Effectiveness of Systemic Antibiotic Therapy on Posttreatment Symptoms Following Root Canal Therapy

A Systematic Review

Group- A
Authors:

Amit Narwal
Hong Zhao Mehdi Noroozi Prabhjot Kaur Preeya Chaly Roya Khoshsar, Shilpesh Parekh

ABSTRACT
Objective: The purpose of this systematic review was to find a scientific and evidence based answer to the effectiveness of systemic antibiotic therapy on prevention or reduction of postoperative symptoms following root canal therapy/surgical endodontics. Methods: Literature search in Pub Med based on inclusion criteria (Randomized Control Trials, Human studies, adults age 19 or older, English Language, Permanent teeth) followed by systematic review of selected articles. Results: Through literature search we identified 30 articles, then relevance to our study was established by reviewing title/abstract in group and we identified 10 articles to be studied at full text stage. Each article was read and scored in team and finally we selected 6 double blinded placebo controlled randomized control trials for our evidence based report. Recommendations/Conclusion: On the basis of evidence in this literature review: 1- We found no significant difference in the effectiveness of systemic antibiotics administered either prophylactically or therapeutically in endodontic treatment/surgery in comparison to placebo/no intervention. 2- There is a good level of evidence implying no significant advantage in the utilization of systemic antibiotics in prevention/reduction of symptoms following endodontic treatment. 3-More randomized controlled trials, with assessment of loss of follow up and eliminating the factors that make results difficult for interpretation, adequate population of sample size and their global distribution, accurate and universal definition and measurements of flare-ups are required to be taken into account in future studies. Key Words: Endodontic treatment, root canal treatment, endodontic surgery, flare-up, pain percussion, pain, swelling, infection, systemic antibiotics, effectiveness, prevention, permanent teeth

Introduction
The administration of systemic antibiotics as preoperative and/or postoperative on a routine basis in endodontic emergencies and endodontic surgeries has always drawn considerable attention1. Seemingly there is limited empirical evidence to support the effectiveness of this approach and questions have been raised about the safety of indiscriminate antibiotic prescription3. Antibiotics should be prescribed on the basis of a defined need otherwise their use may present more of a risk to the patient than the infection being treated or prevented.2 Antibiotics can be responsible for various adverse effects, including drug interactions, selection2 and overgrowth of resistant microorganisms. This is validated by the fact that at least 60,000 to 100,000 deaths occur annually in United States hospitals due to nosocomial infections caused by antibiotic resistant microorganisms 4, nausea, gastrointestinal upsets, potentially fatal allergic reactions and antibiotic associated colitis. There is clear evidence that antimicrobials are being used inappropriately by dentists for a variety of conditions.2 Postoperative pain and swelling following instrumentation and/or obturation is of concern for endodontic patients, dentists, and dental staff. Investigators have reported varying frequencies of postoperative complications commonly known as a flare-up that occurs in some patients resulting in moderate-to-severe postoperative pain and/ swelling. The incidence of an endodontic flare-up has been reported to be 1- 24% of the time 5, 6 The main factors contributing to postoperative pain and discomfort can be classified as (a)host factors,(b) idiopathic factors, and (c)flora of infected root canals.(5)Among the three major elements ,the role of bacteria and their by products is well established. Irritation of peri apical tissues results in inflammation and the release of a group of chemical substances which initiate inflammatory responses5.Release of these substances can either directly lower the response threshold of the sensory nerve fibers or cause pain indirectly by increasing the vascular permeability and producing edema and swelling 5. The rational use of antibiotics is based upon three variables: a defined indication, the appropriateness of the antibiotic and the adverse effects associated with the drug2. Antibiotic therapy is based on the concept that the primary cause of the periradicular lesion is bacterial and surgical intervention and instrumentation may result in a superimposed bacterial infection in that site 1. A survey on the administration of antibiotics amongst the members of the American Association of Endodontists (AAE) showed that 37% of the endodontists routinely prescribed antibiotics for endodontic surgery 1. A study conducted in the United States on antibiotic use by members of the American Association of Endodontists evaluated 16.7% of endodontists responding prescribed antibiotics for irreversible pulpitis.3
3

This report deals with the evidence available concerning the efficacy of systemic antibiotics as preoperative and/or postoperative care in endodontic emergencies and endodontic surgeries. Only one Cochrane systematic review was found in the literature which has reviewed the use of antibiotics for pain relief in patients with irreversible pulpitis undergoing no endodontic treatment. They found no evidence to support the use of antibiotics for pain relief in irreversible pulpits 3. This review sought to provide reliable evidence concerning the effectiveness of prescribing systemic antibiotics for endodontic treatments/surgeries. Our key questions were whether the antibiotic therapy reduces postoperative endodontic flare-ups? If yes, how effective it is and whether the advantages of antibiotic administration outweigh the disadvantages?

Materials and methods

A systematic review of literature was carried out to identify, appreciate and critically appraise the most relevant research to our topic of interest. Stage 1: Search keywords in PubMed Database We employed the following keywords to execute our research: Permanent teeth, Endodontic treatment, Flare-up, Pain, Percussion pain, Swelling, Infection, Systemic Antibiotics. Following outlining the keywords, we used the PubMed database to get needed articles. We used the combination of PubMed and MESH to extract the scientific evidence. Experts from department of Endodontics at the Toronto Faculty of Dentistry were consulted. 2- Inclusion and exclusion criteria setup Following consultation with experts in the field of endodontics, we set up the inclusion and exclusion criteria as follows: Inclusion Criteria: We focused on: Only studies that had been carried out based on the randomized control trials which assessed the effectiveness of antibiotics on post-treatment symptoms following endodontic treatment. Human studies on all adults age 19 or older. Articles published in English Language. Endodontic treatments carried out on Permanent teeth. Only articles available in PubMed database and available at the libraries of the University of Toronto.
4

Exclusion Criteria: We did not consider the articles which had to do with: Endodontic treatments on primary dentition. Study designs other than RCT due to lower level of evidence. Sources other than PubMed Database. Following combination of key words and putting the limits in to place, the total numbers of 30 articles were retrieved. Table 1: Search Strategy Table
Search endodontics "[MeSH Terms] OR "endodontics"[All Fields]OR "root canal therapy"[MeSH Terms] OR "root canal therapy"[All Fields] OR endodontic[All Fields] OR "pulpectomy"[MeSH Terms] OR "pulpectomy"[All Fields] OR "pulpotomy"[MeSH Terms] OR "pulpotomy"[All Fields] OR "endodontic surgery"[All Fields] OR "apicoectomy"[MeSH Terms] OR "apicoectomy"[All Fields "anti-bacterial agents"[MeSH Terms] OR ("anti-bacterial"[All Fields] AND "agents"[All Fields]) OR "anti-bacterial agents"[All Fields] OR ("antibacterial"[All Fields] AND "agent"[All Fields]) OR "antibacterial agent"[All Fields] OR fluoroquinolones OR "penicillins"[MeSH Terms] OR "penicillins"[All Fields] OR "penicillin"[All Fields] OR "amoxicillin"[MeSH Terms] OR "amoxicillin"[All Fields] OR "metronidazole"[MeSH Terms] OR "metronidazole"[All Fields] OR "clindamycin"[MeSH Terms] OR "clindamycin"[All Fields] OR "cephalosporins"[MeSH Terms] OR "cephalosporins"[All Fields] OR "erythromycin"[MeSH Terms] OR "erythromycin"[All Fields] OR "sulfanilamides"[MeSH Terms] OR "sulfanilamides"[All Fields] OR "quinolones"[MeSH Terms] OR "quinolones"[All Fields] OR "clavulanic acid"[MeSH Terms] OR ("clavulanic"[All Fields] AND "acid"[All Fields]) OR "clavulanic acid"[All Fields] OR ampicillin #1 AND #2 #1 AND #2 Limits: Humans, Clinical Trial, Meta-Analysis, Randomized Controlled Trial, Review, Clinical Trial, Phase IV, Controlled Clinical Trial, English, All Adult: 19+ years

Result
24689

519783

810

30

Stage 3: Study Preferences We applied the title, abstract and full text screening Stages using the PICO-C model. Based on the model, population, intervention, control or comparator, outcome and critical appraisal of each study is assessed and evaluated. Each article reviewed by at least three members of the group for screening. In cases of disagreement the consensus was established. Of 30 retrieved articles, 13 rejected in the title stage by virtue of the fact that topic was absolutely irrelevant to our topic of interest. The remaining 17 articles were undergone the abstract screening stage which resulted in rejecting 7 articles and approving 10 ones. Evaluating the result of Pubmed search did not provide any additional citation.

Stage 4: Study Quality Appraisal Based on the PICO-C model, each article approved at the abstract stage was thoroughly reviewed in full text and appraised critically using Checklist to Assess Evidence of Efficacy of Therapy or Prevention 7 as a guideline by at least three members of the team to minimize the probability of double standards. Regarding the checklist if the answer to question was positive, that question was marked 1 and if the answer was negative, that question was scored 0 and the final score of each study with the maximum possible score of 17 was calculated thereafter by adding theses marks. Upon consultation with the experts in the field of endodontics, we retrieved 2 articles which had been disapproved in the abstract stage. Moreover, 3 articles were rejected given the fact that the intervention groups in the studies were compared with control groups originating from past studies available for authors.

The following chart shows the number of articles approved and rejected in the 3 different screening stages based on our pre-defined inclusion and exclusion criteria.

Limits: Humans, Clinical Trial, Meta-Analysis, Randomized Controlled Trial, Trial, Phase IV, Controlled Clinical Trial, English, All Adult: 19+ years

Stage

1:

Pub Med 30 Title Stage 13 rejected 17 accepted

17

Pub Med Search Result No Further Article

10

Abstract Stage 7 rejected; 10 accepted Full Text Stage 3 rejected; 7 accepted

Citation
# 1 Endodontics in the adult patient: The role of antibiotics.L.P.Longman,A.J.Preston,M .V.Martin,N.H.F.Wilson Journal of Dentistry 28(2000) 539-548 August 2000 2 A comparison of erythromycin and cefadroxil in the prevention of flareups from asymptomatic teeth with pulpal necrosis and associated periapical pathosis. Morse DR, Furst ML, Lefkowitz RD, D'Angelo D, EspositoJV. Oral Surg Oral Med Oral Pathol.1990, May;69(5):619-30.

REASONS EXCLUSIONS

FOR Score

Stage of Exclusion
Full text

The article was a review study. The article discusses the indication and contraindication of antibiotics in healthy patient and medically compromised patients, which also includes use of topical antibiotics. No control used in the current trial.

10/17

11/17 A comparison was done with control taken from another study.

Full text

A prospective randomized trial on efficacy of antibiotic prophylaxis in asymptomatic teeth with pulpal necrosis and associated periapical pathosis. Abbott AA, Koren LZ, Morse DR, Sinai IH, Doo RS, Furst ML. Oral Surg Oral Med Oral Pathol. 1988 Dec; 66(6):722-33. Review.

No control group in the study, Not blinded; Prophylactic Ab group of this study was compared with placebo control group of the other study,

11/17

Full Text

Infectious flare-ups and serious sequelae following endodontic treatment: a prospective randomized trial on efficacy of antibiotic prophylaxis in cases of asymptomatic pulpal-periapical lesions. Morse DR, Furst ML, Belott RM, Lefkowitz RD, Spritzer IB, Sideman BH. Oral Surg Oral Med Oral Pathol. 1987 Jul;64(1):96-109.

Study does not have any control group It was not blinded A comparative analysis of the data from the study and the pooled data from last studies done.

11/17

Full text

Table2: Excluded Articles

Stage 5: Producing Evidence Table We abstracted evidence from selected papers onto abstraction sheets and finally transferred the data into the evidence table under PICOCs heading (Population, Intervention, Control, Outcome and Critical appraisal) Evidence based table was designed for 6 final randomized controlled trial, double blinded and placebo controlled studies which had been systematically reviewed as follows:

1. Henry M, Reader A, Beck M.J Endod. 2001 Feb;27(2):117-2 2. Lindeboom JA, Frenken JW, Valkenburg P, van den Akker HP.Int Endod J. 2005 Dec;38(12):877-81 3. Walton RE, Chiappinelli J.J Endod. 1993 Sep;19(9):466-70. 4. Pickenpaugh L, Reader A, Beck M, Meyers WJ, Peterson LJ.J Endod. 2001 Jan;27(1):53-6. 5. Torabinejad M, Dorn SO, Eleazer PD, Frankson M, Jouhari B, Mullin RK, Soluti A. J Endod. 1994 Sep;20(9):427-31. 6. Torabinejad M, Cymerman JJ, Frankson M, Lemon RR, Maggio JD, Schilder H. J Endod. 1994 Jul;20(7):345-54.

We complied with the guideline recommended by the Canadian Task Force on Preventive Health Care evidence. The system is classified from the highest level of evidence, Level I, containing properly randomized controlled trials to the Level III with opinions of respected authorities, based on clinical experience, descriptive studies, reports of experts committee consensus. In addition, the guideline defines a classification of recommendations for specific clinical preventive interventions (Grade A-E; with Grade A indicating the good evidence to recommend the clinical preventive action and Grade E representing good evidence to recommend against the clinical preventive intervention).8

Results
Our search strategy identified 30 articles. 13 papers were excluded on title stage, and 7 papers were excluded on abstract stage. 4 papers were rejected on full text stage of which one paper was systematic review, and three others did not have control group and were not blinded. Therefore, totally 6 papers were included in this review, which were all double-blinded placebo controlled randomized clinical trials.

Preoperative prophylactic antibiotics on post-endodontic treatment symptoms

Walton and Chiappinelli (1993) carried out a study to test the effect of the prophylactic penicillin on post-endodontic treatment symptoms. They selected 80 patients with asymptomatic periapical periodontitis, and divided them into three groups. Group A (26 patients) received 2 g penicillin before the treatment and 1 g 6 hours after the treatment. Group B (24 patients) received a placebo with same regimen, and group C (30 patients) received no medication. Post treatment symptoms such as pain and swelling were recorded at 4,8,12,24, and 48 hours. Only one flare-up was reported which was in placebo group. 69% of the patients in group A (penicillin) had mildmoderate pain, as compared with 79% in placebo group B and 70% in group C (no medication). Statistics showed no significant difference (p=0.68) among these three groups as to post treatment symptoms.

Pickenpaugh et al.(2001) determined the effect of amoxicillin on endodontic flare-up in asymptomatic necrotic teeth. 34 patients were given a single dose of amoxicillin (3g) an hour before endodontic treatment. 36 patients received placebo. After standard instrumentation which was performed by graduate endodontic students or endodontic faculty, each patient received a 51/2-day diary to record postoperative pain, percussion pain, swelling, and number and type of pain medication taken. A flare-up was defined as moderate-to-severe postoperative pain or swelling that began 12 to 48 hours after treatment and lasted at least 48 hours. The results indicated that among these 70 patients, 7 patients 10had flare-up of which 4 (57%) were in the amoxicillin group and 3 (43%) were in the placebo group. Bivariate analysis revealed no significant differences between the non-flare-up and flare-up patients for prophylactic amoxicillin use (p=0.80), and concluded that a prophylactic amoxicillin had no effect on the occurrence of flare-up.

10

Another trial evaluated the value of clindamycin in the prevention of postoperative infection (Lindeboom et al. 2005). 256 patients undergoing endodontic surgery were included. 1 hour before surgery, 128 of them were given 600mg clindamycin orally, while another 128 patients received placebo. Patients were assessed 1, 2 and 4 weeks after surgery. The infection rate in the clindamyicn group was 1.6% (2 patients) and in the placebo group the infection rate was 3.2% (4 patients), which indicated no significant differences (p=0.448).

Post-treatment antibiotics on post-endodontic treatment pain: Torabinejad et al. (1994) compared the effectiveness of penicillin and erythromycin on postoperative pain for 72 hours following root canal instrumentation. Sample patients had periapical periodontitis with varying levels of pain. Following complete root canal cleaning and shaping, 57 patients received penicillin 500mg; 46 patients received erythromycin base 500mg, and 53 patients were placebo group. All patients scored their levels of discomfort at each 6-h interval for up to 72 hours after instrumentation. Patients questionnaires were collected at the obturation appointment. Data indicated that preoperative pain and apprehension had a strong positive correlation with postoperative pain (p<0.0001, 0.012<p<0.047 respectively). In terms of medications, penicillin and erythromycin base were significantly more effective in reducing moderate and severe pain than placebo within the first 48 hours after instrumentation (p<0.05). Whereas in patients with no or mild pain no statistical significant difference was showed between the effectiveness of antibiotics and placebo. Torabinejad et al. (1994) continued this study to further compare the effectiveness of antibiotics and a placebo on postoperative pain after obturation of the canals. In this study, patients were randomly assigned to penicillin 500mg or erythromycin base 500mg, or placebo following obturation. Levels of discomfort were scored by patients at each 6-h interval for up to 36 hours. They found that the incidence of postoperative pain after obturation is lower than that following instrumentation (5.83% versus 21.76%), and the effectiveness of antibiotics and placebo in controlling postoperative pain following obturation was not significantly different. In the study of Mark Henry et al. 2001, 41 adult patients who presented for emergency treatment participated in this randomized, double-blind, placebo-controlled study. All of the selected teeth were symptomatic and necrotic, and with associated periapical radiolucency. After standard endodontic treatment, patients were randomly assigned to a 7-day oral dose (twenty-eight 500 mg capsules to be taken every 6 h) of either penicillin or a placebo control. Also a 7-day diary to record pain, percussion pain, swelling, and number and type of pain medication taken was given to patients. Data analysis indicated that the administration of penicillin postoperatively did not significantly (p > 0.05) reduce post-endodontic pain for symptomatic necrotic teeth.

11

Discussion
In this evidence based report, we have tried to gather the best studies available, in order to find an answer as to whether or not antibiotics should be taking into consideration in preventing any flare up, pain, swelling or pain on percussion after endodontic treatment of asymptomatic teeth with necrotic pulp and periapical pathology. After a detailed database search, we came out with six articles that might answer our concern. All these articles were randomized clinical trials. The reason for selecting randomized controlled trials for our study was due to the highest level of evidence they provide as the gold standard. They are generally accepted as the most valid method for determining the efficacy of therapeutic intervention, because the biases associated with other experimental designs can be avoided.9 The articles subject to full-text consideration were included. Only articles approved that the antibiotics were administered to relieve post endodontic treatment flare ups. Articles representing antibiotic prophylaxis to only prevent heart diseases or to treat a tooth abscess were discarded. Furthermore, the studies were critically appraised based on the checklist to assess evidence of efficacy of therapy adapted from Fletcher and Wagner 7.

Action of antibiotic in preventing flare up in endodontically treated teeth: The use of prophylactic antibiotics to prevent an infection is based on work of Burke and Miles. They demonstrated in animal models for the antibiotics to be effective, they must be in tissue or wound site prior to the beginning of infections. Any delay of 3-4 hours resulted in infections indistinguishable to those in control animals.6 The article by M. Henry, Al Reader and Mike Beck was one of the strongest evidence in our search report. The study was double-blind, placebo, controlled study with sample size of 41 emergency patients; each had diagnosis of a symptomatic, necrotic tooth with associated periapical radiolucency. After standard endodontic treatment patients received a seven-day oral dose of 500 mg of penicillin V every six hours. The outcome was recorded by patients in terms of pain, percussion pain, swelling and type of pain medication taken. However, the study has its own limitations as the subjective measurement of pain was not very reliable. In another fair study by Lindeboom et al. 2005, had larger sample size of 256 patients with adequate root canal filling ,received clindamycin prophylactically in the prevention of postoperative wound infections who were undergoing endodontic surgery. The study was prospective double-blind clinical trial, comparing oral administration of an oral placebo versus a preoperative 600mg dose of clindamycin one hour before surgery. The duration of surgery, the
12

dosage were standardized for both the groups appropriately and the patients were assessed first, second and fourth week post-operatively. Although, there was no significant difference in the rate of infection, the randomization of surgical site was not ideal. More molars were treated in clindamycin group while more maxillary pre-molars and maxillary anterior teeth, were treated in placebo patients. In a randomized double-blind study Walton et al. 1993, studied the use of antibiotics in preventing flare up between patients receiving penicillin V either 2g single dose(AHA recommendation 1994) at the beginning of treatment and an additional of 1g six hours after the appointment, an inert placebo control or receive no medication at all. A single visit conventional root-canal cleaning and shaping was performed following which the symptoms of flare-ups were self-evaluated by patients using visual pain analog at 4, 8, 12, 24 and 48 hours post-treatment. However, this study has its own drawbacks with small sample size, treatment being rendered by undergraduates and the important factor which we thought that the occlusion was not adjusted, which might be one of the co-factors for flare-ups. Leigh Pickenpaugh t al. 2001, performed a study to determine the effect of prophylactic amoxicillin on the occurrence of flare-up in asymptomatic, necrotic teeth with periapical legion measuring 3x3 mm. They give patients either 3g dosage of amoxicillin orally 1hour before the treatment or an inert placebo. The flare-up was defined as moderate to severe post-operative pain or moderate to severe swelling that began 12-48 hours after the treatment and lasted for at least 48 hours. Pickenpaugh et al. 2001, claims that their results disagree with the work of Morse and co-authors9. Unfortunately their study didnt come without drawbacks such as a lack of sample size, occlusion was not adjusted and its power value was 0.08. In the double-blind study by Torabinejad et al. 1994, using a sample size of 411 patients reported the role of antibiotics and placebo in controlling post-operative flare-up following obturation. After obturation of root canal each patient took one of the medications, penicillin (2x250mg), erythromycin base (2x250mg) or a placebo every 6 hours for 72 hours. The patient registered their degree of discomfort on visual analog scale of 0-9. Despite standardization of the treatment the study did report a loss of follow-up (<20%), a lack of patient compliance in completing the questionnaire and the occlusal adjustment was not reported. Evidence in support of the use of antibiotics in preventing flare-ups: Torabinejad et al. 1994, in a randomized control trial reported in favour of supporting the use of penicillin and erythromycin in controlling flare-ups after complete instrumentation and before obturation. Post-operative pain was assessed by visual analog scale by a sample size of 588 patients after taking penicillin (2x250mg), erythromycin base (2x250mg) and placebo every 6 hours for 72 hours following complete instrumentation. However, there was loss of follow-up

13

less than 20%, instrument steps were not standardized in certain emergency appointments because of time constraints and also there was no reporting on occlusal adjustment. Research supporting the use of antibiotics in preventing flare-up following endodontic treatment has come from investigators at the School of Dentistry at Temple University. Mata et al. 1985 used a randomized control trial to test the incidence of flare-up between the patients receiving either penicillin V or a placebo control. The antibiotic dosage schedule was 250mg tablet of penicillin V every hour for the first 24 hours followed by one tablet every six hours until all tablets were used. Flare-up was defined as pain and or swelling that necessitated an unscheduled emergency visit. After treatment patients were asked to complete a pain and swelling questionnaire for 2 days. It was found that the incidence of flare-up was less in penicillin group as compared to the control group. Amongst the articles in our evidence table all provided highest level of evidence I and only one article favoured the use of antibiotics after complete instrumentation prior to obturation (Torabinejad, M et al. 1994). The other articles did not find any statistically significant difference between the effectiveness of various antibiotics versus placebo in controlling adverse outcomes of flare-ups subsequent to the endodontic treatment. Despite the conclusion drawn from the above papers, there are numerous limitations before any clinician arrives to a decision. A) Factor related to endodontic procedure: i) Difference in clinicians expertise: General dentist v/s Endodontists or undergrad students v/s Postgrad students. Different concentration of sodium hypochlorite: Walton et al (1993) and Pickenpaugh et al (2001) irrigated with 2.5% and 2.62% sodium hypochlorite respectively. Mata et al (1985) irrigated with concentration ranging from 0.5%-2.5% 9.Interestingly, the control groups from the Walton et al (1993) and Pickenpaugh et al (2001) studies were irrigated with 2.5% and 2.62% sodium hypochlorite respectively, and the corresponding incidence of flare-up was low. So variation in irrigant concentration might be responsible for difference in flare-up incidence.10 Use of temporary restoration: Zinc oxide eugenol as a temporary cement has both palliative and antibacterial properties. In the studies by Pickenpaugh et al (2001) and Walton et al (1993), the properties of temporary material have not been stated.10 Adjustment of occlusion: It is assumed that premature occlusal contacts are important in producing pain. So in studies in which occlusion was not
14

ii)

iii)

iv)

adjusted it is impossible to determine if flare-up is due to infection or due to excessive occlusal contacts.10 B) Definition of flare-up: Different studies have different definitions of flare-ups which render it difficult to compare the results concerning efficacy of antibiotics at reducing flare-up.9 C) Use of Analgesics: Many researchers have given their patients analgesics, which they might have used to control their pain and swelling. As in the study of Pickenpaugh et al (2001), Tylenol 3 and Ibuprofen was used to control flare-up. Ibuprofen is both analgesic and anti-inflammatory agent, while Tylenol 3 is purely analgesic. This difference will make it difficult to standardize the definition of flare-up. 10

D) Non-standardized measurement of flare-up: i) Difference in period of flare-up evaluation. ii) Problems associated with report of pain

Walton et al (1993), instructed patients to assess pain using a questionnaire at strict time, while Pickenpaugh et al (2001)instructed patients to keep a diary of pain assessed before going to bed on the day of the treatment, then on arising and before bedtime each for five days . The duration in different studies does not monitor the pain adequately, which might affect the standardization of the study. iii) It is believed that individual tolerance and reaction to pain differed greatly from person to person (Marieb, 2001). This inherited difference make it difficult to standardize flare-up events.10

E) Patient Condition before treatment: Symptomatic V.S Asymptomatic patient

Torabinejad et.al 1994 showed that patient apprehension is associated with increase in post operative pain (P=0.047) and increase in Pre-operative pain is associated with increase in post operative pain. 5 (P <0.0001) .

15

Recommendations/Conclusion
At present, good level of evidence prevail to conclude that Antibiotics DO NOT play a crucial role in subsiding post-treatment symptoms e.g. pain, percussion pain, swelling and discomfort. Based on this systematic review, we found no significant difference in the effectiveness of systemic antibiotics administered either prophylactically or therapeutically on post treatment flare-ups following endodontic treatment/surgery in comparison with placebo/no intervention; however, we need more conclusive evidence to support or refute the administration of systemic antibiotics as a must following endodontic treatments. (Based on the CTFPHC system8, the level of evidence is 1 and the grade of recommendation is E). A protocol adoption for the prescription of systemic antibiotics in endodontics may be advantageous to both patients and clinicians in the future. (Longman etal 2000)

RECOMMENDATIONS FOR FUTURE RESEARCH:

1- There is a good level of evidence implying no significant advantages in the utilization of systemic antibiotics on prevention/reduction of symptoms after endodontic treatment 2-Studies need to be carried out more globally taking in consideration different races and sections of population throughout the world and not merely one country. 3- The factors impacting on post treatment symptoms such as patients condition before treatment, definition of flare-ups, quality of flare-up measurements, endodontic procedure technique should be equalized in future studies to make results valid and reliable in terms of interpretation and extrapolation. Moreover loss of follow up should be assessed in numerical values and considered in interpretation of results.

16

References:
1- Lindeboom JAH, Frenken JWH, Valkenburg P,van den Akker HP. International Endodontic Journel, 38, 877-881, 2005. 2- Longman L.P, A.J. Preston, M.V. Martin, N.H.F. Wilson. Endodontics in the adult patient:the role of antibiotics. Journal of Dentistry ;28(2000)539-548 3- Keenan J .V, Farman AG, Fedorowicz Z, Newton JT. A conchrane Systematic Review No Evidence To support the use of Antibiotics for pain relief in irreversible pulpitis Journal of Endodontics;2006,32,no.2,1-14 4-Krishnan G,.The endodontic dilemma-rationale behind antibiotic usage,Endodontology;2001,vol:13,19-23 5- Torabinejad M, Cymerman JJ, Frankson M, Lemon RR, Maggio JD, Schilder H.J. Effectiveness of various medications on postoperative pain following complete instrumentation.Journal of Endodontics;1994,20,no.7, 345-354 6- Pickenpaugh L, Reader A, Beck M, Meyers WJ, Peterson LJ. Effect of prophylactic amoxicillin on endodontic flare-up in asymptomatic necrotic teeth. J Endod. 2001 Jan;27(1):53-6 7- Adapted from: Fletcher, Fletcher and Wagner. Clinical epidemiology the essentials. 3rd ed. 1996, and Sackett et al. Evidence-based medicine: how to practice and teach EBM. 1997 8- Canadian Task Force on Preventive Health Care evidence. http://www.ctfphc.org/ 9- Abstract Intl. Society Technol Assess Healthcare Meet 1993; 9:27. 10- The use of antibiotics to prevent flare-ups after endodontic treatment of asymptomatic teeth with pulp necrosis and periapical pathosis : Chao AD, Ho J, Maggi Riaz. J, Robertson S, Tang S, Walton P (March 17, 2006).

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Appendix1: Technology Assessment Table Compared to Compared to the placebo/ no medication, placebo, Antibiotic therapy works Antibiotic therapy costs Better The same Less The same More

Worse

Appendix2: CTFPHC Grades of Recommendations and Quality of Published Evidence

A. B. C D E I
The CTF concludes that there is good evidence to recommend the clinical preventive action The CTF concludes that there is fair evidence to recommend the clinical preventive action The CTF concludes that there is conflicting evidence neither recommending nor favoring the clinical preventive action. The CTF concludes that there is fair evidence to recommend against the clinical preventive action. The CTF concludes that there is good evidence to recommend against the clinical preventive action. The CTF concludes that there is insufficient evidence to make a Recommendation.

I II-1 II-2

Evidence from at least 1 properly randomized controlled trial (RCT). Evidence from well-designed controlled trials without randomization. Evidence from well-designed cohort or case-control analytic studies, preferably from more than 1 centre or research group. Evidence from comparisons between times or places with or without the intervention. Dramatic results in uncontrolled experiments could also be included here. Opinions of respected authorities, based on clinical experience, descriptive studies or reports of expert committees.

II-3

III

18

Appendix 3:

Checklist to Assess Evidence of Efficacy of Therapy or Prevention

Citation:

____________________________________________________

____________________________________________________

1. Was the study ethical? 2. Was a strong design used to assess efficacy? 3. Were outcomes (benefits and harms) validly and reliably measured? 4. Were interventions validly and reliably measured? 5. What were the results? Was the treatment effect large enough to be clinically important? ___

___ __ ___ __

Was the estimate of the treatment effect beyond chance and relatively precise? If the findings were no difference was the power of the study 80% or better 6. Are the results of the study valid?

___ ___

Was the assignment of patients to treatments randomised? Were all patients who entered the trial properly accounted for and attributed at its conclusion? ___ ___

___

i) Was loss to follow-up less than 20% and balanced between test and controls ii) Were patients analysed in the groups to which they were randomised? Was the study of sufficient duration? Were patients, health workers, and study personnel blind to treatment? Were the groups similar at the start of the trial? Aside from the experimental intervention, were the groups treated equally? Was care received outside the study identified and controlled for

___ ___ ___ ___ ___

7. Will the results help in caring for your patients? Were all clinically important outcomes considered? Are the likely benefits of treatment worth the potential harms and costs? ___ ___

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Author, Date

Study Design

Population
n

Intervention Medication Regimen Time

Endodontic Procedure n

Control Placebo Assessment

Outcome

Critical appraisal comment s /scores P value

Conclusion, Strength of evidence and classification

Flare-up Incidence

Swelling,

Lindeboom et al. 2005.

2grs Walton RE, Chiappinell i J et al. 1993 Randomized Controlled Trial Double blind Sample size: 80 Age: 17-78 years old. F:32, M:48, divided in 3 groups: Group A: 26, Group B: 24, Group C:30 Location: University of Iowa Permanent teeth with necrotic pulp & chronic apical periodontitis Penicillin V Single Visit Standard endodontic treatment, No intracanal dressing

P = 0.448

Randomized Controlled Trial Double-blind placebocontrolled trial.

Sample size: 256 Mean Age: 44.4 yrs, Range : 18-42 yrs M: 109(42.6%) F: 147(47.4%) Location: University of Amsterdam Non Vital Teeth with apical periodontitis, adequate root canal filling and free of acute symptoms for periapical surgery.

128

Clindamycin

600 mg

1h before endodontic surgery (Prophylactic)

Endodontic Surgery, The same duration of surgery for two groups.

128

Oral Placebo, 1h before surgery

Pts Assessed 1, 2 and 4 weeks postoperativ ely

Post-op wound infection intervention: 2 cases 1.6%; 95% CI: 0.484.72 control: 4 cases 3.2% 95%CI: 0.421.33

P >0.05

# of analgesics taken

P= 0.22

Henry M,Reader A, Beck M, 2001

Randomized controlled Trial/ Double blind

Sample Size:41 emergency adults Age: Penicillin:37+/- 16.5 Placebo:38+/- 18.8 F:20, M:21 Location: The Ohio State University Symptomatic(spontaneo us pain)/ necrotic permanent teeth with periapical radiolucency

19

Penicillin V

500mg q.i.d Oral 7 days

Post Treatment

Treatment by senior Endodontic graduate students Step back technique

22

Lactose packaged by pharmacy

7-day Diary to record pain.

Pain:
Percussion pain

Score: 16.5/17

Score: 14.5 Randomiz ation in surgical sites is not ideal.

No significant reduction in pain , sensitivity to percussion, swelling and number of analgesic medications taken by administration of penicillin postoperativel y Level of Evidence: No statistically significant evidence of difference between preoperative clindamycin prophylaxis and placebo in prevention of postoperative infection in endodontic surgery. Level of Evidence:
Administration of penicillin prophylactically was unrelated to post treatment signs & symptoms. following canal preparation Using penicillin prophylactic ally to control Postop symptoms not recommended Level of Evidence:

26

recomme ndations1984) 6grs Penicillin V

Single dose (AHA

Pts
assessed

P>0.05 P=0.68

Single dose (AHA

At the beginning of treatment

24

group B: Placebo same regimen

Flare-up: group A:0 group B:1 Mild to moderate pain: A: 69% B:79% C:70% Swelling: A: 1 case B: 1case

P =0.8

Score: 14/17 small sample size; Pts under treatment by Endo graduates and undergradu ates. Skills varied

30

6 hours after the appointment

Group C: No Medication

at 4, 8, 12, 24, and 48 hours.

recomme ndations1984)

Author, Date

Study Design

Population
n

Intervention Medication Regimen Time

Assessment

Endodontic Procedure

Control n Placebo

Outcome

Flare-up Incidence

Leigh Pickenpaug h, et al. 2001

Torabinejad et.al,1994

Randomized control Trial Double blinded study

Sample Size:588 Range of age :18-79 yrs F:52% M:48% Location: Loma Linda university Permanent Symptomatic or asymptomatic teeth with pulpal or periapical pathosis.

57

Penicillin

P <0.0001

2*250mg Every 6 hr for 72hrs

46

Erythromycin Base

P<0.047

2*250mg Every 6 hr for 72hrs

Drugs given post operatively after complete instrumentatio n before obturation

Multiple visit Endo Treatment, Standard RCT; complete instrumentati -on but no obturation by 10 endo practices and 4 endo grad program. Irrigation: Sodium hypochlorite 1.5-5.25% Intracanal medicaments used

53

inertexcipients

Post operative pain assessed by visual analog scale every 6hrs for 72 hrs following instrumenta tion

P = 0.80

Randomized Controlled Trial, double-blind Placebocontrolled

Sample size : 70 healthy adults Location: The Ohio State University Asymptomatic permanent teeth with necrotic pulp associated with periapical lesion s3*3

34

Amoxicillin

Oral 3grams, 1 hour before Endo Tx

Pretreatment 1 h before

Two-visit step back technique, k type files, 2.62% sodium hypochlorite, sterile cotton pellet, Temp filling: Cavit

36

3grams, one hour before Endo Tx

5 1/2 day diary to record Pain, percussion pain, swelling, number and type of pain medication taken

moderate-tosevere postoperative pain or swelling that began 12-48 h after endodontic treatment and persisted for an average of 48h Intervention: 4 cases Control: 3 1-Increase in.Preoperative pain associated with increase in post operative pain. Apprehensio n associated with increase in post operative pain Greater decrease in post-op pain with penicillin and erythromycin than placebo in first 48 hours in pts with Moderate & sever pre-op pain.

P value

Critical appraisal comment s /scores

Conclusion, Strength of evidence and classification

Score :14

Prophylactic dose of amoxicillin before endodontic treatment of asymptomatic necrotic teeth had no effect on the endodontic flare-up. Level of evidence:

Loss to follow up was present (<20%) Score: 13.5

P =0.003

Penicillin and erythromycin more effective in controlling moderate to severe post operative pain within first 48 hours compared to placebo. Penicillin and erythromycin might prevent severe postoperative complications in patients with no or mild preoperative pain. Level of Evidence:

Author, Date

Study Design

Population
n

Intervention Medication Regimen Time

Endodontic procedure

Control n Placebo

Outcome

Assessment

Flare-up Incidence

Critical appraisal comment s /scores P value

Conclusion, Strength of evidence and classification

Torabinejad M etal,1994

Randomized control Trial

Range of age :18-79 yrs Sample Size:411 F: 52%, M:48% Location: Loma Linda university

46

Penicillin

2*250mg Every 6 hr for 72hrs Drugs given post operatively after complete obturation

Double blinded study

P < 0.0001

33

Erythromycin Base

2*250mg Every 6 hr for 72hrs

Multiple visits of Endo Treatment, Standard obturation with Gutta Percha performed. Irrigation:

41

inertexcipients

Post operative pain assessed by visual analogue scale of 0 to 9 every 6hr for 72 hrs

Post operative pain at various time intervals after obturation is lower than that following complete instrumentatio n (5.83% vs. 21.76%)

Loss to follow up was present (<20%) Score: 13.5

Intracanal medicaments used

P = 0.0206

Permanent Symptomatic or asymptomatic teeth with pulpal or periapical pathosis.

Sodium hypochlorite 1.5-5.25%

No significant difference between the effectiveness of various antibiotics and placebo in controlling postoperative pain following obturation Level of evidence:

Erythromycin was more effective than placebo only at 6 hour s