to predictably medicaments were not used between appointments,
eliminate bacteria from root canals, the supporting bacterial numbers rapidly i n c r e a ~ e d . " ~ ' ~ ~ ~ ~
action of disinfecting agents was also required. Several authors have stressed the importance of
A subsequent study by the same groupz4demon- using intra-canal medicaments in order to achieve
strated that irrigating solutions must do more than bacteria-free canals in a predictable manner.1z.z8.29
Langelandi7 has stated that if necrosis is established
just flush the canal - they concluded that the irri-
in the root canal, then the success and long-term
gants should also have some antibacterial action.
Sodium hypochlorite (NaOCl) when used sequen- prognosis will depend upon the elimination of
tially with ethylenediamine tetra-acetic acid bacteria from the dentinal tubules. He stated that
this precludes a one-visit technique and supports
(EDTA) was shown to have a more efficient anti-
bacterial activity than when NaOCl was used alone. the use of intra-canal medicaments. Medicaments
placed in the root canal space have been shown to
The ability of several irrigating solutions to add to the efficacy of the treatment of periapical
physically clean the root canal walls when used infection^.^^.^'
during mechanical instrumentation has been inves-
Some medicaments can be used in root canals to
tigated with a scanning electron micro~cope.~~ This
prevent or reduce the incidence of pain following
study demonstrated that, when used alone, neither
initial canal deb~idement.~'.~' Thus they have an
NaOCl nor EDTA was totally effective in removing
anodyne effect which is achieved largely through
debris. However, when the two solutions were used
the actions of anti-inflammatory agents such as
sequentially the canal walls were left free of debris.
corticosteroids that are employed in some
The combination of these solutions was an effec-
medicaments.
tive means of removing both organic and inorganic
matter from the root canal. The smear layer was Peri-radicular tissue repair can be encouraged by
completely removed from the canal walls which left the use of intra-canal medicaments - the medica-
the dentinal tubules open. ments are placed within the root canal and their
purpose is to create an environment that is
A further in viva studyz6has shown that using
conducive to bone and/or cementa1 r e ~ a i r . ~ O , ~ l
both 15 per cent EDTAC (EDTA plus cetrimide)
Medicaments can exert their influence on the peri-
and 1 per cent NaOCl significantly increased the
radicular structures via diffusion of the active
permeability of the root dentine to endodontic
components through the root dentine and the apical
medicaments. Increasing the dentine permeability
foramen.33A suitable environment may be achieved
increases the access of medicaments to the bacteria
by destroying the bacteria (for example, with anti-
that may be present in areas of the canal system that
biotics or antiseptics) or by changing the pH (for
are inaccessible to mechanical instrumentation and
example, with calcium hydroxide).
irrigation.
In essence, medicaments are used as an aid to
These reports support the combined use of two
improve the prognosis of endodontic treatment and
irrigating solutions, NaOCl and EDTAC, during
to improve patient comfort. The inter-appointment
mechanical instrumentation to flush the canal
period is an ideal opportunity to influence tissue
system, destroy bacteria, dissolve organic and in-
reactions prior to the final sealing of the root canal
organic debris, remove the smear layer and increase
system. Some pathological conditions are ideally
dentine permeability. These properties help to
treated over several appointments which may be
achieve clean, bacteria-free root canal systems prior
extended over a long period of time - this extended
to placing a root canal filling.
treatment time permits the use of various medica-
ments that can be chosen according to the status
W h y use medicaments? of the pulp, the periapical tissues, the hard dental
Medicaments may be utilized in endodontic tissues and the apical foramen.
therapyz7in order to:
1. Help eliminate bacteria. Properties of the ideal medicament
2. Reduce inflammation (and thereby reduce The ideal root canal medicament should have the
pain). following properties:

440 Australian Dental Journal 1990;35:5.

 1. Anti-bacterial. Materials within this group have been reported to
2. Anti-inflammatory. be c y t o t o x i ~ , 3to
~ -cause
~ ~ periapical i r ~ i t a t i o n ~ ~ . ~ ~ . ~ ’
3. Ability to stimulate hard tissue repair. and to have systemic Some commer-
cially available preparations contain a corticosteroid
4. Ability to prevent or reduce pain. in addition to the toxic antiseptic agent (for
5. Non-irritant to the periapical and periodontal example, Cresophene). The corticosteroid is utilized
tissues. to counteract the toxic and irritation effects of the
6. Ability to diffuse through dentine. parachlorophenol. However this combination of
7. Quick acting initially. drugs is considered to be undesirable since it is illog-
8. Long lasting. ical to cause inflammation with one substance and
to treat it concurrently with another agent in the
9. Effective in the presence of pus and organic
same preparation. In addition, this type of material
debris.
is unlikely to satisfy several of the requirements for
10. Water soluble. an ideal medicament.
11. Practical to use (easy to place and remove). Some of these materials, for example formocresol,
12. Non-staining to the tooth and soft tissues. have been shown to be mutagenic and carcino-
13. Inexpensive. g e n i ~ . ’ ~Despite
- ~ ~ having enjoyed popularity in the
14. A long shelf-life. past there is now considerable evidence to support
At present there is no single medicament with all the recommendation that these materials should not
of these properties. Therefore, it is necessary to be used in en do don tic^.'^
have more than one root canal medicament avail- The antibacterial action of the antiseptic-
able - this will enable the clinician to choose the containing medicaments is limited28~55-58 and of
appropriate medicament for the condition being short duration. Therefore their efficacy as root canal
treated. medicaments must be questionable.
The majority of the above antiseptic preparations
Materials used as medicaments are used as root canal medicaments by placing a
Many materials have been used as root canal small amount of the liquid on a cotton pellet. The
medicaments throughout the past century. These pellet is then squeezed dry and placed in the pulp
materials can be placed in two groups: those chamber. These materials are quite volatile and the
containing antiseptics and those containing anti- rationale for their use is that the gases diffuse
biotics. Many of these agents contain a number of throughout the root canal system between appoint-
therapeutic or active components to increase their ments. However only a limited volume of the liquid
range of activity. Combinations of materials have can be placed in the tooth and this will restrict the
also been used as medicaments and an example will antibacterial activity and the duration of effective-
be discussed. The efficiency of these volatile materials
is also doubtful within the dentinal tubules, lateral
1. Antiseptic medications canals, fins, anastomoses and peripheral areas of the
root canal system.
Materials that can be included in this group are:
paraformaldehyde, parachlorophenol, camphorated Calcium hydroxide
paramonochlorophenol (CMCP), formocresol,
cresol, creosote, thymol, eugenol, metacresylacetate Calcium hydroxide has been one of the most
extensively used materials in vital pulp therapy
(Cresatint), sodium hypochlorite, various iodine
compounds, quarternary chlorine compounds, quar- since its introduction by Hermann in 1930.63It also
ternary ammonium compounds, Cresophenet and has several uses in the treatment of pulpless teeth
Krig materials. Another material in this category with associated pathology.
is calcium hydroxide which will be discussed The efficacy of calcium hydroxide in endodontic
separately. therapy stems mainly from its bactericidal
Many of these antiseptic agents also contain effect^,^^.^^.^^ its ability to stimulate the formation
tissue-fixative agents. Antiseptics and tissue fixa- of calcified t i s ~ u e “and ~ - ~its~ ability to denature
tives are, by nature, toxic to mammalian cells. protein which aids dissolution of pulpal ti~sue.’~.’’
It is believed that calcium hydroxide stimulates
calcification by causing limited cell death adjacent
to the material. This resultant sterile necrotic layer
?Interdent, Markham, Ontario, Canada.
$Specialities Septodont, St. Maur, France. then undergoes passive calcification. When calcium
SPharmachemie AG, Zurich, Switzerland. hydroxide is placed in a root canal, it will cause an

Australian Dental Journal 1990:35:5. 44 1

 Fig. 3.-An incompletely developed upper left lateral incisor in a 20-year-old male patient with a pulpless and infected root
canal system and a periapical radiolucent area. a, Pre-operative radiographic appearance. b, Root canal filling after 12 months
of calcium hydroxide medication.

Fig. 4.-Lower right second molar tooth with a pulpless infected root canal system and a periapical radiolucent area. a, Radio-
graph taken at the time of referral. b, Root canal filling after 10 months of calcium hydroxide medication.

Fig. 5.-Upper left central incisor with a transverse root fracture. The coronal pulp space was pulpless and infected. Root
canal therapy was performed to the level of the fracture using long-term intra-canal calcium hydroxide dressings. a, Pre-operative
radiograph. b, After 9 months a hard tissue barrier has formed in the coronal fragment and the root canal filling has been placed.

442 Australian Dental Journal 1990;35:5

increase in the pH of root dentine76which indicates Septomixine Forte and Pulpomixine contain
that the hydroxide ion diffuses through the dentine. neomycin (10 million IU) and framycetin (1.675
This is advantageous in that it will help to destroy million IU), respectively. Both of these preparations
bacteria present in the inaccessible areas of the root. also contain polymixine B sulphate (20 million IU
The major early use of calcium hydroxide in and 2 million IU, respectively). None of these
endodontic treatment was related to the treatment antibacterial agents is very effective against the
of incompletely developed tooth roots (Fig. 3). bacteria commonly involved in endodontic lesions.
C ~ e hask ~provided
~ the most comprehensive study Neomycin and framycetin are bactericidal against
of this use of calcium hydroxide. Calcium hydroxide gram negative bacilli but are ineffective against
has also been described as a conservative means of bacteroides, rickettsia, fungae and viruses. Resis-
treating large periapical lesions (Fig. 4), transverse tant strains of enterococcus and streptococcus are
root fractures (Fig. 5), external root resorp- known to exist. Polymixine B sulphate is bacteri-
tion,73.78-81 perforations, internal resorption, and cidal against gram negative bacteria but is
other conditions that require the formation of hard ineffective against gram positive bacteria. Most of
these organisms are not causal agents in endodontic
Calcium hydroxide can be purchased as a paste infections hence these preparations are not the ideal
in several commercial preparations (for example materials for use as endodontic medicaments.
Pulpdent 1 paste, Calxyll, Calasept**, Hypo-Caltt) Septomixine Forte and Pulpomixine both contain
or in powder form. If it is purchased in powder the conicosteroid dexamethasone (0.05 per cent and
form, then it must be mixed with a sterile, isotonic 1.O per cent, respectively) as the anti-inflammatory
liquid such as saline or local anaesthetic solution. component. While dexamethasone is an effective
Of the commercial preparations available, the anti-inflammatory agent, other corticosteroid agents
author prefers Pulpdent paste which contains such as triamcinolone are known to be more potent
calcium hydroxide in a methyl cellulose base. This in their local reaction and with less systemic side
preparation has low solubility in tissue fluids and effects.86
its smooth physical consistency allows it to be easily Ledermix paste is a glucocorticosteroid-antibiotic
introduced into, and removed from, the root compound. This preparation contains, as the active
Pulpdent paste has a pH of 12.2.84 components, triamcinolone (a glucocorticosteroid)
When inhibition of inflammation or active inflam- and demethylchlortetracycline (demeclocyline, a
matory root resorption is necessary, or when there tetracycline antibiotic) at concentrations of 1 per
is pain, calcium hydroxide should not be used cent and 3.21 per cent, respectively. Triamcinolone
as the initial dressing since it has been reported to is approximately 4 times more potent than
be an irritant. This can cause an exacerbation of cortisone86and hence can be used in low concen-
the symptoms or of the already existing trations. Demeclocycline is generally effective
inflammati~n.~~.~~ against most of the common endodontic bacteria at
concentrations ranging from 0.05 to 128 mg/L.I3
2. Antibiotic medications Since demeclocycline is present within Ledermix
There are several commercial preparations avail- paste at a concentration of 3.21 per cent
able that contain both antibiotics and (50 000 mg/L) then this material should be very
anti-inflammatory agents. The most commonly used effective within the root canal itself. However,
preparations include L e d e r m i x t t paste, within the peripheral parts of the dentinal tubules
Septomixine Fortex paste and Pulpomixinet paste. and the peri-radicular tissues, it has been shown to
When considering the efficacy of these preparations be present in insufficient quantities to be predic-
it is essential to study their major components and table against all of these Despite this,
the activity of these components. With respect to Ledermix paste remains the root canal medicament
antibiotics, the susceptibility of endodontic bacteria of choice as an initial dressing agent in all cases (see
to these antibiotics and more importantly the Part 2: Clinical recommendations).
susceptibility at their attainable concentrations in Ledermix paste placed in the root canal has been
the various tissues are the important factors. shown to be capable of diffusing through the
dentinal tubules and cementum to reach the perio-
dontal and periapical This study showed
1 Pulpdent Corporation. Brooklyn, Mass., USA. that the tubules are the major supply route for the
lotto & Co. Frankfun, West Germany. active components to the peri-radicular tissues. The
**Scania Dental AB. Knivsta, Sweden.
ttEllman International Mfg. Inc. Hewlett, NY, USA. apical foramen acts as an opening also but the open
SSLederle Pharmaceuticals. Wolfratshausen, West Germany. foramen was not a significant supply route.

Australian Dental Journal 1990;35:5 443

 Fig. 6.-Both upper central incisors were avulsed and replanted within 15 minutes. The teeth were splinted
with a composite resin splint for two weeks and systemic antibiotics were prescribed. The root canals were
dressed with Ledermix paste for a total period of 4 months followed by a combination dressing of Ledermix
and Pulpdent pastes for 3 months. Finally calcium hydroxide was used alone for 3 months prior to the
root canal fillings being placed. a, Radiographic appearance on referral. b, Root canal fillings in place 10
months after the original trauma.

Various factors will affect the supply of the active 3. Combining medicaments
components to the peri-radicular tissues - these Several reports have discussed the effect of
include the presence or absence of canal wall smear combining Ledermix paste with calcium hydroxide
layer,26the presence or absence of cementum26and in a 50:50 mixture. The first reports concerned the
the presence of other materials within the canal, for use of this combination of materials as pulp capping
example, calcium h y d r o ~ i d e . ~ ~ and pulpotomy agent^.^^^^^^^^ A higher success rate
was reported over conventional calcium hydroxide
The ability of the components of this prepara- therapy, especially in producing calcified
tion to diffuse through dentine adds to its efficacy bridging27.89and in preventing an acute exacer-
and supports the many clinical observations bation of an already existing i n f l a m m a t i ~ n . ~ ~ , ~ ~
regarding Ledermix paste. The material can be used The 5050 mixture has also been advocated for
in all cases involving inflammation and/or infection use as an intra-canal dressing mixture in cases of
associated with the root canal system and periap- infected root canals, necrosis with incomplete root
ical tissues, even if the apical foramen is blocked formation, perforations, root r e s ~ r p t i o n ,inflam-
~~
or closed. The placement of Ledermix paste in the matory periapical bone resorption and the treatment
root canal space has been reported to add to the of large periapical radiolucent lesion^^'^^^^^^ (Fig. 8).
efficacy of the treatment of periapical infection^^^,^' The rationale for the use of this mixture in
and has been reported to reduce the incidence of endodontics is based on the requirement of a root
canal dressing material to induce healing in calci-
pain following initial canal debridement.30.32 fied tissues whilst also being anti-inflammatory and
Ledermix paste has also been shown histologically antibacterial in its a ~ t i o n . ~No
' single material is
to eliminate experimentally induced external currently available that achieves all three of these
inflammatory root resorption in vivo.88 This study actions. In addition, the use of calcium hydroxide
also reported that Ledermix paste had no damaging alone will often initiate an acute exacerbation which
effects upon the periodontal membrane and that this can be avoided by the use of the 50:50 m i x t ~ r e . ~ '
paste was an effective medication for the treatment The antibacterial activity of demeclocycline within
the peripheral areas of the root dentine and the peri-
of progressive root resorption in traumatically radicular tissues has been questioned and the addi-
injured teeth. Ledermix paste can be used to either tion of calcium hydroxide with its good anti-
prevent inflammatory root resorption such as in an bacterial activity is thought to produce a more
avulsed tooth (Fig. 6), or to arrest this resorption predictable antibacterial action than when Ledermix
if already present (Fig. 7). paste is used

444 Australian Dental Journal 1990;35:5.

 Fig. 7.-The upper left central incisor was avulsed and replanted immediately. The patient saw a dentist
5 months later when external inflammatory root resorption was well established. Root canal treatment was
commenced and Ledermix paste was used until there were no signs of any further resorption - a total
of 6 months. Calcium hydroxide was then used for 8 months to encourage apexification and hard tissue
repair in the resorptive defect. a, Working length radiograph showing external inflammatory root resorp-
tion in the apical half of the root. b, After 6 months of Ledermix paste dressings the peri-radicular bone
shows signs of repair and there is no further root resorption. c, The final root canal filling.

Combining Ledermix paste with Pulpdent paste periapical lesions by the use of long-term intra-canal
in a 50:50 mixture as a root canal dressing has been dressings, as advocated by H e i t h e r ~ a y . ~ ~ . ~ ~ . ~ ~
investigated in ‘uit~o.~’
This study showed that the Another studya4has provided further support for
rates of release of the active components of the use of this combination of materials. This in
Ledermix paste were slower when combined with v i m study examined the effects of combining the
Pulpdent paste. This has the effect of making the two materials and found that there was no change
dressing last longer than when Ledermix paste was in the activity or availability of each of the compo-
used alone (more than three months compared with nents. Combining the two preparations tended to
approximately two months). The slower release rate increase the anti-bacterial activity of Ledermix paste
also helps to maintain the sterility of the canal and and there was no change in the pH attained with
the tooth root by maintaining a higher concentra- the mixture. The relative toxicity to tissue culture
tion within the canal itself. This appears to be was also unaltered. This study concluded that an
advantageous in the treatment of extremely large equal parts mixture of Ledermix and Pulpdent

Australian Dental Journal 1990;35:5. 445

 Fig. 8.-The lower left first molar had a peri-radicular radiolucent lesion due to an inadequate root canal filling and subsequent
canal infection. The previous root filling was removed and the 4 canals were dressed with a mixture of Ledermix and Pulpdent
pastes for 3 months prior to the new root filling being placed. a, Pre-operative radiograph showing only 2 canals previously
treated. b, The completed root canal filling of 4 canals after 3 months of dressings.

pastes is likely to have more potent and longer References

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