Clinical Oral Investigations

https://doi.org/10.1007/s00784-020-03415-0

REVIEW

Is there evidence for the use of lesion sterilization and tissue repair
therapy in the endodontic treatment of primary teeth? A systematic
review and meta-analyses
Maysa Lannes Duarte 1 & Paula Maciel Pires 1 & Daniele Masterson Ferreira 2 & Andréa Vaz Braga Pintor 1 &
Aline de Almeida Neves 1,3 & Lucianne Cople Maia 1 & Laura Guimarães Primo 1

Received: 6 February 2020 / Accepted: 15 June 2020

# Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract
Objective To assess whether lesion sterilization and tissue repair (LSTR) technique resulted in similar clinical and radiographic
success outcomes as compared with pulpectomy in primary teeth.
Materials and methods Randomized clinical trials comparing LSTR with pulpectomy by means of clinical and radiographic param-
eters were included. Risk of bias was assessed using Cochrane methodology and the certainty of evidence was determined by GRADE.
Results Six articles were included. Conventional pulpectomy was favored with respect to radiographic success frequency in the
systematic review. Four studies were included in meta-analyses. Based on the clinical results at 6 months (RR = 0.99, 95% CI, 0.94–
1.04, p = 0.67; I2 = 0%), 12 months (RR = 0.97, 95% CI, 0.90–1.04, p = 0.34; I2 = 0%), and 18 months (RR = 0.89, 95% CI, 0.77–
1.04, p = 0.14; I2 = 0%) and radiographic findings at 6 months (RR = 0.91, 95% CI, 0.78–1.06, p = 0.23; I2 = 9%), 12 months (RR =
0.87, 95% CI, 0.65–1.18, p = 0.38; I2 = 64%), and 18 months (RR = 0.84, 95% CI, 0.69–1.02, p = 0.08; I2 = 0%), there was no
difference observed regarding success between the two treatments. The quality of evidence ranged from moderate to very low.
Conclusions No difference between the LSTR and pulpectomy approaches could be confirmed by meta-analyses. The quality of
evidence according to the GRADE scheme ranged from moderate to very low.
Clinical relevance The present meta-analyses could not demonstrate the superiority of one treatment over the other.

Keywords Pulpectomy . Root canal preparation . Root canal treatment . Primary tooth . Antibiotic paste

Introduction teeth with pulp necrosis or irreversible pulp inflammation and

is based on the debridement and modeling of the root canals
The early loss of primary molars may lead to undesirable with manual or rotary instruments together with the use of
consequences in the developing dentition [1]. Pulpectomy antimicrobial irrigation solutions aimed at decontaminating
has been the gold-standard treatment for addressing primary the root canal system for posterior filling with resorbable

* Laura Guimarães Primo Lucianne Cople Maia

lprimo@pobox.com rorefa@terra.com.br
Maysa Lannes Duarte
maysalannes@id.uff.br 1
Department of Pediatric Dentistry and Orthodontics, School of
Paula Maciel Pires Dentistry, Universidade Federal do Rio de Janeiro, Av. Prof.
paulinha_pmp@hotmail.com Rodolpho Paulo Rocco, 325 – Cidade Universitária, Rio de
Janeiro, RJ CEP: 21941-913, Brazil
Daniele Masterson Ferreira
danimasterson@yahoo.com.br 2
Central Library of the Health Science Center, Universidade Federal
do Rio de Janeiro, Rio de Janeiro, Brazil
Andréa Vaz Braga Pintor
andrea_pintor@hotmail.com 3
Centre for Oral Clinical and Translational Sciences, Faculty of
Aline de Almeida Neves Dentistry, Oral & Craniofacial Sciences, King’s College London,
aline.dealmeidaneves@gmail.com London, UK
 Clin Oral Invest

materials [2]. However, the inherent characteristics of the root Information sources and search strategy
canal system in primary teeth make this procedure an end-
odontic challenge, especially in molars. The presence of later- The PubMed, Web of Science, Scopus, Cochrane, BVS
al branches as well as accessory channels at the apex and (LILACS and BBO), ClinicalTrials.gov databases, and the
furcation regions; the anomalous root canal anatomy; and, gray literature (Google Scholar and Trip Database) up to
finally, the fact that the roots of the primary teeth are located December 2019 without language or publication year
close to the germ of the permanent successor and are physio- restrictions were reviewed.
logically programmed to exfoliate [1, 3] all contribute to in- The search strategies, presented in Table 1, were adapted
crease the level of difficulty. according to the syntax rules of each database, using the com-
Given that root canal infection was a common problem in bination of MeSH terms, synonyms, and free terms. A librar-
the primary dentition [4] in the 1990s, a new technique called ian experienced in systematic searches (DMF) guided the pro-
lesion sterilization and tissue repair (LSTR) was proposed as cess. Following article selection, an additional hand search
an alternative biologic approach that sought to facilitate the was performed among the reference lists of each selected ar-
disinfection of dentinal carious lesions, pulp, and periapical ticle in order to elucidate publications that might not have
lesions in primary teeth [5–7] with the advantages of being been found otherwise during the database investigations.
simpler and faster [4, 8]. LSTR has been proposed as one
option to potentially replace pulpectomy as it is simpler and Selection of studies
quicker to perform and does not necessitate multiple visits be
completed, even for teeth with periapical lesions [4]. LSTR is Two of the authors (MLD and AVBP) conducted the search
also known as noninstrumental endodontic treatment (NIET) independently and selected the articles for inclusion.
and consists of the nonmechanical instrumentation of the root Consensus meetings with an expert in systematic reviews
canals and placement of a paste made of a mixture of antibi- (LCM) were held whenever there were any disagreements
otics at the entrance of the root canals [9]. between these two authors. Articles present in more than one
Given the above, the present systematic review sought to electronic database were considered duplicated and, thus, only
answer whether there is adequate scientific evidence to favor included once. The remaining titles and abstracts were evalu-
the use of LSTR therapy in primary teeth as compared with ated, and all potentially eligible studies were read in full.
conventional pulpectomy treatment. Moreover, studies with insufficient data in the title and ab-
stract were read in full to facilitate the making of a clear deci-
sion regarding their inclusion.

Materials and methods Data extraction

This systematic review was reported according to the Preferred The same authors (MLD and AVBP) carried out the data
Reporting Items for Systematic Reviews and Meta-analysis extraction process independently. The data extracted from
(PRISMA) guidelines [10] and the protocol was registered in each included study included (1) authors, year of publication,
the International Prospective Register of Systematic Reviews and geographic location; (2) study design; (3) age range and
database under the number CRD42018107312. mean age of the participants; (4) tooth type; (5) intervention
group(s) and sample size; (6) follow-up time and evaluation
criteria of the treatment; (7) treatment outcomes; and (8) main
Eligibility criteria conclusions.

Based on the PICO strategy, randomized clinical trials (RCTs) Risk of bias in individual studies
involving primary teeth (P) submitted to noninstrumental end-
odontic treatment (I) in comparison with conventional The methodological quality and risk of bias of each selected
pulpectomy (C) with respect to their clinical and radiographic study were evaluated in accordance with the Cochrane
success (O) were identified. Those studies that compared the Collaboration Tool by the same authors (MLD and AVBP),
clinical and radiographic outcomes of LSTR therapy and con- who conducted their evaluations independently and then com-
ventional pulpectomy in primary teeth with at least 6 months pared the results. Disagreements were resolved during consen-
of clinical and radiographic follow-up were included. Review sus meetings with a senior reviewer (LCM).
articles, case reports, editorials, letters to editors, in vitro or in The following key domains were analyzed: selection bias
situ studies, and clinical studies in which, in the LSTR group, (random sequence generation and allocation concealment),
the pulp tissue was extirpated or manipulated using files were performance bias (blinding of participants and professionals),
excluded. Duplicated studies were also removed. detection bias (blinding of outcomes assessment), attrition
Clin Oral Invest

Table 1 Search strategy in the different databases

Database Search strategy

PubMed ((((Pulpectomy [MeSH Terms]) OR (Pulpectom*[Title/Abstract]) OR (Root Canal Preparation [MeSH Terms]) OR (Canal Preparation
Root [Title/Abstract]) OR (Root Canal Therapy [MeSH Terms]) OR (Root Canal Therapy [Title/Abstract]) OR (Canal Therapies
Root [Title/Abstract]) OR (Root Canal Procedures [Title/Abstract]) OR (Root Canal Treatment [Title/Abstract]) OR (LSTR
[Title/Abstract]) OR (NIET [Title/Abstract]) OR (Noninstrumentation Endodontic Treatment [Title/Abstract])))) AND
(((Metronidazole [Mesh]) OR (Metronidazole [Title/Abstract]) OR (Ciprofloxacin [Mesh]) OR (Ciprofloxacin [Title/Abstract]) OR
(Minocycline [Mesh]) OR (Minocycline [Title/Abstract]) OR (Tinidazole [Mesh]) OR (Tinidazole [Title/Abstract]) OR (CTZ
[Title/Abstract]) OR (Chloramphenicol [Title/Abstract]) OR (Tetracycline [mesh]) OR (Tetracycline [Title/Abstract]) OR (Zinc
Oxide [Title/Abstract]) OR (Eugenol [Title/Abstract]) OR (Anti-Bacterial Agents [Mesh]) OR (Agents Anti-Bacterial
[Title/Abstract]) OR (Agents Antibacterial [Title/Abstract]) OR (Agents Antimycobacterial [Title/Abstract]) OR
(Antibiotic*[Title/Abstract]) OR (Antibiotic Paste [Title/Abstract]) OR (Antibacterial Drugs [Title/Abstract])))
Web of Pulpectomy OR Pulpectom* OR “Root Canal Preparation” OR “Canal Preparation Root” OR “Root Canal Therapy” OR “Canal
Science Therapies Root” OR “Root Canal Procedures” OR “Root Canal Treatment” OR LSTR OR NIET OR “Noninstrumentation
Endodontic Treatment”
Metronidazole OR Ciprofloxacin OR Minocycline OR Tinidazole OR CTZ OR Chloramphenicol OR Tetracycline OR “Zinc Oxide”
OR Eugenol OR “Agents Anti-Bacterial” OR “Agents Antibacterial” OR “Agents Antimycobacterial” OR Antibiotic* OR
“Antibiotic Paste” OR “Antibacterial Drugs”
Scopus (TITLE-ABS-KEY (pulpectomy OR pulpectom* OR “root canal preparation” OR “canal preparation root” OR “root canal therapy” OR
“canal therapies root” OR “root canal procedures” OR “root canal treatment” OR LSTR OR NIET OR “noninstrumentation
endodontic treatment”)) AND (TITLE-ABS-KEY (metronidazole OR ciprofloxacin OR minocycline OR tinidazole OR ctz OR
chloramphenicol OR tetracycline OR “zinc oxide” OR eugenol OR “agents anti-bacterial” OR “agents antibacterial” OR “agents
antimycobacterial” OR antibiotic* OR “antibiotic paste” OR “antibacterial drugs”))
Cochrane #1MeSH descriptor: [Pulpectomy] explode all trees
#2(Pulpectom*):ti,ab,kw
#3#1 or #2
#4MeSH descriptor: [Root Canal Preparation] explode all trees
#5(“Canal Preparation Root”):ti,ab,kw
#6#4 or #5
#7MeSH descriptor: [Root Canal Therapy] explode all trees
#8(“Root Canal Therapy”):ti,ab,kw
#9(“Root Canal Procedures”):ti,ab,kw
#10(“Root Canal Treatment”):ti,ab,kw
#11#7 or #8 or #9 or #10
#12(NIET):ti,ab,kw
#13#3 or #6 or #11 or #12
#14MeSH descriptor: [Metronidazole] explode all trees
#15(Metronidazole):ti,ab,kw
#16#14 or #15
#17MeSH descriptor: [Ciprofloxacin] explode all trees
#18(Ciprofloxacin):ti,ab,kw
#19#17 or #18
#20MeSH descriptor: [Minocycline] explode all trees
#21(Minocycline):ti,ab,kw
#22#20 or #21
#23MeSH descriptor: [Tinidazole] explode all trees
#24(Tinidazole):ti,ab,kw
#25#23 or #24
#26(CTZ):ti,ab,kw
#27(Chloramphenicol):ti,ab,kw
#28MeSH descriptor: [Tetracyclines] explode all trees
#29(Tetracycline):ti,ab,kw
#30#28 or #29
#31(“Zinc Oxide”):ti,ab,kw
#32(“Eugenol”):ti,ab,kw
#33MeSH descriptor: [Anti-Bacterial Agents] explode all trees
#34(“Agents Antibacterial”):ti,ab,kw
#35(Antibiotic*):ti,ab,kw
#36(“Antibiotic Paste”):ti,ab,kw
#37(“Antibacterial Drugs”):ti,ab,kw
#38#33 or #34 or #35 or #36 or #37
#39#16 or #19 or #22 or #25 or #26 or #27 or #30 or #31 or #32 or #38
#40#13 and #39
 Clin Oral Invest

Table 1 (continued)

Database Search strategy

LILACS e (tw:((mh:“pulpectomy” OR “pulpectom*” OR mh:“root canal preparation” OR “canal preparation root” OR mh:“root canal therapy”
BBO OR “root canal therapy” OR “canal therapies root” OR “root canal procedures” OR “root canal treatment” OR “LSTR” OR “NIET”
OR “noninstrumentation endodontic treatment”))) AND (tw:((mh:“metronidazole” OR “metronidazole” OR mh:“ciprofloxacin” OR
“ciprofloxacin” OR mh:“minocycline” OR “minocycline” OR mh:“tinidazole” OR “tinidazole” OR “CTZ” OR “chloramphenicol”
OR mh:“tetracycline” OR “tetracycline” OR “zinc oxide” OR “eugenol” OR mh:“agents anti-bacterial” OR “agents anti-bacterial”
OR “agents antibacterial” OR “agents antimycobacterial” OR “antibiotic*” OR “antibiotic paste” OR “antibacterial drugs”)))
Google (pulpectomy OR pulpectom* OR “root canal preparation” OR “canal preparation root” OR “root canal therapy” OR “canal therapies
Scholar root” OR “root canal procedures” OR “root canal treatment” OR LSTR OR NIET OR “noninstrumentation endodontic treatment”)
AND (metronidazole OR ciprofloxacin OR minocycline OR tinidazole OR ctz OR chloramphenicol OR tetracycline OR “zinc oxide”
OR eugenol OR “agents anti-bacterial” OR “agents antibacterial” OR “agents antimycobacterial” OR antibiotic* OR “antibiotic
paste” OR “antibacterial drugs”)
Trip Database (pulpectomy OR pulpectom* OR “root canal preparation” OR “canal preparation root” OR “root canal therapy” OR “canal therapies
root” OR “root canal procedures” OR “root canal treatment” OR LSTR OR NIET OR “noninstrumentation endodontic treatment”)
AND (metronidazole OR ciprofloxacin OR minocycline OR tinidazole OR ctz OR chloramphenicol OR tetracycline OR “zinc oxide”
OR eugenol OR “agents anti-bacterial” OR “agents antibacterial” OR “agents antimycobacterial” OR antibiotic* OR “antibiotic
paste” OR “antibacterial drugs”)
Clinical trials (pulpectomy OR pulpectom* OR LSTR OR NIET OR “noninstrumentation endodontic treatment”) AND (metronidazole OR
ciprofloxacin OR minocycline OR tinidazole OR ctz OR chloramphenicol OR tetracycline OR “zinc oxide” OR eugenol)

bias (incomplete outcome data), and reporting bias (selective Results

reporting). Each key domain was classified as presenting ei-
ther a “low,” “unclear,” or “high risk” of bias. When one key The PRISMA flow diagram presenting the search process and
domain was judged as having “unclear” bias, up to five at- results is presented in Fig. 1. Initially, a total of 3984 studies
tempts to contact the authors of the study for additional infor- were identified and 2811 records remained after the removal
mation and then a posterior final risk of bias judgment was of duplicates using the reference manager EndNote. Another
conducted. If one or more key domain was classified as show- 2797 studies were removed after the retrieved studies were
ing “high” bias, the study was considered to have a high risk scanned based on their titles and abstracts because they did
of bias. not meet the inclusion criteria. Fourteen full texts were read
and eight were excluded due to not fulfilling the inclusion
Meta-analyses criteria. The reasons for the exclusions are described in Fig.
1. Finally, six studies were included in the systematic review,
Extracted data were inserted into the RevMan software (Review four were included in the 6 and 12 months clinical and radio-
Manager v. 5.3; The Nordic Cochrane Centre, Copenhagen, graphic follow-up meta-analyses, and from these, two studies
Denmark) to be analyzed. Analyses were performed for the clin- were included in the 18 months meta-analyses.
ical and radiographic results achieved at 6, 12, and 18 months of
follow-up. Success and failure frequencies were used to calculate Study characteristics
the risk difference with a 95% confidence interval (CI).
Heterogeneity was evaluated using the I2 index. Table 2 presents the characteristics of the six studies selected
for the systematic review. All six studies were RCTs. Three
Certainty of the evidence studies had been conducted in India [12–14], one was per-
formed in Thailand [9], one was from Brazil [15], and one
The quality of the evidence of estimates obtained from the was from Argentina [16]. A total of 263 primary molars were
meta-analyses was evaluated through the application of the treated (specifically, 119 in the control group and 144 in the
Grading Recommendations, Assessments, Development, and intervention group). Four studies included teeth with necrotic
Evaluations approach (GRADE) criteria using the software pulps [9, 13, 14, 16] and two included teeth with both irre-
GRADEpro GDT (available at https://gradepro.org/; versible pulp inflammation and teeth with necrosis [12, 15].
McMaster University, Hamilton, On, Canada and Evidence The evaluation period ranged from 1 to 18 months.
Prime, Inc., Hamilton, On, Canada). The quality of the Several distinct root canal filling pastes were used during
evidence was categorized as recommended as either “high,” conventional pulpectomy among the selected studies, includ-
“moderate,” “low,” or “very low” [11]. The evaluations were ing Vitapex® (Neo Dental International, Federal Way, WA,
carried out by two researchers independently (MLD and USA) [9, 13] and Maisto-Capurro [16], pastes based on iodo-
AVBP) and then compared. form and calcium hydroxide; Endoflas® (Sanlor Laboratories,
Clin Oral Invest

Records idenfied through database searching

PubMed (n = 1.435)

Idenficaon
Web of Science (n = 269)
Scopus (n = 1.610)
Cochrane (n = 280)
LILACS e BBO (n = 158)
Google Scholar (n = 79) Addional records idenfied
Trip Database (n = 152) through other sources
Clinical Trials (n = 1) (n = 0)
Screening

Records aer duplicates removed

(n = 2.811)

Records excluded (n):

Not on the subject (2776)
LSTR only (13)
Pulpectomy only (2)
Literature reviews (2)
Eligibility

Case reports (4)

Full-text arcles assessed Full-text arcles excluded, with

for eligibility reasons (n):
(n = 14) Overlap of studies (1)
Retrospecve study (1)
Manipulaon of the root pulp in
the control group (2)
Studies included in Control group without
qualitave synthesis instrumentaon (2)
(n = 6) Without clinical evaluaon (1)
Included

Less than 6 months of follow-up (1)

Studies included in
quantave synthesis
(meta-analysis)
(n = 4)

Fig. 1 PRISMA flow diagram of the search results from the databases

Miami, FL, USA), an iodoform, calcium hydroxide, and zinc coronary restoration were evaluated and classified as treatment
oxide powder added with propolis instead of eugenol [14]; failures. Among 53 teeth followed in this study, seven showed
zinc oxide and eugenol paste (ZOE) [12]; zinc oxide- restoration failure with marginal leakage, including six in the
ozonated oil-based paste [13]; and calcium hydroxide and zinc intervention group and one in the control group.
oxide paste [15]. For the LSTR technique, four studies [9, 12, In the respective control groups, the reported independent
14, 16] used 3-Mix antibiotic paste composed of ciprofloxa- rate of clinical success at 6 months was 100% [9, 13, 14] and
cin, metronidazole, and minocycline in different proportions 89.4% [16], while at 12 months, it ranged from 88.8% [16] to
and distinct vehicles, while Doneria et al. [13] used a mixture 100% [13, 14] and at 18 months, from 88.8% [16] to 100%
of ornidazole, ciprofloxacin, and cefaclor. CTZ, a combina- [13]. Meanwhile, the rate of radiographic success ranged from
tion of chloramphenicol, tetracycline, zinc oxide, and eugenol 40.0% [14] to 100% [13] at 6 months, from 56.0% [9] to 100%
were also investigated in another study [15]. [13, 14] at 12 months, and from 83.3% [16] to 94.4% [13] at
Regarding the final tooth restoration protocol, stainless steel 18 months.
crowns were used in five studies [9, 12–14, 16] and composite Among the intervention groups, the rate of clinical success
resin was used in one [15]. In the latter, the visible failures of ranged from 90.0% [16] to 100% [9] at 6 months, from 83.3%
Table 2 Description of the included studies

Author, Study Participants Tooth Initial Group Follow-up Time Success Rate p-
Year Design Type Diagnosis in Months value
Country Total Age Range Sex Control (n) Intervention (n) Control Intervention
Number (mean)

Agarwal et RCT 34 4 to 9 (NR) 18

40 primary Irreversible CMP: Normal CMP: 5% sodium Clinical: 1, 3, 6, 6 months: 92.86% 6 months: 0.003
al. M mandibular pulpal saline, H-files hypochlorite, and 12 12 months: 78.57% 38.89% 0.016
[12] India 16 molars inflammation Filling procedure: spoon excavator Radiographic: 3, Overall: 78.5% 12 months:
F and pulp ZOE, lentulo Filling procedure: 6, 33.33%
necrosis spirals 3Mix-MP and 12 Overall:
Restoration: s (ciprofloxacin, NR
tainless steel metronidazole,
crown minocycline,
(n = 20) macrogol and
propylene glycogol)
Restoration: glass
ionomer cement
and stainless
steel crown
(n = 20)
Daher et al. RCT 35 3.6 to 9.4 21 53 Irreversible CMP: 1% CMP: spoon 1, 3, 6, 12, 18, Overall: 68.7% Overall: NR
[13] (6.2) M primary pulpal sodium excavator and 24 or 27.0%
Brazil 14 molars inflammation hypochlorite Filling procedure: until
F and Pulp and K-files CTZ paste tooth
necrosis Filling procedure: (chloramphenicol, exfoliation
calcium tetracycline, zinc
hydroxide oxide and eugenol)
paste (calcium Restoration: GIC and
hydroxide, zinc composite
oxide and restauration
propylene (n = 37)
glycol)
Restoration:
GIC and
composite
restoration
(n = 16)
Divya et al. RCT 17 4 to 9 (6.25) NR 30 Pulp necrosis CMP: 3% sodium CMP: 3% Clinical: 3, 6, Clinical Clinical NR <
[14] India primary hypochlorite sodium and 12 6 months: 100% 6 months: 0.-
molars and normal hypochlorite, Radiographic: 3, 12 months: 100% 100% 05
saline, K-files spoon excavator 6, and 12 Overall: 100% 12 months:
Filling procedure: Filling Procedure: Radiographic: 93.0%
propolis liquid 3Mix 6 months: 40.0% Overall:
mixed with (ciprofloxacin, 12 months: 100% 93.0%
Endoflas®, metronidazole Overall: 100% Radiographic:
incremental and minocycline) 6 months:
technique 20.0%
Clin Oral Invest
Table 2 (continued)

Author, Study Participants Tooth Initial Group Follow-up Time Success Rate p-
Year Design Type Diagnosis in Months value
Clin Oral Invest

Country Total Age Range Sex Control (n) Intervention (n) Control Intervention
Number (mean)

Restoration: GIC Restoration: 12 months:

and stainless GIC and 60.0%
steel crown stainless Overall:
(n = 15) steel crown 60.0%
(n = 15)
Doneria et RCT 43 4 to 8 (NR) NR 44 Pulp necrosis CMP: 1% sodium CMP: 1% sodium Clinical: 1, 6, Clinical Clinical 0.43
al. primary hypochlorite hypochlorite, 12, and 18 6 months: 100% 6 months: 0.43
[15] India molars and spoon excavator Radiographic: 12 months: 100% 95.5% 0.62
normal saline, Filling procedure: 6,12, and 18 18 months: 12 months: 0.03
H‑files 3Mix‑MP 95.5% (ZnO) 95.8% 0.01
Filling procedure: (ornidazole 100% (Vitapex®) 18 months: 0.40
Vitapex® 500, ciprofloxacin Overall: 95.5% 89.5%
(syringe), 500, and cefaclor (ZnO) 100% Overall:
ZnO‑ozonated 250) (Vitapex®) 89.5%
oil Restoration: GIC, Radiographic: Radiographic:
(lentulo spirals) stainless 6 months: 100% 6 months:
Restoration: GIC, steel crowns 12 months: 100% 83.5%
stainless steel (n = 24) 18 months: 94.4% 12 months:
crowns (ZnO) 79.2%
(n = 20 each) 100% (Vitapex®) 18 months:
Overall: 94.4% (ZnO) 80.9%
100% (Vitapex®) Overall:
80.9%
Nakornchai RCT 37 3 to 8 (NR) NR 50 Pulp necrosis CMP: 2.5% CMP: 2.5% Clinical: 6 Clinical Clinical 1.00
et primary sodium sodium and 12 6 months: 100% 6 months: 1.00
al. [9] molars hypochlorite, hypochlorite, Radiographic: 12 months: 96.0% 100% 0.35
Thailand K‑files spoon excavator 6 and 12 Radiographic: 12 months: 0.07
Filling procedure: Filling Procedure: 6 months: 80.0% 96.0%
Vitapex®, 3Mix‑MP 12 months: 56.0% Radiographic:
syringe (ciprofloxacin, 6 months:
Restoration: ZOE, metronidazole 84.0%
stainless steel and minocycline) 12 months:
crowns Restoration: GIC, 76.0%
(n = 25) stainless
steel crowns
(n = 25)
Zacharczuk RCT NR G1: 4.7 to NR 46 Pulp necrosis CMP: 1.0% CMP: 2.5% sodium Clinical: 1, 3, Clinical Clinical NR
et 7.5 (6.15) primary sodium hypochlorite, 6, 12, 6 months: 89.4% 6 months:
al. [16] and G2: molars hypochlorite, spoon excavator and 18 12 months: 88.8% 90.0%
Argentina 4.81 K‑files Filling procedure: Radiographic:1, 18 months: 88.8% 12 months:
to 7.7 Filling procedure: 3Mix-MP 3, 6,12, Overall: 91.5% 83.3%
(6.3) Maisto-Capurro (ciprofloxacin, and 18 Radiographic
Table 2 (continued)

Author, Study Participants Tooth Initial Group Follow-up Time Success Rate p-
Year Design Type Diagnosis in Months value
Country Total Age Range Sex Control (n) Intervention (n) Control Intervention
Number (mean)

Restoration: ZOE, metronidazole 6 months: 84.2% 18 months:

stainless steel and minocycline) 12 months: 83.3% 82.3%
crowns Restoration: ZOE, 18 months: 83.3% Overall:
(n = 23) stainless steel Overall: 88.3% 87.5%
crowns Radiographic
(n = 23) 6 months:
80.0%
12 months:
77.7%
18 months:
76.4%
Overall:
82.3%

RCT: Randomized clinical trial.

NR: not reported.
M: male; F: female.
CMP: chemicomechanical preparation.
ZOE: zinc oxide and eugenol.
H-files: Hedstrom file; K-files: Kerr file.
Clin Oral Invest
Clin Oral Invest

Fig. 2 Risk of bias summary

Zacharczuk et al. 2019

Nakornchai et al. 2010

Agarwal et al. 2011

Doneria et al. 2017

Daher et al. 2015

Divya et al. 2019
Random sequence generation (selection bias)

+
+
+
+
?
-
Allocation concealment (selection bias)

+
+
+
+
?
-
Blinding of participants and personnel (performance bias

+
+
+
+
+
+
+
+

+
Blinding of outcome assessment (detection bias)

-
-
-
Incomplete outcome data (attrition bias)

+
+
+
-
-
+

+
+
+
+
Selective reporting (reporting bias)
-
+
+
+
+
+
+
Other bias

[16] to 96.0% [9] at 12 months, and from 82.3% [16] to 89.5% concealment. Due to differences between the treatments and
[13] at 18 months. Furthermore, the rate of radiographic suc- radiographic final images, participants, operators, and radio-
cess at 6 months ranged from 20.0% [14] to 84.0% [9], while graphic assessors could not be blinded. On the other hand,
at 12 months, it ranged from 60.0% [14] to 79.2% [13] and at blinded clinical evaluations were feasible and reported by
18 months from 76.4% [16] to 80.9% [13]. Agarwal et al. [12], Doneria et al. [13], and Nakornchai
No difference between the success rates of the groups at any et al. [9], which were then classified as having a “low risk of
experimental time was disclosed in two studies [9, 16]. On the bias” for the detection bias domain. The studies that did not
contrary, Agarwal et al. [12] disclosed statistical differences in perform blinded clinical evaluations [14–16] were classified
overall success considering the clinical and radiographic per- as “high risk.” In one of them [14], only the statistical assessor
formance at both 6 (p = 0.003) and 12 months (p = 0.016), with was blinded. Doneria et al. [13] excluded overfilled teeth from
better outcomes achieved in the conventional pulpectomy the sample; the study was classified as having a “high risk” in
group. Likewise, Divya et al. [14] and Doneria et al. [13] also the domain attrition bias. Similarly, Zacharczuk et al. [16]
observed better radiographic outcomes (p < 0.05) for the con- were considered “high risk” due to missing data was not prop-
ventional pulpectomy treatment (Table 2). erly reported.
Examples of reported treatment failures included gingival In summary, one study was classified as showing an “un-
abscess [9, 13], new fistula [15], pathological mobility [13], clear risk” of bias per the authors’ judgment even after
increased radiolucency in the furcation area [13, 15], exten- contacting the authors via email, one was classified as having
sive external root resorption [15], internal radicular reabsorp- a “low risk,” and four were deemed to show a “high” degree of
tion [9, 13–15], and deviation in the eruption path of the suc- risk. Figure 2 presents the bias descriptions of the six selected
cessor [14]. Two studies [12, 16] did not report on the reasons studies.
for treatment failures.
Staining of the dental crown on 12 teeth after LSTR therapy
and statistically significant lower survival rates for teeth treated Meta-analyses of the comparison of the clinical and
with LSTR therapy (p = 0.024) were also reported [15]. radiographic performance

Six meta-analyses were performed; four analyses included

Assessment of risk bias four studies [9, 13, 14, 16] and two analyses included two
studies [13, 16]. The quantitative grouping of these stud-
Among the six included studies, Agarwal et al. [12] did not ies showed no differences between conventional treatment
report enough information for random sequence generation and LSTR. This conclusion was based on the clinical re-
and allocation concealment, thus being considered having an sults at 6 (relative risk (RR) = 0.99, 95% CI, 0.94–1.04,
“unclear risk of bias”. Still considering selection bias, one p = 0.67; I2 = 0%), 12 (RR = 0.97, 95% CI, 0.90–1.04,
study [16] was classified as of “high risk of bias” for inade- p = 0.34; I2 = 0%), and 18 (RR = 0.89, 95% CI, 0.77–
quate random sequence generation and allocation 1.04, p = 0.14; I2 = 0%) months and radiographic findings
 Clin Oral Invest

Fig. 3 Forest plot of the

performance of treatments for
1. Clinical success at 6 months
clinical and radiographic
parameters at 6, 12 and 18 months

2. Clinical success at 12 months

3. Clinical success at 18 months

4. Radiographic success at 6 months

5. Radiographic success at 12 months

6. Radiographic success at 18 months

at 6 (RR = 0.91, 95% CI, 0.78–1.06, p = 0.23; I2 = 9%), Certainty of the evidence
12 (RR = 0.87, 95% CI, 0.65–1.18, p = 0.38; I2 = 64%),
and 18 (RR = 0.84, 95% CI, 0.69–1.02, p = 0.08; I2 = 0%) The GRADE evidence summary is presented in Table 3. The
months, respectively (Fig. 3). quality of the evidence ranged from moderate to very low.
 Clin Oral Invest

Table 3 Quality of the evidence for the overall outcomes

Certainty assessment No. of patients Effect

Number of Study design Risk of bias Inconsistency Indirectness Imprecision Other LSTR Conventional Relative (95% Absolute (95% CI) Certainty
studies considerations Treatment CI)

Clinical success 6 months

4 Randomized Not serious Not serious Not serious Seriousa None 81/87 97/103 (94.2%) RR 0.99 (0.94 9 fewer per 1.000 (from 57 fewer ⨁⨁⨁◯
trial (93.1%) to 1.04) to 38 more) MODERATE
Clinical success 12 months
4 Randomized Not serious Not serious Not serious Seriousa None 76/87 95/103 (92.2%) RR 0.97 (0.90 28 fewer per 1.000 (from 92 ⨁⨁⨁◯
trial (87.4%) to 1.04) fewer to 37 more) MODERATE
Clinical success 18 months
2 Randomized Not serious Not serious Not serious Seriousa None 35/47 55/63 (87.3%) RR 0.89 (0.77 96 fewer per 1.000 (from 201 ⨁⨁⨁◯
trial (74.5%) to 1.04) fewer to 35 more) MODERATE
Radiographic success 6 months
4 Randomized Not serious Not serious Not serious Seriousa None 60/87 82/103 (79.6%) RR 0.91 (0.78 72 fewer per 1.000 (from 175 ⨁⨁⨁◯
trial (69.0%) to 1.06) fewer to 48 more) MODERATE
Radiographic success 12 months
4 Randomized Not serious Very Not serious Very None 61/87 84/103 (81.6%) RR 0.87 (0.65 106 fewer per 1.000 (from 285 ⨁◯◯◯ VERY
trial seriousb,c seriousa,d (70.1%) to 1.18) fewer to 147 more) LOW
Radiographic success 18 months
2 Randomized Not serious Not serious Not serious Seriousa None 32/47 53/63 (84.1%) RR 0.84 (0.69 135 fewer per 1.000 (from 261 ⨁⨁⨁◯
trial (68.1%) to 1.02) fewer to 17 more) MODERATE

LSTR, lesion sterilization and tissue repair; CI, confidence interval; RR, risk ratio
a
Total number of events less than 300
b
Estimation of effect variation in included studies
c
Considerable and significant heterogeneity
d
Upper and lower confidence interval limit greater than 25%
 Clin Oral Invest

Discussion for follow-up in such clinical studies would be 6 months.

Here, the systematic review and meta-analyses evaluated stud-
The focused question of this systematic review was to address ies with follow-up periods ranging from 6 to 18 months of
whether there is adequate scientific evidence to favor the use follow-up.
of LSTR therapy in primary teeth as compared with conven- Due to the broad antibacterial spectrum, especially against
tional pulpectomy treatment. Similar to conventional anaerobic microorganisms, metronidazole was the first drug
pulpectomy, distinct protocols have been proposed for the tested in the disinfection of caries lesions [5]. Subsequently,
LSTR technique [9, 12–18]. In this sense, clinical diversity drug combinations added to metronidazole were tested for
regarding the intervention protocols between the included disinfection in the context of caries, pulp, and periapical le-
studies was expected. However, such diversity was not ob- sions [6, 23]. These studies concluded that several combina-
served considering the criteria applied for participants and tions of drugs are effective for the partial or total elimination
outcomes, which were similar between the studies. of bacteria from samples of carious dentin, infected pulp tis-
Interestingly, distinct methodologies based on sound ratio- sue, dentin of the root canal walls, and dental plaque [6, 23].
nales either for the conventional or for the LSTR therapies These researches supported the development of the LSTR
and followed strictly or carried out properly result in elevated technique [4].
clinical and radiographical frequencies of success, as observed Distinct antibiotics and their combinations have been tested
in the primary studies included as well as in the meta-analyses in clinical trials in relation to the LSTR technique to date [4, 9,
results [9, 12–18]. In addition, the heterogeneity between the 12–18, 24]. The mixture of ciprofloxacin, metronidazole, and
studies was considered on the GRADE quality of evidence minocycline has been that which is the most commonly used
evaluation [11], which showed to range from moderate to very [4, 9, 12, 14, 16, 19, 24], with varying drug ratios ranging
low. Therefore, these results suggest that although the differ- from 1:1:1 to 1:3:3 (triplicate portions of metronidazole and
ences could possibly affect the success of pulp treatment, the minocycline) under the name of 3Mix paste. In our results,
comparison between the included studies was not impaired. four studies employed the combination of ciprofloxacin, met-
In the LSTR technique, with respect to radicular pulp, some ronidazole, and minocycline for treatment [9, 12, 14, 16],
studies used files only to remove pulp tissue [17, 18]. Previous including two using the 1:3:3 formulation [12, 14]. The diver-
authors labeled this treatment as LSTR or NIET, given that the sity of antibiotics, proportions, and vehicles that may possibly
mechanical instrumentation of the root canal was not per- interfere in the LSTR clinical and radiographic outcomes
formed. Prabharkar et al. [19] demonstrated a statistically sig- should be addressed in the future during in vitro and in vivo
nificant difference when comparing the application of nonme- studies.
chanical instrumentation and mixed antibiotic paste in primary Primary teeth with pulp necrosis, especially those with
teeth with and without root pulp extirpation, favoring the periapical lesions, may present a worse prognosis of treatment
group in whom radicular pulp tissue was extirpated. Our study [9]. In such cases, it is justified to use a combination of irri-
did not consider works in which antibiotic paste was used gating solutions, aiming at achieving disinfection and smear
when the radicular pulp was mechanically manipulated. As layer removal in the root canal system [25, 26]. Despite this,
such, these studies were excluded from the systematic review, the LSTR treatment that does not employ irrigation also en-
since we believe there existed differences between the proce- sured improvement in the clinical prognosis (i.e., regarding
dures that may influence the outcome. pain and sensitivity to percussion), especially in teeth in these
Considering the conventional treatment [20, 21], there was situations [8]. Conversely, Daher et al. [15] observed that,
no consensus about the techniques and root canal filling ma- regardless of whether the treatment used is pulpectomy or
terials. Zinc oxide and eugenol, iodoform-based paste (KRI), LSTR, the survival rates were significantly lower among teeth
nonsetting calcium hydroxide paste, or a combination of io- with initial pulp necrosis as compared with teeth with irrevers-
doform paste and calcium hydroxide (e.g., Vitapex®, ible pulp inflammation, pointing to the need for smear layer
Endoflas®) were all employed [2, 22]. However, the clinical removal [25, 26].
and radiographic performance evaluation criteria were usually At the end of any endodontic therapy, the tooth must be
similar between the studies. Specifically, the absence of pain, restored to prevent microleakage at the restoration–tooth in-
fistula, and abnormal mobility, and the absence of pain in terface [2]. Among the six studies included in the systematic
percussion exam were used by Agarwal et al. [12] and review, only one used glass ionomer cement followed by
Zacharczuk et al. [16], while visible restoration failure rating composite resin and classified the restoration having visible
was employed by Daher et al. [15]. Any clinical signs and flaws during follow-up as an example of treatment failure
symptoms should resolve within a few weeks [2]. [15]. This observation is relevant as it is known that restorative
Meanwhile, radiographic signs should resolve within 6 months failure can influence the performance of endodontic treat-
[2], as evidenced by bone deposition in the radiolucent pre- ments [27]. Also, previous studies involving primary teeth
treatment areas. Thus, the minimum period considered ideal have reported that the type of material and the time between
Clin Oral Invest

temporary and final restoration influence the success of good methodological quality and longer follow-up could pos-
pulpectomies [28, 29] and LSTR [28]. The other five studies sibly disclose differences between the treatments.
employed stainless steel crowns as a final restorative material.
However, the time between endodontic treatment and the final
restoration ranged from the same appointment [9, 14], after Conclusion
24 h [12], after a week [16], and even 15 days later [13]. The
clinical success among those who employed stainless steel Considering the six studies included in the present systematic
crowns was similar for those patients who underwent the res- review, three demonstrated that conventional endodontic
toration at the same appointment [9] and after 15 days [13]. treatment for primary teeth was statistically more favorable
Considering radiographic success, Nakornchai et al. [9] re- based on the radiographic criteria. However, through the me-
vealed that those who experienced restoration immediately ta-analyses, it was not possible to disclose any difference be-
obtained worse results as compared with the findings of tween the treatments, regardless of follow-up (6, 12, or
Doneria et al. [13]. Despite the importance of the restoration 18 months) and type of evaluation (clinical or radiographical).
to the prognosis of the treatment already demonstrated in the GRADE indicated the quality of evidence was from moderate
literature, the authors did not correlate the success of endodon- to very low.
tic therapy with final restoration.
Considering the qualitative analysis of the clinical and ra- Funding information This study was financed in part by the
diographic results in this systematic review, there were lower Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil
(CAPES) (finance code 001) and Fundação Carlos Chagas Filho de
radiographic success rates than clinical performance rates Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) – APQ1
achieved with the LSTR technique. As observed in our results, 2010.352/2019 and E-26/202-399/2017.
most treatment failures were exclusively radiographic in na-
ture [15] as revealed through the finding of a statistically sig- Compliance with ethical standards
nificant difference when comparing the outcomes for radio-
graphic success between the two techniques [13, 14]. Conflict of interest The authors declare that they have no conflict of
This result corroborates with those of a previous retrospec- interest.
tive study that describes failures in LSTR treatment as being
Ethical approval This article does not contain any studies with human
mostly related to radiographic aspects [28]. Though Qadeer participants or animals performed by any of the authors.
et al. [30] showed that a reduction in periapical radiolucency
was statistically higher in teeth treated with LSTR when com- Informed consent For this type of study, formal consent is not required.
pared with pulpectomy, this result should be interpreted with
caution, due to the short follow-up period of the study of only
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