INTRODUCTION primary role of pathological bacteria for


osteitis (AO), most commonly known as ´Dry Socket’ is a postoperative painful,
debilitating condition that occurs as a complication of tooth extraction in
permanent dentition1. The
frequency of AO in dental extraction normally ranges from 3% to 4%. However,
very high incidences, from 25% to 30% of all cases, occur after extraction of
impacted mandibular third molar.2

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symptoms of AO appear after 24 to 48 hours of surgery as severe throbbing pain, that
can last for up to three weeks.3
The alveolar socket may contain partially or totally disintegrated blood clot
with or without fetid breath.4 Based
on different theories for the causative factors , numerous techniques have been
used for its prevention such as, the use of saline mouthwashes, topical
placement of antibiotics, antiseptic rinses, anti-fibrinolytic agents,
tranquilizer dressings, occlusive dressings as well as application of
polylactic acid.5 However, as the
primary role of pathological bacteria for the development of AO has been
constantly reported in the literature, the most effective method in the prevention
of AO has been the use of agents that systemically or locally reduce the
pathological microbes at the surgical site.6-7

efficacy of systemic antibiotic as well as topical antiseptic agents have been
studied and analyzed by different researchers. For example, Ramos et al8 have performed a systematic review and
meta-analysis and concluded that systemic antibiotics significantly reduce the
risk of dry socket after extraction of lower third molar. Similarly, Reza and
Khazaei9 have reviewed and
performed a meta-analysis to determine the efficacy of 0.2% chlorhexidine bio
adhesive gel for prevention of AO incidence after extraction of lower third
molar. However, I have not found any study that makes a comparison of efficacy
of systemic antibiotic and topical antiseptic agents for the prevention of AO.
The aim of this study is to review and analyze published studies and compare
the effectiveness of systemic antibiotics and topical antiseptics such as
chlorhexidine for the prevention of AO after extraction of lower third molar.


This review is
composed of publications that were published during 2006 to 2017, reporting on systemic
antibiotics and/or topical antiseptics in the prevention of AO after extraction
of lower third molar. Only studies that were based on randomized clinical
trials and had at least one control group have been included in the review. The
literature search was carried out with questions structured in the Patient,
Intervention, Comparison and Outcome (PICO) format.10-11

Eligibility Criteria

Patient: This review
includes the studies with individuals of any age and gender, who had lower
third molar extraction, regardless of how much were the degree of impaction.
All patients were otherwise healthy, without any underlying medical problem.

Intervention: The included
studies had tested the efficacy of different systemic antibiotics, administered
through oral or parental rout as well topical antiseptics in the form of oral
rinses or bio adhesive gel. However, the only antiseptic that was evaluated was
the chlorhexidine gluconate.

Comparison: All studies were
randomized clinical trials having a control group. The controls were the
placebo in the same form and shape of active regime.  However, the controls were in the same
patients (split-mouth technique) or in different patients.

 Outcome: This review includes
those studies who studied alveolar osteitis (dry socket) or infection or both
as post-operative complication, occurring after 3 to 5 days of surgery. It is
likely that investigators tested other outcomes such as inflammatory conditions
(pain, fever, size of mouth-opening etc.) along with alveolar osteitis or
infection. However, only alveolar osteitis or infection fragment was included
in this review.


Characteristics of studies

All included
studies were randomized clinical trials having at least one control where the control
group received placebo replica of active ingredient. However, in some studies
the control group did not receive any placebo12.
In such studies, the patients or extracted tooth sockets without any placebo
were considered as control. Similarly, the control was either an another group
of identical patients or it was the same patient where corresponding tooth in
the opposite side of the mouth (studies using split-mouth technique) was considered
as control. Though majority of the studies were double blinded, in some studies
the investigator’s blinding was not mentioned. However, there was one study
that was single-blinded.13 There
existed a large variation in the type and administration of experimental
material. For instance, the route of administration of antibiotics was either
oral or parental but the route of administration of chlorhexidine was always topical,
either in the gel or in the mouth rinse form. Similarly, the timing of
administration was either pre-operative where the drug was given before surgery
or post-operative when the drug was administered after the surgery. All
included studies tested a single regimen at one time, testing either antibiotic
or chlorhexidine gluconate. However, one study14
tested the effects of 0.2% chlorhexidine gluconate as well as 0.2%
chlorhexidine gluconate in combination with amoxicillin plus clavulanic acid in
two different groups. To avoid the complication, the results of 0.2%
chlorhexidine gluconate from first group were included in this review and
results from the second group were discarded. The outcome was alveolar
osteitis. The AO was established if there was sever pain after 24 to 48 hours
of extraction with exposed bony socket. Similarly, surgical wound infection was
diagnosed if there was purulent discharge from the wound along with symptoms of
the infection such as pain, fever and lymphadenopathy. 


Statistical analysis

The extracted
data from selected studies were analyzed using statistical software R (version
3.3.2)15 and package ‘metafor.’16 The effect of treatment was analyzed with
a random effect model, using the Relative Risk (RR) as effect size of
individual studies. Treatment antibiotic or antiseptic were used as a modifier.
A funnel plot was designed to check the precision and/or existence of
publication bias of the selected studies.


Out of 31
potentially eligible full-text studies, 16 were selected for quantitative
analysis. However, some studies17,18 used
more than 1 group to check the efficacy of the treatment. In such cases, every
group was taken as a single study, thus making 20 suitable trials for
meta-analysis.  Figure 1 shows the
selected studies and the flow chart of the selection process. Fifteen studies
failed to fulfill the inclusion criteria and, therefore, were excluded. The
excluded studies and the reason for their exclusion are summarized in appendix

Analysis of efficacy

This quantitative
analysis included 2136 tooth extractions in antibiotic group and 868 tooth
extractions in antiseptic group, thus making total 3004 dental extractions for
meta-analysis. Out of 2136 dental extractions in antibiotic group, 1089 cases
received antibiotics with 53 infections (4.87%) and 1047 were in control group
with 91 infections/dry sockets (8.69%). Similarly, 439 cases were treated with
antiseptics where 43 cases developed infections/dry sockets (9.79%) whereas 101
resulted with infections out of 429 extractions in control group (23.54%). The
overall RR was 0.49, with 95% confidence interval, ranging from 0.35 to 0.68.
This was statistically significant (P

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