This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library
2013, Issue 12
http://www.thecochranelibrary.com
Zbys Fedorowicz1 , Esther J van Zuuren2 , Allan G Farman3 , Anirudha Agnihotry4 , Jassim Hasan Al-Langawi5
1
Bahrain Branch, The Cochrane Collaboration, Awali, Bahrain. 2 Department of Dermatology, Leiden University Medical Center,
Leiden, Netherlands. 3 Department of Surgical and Hospital Dentistry, The University of Louisville School of Dentistry, Louisville,
Kentucky, USA. 4 Department of Conservative Dentistry, Mahatma Gandhi Dental College and Hospital, Jaipur, India. 5 College of
Medicine, Arabian Gulf University, Salmaniya, Bahrain
Contact address: Zbys Fedorowicz, Bahrain Branch, The Cochrane Collaboration, Box 25438, Awali, Bahrain.
zbysfedorowicz@gmail.com.
Citation: Fedorowicz Z, van Zuuren EJ, Farman AG, Agnihotry A, Al-Langawi JH. Antibiotic use for irreversible pulpitis. Cochrane
Database of Systematic Reviews 2013, Issue 12. Art. No.: CD004969. DOI: 10.1002/14651858.CD004969.pub3.
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
ABSTRACT
Background
Irreversible pulpitis, which is characterised by acute and intense pain, is one of the most frequent reasons that patients attend for
emergency dental care. Apart from removal of the tooth, the customary way of relieving the pain of irreversible pulpitis is by drilling
into the tooth, removing the inamed pulp (nerve) and cleaning the root canal. However, a signicant number of dentists continue to
prescribe antibiotics to stop the pain of irreversible pulpitis.
Objectives
Search methods
We searched the Cochrane Oral Health Groups Trials Register (to 5 September 2013); the Cochrane Central Register of Controlled
Trials (CENTRAL) (The Cochrane Library 2013, Issue 9); MEDLINE via OVID (1946 to 5 September 2013); EMBASE via OVID
(1980 to 5 September 2013) and the US National Institutes of Health Trials Register (http://clinicaltrials.gov). There were no language
restrictions in the searches of the electronic databases.
Selection criteria
Randomised controlled trials which compared pain relief with systemic antibiotics and analgesics, against placebo and analgesics in the
acute preoperative phase of irreversible pulpitis.
Two review authors screened studies and extracted data independently. We assessed the quality of the evidence of included studies using
GRADEPro software. Pooling of data was not possible and a descriptive summary is presented.
Antibiotic use for irreversible pulpitis (Review) 1
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Main results
One trial assessed at low risk of bias, involving 40 participants was included in this update of the review. The quality of the body of
evidence was rated low for the different outcomes. There was a close parallel distribution of the pain ratings in both the intervention
and placebo groups over the seven-day study period. There was insufcient evidence to claim or refute a benet for penicillin for
pain intensity. There was no signicant difference in the mean total number of ibuprofen tablets over the study period: 9.2 (standard
deviation (SD) 6.02) in the penicillin group versus 9.6 (SD 6.34) in the placebo group; mean difference -0.40 (95% condence interval
(CI) -4.23 to 3.43; P value = 0.84). This applied equally for the mean total number of Tylenol tablets: 6.9 (SD 6.87) used in the
penicillin group versus 4.45 (SD 4.82) in the placebo group; mean difference 2.45 (95% CI -1.23 to 6.13; P value = 0.19). Our
secondary outcome on reporting of adverse events was not addressed in this study.
Authors conclusions
This systematic review which was based on one low powered small sample trial assessed as a low risk of bias, illustrates that there is
insufcient evidence to determine whether antibiotics reduce pain or not compared to not having antibiotics. The results of this review
conrm the necessity for further larger sample and methodologically sound trials that can provide additional evidence as to whether
antibiotics, prescribed in the preoperative phase, can affect treatment outcomes for irreversible pulpitis.
Key results
Antibiotics do not appear to signicantly reduce toothache caused by irreversible pulpitis. Furthermore, there was no difference in the
total number of ibuprofen or Tylenol tablets used over the study period between both groups. The administration of penicillin does not
signicantly reduce the pain perception, the percussion (tapping on the tooth) perception or the quantity of pain medication required
by people with irreversible pulpitis. There was no reporting on adverse events or reactions.
Quality of the evidence
This was a study with a small number of participants and the quality of the evidence for the different outcomes was rated as low. There
is currently insufcient evidence to be able to decide if antibiotics help for this condition. This review highlights the need for more
and better quality studies on the use of antibiotics for irreversible pulpitis.
Outcomes Illustrative comparative risks* (95% CI) Relative effect No of participants Quality of the evidence Comments
(95% CI) (studies) (GRADE)
Control Antibiotics
Patient-reported pain in- Study population Not estimable 40
The in-between group dif-
tensity (1 study) low1 ferences in SPID and SP-
(sum of pain intensity dif- PID were not statistically
ference (SPID) and sum significant2
of pain percussion inten- Moderate
sity difference (SPPID))
Patient-reported pain re- See comment See comment Not estimable - See comment Not assessed
lief - not reported
Total number of ibupro- The mean total number The mean total number 40
The administration of
fen tablets of ibuprofen tablets in the of ibuprofen tablets in the (1 study) low3 penicillin over placebo did
control groups was intervention groups was not appear to significantly
9.6 tablets 0.40 lower reduce the quantity of
(4.23 lower to 3.43 ibuprofen consumed for
higher) irreversible pulpitis
Total number of parac- The mean total num- The mean total num- 40
The administration of
etamol (acetaminophen) ber of acetaminophen + ber of acetaminophen + (1 study) low3 penicillin over placebo did
+ codeine tablets codeine tablets in the codeine tablets in the in- not appear to significantly
control groups was tervention groups was reduce the quantity of
3
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Antibiotic use for irreversible pulpitis (Review)
Number of adverse See comment See comment Not estimable - See comment Not assessed
events - not reported
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the
assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI)
CI: confidence interval
important difference
4
BACKGROUND Pulpitis is an inammatory reaction of the pulp and often occurs
without any evidence of bacteria in the pulp chamber. Antibiotics
Dental emergencies are extremely common, a survey conducted have bactericidal or bacteriostatic properties or both and are used
in the USA recorded that 12% of the population had experienced widely to control or eliminate bacteria, but the mode of action and
toothache in the preceding six months (Lipton 1993). Non-trau- extent to which antibiotics have an anti-inammatory or analgesic
matic dental condition visits account for 1.4% of all emergency effect in irreversible pulpitis remains less clear.
dental visits in the USA and have shown an annual rise of 4%
(from 1.0% in 1997 to 1.7% in 2007) (Onkunseri 2012). Dental
caries (tooth decay) is the result of bacterial attack on a tooth and is
Why it is important to do this review
the precursor to irreversible pulpitis, which is considered to be an
immune system mediated event affecting the dental pulp (nerve) There is limited and what appears to be largely anecdotal evidence
(Bergenholtz 1990). Acute and intense pain are the most typical to support the routine prescribing of antibiotics for irreversible
presenting symptoms of irreversible pulpitis. It occurs more com- pulpitis. It is likely that the practice of prescribing of antibiotics
monly in vital teeth beneath deep caries before the bacteria have may have arisen due to a misconception of the pathological process
even reached the pulp (Hahn 1991). Thus the involved tooth will of pulpitis or the perception that antibiotics should be prescribed
usually have an extensive restoration (lling) or caries or both un- prophylactically in anticipation of pain arising prior to endodontic
der which death of the pulp may occur quite quickly or which may treatment. Either of these approaches may have promoted the in-
take years to occur even if the dental caries is removed (Tronstad appropriate prescribing of antibiotics for endodontic emergencies.
1991). A study conducted in the USA of members of the American Asso-
ciation of Endodontists (AAE) surveyed their prescribing practices
and reported that 16.7% of the specialist endodontists prescribed
antibiotics for cases of irreversible pulpitis (Yingling 2002). Gen-
Description of the condition eral dental practitioners are often the rst point of contact for pa-
The symptoms are a continuum and can vary but usually include a tients with irreversible pulpitis and although one study conducted
history of spontaneous pain which may also involve an exaggerated in Belgium reported that a smaller proportion (4.3%) of general
response to hot or cold that lingers after the stimulus is removed ( dentists continue to prescribe antibiotics for irreversible pulpitis
Soames 1998). Any tooth may be affected by irreversible pulpitis, it (Mainjot 2009), a more recent study conducted in Spain indicated
is not restricted to particular age groups, it usually occurs as a direct that a substantial number (86%) of respondents continue to do
result of dental caries, a cracked tooth or trauma and thus tends so (Segura-Egea 2010).
to occur more frequently in older patients. The involved tooth It is believed that the indiscriminate use of antibiotics may have
is usually not sensitive to percussion, and palpation tests do not added signicantly to the increase in methicillin resistant Staphy-
produce an untoward reaction. The characteristics of irreversible lococcus aureus (MRSA) infections with concomitant staggering
pulpitis are a vital pulp which responds to cold and electric pulp cost implications (Cox 1995). The US Centers for Disease Con-
testing. Not infrequently, cold may actually alleviate the pain of trol and Prevention estimates that about 100 million courses of
irreversible pulpitis and thus, can be used as a diagnostic test (Cecic antibiotics are prescribed by ofce-based physicians each year, and
1983). A number of variations of irreversible pulpitis have been that approximately one half of those prescriptions appear to be
recognised (Cohen 2006). These include acute, subacute, chronic, unnecessary (Colgan 2001). Although the inappropriate prescrib-
partial or total, infected or sterile, however it is not possible to ing of antibiotics for endodontic emergencies has received much
clearly differentiate these except by histopathological methods. attention (Fouad 1996; Palmer 2003) it is unclear to what extent
this may have contributed to the development of resistant strains
of bacteria and the growing problem of antibiotic resistance (CDC
2008; SMAC 1997).
Description of the intervention
Irreversible pulpitis, at least in the early phase, is not normally ac-
A range of oral antibiotics with differing dosing regimens may companied by the clinical signs of bacterial infection, i.e. swelling
be prescribed e.g. azithromycin (500 mg daily for three days); and tenderness of adjacent mucosa, which more generally mani-
clindamycin (150 mg four times a day for seven days); penicillin V fests itself after the pulp has become necrotic and the infected pul-
(250 mg four times a day for seven days); metronidazole (200 mg pal tissues pass into the periapical region. Although some dentists
three times a day for three days); amoxicillin (250 mg + clavulanic continue to prescribe antibiotics, there appears to be very limited
acid 125 mg three times a day for ve days) (Matthews 2003). evidence that penicillin reduces pain, percussion sensitivity, or the
amount of analgesics required in untreated teeth diagnosed with
irreversible pulpitis (Nagle 2000).
How the intervention might work Immediate pulpectomy is now widely accepted as the standard of
care for irreversible pulpitis (Walton 2009) and yet in certain parts
OBJECTIVES
Summary of findings table
To assess the effects of systemic antibiotics for irreversible pulpitis. We established a Summary of ndings table 1 table using the fol-
lowing outcomes listed according to priority.
1. Patient-reported pain intensity (sum pain intensity
METHODS differences and sum pain percussion intensity differences).
2. Patient-reported pain relief.
3. Total number of ibuprofen tablets.
4. Total number of paracetamol (acetaminophen) + codeine
Criteria for considering studies for this review tablets.
5. Number of adverse events.
Types of studies
Randomised controlled trials (RCTs) were considered in this re-
Search methods for identification of studies
view.
Description of studies
Assessment of reporting biases
If a sufcient number (> 10) of trials investigating similar inter- Results of the search
ventions are identied for inclusion in future updates of this re- The search strategy used in the earlier version of this review in
view, publication bias will be assessed according to the recommen- 2005 identied 39 references of which all but four were excluded
dations on testing for funnel plot asymmetry as described in sec- from further analysis. Full-text copies of these four papers were
tion 10.4.3.1 of the Cochrane Handbook for Systematic Reviews of obtained for further assessment. Only one study (Nagle 2000) met
Interventions (Higgins 2011). If asymmetry is identied, we will the inclusion criteria and is included in the review. No additional
try to assess other possible causes and these will be explored in the studies were identied for inclusion based on the updated searches
discussion if appropriate. in February 2009 or September 2013 (Figure 1).
Allocation
The measures used to blind study participants and personnel from
knowledge of which intervention a participant received as well as
blinding of outcomes assessors were described in sufcient detail.
Sequence generation The medications were blinded, randomised, and packaged by a
In this study the intervention (penicillin) and control (placebo) pharmacy. Each 500 mg gelatin capsule of either penicillin or
groups were assigned before the experiment by using four-digit placebo was identical in form. The 500 mg tablets of penicillin VK
numbers from a random number table. The method used to gen- were ground into a powder and placed into the clear, unlabelled
erate the allocation sequence was described in sufcient detail; gelatin capsules. The white powder of the lactose placebo was
therefore, this domain was judged as at low risk of bias. indistinguishable from the white powder of the penicillin tablets
when viewed through the capsule.
Allocation concealment
To ensure adequate concealment only the random numbers were Incomplete outcome data
recorded on the data collection and postoperative diary sheets and
The report was complete and there were no missing data and this
it was unlikely that allocation could be foreseen and therefore this
domain was judged as at low risk of bias.
domain was judged as at low risk of bias.
REFERENCES
Nagle 2000
Methods Prospective randomised double-blind trial in the USA. Before the experiment, patient
groups (penicillin or placebo) were assigned by using 4-digit numbers from a random
number table. Only the random numbers were recorded on the data collection and
postoperative diary sheets to blind the experiment.
The medications were blinded, randomised, and packaged by a pharmacy
Participants Adults: (40) 17 male, 23 female. Mean age and standard deviation (SD) in the penicillin
group 30 (9.8), placebo group 34 (11.6).
2 groups of 20: penicillin group 7 women and 13 men, placebo 16 women and 4 men
Inclusion criteria:
participants in good health,
clinical diagnosis of irreversible pulpitis (spontaneous moderate/severe pain),
percussion sensitivity,
tooth vital to electric pulp tester (EPT) and painful response to Endo Ice,
radiographically widened periodontal ligament space.
Exclusion criteria:
tooth not responsive to EPT,
participants taking antibiotics or in the preceding 30 days.
Interventions Oral penicillin or placebo control (lactose) and all patients received analgesics.
7-day oral dose 500 mg 6 hourly; penicillin (Penicillin VK; Wyeth Laboratories, Philadel-
phia, Pa) or a placebo control (lactose).
Analgesics: 600 mg ibuprofen (Motrin; HN Norton Co, Shreveport, La); paracetamol
(acetaminophen) with 30 mg of codeine (Tylenol No 3; McNeil Consumer Products,
Fort Washington, Pa)
Outcomes Primary outcomes: between-group differences in sum of pain intensity difference (SPID)
, sum of pain percussion intensity difference (SPPID) and quantity of pain medications
taken
Risk of bias
Random sequence generation (selection Low risk Quote: Before the experiment, patient
bias) groups (penicillin or placebo) were assigned
by using 4-digit numbers from a random
number table.
Comment: Probably done.
Allocation concealment (selection bias) Low risk Quote: Only the random numbers were
recorded on the data collection and postop-
erative diary sheets to blind the experiment.
The medications were blinded, random-
ized, and packaged by a pharmacy.
Comment: Central randomisation, proba-
bly done.
Incomplete outcome data (attrition bias) Low risk Outcome data were complete for all of the
All outcomes participants.
Comment: We judged this as at low risk of
bias.
Selective reporting (reporting bias) Low risk No evidence of selective choice of data for
outcomes. Outcomes listed in the methods
section comparable to the reported results
Comment: We judged this as at low risk of
bias.
Fouad 1996 This study combined antibiotic or placebo or neither as an adjunct to operative endodontic treatment in resolving
the acute apical abscess
ADDITIONAL TABLES
Table 1. Baseline pain and percussion values for penicillin and placebo groups
Penicillin Placebo
Initial pain (median & interquartile range) 2.00 +/- 0.00 2.00 +/- 1.00
Initial percussion pain (median & in- 2.00 +/- 0.50 2.00 +/- 1.00
terquartile range)
Sum of pain intensity differ- 6.0 +/- 10.5 6.0 +/- 9.5 .776
ence (median and interquartile
range)
Sum of percussion pain inten- 3.5 +/-7.5 2.0 +/- 7.0 .290
sity difference (median and in-
terquartile range)
Table 3. Use of pain medication for penicillin and placebo groups (n and quantity)
DAY 1
No of tablets 33 21 0
No of tablets 28 11 0
DAY 2
No of tablets 30 28 0
No of tablets 31 18 0
DAY 3
No of tablets 27 20 0
No of tablets 28 14 0
DAY 4
No of tablets 24 23 0
No of tablets 28 8 0
DAY 5
No of tablets 21 15 0
No of tablets 32 11 0
DAY 6
No of tablets 24 15 0
No of tablets 24 13 0
DAY 7
No of tablets 25 16 0
No of tablets 20 14 0
Table 4. Research recommendations based on a gap in the evidence of the effects of antibiotics for irreversible pulpitis
Evidence (E) What is the current state of the evidence? This systematic review identied 1 randomised con-
trolled trial
Population (P) Diagnosis, disease stage, comorbidity, risk factors, gen- Inclusion criteria
der, age, ethnic group, specic inclusion or exclusion Adult patients > 18 years with a single tooth with
criteria, clinical setting a clinical diagnosis of irreversible pulpitis
Exclusion criteria
If pulpectomy is to be provided immediately
Intervention (I) Type, frequency, dose, duration, prognostic factor Any systemic antibiotic at any dosage and any analgesic
at any dosage prescribed in the acute preoperative phase
of irreversible pulpitis
Comparison (C) Type, frequency, dose, duration, prognostic factor Placebo and any analgesic, at any dosage, prescribed in
the acute preoperative phase of irreversible pulpitis
Outcome (O) Which clinical or patient-related outcomes will the re- Patient-reported pain (intensity/duration) and
searcher need to measure, improve, inuence, or accom- pain relief measured on a categorical scale in the
plish? Which methods of measurement should be used? preoperative phase of irreversible pulpitis
Any adverse effects related to any clinically
diagnosed hypersensitivity or other reactions to either
the antibiotics or analgesics
Type, dose and frequency of medication required
for pain relief
Study type What is the most appropriate study design to address Randomised controlled trial (adequately
the proposed question? powered/multicentred)
Methods: concealment of allocation sequence
Blinding: participants, trialists, outcomes
assessors, data analysts
APPENDICES
WHATS NEW
Last assessed as up-to-date: 5 September 2013.
17 December 2013 New citation required but conclusions have not New review authors added. Modications in text and
changed style in conformity with MECIR (Methodological Ex-
pectations of Cochrane Intervention Reviews) stan-
dards
6 September 2013 New search has been performed Searches updated to September 2013. No additional
eligible studies identied
HISTORY
Protocol rst published: Issue 4, 2004
Review rst published: Issue 2, 2005
16 February 2009 New search has been performed New searches: February 2009. New studies sought but none found. Text in
Assessment of risk of bias in included studies modied. Risk of bias table
added
CONTRIBUTIONS OF AUTHORS
Zbys Fedorowicz (ZF), Esther van Zuuren (EvZ), Anirudha Agnihotry (AA), Allan Farman (AF) and Jassim Hasan Al-Langawi (JHL)
were responsible for: data collection for the review; screening search results; screening retrieved papers against inclusion criteria;
appraising risk of bias of papers; extracting data from papers; obtaining and screening data on unpublished studies; entering data into
RevMan; analysis and interpretation of data; and writing the review.
ZF was responsible for: organising retrieval of papers.
ZF and EvZ were responsible for writing to authors of papers for additional information; and providing additional data about papers.
ZF was responsible for: designing and co-ordinating the review; and performing previous work that was the foundation of current
study.
ZF and EvZ were responsible for data management for the review.
ZF conceived the idea for the review and will also be the guarantor for the review.
DECLARATIONS OF INTEREST
There are no nancial conicts of interest and the review authors declare that they do not have any associations with any parties who
may have vested interests in the results of this review.
SOURCES OF SUPPORT
Internal sources
No sources of support, Not specied.
External sources
Cochrane Oral Health Group Global Alliance, UK.
All reviews in the Cochrane Oral Health Group are supported by Global Alliance member organisations (British Association of Oral
Surgeons, UK; British Orthodontic Society, UK; British Society of Paediatric Dentistry, UK; British Society of Periodontology, UK;
Canadian Dental Hygienists Association, Canada; National Center for Dental Hygiene Research & Practice, USA; Mayo Clinic,
USA; New York University College of Dentistry, USA; and Royal College of Surgeons of Edinburgh, UK) providing funding for the
editorial process (http://ohg.cochrane.org/)
National Institute for Health Research (NIHR), UK.
CRG funding acknowledgement:
The NIHR is the largest single funder of the Cochrane Oral Health Group
Disclaimer:
Antibiotic use for irreversible pulpitis (Review) 24
Copyright 2013 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
The views and opinions expressed therein are those of the authors and do not necessarily reect those of the NIHR, NHS or the
Department of Health
INDEX TERMS