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UNIVERSIDADE FEDERAL DE SANTA CATARINA 
CENTRO DE CIÊNCIAS DA SAÚDE 
DEPARTAMENTO DE ODONTOLOGIA 
CURSO DE ODONTOLOGIA 
 
 
 
 
 
RAYSSA SABINO DA SILVA 
 
 
 
 
 
 
 
Influência da concentração do hipoclorito de sódio na ocorrência e 
intensidade da dor pós-operatória do tratamento endodôntico: Revisão 
sistemática e meta-análise 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Florianópolis 
 
2022 
 
 
Rayssa Sabino da Silva 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Influência da concentração do hipoclorito de sódio na ocorrência e 
intensidade da dor pós-operatória do tratamento endodôntico: Revisão 
sistemática e meta-análise 
 
 
 
 
 
 
Trabalho de Conclusão do Curso de Graduação em 
Odontologia do Centro de Ciências da Saúde da 
Universidade Federal de Santa Catarina como requisito 
para a obtenção do Título de Cirurgiã-Dentista. 
Orientadora: Profª. Drª. Cleonice da Silveira Teixeira 
Co-orientador: Me. Ihan Vitor Cardoso 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Florianópolis 
2022 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RAYSSA SABINO DA SILVA 
 
 
 
 
Influência da concentração do hipoclorito de sódio na ocorrência e intensidade da dor 
pós-operatória do tratamento endodôntico: Revisão sistemática e meta-análise 
 
 
 
Este Trabalho Conclusão de Curso foi julgado adequado para obtenção do Título de 
“Cirurgião-Dentista” e aprovado em sua forma final pelo Curso de Odontologia. 
 
Florianópolis, 14 de fevereiro de 2022. 
 
 
 
 
_________________________________ 
Profª. Glaucia Santos Zimmermann, Dra. 
Coordenadora do Curso 
 
 
Banca Examinadora: 
 
 
 
_________________________________ 
Prof.ªCleonice da Silveira Teixeira, Dra. 
Orientadora 
Universidade Federal de Santa Catarina 
 
 
 
________________________ 
Prof. Ana Maria Hecke Alves, Dra 
Universidade Federal de Santa Catarina 
 
 
 
 
________________________ 
Filipe Colombo Vitali, Me 
Universidade Federal de Santa Catarina 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
À minha mãe, exemplo de garra e humildade, 
por ter escolhido viver esse sonho comigo. 
Esta conquista hoje é sua!
AGRADECIMENTOS 
 
“A vida é uma ópera”, teorizou Machado de Assis em Dom Casmurro. No livro, o 
narrador recorda que o princípio de sua ópera fora em uma tarde de novembro de 1857 onde 
um evento desencadeara o início de sua vida. O início não era o nascimento em si, mas um 
evento clímax no decorrer da própria vida! Em minha última releitura, o trecho me impôs a 
deliciosa tarefa de pensar quando fora o princípio da minha ópera. Recordei, então, de uma 
manhã chuvosa e fria de agosto de 2016: meu primeiro dia de caloura. Minha vida até então 
havia sido apenas os bastidores: “o pintar e vestir das pessoas que tinham de entrar em cena 
[...]” (ASSIS, Machado de. Dom Casmurro. Rio de Janeiro: Nova Aguilar, 1994). Hoje, como 
protagonista de meu espetáculo, cito-as, como forma de agradecimento por terem preparado o 
palco para mim. 
A Deus, primeiramente, que sempre tem reservado o melhor para mim. Por ter realizado 
meus sonhos mesmo quando eu já os havia esquecido. Por ter feito não a minha, mas a Sua 
vontade: boa, perfeita e agradável. 
 A minha mãe, Inês Leite, primeira pessoa que me incentivou a trilhar os caminhos da 
educação. Obrigada por não ter desistido disso nem mesmo quando as dificuldades nos 
acometeram e por estar fazendo o possível e o impossível para que eu estivesse aqui hoje. 
A minha única irmã, Mariana Sabino, Anna de minha Elsa. Obrigada por sempre orar 
por mim, torcer pelo meu sucesso e acreditar nas minhas qualidades. Espero sempre te orgulhar 
como irmã mais velha, e com este trabalho não é diferente. 
Ao meu namorado, Eric Machado, por ser meu parceiro não somente no amor, mas 
também na vida. Por ter acolhido meu sonho e ter feito dele seu também. Obrigada por todo o 
apoio e compreensão nesses últimos tempos, pelo incentivo de sempre e a confiança 
incondicional na minha capacidade. 
A profa. Dra. Cleonice da Silveira Teixeira, minha orientadora, por ter me acolhido à 
família de orientados. Obrigada por todos os conselhos – acadêmicos e da vida –, por todos os 
puxões de orelha, pela ética, paciência e maestria com que conduziu esse trabalho. Obrigada 
por ser meu role model da Odontologia, exemplo de cirurgiã-dentista, professora e 
pesquisadora. Quando crescer quero ser como você. 
Ao Ihan Cardoso, meu co-orientador, por todo o auxílio e cooperação desenvolvendo 
e escrevendo esse estudo. Ao Filipe Vitali, por toda a dedicação dispensada a esse trabalho: 
por ter me ensinado o risco de viés, a análise da qualidade da evidência e a como rodar uma 
meta-análise. A importância de você nesse trabalho foi estatisticamente significativa (p < 0.05). 
A profa. Dra. Carolina Barcellos por ter me apresentado a Revisão Sistemática e ter 
orientado a minha primeira produção científica. A Elis Batistella por ter me ensinado na prática 
tudo o que precisava saber para trabalhar com Revisão Sistemática. Sem dúvidas que essa 
experiência prévia contribuiu para a realização desse estudo. 
A minha dupla, Alessandra Cadore, por toda a amizade, companheirismo e apoio 
dentro e fora da clínica. Dupla essa que somente minha orientadora poderia ter formado. Aos 
demais amigos que conquistei no curso, pois certamente que vocês contribuíram para que a 
graduação se tornasse o melhor momento da minha vida. 
 A Marta e Oziel Almeida, em nome de todos amigos e familiares que de alguma forma 
contribuíram para que eu chegasse aqui hoje. Esse trabalho aqui também tem um pedacinho de 
vocês: Os meus mais sinceros agradecimentos. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
‘A palavra é meu domínio sobre o mundo’ 
 (Clarice Lispector, 1984) 
RESUMO 
 
Introdução: Dentre as soluções irrigadoras utilizadas no tratamento endodôntico, o hipoclorito 
de sódio (NaOCl) tem destaque por ser a solução irrigadora mais comumente utilizada, sendo 
comercializado em diferentes concentrações. No entanto, existem controvérsias na literatura se 
o uso de baixas ou altas concentrações de NaOCl está relacionado à menor ou maior ocorrência 
de dor pós-operatória. 
Objetivo: Avaliar sistematicamente a literatura a fim de responder se as diferentes 
concentrações de NaOCl utilizadas durante o tratamento endodôntico, realizado em uma ou 
múltiplas sessões, interferem na ocorrência de dor pós-operatória. 
Metodologia: Dois revisores pesquisaram, de forma independente e abrangente, a literatura nas 
seguintes bases de dados eletrônicas: Cochrane Library, EMBASE, Literatura Latino-
americana e do Caribe em Ciências da Saúde (LILACS), MEDLINE PubMed, Scopus e Web 
of Science. Adicionalmente, uma pesquisa complementar foi realizada na literatura cinzenta, 
incluindo as bases de dados Google Scholar, OpenGrey e ProQuest teses e dissertações. Foram 
incluídos estudos clínicos randomizados que avaliaram a influência das diferentes 
concentrações de NaOCl na dor pós-operatória. Foram excluídos estudos que avaliaram 
retratamentos endodônticos, dentes decíduos, dentes com rizogênese incompleta ou com 
fraturas e reabsorções, estudos que não utilizaram NaOCl como irrigante e estudos de revisão, 
caso-controle e relatos de caso. Após a seleção dos estudos e extração de dados, as 
concentrações de NaOCl foram dicotimizadas em alta concentração (acima de 3%) e baixa 
concentração (entre 0.5% e 3%). A avaliação do risco de viés foi realizada por meio da 
ferramenta Cochrane Collaboration’s Risk-of-Bias Assessment Tool 2.0. A prevalência de dor 
pós-operatória foi avaliada por meio de meta-análise de proporçãopelo software MedCalc. A 
qualidade geral da evidência foi avaliada pela ferramenta GRADE. 
Resultados: 705 estudos foram inicialmente identificados. Após a leitura dos títulos e resumos, 
18 estudos foram selecionados para a leitura completa. Após a aplicação dos critérios de 
elegibilidade e exclusão, nove estudos foram incluídos na presente revisão sistemática. Na 
avaliação do risco de viês, três estudos foram julgados como ‘alto risco’ e um como ‘algumas 
preocupações’. A prevalência geral agrupada de dor pós-operatória foi de 36.31% para o NaOCl 
em maiores concentrações e de 45.35% para o NaOCl em menores concentrações. Após 24h, 
39.11% dos pacientes do grupo de alta concentração apresentou dor, enquanto que apenas 
28.83% dos pacientes do grupo de baixa concentração teve dor. Após 7 dias, nenhum grupo 
apresentou dor moderada ou severa, 94,89% dos pacientes do grupo de alta concentração e 
96,58% dos pacientes do grupo de baixa concentração relatando ausência de sintomatologia. 
Conclusões: A prevalência geral de dor pós-operatória foi de 36,31% no grupo de alta 
concentração de NaOCl e de 45,35% no grupo de baixa concentração de NaOCl. Após 7 dias, 
nenhum caso de dor moderada ou severa foi observada em ambos os grupos. 
Palavras-chave: Dor pós-operatória. Meta-análise. Hipoclorito de sódio. Revisão sistemática. 
ABSTRACT 
 
Introduction: Among the solutions used in endodontic treatment, sodium hypochlorite 
(NaOCl) stands out for being the most commonly used irrigant, being sold in different 
concentrations. However, there are controversies in the literature about whether its use of low 
and high concentrations is related to postoperative pain. 
Objective: to systematically assess the literature in order to answer whether the different 
concentrations of NaOCl used during endodontic treatment, performed in one or multiple 
sessions, interfere with the occurrence of postoperative pain. 
Methodology: Two reviewers independently and comprehensively searched the literature in 
the following electronic databases: Cochrane Library, EMBASE, Latin American and 
Caribbean Health Sciences Literature (LILACS), MEDLINE PubMed, Scopus, and Web of 
Science. Additionally, a complementary research was carried out in the gray literature including 
the databases Google Scholar, OpenGrey, and ProQuest theses and dissertations. It was 
included randomized clinical trials that evaluated the influence of different concentrations of 
NaOCl on postoperative pain. Studies that evaluated endodontic retreatments, studies that 
evaluated primary teeth, teeth with incomplete root formation or fractures and resorptions, 
studies that did not use NaOCl as an irrigant and review studies, case-control, and case reports 
were excluded. After selection of studies and data extraction, NaOCl concentrations were 
dichotimized into high concentration (above 3%) and low concentration (between 0.5% and 
3%). The risk of bias assessment was performed using the Cochrane Collaboration's Risk-of-
Bias Assessment Tool 2.0 (Sterne et al. 2019). The incidence of postoperative pain was assessed 
through proportion meta-analyses using the MedCalc software. The general quality of the 
evidence was evaluated by the GRADE tool. 
Results: 705 studies were initially identified. After screening titles and abstracts, 18 abstracts 
were selected for full reading, and with the application of the criteria of eligibility and exclusion, 
nine studies were included in this systematic review. In the assessment of the risk of bias, three 
studies were judged as "high risk" and one as "some concerns". The overall pooled prevalence 
of postoperative pain was 36.31% in the high NaOCl concentration group and 45.35% in the 
low NaOCl concentration group After 24h, 39.11% of patients in the high concentration group 
reported pain, while only 28.83% of patients in the low concentration group had pain. After 7 
days, neither group had moderate or severe pain, with 94.89% of patients in the high-
concentration group and 96.58% of patients in the low-concentration group reporting no 
symptoms. 
Conclusions: The overall pooled prevalence of postoperative pain was 36.31% in the high 
concentration NaOCl group and 45.35% in the low concentration NaOCl group, with no 
patients experiencing moderate or severe pain after 7 days in both groups. 
 
Keywords: Postoperative pain. Meta-analysis. Sodium hypochlorite. Systematic review. 
 
LISTA DE FIGURAS 
 
FIGURE 1 – FLOW DIAGRAM OF LITERATURE SEARCH AND SELECTION 
CRITERIA1………………………………………………………..…………………………45 
FIGURE 2 – Risk of bias (RoB) graph: review authors’ judgments about each risk of bias item 
presented with all included studies (Cochrane Collaboration’s Risk-of-Bias Assessment Tool 
2.0). ...........................................................................................................................................46
LISTA DE TABELAS 
 
 
TABLE 1– Characteristics of the included studies........................................................ 29 
TABLE 2– Measures of the pooled proportion values [n (% - random effect)] of 
overall incidence of postoperative pain for high and low sodium 
hypochlorite (NaOCl) concentrations......................................................... 
 
 
31 
TABLE 3 – Measures of the pooled proportion values [n (% - random effect)] of the 
incidence of pain at the postoperative times (24 and 48h) for high and 
low sodium hypochlorite (NaOCl) concentrations...................................... 
 
 
32 
TABLE 4 – Measures of the pooled proportion values [n (% - random effect)] of pain 
at the different categories and postoperative times (24, 48h, and 7 days) 
for high and low sodium hypochlorite (NaOCl) concentrations................. 
 
 
34 
TABLE 5 – Measures of the pooled proportion values [n (% - random effect)] of the 
number of patients who used analgesics to control postoperative pain....... 
 
35 
TABLE 6 – GRADE assessment..................................................................................... 36 
 
 
 
 
 
 
 
LISTA DE APÊNDICES 
 
 
Apêndice A – Registro do protocolo no site Internacional Prospective Register of 
Systematic Reviews (PROSPERO, CRD42021258830) ........................... 
 
53 
 
Apêndice B – Estratégias de busca das bases de dados..................................................... 54 
Apêndice C – Estudos excluídos e justificativa................................................................. 56 
 
Do artigo em inglês: 
 
Appendix 1 – Database search strategy............................................................................. 54 
Appendix 2 – Studies excluded and reasons..................................................................... 56 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LISTA DE ANEXOS 
 
 
ANEXO 1– Ata da defesa............................................................................................. 57 
ANEXO 2– NORMAS DA REVISTA…..…………………………………………... 58 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
LISTA DE ABREVIATURAS E SIGLAS 
 
NaOCl – Hipoclorito de sódio 
 
Do artigo em inglês: 
CI – Confidential interval 
GRADE – The Grading of Recommendations Assessment, Development and Evaluation 
NaOCl – Sodium hypochlorite 
NRS – Numerical Rating Scale 
PRISMA – Preferred reporting items for systematic reviews and meta-analysis 
RoB – Risk of bias 
VAS – Visual Analog Scale 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SUMÁRIO 
 
1 INTRODUÇÃO ................................................................................................................... 16 
2 OBJETIVOS ......................................................................................................................200 
2.1 OBJETIVO GERAL ........................................................................................................................... 20 
2.2 OBJETIVOS ESPECÍFICOS ........................................................................................................... 20 
3 ARTIGO .............................................................................................................................. 21 
4 CONSIDERAÇÕES FINAIS ............................................................................................. 47 
REFERÊNCIAS ..................................................................................................................... 48 
APÊNDICES .......................................................................................................................... 53 
APÊNDICE A – REGISTRO DO PROTOCOLO ........................................................................................ 53 
APÊNDICE B – ESTRATÉGIAS DE BUSCA NAS BASES DE DADOS ................................................... 54 
APÊNDICE C – ARTIGOS EXCLUÍDOS E JUSTIFICATIVAS ................................................................ 56 
ANEXOS.................................................................................................................................57 
 ANEXO 1 – ATA DA DEFESA.........................................................................................................57 
 ANEXO 2 – NORMAS DA REVISTA.........................................................................................................58 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
16 
 
1 INTRODUÇÃO 
 
O tratamento endodôntico é um procedimento odontológico que pode estar relacionado 
à ocorrência de sensibilidade dolorosa, sendo por vezes causa de ansiedade em muitos 
pacientes (PAK; WHITE, 2011). A dor pós-operatória é uma ocorrência comum após o 
tratamento endodôntico (RAMAMOORTHI; NIVEDHITHA; DIVYANAND, 2015; 
MOSTAFA et al., 2020), sendo incidente em até 80% dos casos nas primeiras 24 horas 
(MOSTAFA et al., 2020). 
A etiologia da dor é primariamente atribuída a fatores mecânicos, químicos e/ou 
microbiológicos que podem originar sintomas dolorosos previamente, durante e/ou após o 
tratamento endodôntico (MOSTAFA et al., 2020). Dentre os fatores associados à ocorrência 
de dor pós-operatória estão: a existência de dor pré-operatória (PAK;WHITE, 2011; 
RAMAMOORTHI; NIVEDHITHA; DIVYANAND, 2015), o uso de analgésicos e 
antibióticos, o número de sessões e fatores intrínsecos ao paciente (PAK;WHITE, 2011). 
Durante o tratamento, os principais fatores são o número de visitas, a cinemática empregada 
na instrumentação, a técnica de obturação e o tipo de solução irrigadora utilizada (MOSTAFA 
et al., 2020). Dessa forma, um dos métodos para prevenir a sensibilidade pós-operatória incluia 
cuidadosa escolha do irrigante a ser utilizado durante o tratamento (MOSTAFA et al., 2020). 
O uso de soluções irrigadoras no tratamento endodôntico é essencial para promover 
eficaz desinfecção dos canais radiculares, pois grandes áreas do canal podem não ser atingidas 
pela ação dos instrumentos endodônticos (MOHAMMADI, 2008; HAAPASALO et al., 2014; 
ABUHAIMED; NEEL, 2017; TOPÇUOĞLU; TOPÇUOĞLU; ARSLAN, 2018; DEMENECH 
et al., 2021; HOSNY et al., 2021). Dentre as funções da solução irrigadora, estão: remover 
restos teciduais e neutralizar a carga microbiana ou os produtos tóxicos decorrentes da 
decomposição pulpar (MOHAMMADI, 2008; ABUHAIMED;NEEL, 2017), bem como 
promover a lubrificação das paredes dentinárias e o desbridamento foraminal 
(ABUHAIMED;NEEL, 2017). No entanto, ainda não há um irrigante que possua todas as 
características ideais, mesmo quando sua função é potencializada por alterações no pH, 
aumento de temperatura ou adição de surfactantes (MOZO; LLENA; FORNER, 2012; 
RAMAMOORTHI; NIVEDHITHA; DIVYANAND, 2015). 
Na prática clínica, duas substâncias têm sido empregadas com maior frequência como 
irrigantes durante o preparo do canal radicular: o hipoclorito de sódio (NaOCl) e o digluconato 
de clorexidina (MOZO; LLENA; FORNER, 2012; RAMAMOORTHI; NIVEDHITHA; 
17 
 
DIVYANAND, 2015). A solução de NaOCl geralmente é utilizada sozinha durante o preparo 
e, ao final, após o uso de um agente quelante, tal como o ácido etilenodiaminotetracético 
(EDTA) (MOZO; LLENA; FORNER, 2012; RAMAMOORTHI; NIVEDHITHA; 
DIVYANAND, 2015). Tal combinação é necessária, haja visto que o NaOCl é incapaz de 
remover a lama dentinária (WRIGHT;KAHLER;WALSH, 2017; IANDOLO et al., 2019). A 
clorexidina, por sua vez, tem sido escolhida por sua capacidade desinfetante, substantividade e 
baixa toxicidade (BERNARDI; TEIXEIRA, 2015), mesmo não sendo capaz de dissolver tecido 
orgânico (BERNARDI; TEIXEIRA, 2015; DEMENECH et al., 2021). 
O NaOCl é o irrigante mais comumente empregado em endodontia (BERNARDI; 
TEIXEIRA, 2015; GONÇALVES et al., 2016; FARZANEH et al., 2018; IANDOLO et al., 
2019; BORGO SARMENTO et al., 2020; VERMA et al., 2019; MOSTAFA et al., 2020; 
DEMENECH et al., 2021). Dentre as inúmeras propriedades do NaOCl, que o tornam o 
irrigante de escolha para a maioria dos casos, estão: a ação antimicrobiana, a capacidade de 
dissolver tecido orgânico, a ação clareadora, a dupla ação detergente e ação desodorizante do 
canal radicular (GONÇALVES et al., 2016; FARZANEH et al., 2018; IANDOLO et al., 2019; 
VERMA et al., 2019; MOSTAFA et al., 2020). Também se trata de uma solução com baixo 
custo, acessível e com um período de vida satisfatório (MOHAMMADI, 2008). 
As propriedades antissépticas do NaOCl provêm da formação de ácido hipocloroso e 
consequente liberação de cloramina, potente agente bactericida (IANDOLO et al., 2019). O 
ácido hipocloroso em contato com o tecido orgânico, libera cloro que reage com o grupo amino 
(-NH) dos aminoácidos, formando cloraminas, a chamada reação de cloraminação 
(MOHAMMADI, 2008). Por sua vez, a cloramina livre dissolve o tecido necrótico pois possuí 
ação proteolítica: consegue quebrar as proteínas em aminoácidos (IANDOLO et al., 2019) e 
depois os neutraliza formando água e sal (MOHAMMADI, 2008). 
A capacidade de dissolver o conteúdo orgânico da polpa dental decorre da formalçao 
de hidróxido de sódio a partir da dissolução do NaOCl, o que confere ao irrigante um pH 
extremamente alcalino (IANDOLO et al., 2019), podendo atingir valores de 11 à 12 (GONDIM 
et al., 2010; WRIGHT; KAHLER;WALSH, 2017). A predominância dos íons OH− e OCl− 
aumentam o pH da solução, conferindo um pH superior a 9, o que garante maior dissolução de 
tecidos orgânicos (ABUHAIMED;NEEL, 2017; WRIGHT; KAHLER; WALSH, 2017). A 
capacidade dissolvente do NaOCl também pode ser potencializada com o aumento da 
temperatura ou da concentração da solução (ABUHAIMED; NEEL, 2017). Já quando o pH 
está mais próximo do neutro, há maior concentração de ácido hipocloroso (WRIGHT; 
18 
 
KAHLER; WALSH, 2017), onde a atividade antimicrobiana é maximizada ABUHAIMED; 
NEEL, 2017; WRIGHT; KAHLER; WALSH, 2017). 
As concentrações do NaOCl utilizadas na prática clínica variam de 0.5% até 8,25% 
(MOSTAFA et al. 2020), (DEMENECH et al. 2021a), não havendo consenso na literatura 
acerca da concentração ideal (GONÇALVES et al., 2016; FARZANEH et al., 2018; 
IANDOLO et al., 2019; VERMA et al., 2019, MOSTAFA et al., 2020; DEMENECH et al., 
2021a). Já é sabido na literatura que, maiores concentrações de NaOCl possuem maior poder 
de desinfecção (IANDOLO et al., 2019) e dissolução de restos pulpares (DEMENECH et al., 
2021a), porém geram dúvidas quanto à segurança clínica de tais soluções (IANDOLO et al., 
2019; MOSTAFA et al., 2020), que podem ser muito irritantes quando acidentalmente 
extravasadas para os tecidos periapicais (GONÇALVES et al., 2016; VERMA et al., 2019; 
BORGO SARMENTO et al., 2020; MARTINS et al., 2020; MOSTAFA et al., 2020; 
DEMENECH et al., 2021a; HOSNY et al., 2021),O inverso ocorrecom as baixas 
concentrações, que apesar de mais seguras, geram dúvidas sobre sua capacidade antimicrobiana 
(IANDOLO et al., 2019). Algumas vertentes defendem que baixas concentrações de NaOCl 
podem ter a mesma eficácia que as de altas concentrações compensando com outros meios, 
como maior volume, agitação ou aumento da temperatura (MOSTAFA et al., 2020). 
Diferentes técnicas utilizadas na irrigação do canal geram debris (PARIROKH et al., 
2012), que são nada mais do que remanescentes pulpares, microorganismos, lascas de dentina 
e irrigantes (PARIROKH et al., 2012). Um estudo in vitro demonstrarou que quanto maior a 
concentração de NaOCl, maior é a extrusão de debris (PARIROKH et al., 2012). Como já 
mencionado, a extrusão do NaOCl é irritante aos tecidos periapicais (GONÇALVES et al., 
2016; VERMA et al., 2019; BORGO SARMENTO et al., 2020; MARTINS et al., 2020; 
MOSTAFA et al., 2020; DEMENECH et al., 2021a; HOSNY et al., 2021),e pode ser uma das 
causas de dor pós-operatória (HAAPASALO et al., 2014; 
TOPÇUOĞLU;TOPÇUOĞLU;ARSLAN, 2018; DEMENECH et al., 2021a). Sendo assim, 
pressupõe-se que a concentração do irrigante influencie na dor pós-operatória (VERMA et al., 
2019). 
Estudos clínicos randomizados já avaliaram o efeito de diferentes concentrações de 
NaOCl na ocorrência e intensidade de dor pós-operatória ( FARZANEH et al., 2018; VERMA 
et al., 2019; MOSTAFA et al., 2020; ULIN et al., 2020; DEMENECH et al., 2021), com 
resultados conflitantes entre si. FARZANEH et al., (2018) reportou melhores índices de 
ausência de dor pós-operatória quando utilizou maiores concentrações de NaOCl (5.25%) em 
molares inferiores com pulpite irreversível, enquanto que MOSTAFA et al., (2020) apresentou 
19 
 
resultados inversos quando utilizou molares inferiores com necrose pulpar. DEMENECH et 
al., (2021) também defendeu o uso de soluções mais concentradas quando o tempo do preparo 
endodôntico for reduzido. Já VERMA et al., (2019) e ULIN et al., (2020) argumentam que 
maiores concentrações não trazem benefícios adicionais. 
Diante do exposto, percebe-se a necessidade de que outros estudos com protocolos bem 
padronizados sejam conduzidos sobre o tema, inclusive revisões sistemáticas, a fim de elucidar 
qual concentração de NaOCl propicia a menor ocorrência de dor pós-operatória. Pois, com esse 
conhecimento, pode-se encontrar formas de diminuir o incômodo sofrido pelos pacientes 
(FARZANEH et al., 2018) e, assim, aumentar a aceitação dos mesmos em relação ao 
tratamento endodôntico (FARZANEH et al., 2018). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
20 
 
2 OBJETIVOS 
 
 
2.1 OBJETIVO GERAL 
 
 Avaliar se existe associação entre a concentração do NaOCl e a ocorrência e intensidade 
de dor pós-operatória no tratamento endodôntico. 
 
 
2.2 OBJETIVOS ESPECÍFICOS 
 
 Comparar o uso do NaOCl em baixa (entre 0,5% a 3%) e alta concentração (superior a 
3%) quanto à ocorrência e intensidade de dor pós-operatória; 
 Observar a ocorrência de dor pós-operatória nos diferentes períodos avaliados nos 
estudos (24h, 48h e 7 dias); 
 Observar a dor pós-operatória ocorrida após uma ou múltiplas sessões; 
 Comparar o consumo de analgésicos entre os pacientes do grupo de baixa concentração 
de NaOCl e alta concentração de NaOCl. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
21 
 
3 ARTIGO 
 
Influence of low and high concentrations of sodium hypochlorite on the post-operative pain 
after endodontic treatment: A systematic review and meta-analysis 
Rayssa Sabino-Silva, Ihan Vitor Cardoso, Filipe Colombo Vitali, Ana Maria Hecke Alves, Beatriz 
Dulcineia Mendes Souza, Eduardo Antunes Bortoluzzi, Lucas da Fonseca Roberti Garcia, Cleonice da 
Silveira Teixeira* 
 
1Department of Dentistry, Federal University of Santa Catarina, Florianopolis, Santa Catarina, 
Brazil. 
 
*Corresponding author: 
Department of Dentistry - Endodontics Division, Health Sciences Center, Federal University 
of Santa Catarina. Adress: Campus João David Ferreira Lima, Trindade, Florianópolis, Santa 
Catarina, Brazil. 
CEP: 88040-900, Telephone: +55 48 3721-5840; +55 48 3721-9520 
E-mail: cleonice.teixeira@ufsc.br / cleotex@uol.com.br 
 
Short Title: Influence of sodium hypochlorite concentration on postoperative pain 
Keywords: Meta-analysis; postoperative pain; sodium hypochlorite; systematic review. 
Conflict of interest: 
The authors deny any conflict of interest related to this study 
 
Contribution Statements 
All authors contributed to the study conception and design, especially Cleonice Silveira 
Teixeira and Rayssa Sabino-Silva. Material preparation, data collection and analysis were 
performed by Rayssa Sabino-Silva, Ihan Vitor Cardoso, Filipe Colombo Vitali and Cleonice 
Silveira Teixeira. The first draft of the manuscript was written by Rayssa Sabino-Silva, Ihan 
Vitor Cardoso, Filipe Colombo Vitali and Cleonice Silveira Teixeira. All authors commented 
on previous versions of the manuscript. All authors read and approved the final manuscript. 
 
 
 
 
 
22 
 
ABSTRACT 
 
Introduction: Among the solutions used in endodontic treatment, sodium hypochlorite 
(NaOCl) stands out as being the most commonly used irrigant, being sold in different 
concentrations. However, there are controversies in the literature about whether its use during 
endodontic treatment is related to postoperative pain. 
Objective: To systematically assess whether the different concentrations of NaOCl used in 
clinical practice interfere with the patient's postoperative pain. 
Methodology: Two independent reviewers searched the literature in the following databases: 
Cochrane Library, EMBASE, Latin American and Caribbean Health Sciences Literature 
(LILACS), MEDLINE PubMed, Scopus, and Web of Science. Additionally, complementary 
research was conducted in the gray literature including Google Scholar, OpenGrey, and 
ProQuest. Randomized clinical trials that evaluated the influence of different concentrations of 
NaOCl on postoperative pain were included. Studies that evaluated endodontic retreatments, 
studies that evaluated primary teeth, teeth with incomplete root formation or fractures and 
resorptions, studies that did not use NaOCl as an irrigant and review studies, case-control, and 
case reports were excluded. The concentrations of NaOCl were dichotomized into high 
concentration (above 3%) and low concentration (between 0.5% and 3%). The risk of bias 
assessment was performed using the Cochrane Collaboration's Risk-of-Bias Assessment Tool 
2.0. The pooled prevalence of postoperative pain was assessed through a proportion meta-
analyses. 
Results: After search, 705 potential studies were identified. After screening titles and abstracts, 
23references were selected for full reading, where nine studies were included in the systematic 
review. Three studies were assessed as ‘high risk of bias’, one was assessed as ‘some concerns’ 
and the others were assessed as ‘low risk of bias’. The overall pooled prevalence of 
postoperative pain was 36.31% in the high NaOCl concentration group and 45.35% in the low 
NaOCl concentration group. After 24h, 39.11% of patients in the high concentration group 
reported pain, while only 28.83% of patients in the low concentration group had pain. After 7 
days, neither group had moderate or severe pain, with 94.89% of patients in the high-
concentration group and 96.58% of patients in the low-concentration group reporting no 
symptoms. 
Conclusions: The overall pooled prevalence of postoperative pain was 36.31% in the high 
concentration NaOCl group and 45.35% in the low concentration NaOCl group, with no 
patients experiencing moderate or severe pain after 7 days in both groups. 
 
 
 
 
23 
 
INTRODUCTION 
 
Knowledge of the causes of postoperative pain after endodontic treatment is important for 
clinicians, since it is relatively common, and canimpact the quality of life of the patients (Pak 
& White 2011, Farzaneh et al. 2018, Borgo Sarmento et al. 2020, Mostafa et al. 2020). 
Furthermore, avoiding unnecessary pain can increase the acceptance of endodontic treatment 
by patients (Farzaneh et al. 2018). 
Although common, postoperative pain can be considered a subjective outcome and it is 
not restricted to one etiological factor (Topçuoğlu et al. 2018, Borgo Sarmento et al. 2020, 
Mostafa et al. 2020). The presence of periapical diseases and extrusion of debris or irrigating 
solutions during treatment into the periapical tissues are highlighted as major etiological factors 
(Topçuoğlu et al. 2018, Borgo Sarmento et al. 2020). Among the secondary factors, the number 
of visits, the obturation technique, and the type and concentration of irrigating solution used 
during the endodontic treatment can be cited (Mostafa et al. 2020). 
Sodium hypochlorite (NaOCl) is the most used irrigating solution in endodontics, due 
to its advantages such as antimicrobial activity and organic tissue dissolving ability (Gonçalves 
et al. 2016; Farzaneh et al. 2018, Iandolo et al. 2019, Verma et al. 2019, Borgo Sarmento et al. 
2020, Mostafa et al. 2020, Hosny et al. 2021). However, NaOCl can be associated with 
postoperative pain when not properly used, as it acts as a tissue irritant when extravasated 
beyond the apical limits of the root canal (Gonçalves et al. 2016, Verma et al., 2019, Borgo 
Sarmento et al. 2020, Martins et al. 2020, Mostafa et al. 2020, Demenech et al. 2021a, Hosny 
et al. 2021) 
Higher concentrations of NaOCl are associated with higher extrusion of debris in vitro 
and greater damage to periapical tissues (Parirokh et al. 2012, Gonçalves et al. 2016, Mostafa 
et al. 2020). In the clinical practice, the NaOCl concentrations used vary from 0.5% to 8,25%, 
with no consensus in the literature on the ideal concentration of NaOCl (Gonçalves et al. 2016, 
Farzaneh et al. 2018, Verma et al. 2019, Mostafa et al. 2020, Demenech et al. 2021a). When 
choosing the concentration of NaOCl solution for endodontic purposes, clinicians generally 
consider the pulp condition, if necrotic or vital (De Gregorio et al. 2015). The antimicrobial 
effectiveness and the ability to dissolve organic tissue are directly related to the increase in the 
concentration of the NaOCl solution, but also its cytotoxicity, which can generate clinical 
problems when this irrigant comes into contact with oral tissues (Haapasalo et al. 2014). 
In recent years, a systematic review has sought to assess the occurrence of postoperative 
pain after endodontic treatment using different concentrations and types of irrigating solutions 
24 
 
(Fedorowicz et al. 2012). However, this study was not specific regarding the use of different 
concentrations of NaOCl and did not include recently published randomized clinical studies on 
this subject (Borgo Sarmento et al. 2020, Martins et al. 2020). Therefore, a review assessing 
the influence of different concentrations of NaOCl on postoperative pain and with the newest 
clinical trials is still needed. Therefore, this systematic review and meta-analysis aimed to 
answer the following focused question: “In permanent teeth with complete root formation, does 
the concentration of NaOCl used in endodontic treatment performed in single or multiple visits 
influence the occurrence of postoperative pain?”. 
 
MATERIALS AND METHODS 
 
Registration and protocol 
The present systematic review is reported in accordance with the Preferred Reporting Items for 
Systematic Reviews and Meta-Analyses statement (PRISMA 2020) (Page et al. 2021). A 
protocol based on the PRISMA 2020 statement was registered at the International Prospective 
Register of Systematic Reviews (PROSPERO) under the code CRD42021258830. 
 
Eligibility criteria 
This systematic review was conducted using the acronym PICOS, in which the participants (P) 
were healthy adult patients undergoing primary endodontic treatment of mature permanent 
teeth; intervention (I) was represented by the endodontic treatment performed with NaOCl as 
an irrigating solution; comparison (C) was studies using another concentration of NaOCl or 
other irrigating solution; the outcome (O) was the occurrence of post-operative pain, and 
studies (S) were randomized or quasi-randomized clinical trials. An additional outcome was 
the comparison of postoperative pain after single or multiple sessions of the endodontic 
treatment. 
The following exclusion criteria were applied: 1) Studies with teeth not fully developed 
(open apex); 2) Studies with deciduous/primary teeth; 3) Studies with previously endodontic 
treated teeth or studies with retreatments; 4) Studies with teeth with cracks, fractures, or any 
type of root resorption; 5) Studies without control group; 6) Reviews, control cases, cohort 
studies, case-reports, case series, protocols, short communications, personal opinions, letters, 
abstracts, posters, and conference abstracts. 
 
Information sources and search strategy 
25 
 
Electronic searches were conducted in the following databases: The Cochrane Library, 
EMBASE, Latin American and Caribbean Health Sciences Center (LILACS), MEDLINE 
PubMed, Scopus, and Web of Science. Additional searches on grey literature were performed 
on Google Scholar, OpenGrey, and ProQuest dissertations & theses. The first literature search 
was performed up to April 23rd, 2021, updated on October 31st, 2021. Individual search 
strategies for each database are available in Appendix I. In addition, manual searches were 
performed in the reference list of the articles included, to identify potentially relevant articles 
that were not identified in the initial search. Experts were also contacted to suggest studies on 
the topic. A reference manager software (EndNote X7, Thomson Reuters, Philadelphia, USA) 
was used to collect references and remove the duplicate ones. 
 
Selection process 
Two reviewers (R.S.S. and I.V.C.) independently examined the titles and abstracts using the 
electronically available application, Rayyan QCRI (Qatar Computing Research Institute - Data 
Analytics, Doha, Qatar). Disagreements were resolved between them and, if there was no 
consensus, a third reviewer (F.C.V.) was consulted. Next, the full texts were read, and the 
articles were selected to be part of the study. 
 
Data collection process, data items, and effect measures 
A data collection form was developed and tested in a pilot study. After training, two 
independent reviewers (R.S.S. and I.V.C.) collected the following critical data: authors, year 
of publication, country, characteristics of participants (number, age), NaOCl concentrations, 
pulp status, number of sessions/visits, occurrence and intensity of postoperative pain in 
assessed times, pertinent results and conclusions. Any disagreement was resolved between 
them and, if there was no consensus, a third reviewer (F.C.V.) was involved to steer the 
decision. 
 
Risk of bias assessment 
The risk of bias of each included article was assessed using the Cochrane Collaboration’s Risk-
of-Bias Assessment Tool 2.0 (Sterne et al. 2019). This tool consists of assessing the risk of bias 
in six domains: randomization process, deviations from intended interventions, missing 
outcome data, measurement of the outcome, selection of the reported result, and overall bias. 
To use this tool, two reviewers (R.S.S. and I.V.C) were previously trained and calibrated. Then, 
the reviewers independently rated each domain as ‘low risk of bias’, ‘high risk of bias’, or 
26 
 
‘some concerns’. Studies judged to be ‘low’ for all domains were classified as ‘low risk of 
bias’, studies considered to have ‘some concerns’ in at least one domain were classified as 
‘some concerns’, and studies judged to be at ‘high risk of bias’ in at least one domain, or if 
they were considered to have ‘someconcerns’ for multiple domains, were classified as ‘high 
risk of bias’. In the event of disagreement, a third reviewer (F.C.V.) was involved to guide the 
decision. 
 
Meta-analysis 
First, the NaOCl concentrations used in the included studies were dichotomized into ‘low 
concentration’ (0.5% to 3%) and ‘high concentration’ (more than 3%). Then, a meta-analysis 
of proportions was applied to data combined in the following categories: pooled proportion of 
overall postoperative pain - after 24h and 48h - for groups with low and high NaOCl 
concentrations; pooled proportion of postoperative pain categorized into 'absent', 'mild', 
'moderate' and 'severe' – after 24h, 48h and 7 days - for groups with low and high NaOCl 
concentrations; pooled proportion of patients who needed to use medication to 
controlpostoperative pain after endodontic treatment with low and high NaOCl concentrations. 
In case of studies in which two or more concentrations of NaOCl were used, a separate register 
of postoperative pain for each concentration was recorded and included in the analysis 
(Farzaneh et al. 2018,Verma et al. 2019, Mostafa et al. 2020, Ulin et al. 2020, Demenech et al. 
2021) . This analysis was carried out in the MedCalc software (version 15.8; Ostend, Belgium). 
A significance level of 5% was applied. Between-study heterogeneity was explored using the 
I2 index. Given the clinical heterogeneity, a random-effect model was used to compute the 
pooled data analyses. 
 
Certainty of evidence assessment 
The certainty of evidence and recommendations' strength was assessed using the GRADE 
(Grading of Recommendations Assessment, Development, and Evaluation) approach. The 
GRADE assessment was performed independently by the two reviewers (R.S.S. and I.V.C.), 
and any disagreement was resolved between them, otherwise, a third reviewer (F.C.V.) was 
consulted. The assessed topics were ‘study design’, ‘risk of bias’, ‘indirectness’, 
‘inconsistency’, ‘imprecision’ and ‘publication bias’. The ‘study design’ is the randomized 
clinical trial; the ‘RoB’ was assessed using the Cochrane Collaboration’s Risk-of-Bias 
Assessment Tool 2.0 (Sterne et al. 2019); ‘indirectness’ stands for the direct evidence; 
‘inconsistency’ is related to the consistency of the results; ‘imprecision’ refers to a wide 
27 
 
confidence interval (CI); and ‘publication bias’ analyses if there was a selection of studies. 
 
RESULTS 
 
Study selection 
The study selection process is summarized in Figure 1. The search strategy from databases and 
grey literature resulted in 1,545 references. After removing the duplicates, 705 articles 
remained. After reading the titles and abstracts, 20 articles were selected for full-text reading 
and 4 articles were rescued from citation searching that corresponded to the eligibility criteria. 
Nevertheless, after careful reading, only nine could be included in the systematic review as 
Figure 1 shows. Yet, only seven had available and sufficient data that could be included in the 
meta-analysis (Almeida et al. 2012, da Silva et al. 2015, Verma et al. 2019, Mostafa et al. 2020, 
Ulin et al. 2020, Demenech et al. 2021a, Hosny et al. 2021). 
 
Study characteristics 
The included articles were published between 2010 and 2021 and are presented in Table 1. 
Eight articles were randomized (Bashetty & Hedge 2010, Almeida et al. 2012, da Silva et al. 
2015, Farzaneh et al. 2018, Verma et al. 2019, Mostafa et al. 2020, Demenech et al. 2021a, 
Hosny et al. 2021), and one was a quasi-randomized clinical trial (Ulin et al. 2020). Regarding 
the blinding of outcome assessment, one was single-blinded (Ulin et al. 2020), four were 
double-blinded (Verma et al. 2019, Mostafa et al. 2020, Demenech et al. 2021a, Hosny et al. 
2021), and two was triple-blinded (Bashetty & Hedge 2010, Farzaneh et al. 2018). Two studies 
did not inform any type of blinding (Almeida et al. 2012 and da Silva et al. 2015). 
Regarding the participants’ data, the ages ranged from 16 to 89 years old (Ulin et al. 
2020, Hosny et al. 2021). The participants included in the studies could not be 
immunocompromised (Almeida et al. 2012, da Silva et al. 2015, Farzaneh et al. 2018, Verma 
et al. 2019, Hosny et al. 2021), pregnant (da Silva et al. 2015, Farzaneh et al. 2018, Verma et 
al. 2019, Mostafa et al. 2020, Hosny et al. 2021) and lactating females (Farzaneh et al. 2018, 
Mostafa et al. 2020), or being allergic to the materials or medications used (Bashetty & Hedge 
2010, Mostafa et al. 2020, Demenech et al. 2021a). They also should not have been taking any 
medication to prevent pain in eight of the nine studies (Bashetty & Hedge 2010, Almeida et al. 
2012, da Silva et al. 2015, Farzaneh et al. 2018, Verma et al. 2019, Demenech et al. 2021a, 
Hosny et al. 2021, Mostafa et al. 2020). Ulin et al. (2020) did not report this information. 
As for their dental condition, periodontally compromised teeth (Almeida et al. 2012, da 
28 
 
Silva et al. 2015; Farzaneh et al. 2018; Verma et al. 2019; Hosny et al. 2021) are not suitable 
for rubber dam isolation (Farzaneh et al. 2018; Verma et al. 2019, Ulin et al. 2020), severely 
curved root canals (Mostafa et al. 2020), or alterations such as root calcification (Almeida et 
al. 2012, Ulin et al. 2020, Demenech et al. 2021a, Hosny et al. 2021), perforation (Ulin et al. 
2020; Demenech et al. 2021; Hosny et al. 2021), fractures (Demenech et al. 2021a, Hosny et 
al. 2021) or even resorptions (Hosny et al. 2021) prevented them from being included in the 
studies. 
 In total, the studies have contemplated 1,067 teeth that required endodontic treatment. 
The most commonly treated teeth were mandibular molars, which were the exclusive subject 
analysis of the four studies (Farzaneh et al. 2018, Verma et al. 2019, Mostafa et al. 2020, Hosny 
et al. 2021). Regarding the pulp condition, most of them included necrotic pulps with apical 
periodontitis (Bashetty & Hedge 2010, Almeida et al. 2012, da Silva et al. 2015, Verma et al. 
2019, Mostafa et al. 2020 Demenech et al. 2021a, Hosny et al. 2021). As for the endodontic 
protocol, four studies were performed in a single visit (Almeida et al. 2012, da Silva et al. 2015, 
Farzaneh et al. 2018, Demenech et al. 2021a) and four were performed in two visits (Bashetty 
& Hedge 2010, Verma et al. 2019, Mostafa et al. 2020, Hosny et al. 2021). In these, only one 
used calcium hydroxide as intracanal medication (Verma et al. 2019). Finally, four studies 
performed the treatment in a single session (Almeida et al. 2012, da Silva et al. 2015, Farzaneh 
et al. 2018, Demenech et al. 2021a), other four studies performed in two sessions (Bashetty & 
Hedge 2010, Verma et al. 2019, Mostafa et al. 2020, Hosny et al. 2021), and one study 
performed the treatment in one, two or more sessions at the operator’s criteria (Ulin et al. 2020). 
The concentration of NaOCl varied among the included studies: 0.5% (Ulin et al. 2020), 
1% (Verma et al. 2019), 1.3% (Mostafa et al. 2020), 2.5% (Farzaneh et al. 2018, Demenech et 
al. 2021, Hosny et al. 2021), 3% (Ulin et al. 2020), 5% (Verma et al. 2019), 5.25% (Almeida 
et al. 2012, da Silva et al. 2015, Farzaneh et al. 2018, Mostafa et al. 2020, Demenech et al. 
2021a) and 8.25% (Demenech et al. 2021a). The post-operative pain was measured using a 
Visual Analog Scale (VAS) in five studies, where two rated the pain from ‘0 to 9’ (Farzaneh 
et al. 2018, Verma et al. 2019), and two from ‘0 to 10’ (Ulin et al. 2020, Demenech et al. 
2021a). Two articles assessed post-operative pain by a numeric rating scale (NRS) numeric 
scale from ‘0 to 10’ (Hosny et al. 2021) or from ‘1 to 10’ (Mostafa et al. 2020). Almeida et al. 
(2012) assessed the pain in a questionnaire and Da Silva et al. (2015) scored the pain from 1-
to 4. Pain assessment time ranged from three hours (Mostafa et al. 2020) to seven days after 
the treatment (Bashetty & Hedge 2010, Almeidaet al. 2012, Farzaneh et al. 2018, Verma et al. 
2019, Mostafa et al. 2020) among studies. 
29 
 
Table 1. Characteristics of the included studies 
Authors 
(year), 
Country 
 
(n) patients, 
Age range 
(Age mean 
±SD) 
Evaluated 
Teeth, Pulp 
Condition 
Irrigation 
Protocol* 
Evaluated 
Times and 
Method 
NaOCl concentration 
x 
Postoperative Pain 
(n) 
of sessions 
Conclusion 
 
Almeida et 
al. (2012), 
Brazil 
 
n = 63, 
18 to59y 
(38y) 
 
63 teeth with pulp 
necrosis and 
apical 
periodontitis 
2ml of 5.25% 
NaOCl 
E o 0,9%?? 
 
 
24h, 48h, 72h, 
7d with - 
questionnaire 
 
24h: 19% (12/63) reported 
mild pain and 3% reported 
(2/63) moderate pain 
 
1 Both of the irrigants tested in this study (5.25% NaOCl and 2% CLX gel 
with 0.9% NaCl) were associated with low rates of postoperative pain 
among patients undergoing single-visit endodontic treatment for chronic 
apical periodontitis with pulp necrosis. It is likely that as long 
as the selected irrigant is kept inside the root canal by means of a low-
pressure irrigation technique, postoperative pain and flare-ups can be 
avoided. 
Bashetty & 
Hedge 
(2010), 
India 
n = 20, 
21 to 40y 
 
10 teeth with pulp 
necrosis, 8 with 
acute apical 
periodontitis, and 
3 with irreversible 
pulpitis 
5.25% NaOCl 6h, 24h, 4d, 7d - 
VAS 
24h: mean VAS score of 
1.5 
2 A significant difference in the pain level was observed between 2% 
chlorhexidine and 5.25% sodium hypochlorite only at the 6th hour 
postoperatively. The pain was present more in the sodium hypochlorite 
group compared to the chlorhexidine group. 
 
da Silva et al. 
(2015), 
Brazil 
 
n = 31 , 
>18y 
(43.9y) 
 
31 teeth with 
asymptomatic 
Necrosis 
 
3ml of 5.25% 
NaOCl 
 
24h, 48, 72h 
-unspecified 
questionnaire 
 
24h: 15% reported mild 
pain, 20% moderate pain, 
and 2% severe pain 
 
1 
5.25% NaOCl or 2% CHX gel resulted in similar levels of postoperative 
pain. Therefore, it may be concluded that both irrigants are acceptable 
regarding short-term postoperative pain during root canal instrumentation 
with foraminal instrumentation. 
 
Demenechet 
al. 
(2021), 
Brazil 
 
 
n = 126 , 
(38.6y) 
 
125 teeth, 101 
with pulp 
necrosis, and 25 
with irreversible 
pulpitis 
 
6ml of NaOCl 
(2.5%, 5.25% 
or 8.25%) 
 
24, 48h, 72h 
-VAS 
 
24: 4.7% reported pain in 
the 2.5% NaOCl group, 
16.7% in the 5.25% and 
17.1% in the 8.25% group. 
 
1 
 
The 8.25% NaOCl solution was not significantly more associated with 
either the presence or intensity of pain compared with other solutions. 
Farzaneh et 
al. 
(2018), 
Iran 
n = 110, 
(28.45y) 
 
110 mandibular 
molars with 
irreversible 
pulpitis 
2ml of NaOCl 
(2.5% or 
5.25%) 
6h, 12h, 24h, 
48h, 72h, 4d, 
5d, 6d, 7d – 
VAS 
 
 
NC 
1 
Up to 3 days following root canal treatment, the use of 5.25% NaOCl as an 
irrigant was associated with significantly less pain than the use of 2.5% of 
NaOCl. 
 
Hosny et al. 
(2021), 
Egypt 
 
n = 25 , 
(29y) 
 
25 teeth with pulp 
necrosis, 10 
presented 
periapical lesion 
 
3ml of NaOCl 
for 1 minute 
 
6h, 12h, 24h, 
48h -NRS 
 
24h: 44% (11/25) reported 
mild pain and 4% (1/25) 
reported moderate pain 
 
2 
 
 
Neem and 2.5% NaOCl were not significantly different in terms of reducing 
the intensity of post-operative pain during all follow-up periods. 
Mostafa et al. 
(2020), 
Egypt 
n = 308, 
(31.87y) 
308 mandibular 
molars with pulp 
necrosis (with or 
3ml of NaOCl 
(1.3% or 
5.25%) 
3h, 24h, 48h, 7d 
after first 
session and 
24h: 51.3% (79/154) 
reported pain in the 1.3% 
NaOCl group and 88.3% 
2 
Using 1.3% NaOCl was associated with less intense and less frequent post-
endodontic pain than5.25% NaOCl in mandibular molars with nonvital 
30 
 
without apical 
periodontitis) 
immediately 
after obturation 
in second 
session - NRS 
(136/154) reported pain in 
the 5.25% NaOCl group. 
pulps treated in two visits. The incidence of pain was reduced by up to 60% 
within the week post-instrumentation and 80% after root canal filling and 
the rescue analgesic intake by about 70% on using 1.3% NaOCl compared 
to 5.25% NaOCl. 
 
Ulin et al. 
(2020), 
Sweden 
 
 
n = 211 
 
106 teeth in the 
0.5% NaOCl 
group and 105 
teeth in the 3% 
NaOCl group 
 
NaOCl 
(0.5% or 3%) 
 
24h, 48h, 72h, 
4d, 5d, 6d, 7d - 
VAS 
 
53.8% (57/106) reported 
pain in the 0.5% group and 
53.3% (56/105) group 
reported pain in the 3% 
NaOCl 
 
1, 2 or 
more at the 
operator’s 
criteria 
 
 0.5% NaOCl irrigation with a 3.0% NaOCl solution did not result in fewer 
postoperative samples with cultivable bacteria nor higher frequency or 
magnitude of postoperative pain. 
 
Verma et al. 
(2019), 
India 
n= 86 , 
18 to47y 
(28.91y) 
86 mandibular 
molars with pulp 
necrosis and 
chronic apical 
periodontitis 
5ml of NaOCl 
(1% or 5%) 
24h, 48h, 72h, 
4d, 5d, 6d, 7d - 
VAS 
24h: 37.78% (17/45) 
reported pain in the 1% 
NaOCl group and 46.67% 
(21/45) in the 5%NaOCl 
group. 
2 1% NaOCl as an endodontic irrigant is adequate, and higher concentrations 
may not provide any additional benefit. 
Legend: (n)= number. SD = standard deviation. NC = Not clear. VAS = visual analog scale. NRS= numeric rating scale. NaOCl= sodium hypochlorite. y= years. d=days. 
* Quantity of irrigating solution used at each insertion of the instrument and at the end of the root canal preparation. 
 
31 
 
Results of individual studies 
Seven studies that reported the occurrence of postoperative pain - regardless of the 
evaluation time – were included in a meta-analysis of proportion, to assess the overall 
incidence of postoperative pain (Almeida et al. 2012, da Silva et al. 2015,Verma et al. 
2019, Mostafa et al. 2020, Ulin et al. 2020, Demenech et al. 2021a, Hosny et al. 2021) 
(Table 2). Of these, five studies were included in the high concentration group (Almeida 
et al. 2012, da Silva et al. 2015, Verma et al. 2019, Mostafa et al. 2020, Demenech et al. 
2021a), and five studies in the low concentration group (Verma et al. 2019, Mostafa et al. 
2020, Ulin et al. 2020, Demenech et al. 2021a, Hosny et al. 2021). The overall incidence 
of postoperative pain was 45.36% (95% CI [22.55 – 51.32%]) for low concentrations of 
NaOCl, and 36.31% (95% CI [33.41 – 57.58%]) for high concentrations of NaOCl (Table 
2). 
 
Table 2. Measures of the pooled proportion values [n (% - random effect)] of overall 
incidence of postoperative pain for high and low sodium hypochlorite (NaOCl) 
concentrations 
Studies Sample size Pain No pain 
High concentrations of NaOCl 
Almeida et al. (2015) 63 14 (22.22%) 49 (77.78%) 
Da Silva et al. (2015) 31 13 (41.94%) 18 (58.06%) 
Demenech et al. (2021) 42 12 (28.57%) 30 (71.43%) 
Demenech et al. (2021) 41 8 (19.51%) 33 (80.49%) 
Mostafa et al. (2020) 154 90 (58.44%) 64 (41.56%) 
Verma et al. (2019) 45 21 (46.67%) 24 (53.33%) 
Total (random effects) 376 158 (36.31%) 218 (63.69%) 
95% CI 22.55 – 51.32% 48.68 – 77.45% 
 I² 87.84% 87.84% 
Low concentrations of NaOCl 
Demenech et al. (2021) 43 6 (13.95%) 37 (86.05%) 
Hosny et al. (2021) 25 14 (56.00%) 11 (44.00%) 
Mostafa et al. (2020) 154 88 (57.14%) 66 (42.86%) 
Ulin et al. (2020) 106 57 (53.77%) 49 (46.23%) 
Ulin et al. (2020) 105 56 (53.33%) 49 (46.67%) 
Verma et al. (2019) 45 17 (37.78%) 28 (62.22%) 
Total (random effects) 478 238 (45.35%) 240 (54.65%) 
95% CI 33.41 – 57.58% 42.42 – 66.59% 
 I² 85.24% 85.34% 
Legend. CI: confidential interval. 
 
 Table 3 presents the overall prevalence of postoperative pain after 24h and 48h. 
Ulin et al. 2020 did not report data regarding this time, thus, it was not included in this 
32 
 
meta-analysis. Similarly, Verma et al. (2019) was not included in the 48h meta-analysis. 
The intensity ofpostoperative pain was classified in absent, mild, moderate and 
severe as shown in Table 4. Mild pain was more common than severe pain in all the times 
assessed (24h, 48h and 7 days) and in both concentrations. The prevalence of mild pain 
was 29.45% (95% CI [8.40 – 56.76%]) in the first 24h of the high concentration group, 
and of 3.44% (95% CI [2.30 – 57.29%]) in the first 24h of the low concentration group. 
In the course of 7 days, no patient experienced moderate or severe pain in both 
concentrations. 
 
 
Table 3. Measures of the pooled proportion values [n (% - random effect)] of the 
incidence of pain at the postoperative times (24 and 48h) for high and low sodium 
hypochlorite (NaOCl) concentrations 
 
Studies Sample size Pain No pain 
After 24h 
High concentrations of NaOCl 
Almeida et al. (2015) 63 14 (22.22%) 49 (77.78%) 
Da Silva et al. (2015) 31 13 (41.94%) 18 (58.07%) 
Demenech et al. (2021) 42 7 (16.67%) 35 (83.33%) 
Demenech et al. (2021) 41 7 (17.07%) 34 (82.93%) 
Mostafa et al. (2020) 154 136 (88.31%) 18 (11.69%) 
Verma et al. (2019) 45 21 (46.67%) 24 (53.33%) 
Total (random effects) 376 198 (39.11%) 178 (60.89%) 
95% CI 12.50 – 69.88% 30.128 – 87.50% 
 I² 97.20% 97.20% 
Low concentrations of NaOCl 
Demenech et al. (2021) 43 2 (4.65%) 41 (95.35%) 
Hosny et al. (2021) 25 2 (8.00%) 23 (92.00%) 
Mostafa et al. (2020) 154 79 (51.29%) 75 (48.70%) 
Verma et al. (2019) 45 17 (37.51%) 28 (62.22%) 
Total (random effects) 267 100 (28.83%) 167 (76.17%) 
95% CI 5.00 – 50.90% 49.10 – 95.00%) 
 I² 94.54% 94.54% 
After 48h 
High concentrations of NaOCl 
Almeida et al. (2015) 63 6 (9.52%) 57 (90.47%) 
Da Silva et al. (2015) 31 12 (38.71%) 19 (61.29%) 
Demenech et al. (2021) 42 3 (7.14%) 39 (92.86%) 
Demenech et al. (2021) 41 1 (2.44%) 40 (97.56%) 
Mostafa et al. (2020) 154 102 (66.23%) 52 (33.77%) 
Total (random effects) 331 124 (21.88%) 207 (78.12%) 
95% CI 2.22 – 53.86% 46.14 – 97.78% 
 I² 97.15% 97.15% 
33 
 
Low concentrations of NaOCl 
Demenech et al. (2021) 43 0 (0.00%) 43 (100.00%) 
Hosny et al. (2021) 25 0 (0.00%) 25 (100.00%) 
Mostafa et al. (2020) 154 42 (27.27%) 112 (72.73%) 
Total (random effects) 222 42 (6.03%) 180 (93.97%) 
95% CI 1.18 – 32.35% 67.65 – 98.82% 
 I² 95.25% 95.25% 
Legend. CI: confidential interval. 
 
 
34 
 
Table 4. Measures of the pooled proportion values [n (% - random effect)] of pain at the different 
categories and postoperative times (24, 48h and 7 days) for high and low sodium hypochlorite 
(NaOCl) concentrations 
Studies 
Sample
 size 
Absent Mild Moderate Severe 
After 24h 
High concentrations of NaOCl 
Almeida et al. (2015) 63 49 (77.78%) 12 (19.05%) 2 (3.18%) 0 (0.00%) 
Da Silva et al. (2015) 31 18 (58.06%) 5 (16.13%) 7 (22.58%) 1 (3.23%) 
Mostafa et al. (2020) 154 18 (11.69%) 82 (53.25%) 37 (24.03%) 17 (11.04%) 
Total (random effects) 248 85 (47.61%) 99 (29.45%) 46 (15.52%) 18 (4.38%) 
95% CI 6.73 – 90.68% 8.40 – 56.76% 3.62 – 33.61% 0.06 – 14.99% 
 I² 98.09% 93.86% 89.42% 86.15% 
Low concentrations of NaOCl 
Hosny et al. (2021) 25 23 (92.00%) 2 (8.00%) 0 (0.00%) 0 (0.00%) 
Mostafa et al. (2020) 154 75 (48.66%) 60 (38.96%) 14 (9.09%) 5 (3.25%) 
Total (random effects) 179 98 (71.40%) 62 (3.44%) 14 (4.92%) 5 (3.08%) 
95% CI 25.78 – 99.19% 2.30 – 57.29% 0.04 – 17.24% 1.07 – 6.08% 
 I² 95.22% 91.38% 75.04% 0.00% 
After 48h 
High concentrations of NaOCl 
Almeida et al. (2015) 63 57 (90.48%) 6 (9.52%) 0 (0.00%) 0 (0.00%) 
Da Silva et al. (2015) 31 19 (61.29%) 8 (25.81%) 4 (12.90%) 0 (0.00%) 
Mostafa et al. (2020) 154 52 (33.77%) 67 (43.51%) 29 (18.83%) 6 (3.90%) 
Total (random effects) 248 128 (63.27%) 81 (25.67%) 33 (8.72%) 6 (1.765%) 
95% CI 23.74 – 94.48% 6.99 – 50.95% 0.18 – 27.97% 0.10 – 5.43% 
 I² 97.22% 93.09% 92.76% 54.14% 
Low concentrations of NaOCl 
Hosny et al. (2021) 25 25 (100.00%) 0 (0.00%) 0 (0.00%) 0 (0.00%) 
Mostafa et al. (2020) 154 112 (72.73%) 32 (20.78%) 9 (5.84%) 1 (0.65%) 
Total (random effects) 179 137 (89.27%) 32 (8.61%) 9 (3.98%) 1 (0.95%) 
95% CI 50.86 – 98.81% 0.50 – 38.23% 0.38 – 11.11% 0.06 – 2.87% 
 I² 94.51% 92.10% 51.01% 0.00% 
After 7 days 
High concentrations of NaOCl 
Almeida et al. (2015) 63 62 (98.41%) 1 (1.59%) 0 (0.00%) 0 (0.00%) 
Mostafa et al. (2020) 154 125 (81.17%) 29 (18.83%) 0 (0.00%) 0 (0.00%) 
Verma et al. (2019) 53 53 (100.00%) 0 (0.00%) 0 (0.00%) 0 (0.00%) 
Total (random effects) 270 240 (94.89%) 30 (5.11%) 0 (0.26%) 0 (0.26%) 
95% CI 78.68 – 99.94% 0.06 – 21.32% 0.00 – 1.21% 0.00 – 1.21% 
 I² 93.64% 93.64% 0.00% 0.00% 
Low concentrations of NaOCl 
Mostafa et al. (2020) 154 143 (92.86%) 11 (7.14%) 0 (0.00%) 0 (0.00%) 
Verma et al. (2019) 43 43 (100.00%) 0 (0.00%) 0 (0.00%) 0 (0.00%) 
Total (random effects) 197 186 (96.58%) 11 (3.42%) 0 (0.23%) 0 (0.23%) 
95% CI 86.17 – 99.99% 0.01 – 13.83% 0.05 – 1.38% 0.05 – 1.38% 
 I² 81.79% 81.79% 0.00% 0.00% 
Legend. CI: confidential interval. 
 
35 
 
Five studies reported the number of patients who needed to consume analgesics 
after endodontic treatment (at any time) with different concentrations of NaOCl (da Silva 
et al. 2015, Farzaneh et al. 2018, Verma et al. 2019, Mostafa et al. 2020, Demenech et al. 
2021). The proportion of patients who used analgesics to control postoperative pain in 
the high concentration group was 16.51% (95% CI [9.72 – 24.67%]), and 9.54% (95% CI 
[3.12 – 18.96%]) (Table 5) in the low concentration group (Table 5). 
 
Table 5. Measures of the pooled proportion values [n (% - random effect)] of the number 
of patients who used analgesics to control postoperative pain. 
Studies Sample size Yes No 
High concentration of NaOCl 
Demenech et al. (2021) 42 7 (16.67%) 35 (83.33%) 
Demenech et al. (2021) 41 2 (4.88%) 39 (95.12%) 
Mostafa et al. (2020) 154 29 (18.83%) 125 (81.17%) 
Verma et al. (2019) 45 11 (24.44%) 34 (75.56%) 
Total (random effects) 282 49 (16.51%) 233 (83.49%) 
95% CI 9.72 – 24.67% 75.33 – 90.28 
 I² 60.66% 60.66% 
Low concentration of NaOCl 
Demenech et al. (2021) 43 2 (4.65%) 41 (95.35%) 
Mostafa et al. (2020) 154 9 (5.84%) 145 (94.16%) 
Verma et al. (2019) 45 9 (20.00%) 36 (80.00) 
Total (random effects) 242 20 (9.54%) 222 (90.46%) 
95% CI 3.12 – 18.96% 81.04 – 96.88% 
 I² 73.35% 73.35% 
Legend. CI: confidential interval; NaOCl: sodium hypochlorite. 
 
 
Risk of bias assessment 
The inter-observer agreement for the risk of bias assessment (Kappa = 0.817 [0.228]) was 
considered excellent (Chmura Kraemer et al. 2002). Figure 2 shows the risk of bias 
assessment of the included studies. 
Using the Cochrane Collaboration’s Risk-of-Bias Assessment Tool 2.0 (Sterne et 
al. 2019), three studies were classified as ‘high risk of bias’ (Almeida et al. 2012, da Silva 
et al. 2015, Ulin et al. 2020), five as ‘low risk of bias’ (Farzaneh et al. 2018, Verma et al. 
2019, Mostafa et al. 2020, Demenech et al. 2021, Hosny et al. 2021) and one as ‘some 
concerns’ (Bashetty & Hedge 2010). The main source of bias was the lack of a protocol 
registration (Bashetty & Hedge 2010, Almeida et al. 2012, Ulin et al. 2020), the use of a 
non-standard visual scale – which was applied in all of the three studies with high risk of 
bias (Almeida et al. 2012, da Silva et al. 2015, Ulin et al. 2020). Finally, the lack of 
36 
 
specification of how the randomization process was performed was also a major source 
of bias (Bashetty & Hedge 2010, Almeida et al. 2012, da Silva et al. 2015, Ulin et al. 
2020). 
 
Certainty of evidence assessment 
Based on the GRADE approach, the certainty of evidence about the occurrence of 
postoperative pain after irrigation with low and high concentrations of NaOCl was 
considered ‘very low’. Table 6 shows the authors' judgment for the assessed domains. 
 
Table 6. GRADE assessment.Outcomes 
Quality assessment 
GRADE 
Quality Studies (n) 
Risk of 
bias 
Inconsistency Indirectness Imprecision 
Postoperative 
pain 
9 
randomized 
trials 
very 
serious1 
very serious2 serious3 serious4 
⨁◯◯◯ 
Very low 
Legend: 
(RoB): risk of bias. 1Three studies were classified as high RoB; 2The methodological heterogeneity between the 
included studies was considerable high; 3 Anwers were considered roughly satisfactory 4Absence or extended 
confidence interval. 
 
 
DISCUSSION 
 
Postoperative pain after endodontic treatment is relatively common in dental offices, 
therefore it is a frequent subject of study (Pak and White 2011, Farzaneh et al. 2018, 
Mostafa et al. 2020). Previous systematic reviews assessed the influence of NaOCl and 
chlorhexidine on postoperative pain (Borgo Sarmento et al. 2020, Martins et al. 2020) 
 [reference], These studies showed similar results, with no significant difference between 
these root canal irrigants on postoperative pain (Borgo Sarmento et al. 2020, Martins et 
al. 2020). In our study, chlorhexidine was not analyzed even if the included studies 
reported it, as the focus of this systematic review was to answer whether the concentration 
of NaOCl used in endodontic treatment influences the occurrence of postoperative pain. 
About those previous studies, Borgo Sarmento et al. (2020) limited their study 
with teeth with pulp necrosis and Martins et al. (2020) included one study with 
irreversible pulpitis (Bashetty & Hedge 2010), while our study included both pulp 
diagnoses. Our results demonstrated that the overall incidence of postoperative pain 
reached 45.35% of the patients treated with low concentrations of NaOCl (Table 2). 
37 
 
Interestingly, this result was higher than the incidence of pain (36.31%, Table 2) 
presented by studies that used higher concentrations of NaOCl (5% or more). Although 
unusual in the literature, it is in accordance with the results of Farzaneh et al. (2018), 
whose study included only teeth with irreversible pulpitis. 
Postoperative pain has a peak and then has a tendency of decrease over the first 
24h (Pak & White 2011, Martins et al. 2020). This tendency was observed in our study, 
since the incidence of postoperative pain decreased in both groups assessed after 24h 
(28.83% in the NaOCl low concentration group, and 39.11% in the high concentration 
group, Table 3). Postoperative pain tended to decrease over time, as expected, and in 
seven days, most of the patients reported no pain: 96.58% in the low concentration group 
and 94.89% in the high concentration group (Table 4). In those patients with pain, none 
had moderate or severe pain, only mild. 
It is well known that the type of irrigant solution can influence on postoperative 
pain (Mostafa et al. 2020; Demenech et al. 2021a). In the case of NaOCl, the postoperative 
pain is mainly a result of periapical extrusion, since it is a cytotoxic irrigant when in 
contact with periapical tissues (Gonçalves et al. 2016, Borgo Sarmento et al. 2020; 
Martins et al. 2020, Mostafa et al. 2020, Demenech et al. 2021a, Hosny et al. 2021). All 
instrumentation techniques produce debris and usually, higher concentrations are 
associated with higher extrusion and therefore, more pain (Parirokh et al. 2012, Gonçalves 
et al. 2016, Mostafa et al. 2020, Demenech et al. 2021a). Yet, a recent study demonstrated 
that higher concentrations of NaOCl possess the same toxicity of lower concentrations 
(Demenech et al. 2021b). Thus, the relation between high concentration and pain intensity 
is a controversial topic in literature (Demenech et al. 2021a) 
Among the studies that used only NaOCl in different concentrations, the overall 
conclusion was that there was no significant statistical difference on the postoperative 
pain between groups (Farzaneh et al. 2018, Verma et al. 2019, Mostafa et al. 2020, 
Demenech et al. 2021a, Ulin et al. 2020). Nevertheless, the concentrations analyzed by 
these studies were quite different: 0.5% and 3% (Ulin et al. 2020) and 2.5%, 5.25% and 
8.25% (Demenech et al. 2021a). Verma et al. (2019) and Mostafa et al. (2020) were more 
inclined to the use of lower concentrations, while Farzaneh et al. (2018) reported more 
favorable outcome with higher concentrations. It must be clarified that Verma et al. 
(2019) and Mostafa et al. (2020) worked with non-vital mandibular molars while 
Farzaneh et al. (2018) picked up mandibular molars with irreversible pulpitis, which with 
the difference in the irrigating protocol could be possible reasons for the conflicting 
38 
 
conclusions. Demenech et al. (2021a) and Ulin et al. (2020) included groups with both 
vital and non-vital teeth. 
The pooled proportion of analgesic intaking was low in our meta-analysis (Table 
5) due to the low consumption of analgesics reported in the included studies (Verma et 
al. 2019; Mostafa et al. 2020; Demenech et al. 2021). In those studies , patients could not 
be consumpting any analgesic at least 12h prior to the endodontic treatment (Mostafa et 
al. 2020) or even 3 days prior (Verma et al. 2019). After the treatment, Mostafa et al. 
(2020) oriented the patients to take a sham capsule and, if the pain persisted, they were 
given an analgesic. The patients were oriented to record wheter they took the sham 
capsule or the analgesic or both. Other studies also provided analgesic prescription 
(Almeida et al. 2012; da Silva et al. 2015; Farzaneh et al. 2018; Hosny et al. 2021), but 
they could not be included in the meta-analysis due to missing data. 
Actually, not all studies could have been included in the meta-analysis (Bashetty 
& Hedge 2010; Almeira et al. 2012; da Silva et al. 2015; Farzaneh et al. 2018; Verma et 
al. 2019b; Mostafa et al. 2020; Ulin et al. 2020; Demenech et al. 2021; Hosny et al. 2021) 
due to the missing data in the articles, mostly the mean and standard deviation of the 
incidence of postoperative pain between the groups. The authors were contacted by e-
mail but still some did not answer. Thus, our study had to perform a meta-analysis of 
proportion since there was not enough data to perform a meta-analysis of association. 
Therefore, this meta-analysis is not able to affirm if there is a significant statistical 
difference on the incidence of postoperative pain between the high concentration group 
and the low concentration group. 
In the present systematic review, the major source of bias of the included articles 
were the lack of information concerning the randomization and blinding process 
(Bashetty & Hedge 2010, Almeida et al. 2012, da Silva et al. 2015, Ulin et al. 2020). 
Another concern was the lack of a reliable and standardized tool for accessing the 
postoperative pain which compromises the truthfulness of the results (Almeida et al. 
2012, da Silva et al. 2015, Ulin et al. 2020). Besides, the certainty of the evidence was 
‘very low’ because the risk of bias and the inconsistency were considered very serious, 
while the indirectness and the imprecision were judged as serious. 
 Our study has some limitations due to the heterogeneity of the studies, mainly 
about assessment of pain, endodontic procedures and type of teeth included. The great 
heterogeneity among the studies did not allow us to assess the effect of the number of 
sessions/visits performed during endodontic treatment in terms of postoperative pain. For 
39 
 
this analysis to be carried out in the future, further randomized clinical trials are needed 
on this subject with stricter and more standardized protocols, in order to provide better 
data on the incidence of postoperative pain after endodontic treatment using different 
NaOCl concentrations as root canal irrigant. 
 
CONCLUSION 
The overall incidence of postoperative pain was 45.36% for low concentrations of 
NaOCl and 36.31% for high concentrations of NaOCl. In the first 24h, the prevalence ofmild pain was 29.45% in the high concentration group and 3.44% in the low concentration 
group, with no patient experiencing moderate or severe pain after 7 days in both groups. 
The different concentrations of NaOCl did not present a statistically significant difference 
in relation to the prevalence of pain, even in the different evaluated pos-operative times. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
40 
 
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