Prevalence of endodontic flare-up following intracanal medicament placement in permanent teeth undergoing endodontic treatment - A systematic review.

Background: Endodontic flare-up can occur in teeth undergoing root canal treatment. Intracanal medicaments are most commonly used in between appointments to eliminate microbial flora in the canal. However, extrusion of medicaments in the periapical region can cause an inflammatory reaction leading to postoperative pain. Aim: The aim of this study was to evaluate the prevalence of endodontic flare-up following intracanal medicament placement in permanent teeth undergoing endodontic treatment. Study Design: A comprehensive search was done in MEDLINE through PubMed, Cochrane, EBSCOhost, and Google Scholar from July 31, 1999 to July 31, 2019 to identify randomized trials involving the use of intracanal medicaments in teeth undergoing root canal treatment.
Methods: The titles and abstracts of all retrieved articles were screened by two independent reviewers, and irrelevant studies were excluded. Full texts of the eligible studies were obtained and thoroughly assessed. Seventeen randomized control trials comprising 2665 subjects were included. Statistical Analysis: Narrative synthesis was provided for the findings obtained from the studies, mainly focusing on the intervention details. Heterogeneity of the previously mentioned characteristics was assessed using the Chi-square test and I2 statistics.
Results: Placement of intracanal medicament was not associated with the occurrence of pain.
Conclusion: The present review suggests that intracanal medicament do not cause endodontic flare-up rather reduces inter-appointment pain during endodontic treatment. Copyright:

INTRODUCTION

Pain is common during an individual's life as an unpleasant sense. Most of the time, endodontic treatment procedures are associated pain. Despite recent advances in pain management, pain has been reported with a prevalence of 2.53%–58%.[1]

Endodontic pain may occur before, during, or after endodontic treatment. A flare-up can be defined as pain or swelling of the facial soft tissues and the oral mucosa in the area of the endodontically treated tooth that occur within a few hours or a few days following endodontic treatment.[2] It requires an unscheduled visit and active treatment to relieve pain.[3]

The origin of the postendodontic flare-up can be mechanical, chemical, and microbial. Many patients complain of mild-to-moderate pain after endodontic treatment of teeth. Placement of intracanal medicament is often preferred when the tooth is treated in multiple visits.

Irrigation solutions, intracanal medicaments, and root fillings can cause chemical irritation and posttreatment pain. The more filling from the root canal is extruded to periodontal tissues, the more intense inflammatory reaction occurs. Resorcinol–formaldehyde resin-based intracanal medicaments are often associated with endodontic flare-up. These pastes are cytotoxic and cause necrosis after contacting live tissue or when extruded into apical periodontal area. This causes postoperative pain and swelling.[3]

The aim of this study is to gauge the prevalence of endodontic flare-ups following intracanal medicament placement in permanent teeth undergoing endodontic treatment.

METHODS

Protocol and registration

The present systematic review was registered at the National Institute for Health Research PROSPERO International Prospective Register of Systematic Reviews (registration number: CRD42019137524). This research protocol is designed according to the (Preferred Reporting Items for Systematic Review and Meta-Analyses [PRISMA]) guidelines 2009.

Eligibility criteria

The eligibility criteria for inclusion of the studies in regard to participants, intervention, comparator, and outcomes are as shown in Table 1.

Table 1

Shows the eligibility criteria for inclusion of the studies in regard to participants, intervention, comparator, and outcomes

Inclusion criteria	Exclusion criteria
Participants (P): Permanent teeth undergoing nonsurgical root canal treatment/Re RCT	Case reports
Intervention (I): Placement of intracanal medicament	Retrospective studies
Comparator (C): Intergroup comparisons	Studies in which full-text articles not retrieved
Outcomes (O): Main outcomes-placement of medicament is associated with flare-up in Re RCT	Articles in other languages than English
Study design (S): Clinical trials (randomized)

Databases (MEDLINE through PubMed, Cochrane, EBSCOhost, and Google Scholar), relevant journals, books, bibliographies, reviews, and conference proceeding were searched from July 31, 1999 to July 31, 2019 using various combinations of following MeSH terms and keywords. Boolean operators odds ratio within the same category and between the disease and intervention category.

For disease category – nonsurgical root canal treatment, endodontic flare-up, postoperative pain, posttreatment endodontic pain, and inter-appointment pain

For intervention category – intracanal medicament, calcium hydroxide, intracanal dressing, triple antibiotic paste, and chlorhexidine digluconate

Study selection

The titles and abstracts of all retrieved articles were screened by two independent reviewers, and irrelevant studies were excluded. Full texts of the eligible studies were obtained and thoroughly assessed by the two reviewers for inclusion. Disagreements were resolved by the 3rd reviewer. Concerned study authors were communicated for the unreported data or additional details.

Data collection process

Data collection was performed using a customized data extraction form including contents such as title of the study, author's name, duration of study, year of publication, study setting, study design, study population, method of randomization, types of intervention, types of the comparator, characteristics of participants (age and gender), inclusion and exclusion criteria, indicators of acceptability of users, times of measurement, outcomes (primary and secondary), and concluding remarks.

Risk of bias in individual studies.

To evaluate the risk of bias in individual studies, Cochrane collaboration's risk of bias tool was used for randomized controlled trials.

Synthesis of results

The narrative synthesis was provided for the findings obtained from the studies, mainly focusing on the intervention details (postoperative pain, intracanal medicament, etc.), characteristics of participants (gender, age, and history of preoperative pain), and outcome assessment. Summaries of intervention effects for each study were provided by calculating risk ratio (for dichotomous outcomes) or standardized mean difference (for continuous outcomes). Heterogeneity of the previously mentioned characteristics was assessed using Chi-square test (significance: 0.1) and I statistics.

Literature search and study selection

Figure 1 shows the study search process according to the PRISMA guidelines. The initial online search yielded a total of 726 studies. After the removal of duplicate studies, the remaining 89 studies were screened for title and abstract, and 41 studies were obtained. Out of 41 studies, 24 studies were found irrelevant (10 reviews and 14 irrelevant trials) and were excluded. Full-text articles of the remaining 17 studies were obtained and thoroughly assessed for eligibility criteria by two authors. These studies met the eligibility criteria and were included in the systematic review.

Figure 1

Flow chart of methodology according to (Preferred Reporting Items for Systematic Review and Meta-Analysis) guidelines

The general characteristics of the included studies are listed in Table 2 for 17 randomized control trials.

Table 2

Details of population, study groups and outcome participants, intervention, comparator, and outcomes of included randomized controlled trials

Author, year, and country	Teeth	Medicament used	Finding
Fava, 1998[4]	60 incisors with acute apical periodontitis	Ca (OH) 2, steroid antibiotic combination	No difference between pain incidence and severity between the two intracanal medicaments
Negm, 2001,[5] Egypt	Total 988 patients, 480 experienced postoperative pain after complete RCT (475 included in study) Age group-15-75 years	Group 1-kenacomb corticosteroid-antibiotic group (245 patients) Group 2-placebo 93% cases showed complete relief of pain within first 24 h	Complete relief of pain after 24 h
Siqueira et al., 2002,[6] Brazil	Total 627 teeth (necrotic pulp) Age group-18-75 years	Calcium hydroxide and camphorated paramonochlorophenol paste	Low incidence of flare-up after dressing with Ca (OH) 2 and camphorated para-monochlorophenol paste
Ehrmann et al., 2007[7] Australia	Total 223 teeth, 29 were excluded	Group 1-Ledermix paste Group 2-calcium hydroxide paste Group 3-no dressing	Ledermix is an effective intracanal medicament for the treatment of postoperative pain
Walton et al., 2003,[8] Georgia	Total 140 patients 56% female, 44% male with mean age of 38 years	Group 1-intracanal placement of calcium hydroxide Group 2-placebo	Ca (OH) 2 is unrelated to the incidence or severity of posttreatment pain
Yoldas et al., 2004,[9] Turkey	Total 227 patients above 18 years of age were selected	Calcium hydroxide-chlorhexidine paste was used as intracanal medicament for 7 days	Intracanal medication was effective in reducing postoperative pain in previously symptomatic teeth and decreased the number of flare-ups in all retreatment cases
Ghoddusi et al., 2006,[10] Iran	69 patients (39 females and 30 males), necrotic teeth	Calcium hydroxide	Calcium hydroxide is found to be effective in reducing postoperative pain and swelling
Ehrmann et al., 2003,[11]Australia	Total-223 teeth (28 excluded)	Group 1-Ledermix paste Group 2-calcium hydroxide paste Group 3-no dressing	Use or type of intracanal medicament did not alter the frequency of flare-ups
Gama et al., 2008,[12] Brazil	Total 138 patients in age group of 9-72 years	0.12% chlorhexidine in natrosol gel or Ca (OH) 2/CPMC/Glycerine paste	No statistically significant difference between the use of two medicaments
Dall et al., 2011,[13] Karachi	Total 222 patients in age group of 14-60 years	Ledermix paste, placebo	Ledermix reduced postoperative pain
Singh et al., 2013[14]	64 teeth, necrotic pulp and acute apical periodontitis	Ca (OH) 2 paste with chlorhexidine gel, 2% CHX gel, Ca (OH) 2	Chlorhexidine alone or Ca (OH) 2 plus chlorhexidine gave rise to less pain than calcium hydroxide alone or no dressing at all
Menakaya et al., 2015,[15] Nigeria	This study is a part of larger study carried out. Age range was 17 years or above	Calcium hydroxide/N.Saline or+chlorhexidine paste	Postoperative pain is less in calcium hydroxide/N.Saline group
Sinhal et al., 2017,[16] India	36 diabetic patients with age 20 years or above	Group 1-calcium hydroxide paste Group 2-triple antibiotic paste Group 3-2% chlorhexidine gel	Both triple antibiotic paste and 2% chlorhexidine gel were effective in reducing interappointment flare-ups and postoperative pain in diabetic patients
Abouelenien et al., 2018,[17] Egypt	36 patients with single-rooted necrotic premolars with apical periodontitis	Group 1-calcium hydroxide paste Group 2-double antibiotic paste	Both medicaments are equally effective in reducing postoperative pain
Alferra 2018,[18]Egypt	Total 44 patients Age group of 25-45 years old Nonvital mandibular molars	Calcium hydroxide or Ledermix used as intracanal medicament	With the limitation of study, there were slightly different between both groups
Ahmed, 2019,[19]Egypt	84 patients	Group 1-calcium hydroxide Group 2-triple antibiotic paste with diclofenac potassium	Both intracanal medicaments are effective in reducing postoperative pain in asymptomatic uniradicular necrotic teeth
Ghanbarzadegan et al., 2018[1] Iran	90 teeth	Group 1-calcium hydroxide+normal saline Group 2-chlorhexidine 2% Group 3-dexamethasone	The combination of calcium hydroxide and dexamethasone is effective in reducing pain during the root canal treatment sessions

CPMC: Camphorated paramonochlorophenol, CHX: Chlorhexidine

Randomized clinical trials included 2665 study participants. The age of participants ranged from 9 to 75 years with female dominance in most of the studies. Most of the studies used visual analog scale (VAS) for pain assessment. Assessment for incidence of postoperative pain was done at interval of 1-day, 1-week, 1-month, 3-month, and 6-month postobturation.

It was found that in most of the studies, calcium hydroxide was used as intracanal medicament. Placement of intracanal medicament was not associated with occurrence of pain rather it controlled the microbial growth and aid in reducing postoperative pain.

Quality of included studies

The results of the quality assessment were evaluated according to Cochrane Tool. Based on Cochran's quality assessment tool for randomized control trial, included studies showed good quality assessment [Figure 2]. Selection and attrition bias was found in most of the studies [Figure 3].

Figure 2

Risk of bias graph: review authors’ judgments about each risk of bias item presented as percentages across all included studies

Figure 3

Risk of bias summary: review authors’ judgements about each risk of bias item for each included study

DISCUSSION

The incidence of postoperative pain is not a rare event even after following all standard protocols. Mild pain after chemo-mechanical preparation can develop in 10%–30% cases. Endodontic flare-up constitutes a true emergency and usually requires unscheduled visit for treatment. Postoperative pain is considered a poor indicator for long-term success of root canal treatment. Its incidence ranges from 1.5% to 5.5% and sometimes up to 50% in some studies.[1116] Various risk factors that significantly influence the inter-appointment flare-up can be related to patient or treatment procedure. After mechanical preparation of root canal, the intracanal medicaments restrict the proliferation of microbes. These medications have antibacterial, sedating, and anti-inflammatory properties. Intracanal medication rapidly reduces pulpal pain between the sessions of root canal treatment.[18] Various intracanal medications include calcium hydroxide, triple antibiotic paste, double antibiotic paste, Ledermix paste, 2% chlorhexidine gel, and corticosteroid-antibiotic compound. This review critically evaluated the available evidence on the prevalence of endodontic flare-ups following intracanal medicament placement in permanent teeth undergoing endodontic treatment or re-root canal treatment.

Previous studies used different scales and methods to assess pain after endodontic therapy. Among them, the VAS scale is considered to be a valid and reliable ratio scale for measurement of pain. Pain perception is highly subjective and variable experience modulated by various factors. Another methods used to record postoperative pain are Facial Grimace Scale. Ghoddusi et al. used a modified version of the 10° form of visual analog scale to measure the severity of pain 6 hourly for up to 72 h reported a 15% incidence of postoperative pain.[10]

Most studies have mentioned age of participants, whose age range is 18–75 years. Some studies by Abouelenien et al., Ehrmann et al., Ghoddusi et al. did not mention the age of participants in their study.[101117] According to Ehrmann et al., patients with Ledermix intrcanal medicament experienced significantly less postoperative pain than with no intracanal medicament.[7] Mohmmadi et al. concluded that Ledermix is better intracanal dressing material compared to calcium hydroxide.[19] Yoldas et al. used calcium hydroxide mixed with 0.2% chlorhexidine as intracanal medicament in re-treatment cases. They observed higher incidence of postoperative pain in pretreatment symptomatic group.[9]

Sinhal et al. evaluated the incidence of inter-appointment flare-up in diabetic patients and found that both triple antibiotic paste and 2% chlorhexidine gel were effective in reducing inter-appointment flare-up and postoperative pain.[16] In this review, all included studies showed that postoperative pain is reduced following the use of intracanal medicaments.

Limitation of the present systematic review may be relative heterogeneity among studies with respect to patient age, gender, comparator groups, medicaments used, and outcome measurement.

CONCLUSION

The results of the present systematic review suggest that minimal-to-moderate type of pain normally subsides with time. Intracanal medicament does not cause endodontic flare-up rather helps in reducing postoperative pain.

Financial support and sponsorship

Self-supported.

Conflicts of interest

There are no conflicts of interest.