DENTOALVEOLAR SURGERY

A Double-Blind Randomized Study

Evaluating the Effect of Intra-Alveolar
Chlorhexidine Gel on Alveolar Osteitis After
Removal of Mandibular Third Molars
Nelly Freudenthal, DDS,* Mika Sternudd, DDS,y Leif Jansson, DDS, PhD,z
and Karin Wannfors, DDS, PhDx
Purpose:

The main purpose of the present investigation was to determine whether intra-alveolar chlorhexidine (CHX) gel is an effective preventative treatment for alveolar osteitis (AO), as has been strongly
suggested by previous investigators. Another goal was to evaluate whether there is a correlation between
the use of analgesics during the postoperative week and the development of AO, a correlation that could
be a supplement to the commonly used diagnostic criteria for AO.

Materials and Methods:

A double-blinded randomized study was performed to assess whether intraalveolar administration of CHX decreases AO. To achieve this objective, the extraction and postoperative
course of 100 impacted mandibular third molars were studied. Ninety-seven percent of teeth operated on
had a diagnosed pathology. The extraction alveoli were treated with CHX or placebo. The intake of
analgesics was recorded for 7 days after the operation.

Results:

Statistically important differences in AO between the control and experimental groups were
not found. The intake of analgesics reflected the occurrence of AO with a high degree of importance.

Conclusion:

The present study did not verify that application of CHX gel improves healing after removal
of impacted third molars. The patients postoperative analgesic intake reflected the development of AO.
2015 American Association of Oral and Maxillofacial Surgeons
J Oral Maxillofac Surg 73:600-605, 2015

In 10 to 40% of cases in which lower third molars are

removed, alveolar osteitis (AO) occurs as a postoperative complication.1,2 AO is the most common
complication after removal of impacted third molars;
it is a painful condition that usually develops 3 to 4
days after tooth extraction. AO is an inflammatory
condition of the extraction socket. The etiology is
not fully understood, but an infectious component is
suspected. An increased local fibrinolysis, as a result
of plasminogen pathway activation leading to
disintegration of the clot, has been suggested as an
explanation for the pathogenesis of AO.2 Factors such
as surgical trauma, difficulty of surgery, smoking, and

bacterial infection have been suggested as contributing

factors.2 As prevention against AO, preoperative
rinsing with 0.2% chlorhexidine (CHX) solution has
been used,3,4 and encouraging reports have been
presented for using CHX rinsing of extraction
sockets.5,6 Two reports have stated good results from
the postoperative application of CHX gel directly into
the socket.7,8 Thus, the aim of the present study was
to determine whether CHX gel is an effective
treatment against AO and to verify previous results
showing the advantages of this procedure. A second
goal of the study was to determine whether
postoperative intake of analgesics is correlated to the

*Eastman Institute Maxillofacial Surgery, Public Dental Service,

Address correspondence and reprint requests to Dr Freudenthal:

Stockholm County Council, Stockholm, Sweden.

Eastman Institute Maxillofacial Surgery, Dalagatan 11, 11324 Stock-

yPublic Dental Service, Gotland County, Visby, Sweden.

zHead, Department of Periodontology, Public Dental Service at

holm, Sweden; e-mail: nelly.freudenthal@ftv.sll.se

Received May 15 2014

Kista and Skanstull, Stockholm County Council, Stockholm;

Accepted August 27 2014

Adjunct Lecturer, Division of Periodontology, Department of

2015 American Association of Oral and Maxillofacial Surgeons

Dental Medicine, Karolinska Institutet, Huddinge, Sweden.

0278-2391/14/01407-4

xFormer Head, Oral and Maxillofacial Clinic, Sodersjukhuset,

http://dx.doi.org/10.1016/j.joms.2014.08.035

Stockholm, Sweden.

600

601

FREUDENTHAL ET AL

development of AO and thus could be used as a

complementary diagnostic criterion for AO.

Materials and Methods

STUDY DESIGN

This study was designed as a controlled, doubleblinded study carried out at the Oral and Maxillofacial
Surgery Clinic at the South Hospital in Stockholm,
Sweden. Ethical approval (2010/830-32) was obtained
by the regional ethical review board. A high scientific
level was secured by using a randomization process.
The monitoring procedures were performed by a
monitor at the Karolinska Trial Alliance (M62). The
code list (active gel or placebo) was developed in
advance through a randomizing process. The code list
was locked away and was not unlocked until the study
was completed. Neither the surgical team nor the
patients knew whether active gel or placebo was
administered.
The active gel used was legally approved by the
Swedish Medical Products Agency before the study,
because it was not a registered pharmaceutical. The
placebo gel was already registered as a pharmaceutical
product.
To achieve statistical power, 100 mandibular third
molars (95 patients; age range, 19 to 65 yr) were included
in the study. Two third molars were extracted from 5 patients and 1 third molar was extracted from 90 patients.
All teeth had a diagnosed pathology, such as pericoronitis, suspected cyst formation, or resorption of adjacent
teeth. The study was performed from February 2011 to
March 2012. All patients were invited to participate in
the study if they reported no immunodepressive conditions, were not pregnant, or were judged unable to
follow the study because of severe illness or functional
disability. In addition, patients with bisphosphonate or
corticosteroid intake or antibiotic treatment were
excluded, as were those who declared being allergic to
CHX, paracetamol, or codeine. All invited patients carefully read the study instructions and agreed to participate. The included teeth were randomly divided into 2
study treatment groups and subsequently numbered.
The following background variables were registered
during the study:





age
gender
smoking habits
daily medication intake

The following variables were recorded in connection to surgery:

 surgeon
 anatomic variations of the third molar

 reason for surgery (preoperative diagnosis)

 surgery time (minutes)
The criterion for the AO diagnosis was postoperative pain that increased in severity with time and
was accompanied by a partially or totally disintegrated
blood cloth within the alveolar socket with or without
halitosis.8 The main variable evaluated was the AO
diagnosis (yes vs no) for each tooth in relation to the
use or nonuse of the active gel. The intake of analgesic
tablets (type and frequency) 1 to 7 days after surgery
was registered by the patients.
SURGERY

The patients were operated on by 3 senior house officers working at the Oral and Maxillofacial Surgery
Clinic at the South Hospital. Neither the surgeons nor
their assistant nurses were involved in the randomization procedure. All patients were given Alvedon (paracetamol, [Famar A.V.E, Anthoussa Plant, Greece]) 1 g
before the surgical procedure. They also were offered
oral sedation with Dormicum (midazolam, [APL, Stockholm, Sweden]) 1 mg/mL and those who accepted
were given 10 to 15 mL. All patients were operated
on under local anesthesia using lidocaine 20 mg/mL
plus epinephrine 12.5 mg/mL (Xylocain-Adrenalin,
Pierrel Farmaceutica, Capua, Italy). The surgical procedure followed a standard protocol. A buccal mucoperiosteal flap was raised and all bone covering the crown
of the tooth was removed using a round burr. Saline
was used for cooling. The crown was separated from
the root, the root was divided, and all parts were
removed together with remaining coronary sac tissue.
The socket was rinsed with saline. Thirty seconds after
removal, Cervitec gel (Ivoclar Vivadent AG, Schaan,
Lichtenstein) 10 mL, containing 0.2% CHX and 0.2%
NaF, was placed into the alveolus in the experimental
group. In the control group, placebo gel (APL dentalgel, APL, Stockholm, Sweden) containing 0.2% NaF
was applied. The wound was tightly closed using Vicryl
Rapid (Johnson & Johnson Eticon GmbH, Norderstedt, Germany).
Postoperatively, the patients were prescribed
Alvedon (paracetamol 1 g) and Citodon (paracetamol
500 mg and codeine 30 mg, [Orion, Espoo, Finland]).
They were informed to start using only Alvedon and
to add Citodon when needed. All analgesic medication
during 7 days was recorded by the patients. The patients second visit was scheduled for 1 week after surgery. The following measurements were registered by
1 of the surgeons not taking part in the actual surgical
procedure: 1) the occurrence of postextraction AO
(yes vs no) and 2) the patients intake of analgesics 1
to 7 days after surgery. The registration was saved
with the patients individual study protocol.

602
STATISTICS

The descriptive statistics and statistical analyses were

performed using a statistical package (IBM SPSS Statistics 19.0, IBM, Armonk, NY). Differences between the
treatment and placebo groups were analyzed using unpaired t tests and c2 tests. Stepwise logistic regression
analysis, using the incidence of AO as the dependent
variable, was adopted to investigate the influence of potential background factors and risk indicators for the
occurrence of AO. Results are presented as mean and
standard deviation (SD). Results were considered statistically significant at a P value less than .05. A power
calculation showed that 100 patients were required to
obtain a power of 80% and a significance level of 5% if
the hypothesis was a difference of 20% between groups
according to AO frequency (5% and 25%, respectively).

Results
Five teeth had to be excluded from the study owing
to medical complications during surgery or the immediate postoperative period. In 2 cases, the surgery could
not be completed owing to the patients anxiety. In 1
case, it was discovered immediately after surgery that
the patient had started corticoid medication. In another
2 cases, the surgery was complicated by a postoperative purulent infection disabling a correct AO diagnosis.
Therefore, the total number of teeth available for analysis was 95. The mean age of the patients was 33 years
(SD, 10.3 yr) and 47% were men. Ten percent declared
that they were smokers. Thirty-two percent of patients
took some kind of daily medicine. However, none of
them had been under antibiotic treatment 14 days
before the actual surgery. There were no statistically
important differences between the 2 groups according
to individual background variables (Table 1). The preoperative diagnoses or conditions for mandibular third
molars are presented in Table 2. The most frequent
diagnosis was pericoronitis (59%). In 3 cases, the teeth
were extirpated prophylactically.
The total incidence of AO was 21%. The incidence
rate of AO was 19% in the placebo gel group (control
group) and 23% in the CHX gel group (experimental
group; Table 3). This difference was not statistically
important. The incidences of AO did not differ importantly among the 3 surgeons and the frequencies were
17%, 18%, and 25%, respectively.
AO was diagnosed after surgical removal of 1 of 2
retained mandibular third molars (Table 4). The 2
retained teeth had the preoperative diagnosis of a
widened follicular sac. For partially erupted molars in
a mesial or horizontal position, the AO incidence was
24% after surgical removal, whereas the incidence was
lower (17%) for partial erupted teeth in a distal or a vertical position. However, these differences were not statistically different. The incidence of AO was 25% (14

CHLORHEXIDINE GEL ON ALVEOLAR OSTEITIS

Table 1. BACKGROUND AT INDIVIDUAL LEVEL FOR

TREATMENT GROUPS

Variable
Age (yr), mean
(range)
Men/women, %
Smokers, %
Daily medication
intake, %

Placebo
Gel

Chlorhexidine
Gel

P
Value

34 (20-65)

33 (19-62)

NS

44/56
12
27

51/49
8
37

NS
NS
NS

Abbreviation: NS, not significant.

Freudenthal et al. Chlorhexidine Gel on Alveolar Osteitis. J Oral
Maxillofac Surg 2015.

of 56 cases) for teeth with the preoperative diagnosis

of pericoronitis (Table 2). No important correlation
was found between preoperative diagnosis and incidence of AO. The mean surgery time was 23.5 minutes
(SD, 1.04 minutes) and the surgery time was not statistically correlated to the incidence of AO (Table 4). In
smokers (10%), the AO incidence was 30% and in nonsmokers the incidence was 20%. This difference was
not statistically important. In the multiple logistic regression analysis with the incidence of AO as the dependent
variable, none of the independent variables were meaningfully associated to the incidence of AO.
The mean total number of consumed analgesic tablets (Citodon, Alvedon, and other analgesic tablets) during the first week after surgery is illustrated in Figure 1.
The relative frequency of patients who used Citodon
decreased from 47% on the first day to 12% after
7 days. The corresponding percentages for the

Table 2. PREOPERATIVE DIAGNOSES OR

CONDITIONS FOR MANDIBULAR THIRD MOLARS AND
INCIDENCES OF ALVEOLITIS

Preoperative Diagnosis or Condition

Alveolitis,
n

Pericoronitis
Caries
Deepened periodontal pocket on
distal site on adjacent second
mandibular molar
Widened dental follicular sac
No pathology
Apical periodontitis
Crown fracture
Food impaction
Resorption on distal surface on
adjacent second mandibular molar

56
12
11

14
1
3

8
3
2
1
1
1

2
0
0
0
0
0

Freudenthal et al. Chlorhexidine Gel on Alveolar Osteitis. J Oral

Maxillofac Surg 2015.

603

FREUDENTHAL ET AL

Table 3. FREQUENCY DISTRIBUTIONS OF INCIDENCE

OF ALVEOLITIS FOR TREATMENT GROUPS

Treatment
Placebo gel
Chlorhexidine gel
Total

No Alveolitis

Alveolitis

Total

38
37
75

9
11
20

47
48
95

Freudenthal et al. Chlorhexidine Gel on Alveolar Osteitis. J Oral

Maxillofac Surg 2015.

consumption of Alvedon were 67% and 49%, respectively. The mean number of total analgesic tablets taken
within 7 days was 17.3 (SD, 10.7) for patients without
AO after surgery and 26.6 (SD, 13.8) for those with AO.
This difference was statistically significant (P = .002).
None of the background variables or anatomic variables were meaningfully correlated to the number of
consumed analgesic tablets. There were no statistical
differences according to total intake of Citodon tablets
between the non-AO group (mean, 5.2; SD, 6.5) and the
AO group (mean, 8.0; SD, 11.0). However, the group
with AO consumed 15.0 tablets (SD, 8.1 tablets) of Alveodon and this volume differed significantly (P = .03)
from the non-AO group (mean, 10.8; SD, 7.5). The
mean number of consumed Citodon tablets decreased
from day 1 to day 4 after surgery for patients in the nonAO group (Fig 2A), whereas the daily intake of Citodon
increased from day 1 to day 4 in the AO group (Fig 2B).

Discussion
The design of the present study fulfills the requirements for testing pharmaceuticals. The present study
design is similar to that of Torres-Lagares et al,8 but
with some important differences. The teeth included
in the study by Torres-Lagares et al (and the study by
Babar et al7) were from consecutive patients with referrals. The indication for removal varied from retention or obstructed eruption to a status of pathology.
Table 4. FREQUENCY DISTRIBUTIONS OF ANATOMIC
VARIABLES AND SURGICAL TIME ACCORDING TO
INCIDENCE OF ALVEOLITIS AFTER SURGERY

Variable

No
P
Alveolitis Alveolitis Value

Totally impacted molar

1
Mesial or horizontal position
37
Distal or vertical position
38
Surgery time (minutes)
23  10
mean  SD

1
12
8
25  11

NS
NS
NS
NS

Abbreviations: NS, not significant; SD, standard deviation.

Freudenthal et al. Chlorhexidine Gel on Alveolar Osteitis. J Oral
Maxillofac Surg 2015.

However, in the present study, all teeth had a diagnosed pathology. Minor differences in the mean age
of patients also were apparent such that the present
patients were slightly older. There were nearly as
many women as men in the present study, whereas
there were more women in the study by TorresLagares et al.8 One or a combination of these circumstances might have been important for the differences
in outcome between these studies.
The risk for AO is higher in elderly patients and
women are more susceptible to inflammatory reactions than men.9-12 Although it is difficult to draw
any conclusions from these circumstances, the fact
that all teeth in the present study showed signs of
pathology and the study by Torres-Lagares et al8
seemed to include all patients referred for removal of
third molars might have influenced the results.
Smoking habits have been judged important for the
development of AO.13,14 The present study included
10% who were smokers, whereas 25% of patients
were smokers in the study by Torres-Lagares et al.8
This fact also might have influenced the results. In the
present placebo group, 19% developed AO versus 30%
in the placebo group of Torres-Lagares et al. These
findings might reflect an effect of smoking and the development of AO.13,14 Moreover, Torres-Lagares et al8 reported AO in only 11% of their experimental group,
which suggests that the effect of CHX is more effective
in patients who smoke. As a conclusion, the present
result differs from that of Torres-Lagares et al because
the authors found no difference in AO frequency between the present experimental and placebo groups.
Babar et al7 also described positive effects of CHX
treatment. However, that study evaluated the effect
of CHX as soon as the third postoperative day. This is
undesirable because according to the definition of
Blum,9 AO cannot be reliably diagnosed until 1 week
after surgery.
The authors second hypothesis was that patients
who develop AO would consume more analgesics during the postoperative week than those without AO.
More specifically, they would increase the intake after
3 to 5 days. The present study showed that the mean
number of analgesic tablets increased for patients
with AO. The intake of Citodon increased from day 1
to day 4 in the AO group and decreased from day 1
to day 4 in the non-AO group. The intake of analgesics
reflected the development of AO and thus could be
used as a complementary diagnostic criterion.
In conclusion, treatment with a CHX gel did not
meaningfully decrease the incidence of AO after surgical removal of impacted third molars. The degree of
impact was the only anatomic variable that was best
correlated to the incidence of AO,15 but this was not
statistically important. The intake of analgesics reflected the occurrence of AO with a high degree of

604

CHLORHEXIDINE GEL ON ALVEOLAR OSTEITIS

FIGURE 1. Distribution of mean number of total analgesic tablets intake during 7 days after surgery by patients without and with alveolitis.
Freudenthal et al. Chlorhexidine Gel on Alveolar Osteitis. J Oral Maxillofac Surg 2015.

FIGURE 2. A, Distribution of mean number of Citodon, Alveodon, and other analgesic tablets taken during 7 days after surgery by patients
without alveolitis. B, Distribution of mean number of Citodon, Alveodon, and other analgesic tablets taken during 7 days after surgery by
patients with alveolitis.
Freudenthal et al. Chlorhexidine Gel on Alveolar Osteitis. J Oral Maxillofac Surg 2015.

FREUDENTHAL ET AL

importance. Smoking habits were not recognized as a

risk factor, but this could be due to the low incidence
of smokers in this study.

References
1. Eshgpour M, Nejat AH: Dry socket following surgical removal of
impacted third molar in an Iranian population: Incidence and
risk factors. Niger J Clin Pract 16:496, 2013
2. Kolokythas A, Olech E, Miloro M: Alveolar osteitis: A comprehensive review of concepts and controversies. Int J Dent
249073, 2010
3. Caso A, Hung LK, Beirne OR: Prevention of alveolar osteitis with
chlorhexidine: A meta-analytic review. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod 99:155, 2005
4. Daly B, Sharif MO, Newton T, et al: Local interventions for
the management of alveolar osteitis (dry socket). Cochrane
Database Syst Rev 12:CD006968, 2012
5. Garibaldi JA, Greenlaw J, Choi J, et al: Treatment of
post-operative pain. J Calif Dent Assoc 23:71, 1995
6. Shepherd J: Rinsing with chlorhexidine may reduce incidence of
dry socket after third molar surgery. Evid Based Dent 6:36, 2005
7. Babar A, Ibrahim MW, Baig NJ, et al: Efficacy of intra-alveolar
chlorhexidine gel in reducing frequency of alveolar osteitis in
mandibular third molar surgery. J Coll Phys Surg Pak 22:91,
2012

605
8. Torres-Lagares D, Gutierrez-Perez JL, Infante-Cossio P, et al:
Randomized, double-blind study on effectiveness of intraalveolar chlorhexidine gel in reducing the incidence of alveolar
osteitis in mandibular third molar surgery. Int J Oral Maxillofac
Surg 35:348, 2006
9. Blum IR: Contemporary views on dry socket (alveolar osteitis): A
clinical appraisal of standardization, aetiopathogenesis and
management: A critical review. Int J Oral Maxillofac Surg 31:
309, 2002
10. Benediktsd

ottir IS, Wenzel A, Petersen JK, et al: Mandibular third
molar removal: Risk indicators for extended operation time,
postoperative pain, and complications. Oral Surg Oral Med
Oral Pathol Oral Radiol Endodontol 97:438, 2004
11. Malkawi Z, Al-Omiri MK, Khraisat A: Risk indicators of postoperative complications following surgical extraction of lower third
molars. Med Princ Pract 20:321, 2011
12. Blondeau F, Daniel NG: Extraction of impacted mandibular third
molars: Postoperative complications and their risk factors. J Can
Dent Assoc 73:325, 2007
13. Halab
D, Escobar J, Mu~
noz C, et al: Logistic regression analysis of
risk factors for the development of alveolar osteitis. J Oral
Maxillofac Surg 70:1040, 2012
14. Congiusta MA, Veitz-Keenan A: Study confirms certain risk
factors for development of alveolar osteitis. Evid Based Dent
14:86, 2013
15. Freudlsperger C, Deiss T, Bodem J, et al: Influence of lower third
molar anatomic position on postoperative inflammatory complications. J Oral Maxillofac Surg 70:1280, 2012