Int. J. Oral Maxillofac. Surg.

2006; 35: 348–351

doi:10.1016/j.ijom.2005.08.002, available online at http://www.sciencedirect.com

Clinical Paper
Medicine

Randomized, double-blind D. Torres-Lagares1, J. L.

Gutierrez-Perez1,2, P. Infante-
Cossio1,2, M. Garcia-Calderon1,
M. M. Romero-Ruiz1, M. A. Serrera-
study on effectiveness of intra- Figallo1
1
Department of Oral Surgery, Faculty of
Dentistry, University of Seville, Seville, Spain;

alveolar chlorhexidine gel in 2

Department of Maxillofacial Surgery and
Stomatology, Virgen del Rocio University
Hospital, Seville, Spain

reducing the incidence of

alveolar osteitis in mandibular
third molar surgery
D. Torres-Lagares, J. L. Gutierrez-Perez, P. Infante-Cossio, M. Garcia-Calderon,
M. M. Romero-Ruiz, M. A. Serrera-Figallo: Randomized, double-blind study on
effectiveness of intra-alveolar chlorhexidine gel in reducing the incidence of alveolar
osteitis in mandibular third molar surgery. Int. J. Oral Maxillofac. Surg. 2006; 35:
348–351. # 2005 International Association of Oral and Maxillofacial Surgeons.
Published by Elsevier Ltd. All rights reserved.

Abstract. Chlorhexidine (CHX) mouthwash is a good prophylactic agent for

postextraction alveolar osteitis (AO), a very common complication. Recently, a
bio-adhesive gel to deliver the active substance, CHX, has been introduced. The
intra-alveolar positioning of the bio-adhesive gel allows more direct and
prolonged action of CHX, which could be useful in the prevention of AO
following extraction of impacted third molars. Presented here is a double-blind,
randomised and parallel-group study evaluating the efficacy of the bio-adhesive
0.2% CHX gel (n = 53) applied once within the alveolus during third molar
surgery, compared to placebo gel only (n = 50), in reducing the incidence of
impacted third-molar postextraction AO. A 63.33% reduction in the occurrence
of AO (P = 0.019) was observed in the experimental group. In the control group,
Key words: alveolar osteitis; dry socket; third-
the occurrence of AO was 30% compared to 11% in the experimental group. Bio- molar extraction; chlorhexidine; clinical trials.
adhesive 0.2% CHX gel, applied only once within the alveolus site at the time of
surgery, may reduce the incidence of AO following removal of impacted third Accepted for publication 3 August 2005
molars. Available online 9 November 2005

0901-5027/040348 + 04 $30.00/0 # 2005 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
 Intra-alveolar chlorhexidine gel in reducing the incidence of alveolar osteitis
Alveolar osteitis (dry socket, AO) has
been defined by BLUM3 as ‘postoperative
pain in and around the extraction site,
which increases in severity at any time
between 1 and 3 days after the extraction
accompanied by a partially or totally dis-
integrated blood clot within the alveolar
socket with or without halitosis’. AO is a
very common postextraction complica-
tion, its incidence following removal of
impacted third molars being around 20–
30% and following extraction of any teeth
between 1% and 70%1,13,14,16,17. The con-
dition is characterized by severe self-lim-
iting pain and often requires several
postoperative visits for treatment, signifi-
cantly adding to patient morbidity and the
cost of the procedure. Antiseptics such as
chlorhexidine (CHX) rinses have proved
to be efficient in AO prevention7,18,20. The
introduction of 0.2% CHX on to the mar-
ket in the form of a bio-adhesive gel to
deliver the active substance has opened up
new lines of investigation. The hypothesis
to be tested in this clinical study was that
the bio-adhesive CHX gel could facilitate
a more direct and lasting effect on the
alveolus site of CHX and thus be useful
in the prevention of AO following extrac-
tion of impacted third molars.
Material and methods
The study was a controlled, double-blind,
randomized and parallel-group clinical
trial performed at the Faculty of Dentis-
try of the University of Seville (Spain).
There were 103 patients of both sexes
aged between 18 and 60 years included
consecutively from January 2002 to June
2003, who presented with a mandibular
impacted third molar with a difficulty
index of between 4 and 7 on a scale of
0–10 according to KOERNER11, and who
had no symptoms 10 days presurgery.
The study was to compare the effects
of topical (intra-alveolar) administration
of 10 ml of bio-adhesive gel containing
0.2% CHX digluconate (Gel bioadhesivo
de clorhexidina Lacer1, Laboratorios
Lacer, Barcelona, Spain) and a placebo
gel containing only excipient (Gel pla-
cebo, Laboratorios Lacer, Barcelona,
Spain). The exclusion criteria were a
contra-indication for intervention; AIDS;
immuno-depression; pregnancy or lacta-
tion; allergy to CHX, lidocaine or para-
cetamol; requiring the extraction of two
third molars at once; bone pathology and
ingestion of any medication 4 days
before the operation. We included
patients using birthcontrol pills and those
who were smokers, and divided into the
two study groups randomly. The random
349
assignment was carried out by means of a Table 1. Data on demographics, difficulty
random number list. index of extraction and tolerance of the treat-
The independent variable was the use or ment carried out
not the use of the bio-adhesive gel contain- Experimental Control
ing 0.2% CHX within the alveolus after group group
extraction of a impacted third molar. The Age (years)
patients were operated on under local Mean 27.8 25.7
anaesthesia using a mandibular nerve SD 8.4 8.6
blockade and buccal infiltration (Lido- Gender
caina 2% epinefrina Normon1, Labora- Male 20 14
torios Normon, Madrid, Spain). The Female 33 36
extraction was carried out following a
Smokers
standardized surgical procedure. The side
Yes 12 14
to be operated on was not randomized. The No 41 36
gel was applied into the alveolus in the
intraoperative period after extraction of Contraceptives
the tooth. The gel was identifiable by a Yes 7 3
No 46 47
patient inclusion code number. The alloca-
tion of patients into one group or the other Difficulty index of extractions (no. of teeth)
was carried out by computer before the start 4 23 16
of the study. Neither the patient nor the 5 15 17
operator knew whether or not the patient 6 9 12
7 6 5
received the bio-adhesive gel containing
CHX (double blind). The code list was kept Tolerance*
in a sealed envelope and was not opened 1 38 37
until the study had been completed. As 2 4 10
postoperative treatment, all the patients 3 2 0
4 2 2
took 14.05 mg codeine phosphate and
5 3 0
500 mg of paracetamol upon request Lost 4 1
(Cod-efferalgan1, Bristol-Myers-Squibb,
Madrid, Spain). AO 6 (11%) 15 (30%)
The main variable evaluated was the P-value 0.019
*
Verbal scale of 1 = totally tolerable to
occurrence of postoperative AO, using
the diagnostic criteria standardized by 5 = totally intolerable.
BLUM3. Tolerance of the treatment, on a
verbal scale of 1–5, was also evaluated. statistically significant differences were
The principles of the Helsinki Declaration found between the two groups as regards
were followed and informed consents smoking habits, use of birth-control pills,
obtained. Ethical approval for the study gender, mean age and difficulty index of
was obtained via the Ethics Committee of extraction.
the University of Seville, Spain. Fifteen cases (30%) of AO were found
The x2-test was applied for the compar- in the control group and six cases (11%) in
ison of frequencies and the Student’s t-test the experimental group (statistically sig-
for the comparison of the means of the two nificant difference, x2-test, P = 0.019). No
groups, after confirming the normal dis- significant adverse effects were presented
tribution of the data by means of the and the patients adequately tolerated the
Kolmogorov–Smirnov test. treatment carried out (Table 1).
Results Discussion
The control and experimental groups con- There are different aetiopathological the-
sisted of 50 and 53 patients, respectively. ories on AO, fibrinolytic and bacterial
Five patients (one in the control group and being the main ones1,6,13,14,16,17,19.
four in the experimental group) did not Depending on different aspects of these
have their final check-up visit. A total of theories, numerous medications have been
103 impacted third molars (52 left and 51 used in its prevention. The risk factors that
right) were operated on. The mean age was increase the frequency of this complica-
26 years (range: 18–64 years). There were tion include smoking, oral contraceptives,
69 women and 34 men. Ten women were lack of experience of the surgeon and poor
taking oral contraceptives, and 26 patients oral hygiene6,13. Anti-fibrolytic agents,
were smokers. The data from the study saline mouthwashes20,21, medicated pack-
group on age, sex, smoking habits, taking ing20 and polylactic acid2 have been
of oral contraceptives and difficulty index applied with variable outcome5. Antisep-
of extraction are shown in Table 1. No tics and antibiotics have been demon-
350 Torres-Lagares et al.
strated to be the most effective, but the
latter are expensive, have significant side
effects and may create resistance. Among
the antiseptics, CHX mouthwash has
proved to be a good prophylactic agent
for AO7,18,21.
In spite of differences in protocol, all
published studies have confirmed the suit-
ability of CHX rinses; protocols included
rinsing with CHX only on the day of
surgery and using multiple rinses with
CHX1,8,10,12,15,16. There have been no
clinical trials reported on the use of bio-
adhesive CHX gel placed within the
alveolus site for the prevention of AO
following the removal of impacted third
molars. The results of the meta-analytic
review by CASO et al.6 on the prevention of
AO with CHX reinforce the conclusion
that rinsing at least on the day of surgery
and for several days after the removal of
the third molars reduces the incidence of
AO. The minimum number of days of
rinsing needed to produce this effect could
not however be determined by this analy-
sis.
DELIBALSI et al.8 found similar percen-
tages of AO using mouthwashes of saline
and 0.2% CHX (23.7% versus 20.9%).
The percentage reduction reached with a
mouthwash of CHX with amoxicillin–cla-
vulanate was 8.9%8. BERWICK & LESSIN1
found no differences in the incidence of
AO in the groups under study (CHX
0.12% and cetylpyridium 0.05%). LAR-
14
SEN demonstrated AO in 16% of the
control group (placebo) compared to 8%
of the experimental group (mouthwash
with 0.12% CHX for 1 week pre-extrac-
tion and 1 week postextraction). In the
study carried out by RAGNO & SZKUTNIK16,
0.2% CHX digluconate mouthwash pro-
duced a reduction in AO after the extrac-
tion of impacted third molars (17.5% as
opposed to 36% in a control group).
BONINE4 and HERMESCH et al.10 also found
reductions in AO of around 50% using
0.12% CHX rinses.
The number of patients in the present
study was adequate, in relation to the
principal variable of the study (appearance
or not of postextraction AO). In other
reported studies, the numbers of patients
involved were between 20 and 67 per
group1,8,9,14,16. The mean age of our
patients was higher than that reported by
other authors4,9,10. As regards the propor-
tion of males to females, some published
studies had a male-to-female ratio similar
to ours4,9,10, while other studies used equal
numbers of both the sexes8,14,15. The tak-
ing of oral contraceptives, which in our
study was the case with 14% of the
women, reached 53% or 32% in other
studies10,15, while in BONINE’s study4 it
was 6.66%. Smokers accounted for 25%
of the patients in our sample, in keeping
with other studies4,8,10,14. Although not
statistically significant, there is a differ-
ence worth noting between the group of
smokers (26 patients, 8 AO, 30.76%) and
the group of nonsmokers (77 patients, 13
AO, 16.88%). There were no significant
differences in the occurrence of AO
between the patients who took contracep-
tives and those who did not.
In the experimental group a reduction in
the incidence of AO was observed, being
clinically significant in respect to the con-
trol group (reduction of 63.3%, P = 0.019).
The application of intra-alveolar CHX
(directly within the alveolus) and the use
of a bio-adhesive gel to deliver this active
substance could explain the reduction
found in the incidence of AO. No secondary
effects, as referred to in other similar stu-
dies, were seen,8 and no adverse effect was
detected. New lines of investigation could
be opened by means of clinical studies
combining the bio-adhesive CHX gel form,
in a single intra-alveolar application and the
mouthwash form, for several days follow-
ing the removal of teeth, with a view to
achieve a greater reduction in the incidence
of postextraction AO.
In conclusion, the data presented in this
clinical study show that a bio-adhesive gel
containing 0.2% CHX applied only once
postextraction in the alveolus site
decreased AO. Intra-alveolar CHX gel
may thus prove to be a good prophylactic
agent for this condition.
Acknowledgements. The authors would
like to acknowledge Laboratorios Lacer,
Barcelona, Spain, for donating the medi-
cation used in this study.
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