Comparative study of two local anesthetics in the surgical extraction of mandibular third molars: bupivacaine and articaine.

Abstract

The third molar extraction is one of the most common surgical procedures in oral surgery and is usually accompanied by postoperative discomfort. It has been suggested that the longer duration of action of bupivacaine associated with the residual analgesia and the gradual onset of pain, could decrease the need for analgesics during the postoperative period. This study aims to compare the efficacy and safety of bupivacaine and articaine as local anesthetics for the extraction of mandibular third molars and to check whether bupivacaine produced residual analgesia.
We compared bupivacaine 0.5% and articaine 4% with an epinephrine concentration of 1:200 000 in a crossover design model of extraction of bilaterally symmetrical mandibular third molars.
Regarding efficacy, patients experienced less postoperative pain at 6 and 12 hours and shorter duration of soft tissue anesthesia with articaine. With respect to safety, no differences were found between the anesthetics compared, showing a similar local and systemic toxicity. With regard to the preference of patients, it was higher for articaine, the main reasons being the greater postoperative pain and swelling with bupivacaine.
It can be concluded that articaine seems to be a more appropriate anesthetic for the extraction of mandibular third molars due to the shorter duration of the anesthetic effect in the soft tissues, lower pain reported by patients during the immediate postoperative period and the personal preference of patients for this drug.

Full text

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Med Oral Patol Oral Cir Bucal. 2011 May 1;16 (3):e390-6. Comparative study of bupivacaine and articaine
e390
Journal section: Oral Surgery
Publication Types: Research
Comparative study of two local anesthetics in the surgical extraction
of mandibular third molars: Bupivacaine and articaine
Anna Trullenque-Eriksson 1, Blanca Guisado-Moya 2
1 Bachelor of Dentistry. Master in Dentistry Science. Universidad Complutense de Madrid
2 Professor of Oral Surgery, Department of Oral and Facial Medicine and Surgery. Faculty of Dentistry. Universidad Complu-
tense de Madrid
Correspondence:
Faculty of Dentistry
Plaza Ramón y Cajal s/n.
Ciudad Universitaria
28040 Madrid
anna@trullenque.com
Received: 15/06/2010
Accepted: 14/11/2010
Abstract
Objective: The third molar extraction is one of the most common surgical procedures in oral surgery and is usually
accompanied by postoperative discomfort. It has been suggested that the longer duration of action of bupivacaine
associated with the residual analgesia and the gradual onset of pain, could decrease the need for analgesics during
the postoperative period. This study aims to compare the efficacy and safety of bupivacaine and articaine as lo-
cal anesthetics for the extraction of mandibular third molars and to check whether bupivacaine produced residual
analgesia.
Study design: We compared bupivacaine 0.5% and articaine 4% with an epinephrine concentration of 1:200 000
in a crossover design model of extraction of bilaterally symmetrical mandibular third molars.
Results: Regarding efficacy, patients experienced less postoperative pain at 6 and 12 hours and shorter duration
of soft tissue anesthesia with articaine. With respect to safety, no differences were found between the anesthetics
compared, showing a similar local and systemic toxicity. With regard to the preference of patients, it was higher
for articaine, the main reasons being the greater postoperative pain and swelling with bupivacaine.
Conclusion: It can be concluded that articaine seems to be a more appropriate anesthetic for the extraction of man-
dibular third molars due to the shorter duration of the anesthetic effect in the soft tissues, lower pain reported by
patients during the immediate postoperative period and the personal preference of patients for this drug.
Key words: Anesthesia, dentistry, bupivacaine, articaine, oral surgery.
Trullenque-Eriksson A, Guisado-Moya B. Comparative study of two
local anesthetics in the surgical extraction of mandibular third molars:
Bupivacaine and articaine. Med Oral Patol Oral Cir Bucal. 2011 May 1;16
(3):e390-6.
http://www.medicinaoral.com/medoralfree01/v16i3/medoralv16i3p390.pdf
Article Number: 17153 http://www.medicinaoral.com/
© Medicina Oral S. L. C.I.F. B 96689336 - pISSN 1698-4447 - eISSN: 1698-6946
eMail: medicina@medicinaoral.com
Indexed in:
Science Citation Index Expanded
Journal Citation Reports
Index Medicus, MEDLINE, PubMed
Scopus, Embase and Emcare
Indice Médico Español
doi:10.4317/medoral.16.e390
http://dx.doi.org/doi:10.4317/medoral.16.e390

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Med Oral Patol Oral Cir Bucal. 2011 May 1;16 (3):e390-6. Comparative study of bupivacaine and articaine
e391
Introduction
Local anesthetics are chemicals that block nerve con-
duction in a specific, temporary and reversible man-
ner, without affecting the patient’s consciousness. The
molecule consists of two poles: a hydrophilic tertiary or
secondary amino group and a lipophilic aromatic ring.
According to the type of intermediate alkyl linkage be-
tween them, they are classified in ester-type anesthetics,
with an amino-ester bond and whose prototype is pro-
caine, and the amide-type with an amino-amide bond
and whose prototype is lidocaine (1).
Until the beginning of the twentieth century, cocaine was
the drug of choice for surgical and dental pain control
despite its significant limitations such as its low therapeu-
tic index, the risk of addiction and potentially lethal ar-
rhythmias. After its synthesis in 1904 by Alfred Einhorn
procaine became the main local anesthetic in medicine
and dentistry. Because of the long latency period of pro-
caine and allergies to ester anesthetics, lidocaine, the first
amide anesthetic, quickly became the gold standard after
its synthesis in 1943 by Nils Löfgren. Other amide anes-
thetics have subsequently been introduced (2, 3).
Bupivacaine was developed in 1957 by Ekenstam, Eg-
ner and Pettersson. Its clinical use was described by
Widman in 1964, and in 1983 it became commercially
available in dental cartridges. It is a powerful amide
anesthetic, with intermediate onset of action and long
duration, allowing a slow return to normal sensation,
which has been associated with a corresponding gradu-
al onset of pain (Table 1) (1-6).
It has been suggested that long-acting local anesthetics
such as bupivacaine, could provide additional analge-
sia time known as “residual analgesia” and minimize
the duration of postoperative pain, facilitating postop-
erative care and maintenance of proper oral hygiene. Its
main indications are lengthy procedures and postopera-
tive pain management (5, 7, 8).
Carticaine was synthesized in 1969 by Rusching et al.,
changing its name to articaine in 1976, when it was in-
troduced in German dentistry. It was first used in Can-
ada in 1983, the United Kingdom in 1998 and in the
United States in 2000. It is an amide anesthetic that
contains a thiophene ring, being the only widely used
anesthetic that contains an ester group. It is a powerful
anesthetic, with rapid onset of action and intermediate
duration (Table 1) (2, 9, 10).
Some professionals claim that its effect is quicker, is
associated with few failures and provides anesthesia
in cases where other anesthetics fail. However, there is
little scientific evidence to demonstrate its superiority
over other local anesthetics. Its use in oral surgery is
very common (2).
Because of its diverse pathology, third molar extraction
is one of the most common surgical procedures in oral
surgery, and is generally accompanied by postoperative
discomfort, leading to the intake of analgesics, anti-in-
flammatories and antibiotics, and sometimes absentee-
ism from work. It has been suggested that the longer
duration of action of bupivacaine associated with the
residual analgesia and the gradual onset of pain, may
reduce the need for analgesics, which could be interest-
ing given the side effects that these are associated with
(3-5, 11-13).
This study aims to compare the efficacy and safety of
bupivacaine and articaine as local anesthetics for the ex-
traction of mandibular third molars, and verify whether
bupivacaine produced residual analgesia. The following
hypotheses were tested:
- Bupivacaine has a greater efficacy than articaine when
used as an anesthetic for extraction of mandibular third
molars, providing a period of residual analgesia, which
reduces the need for analgesics during the postoperative
period.
- Bupivacaine is as safe as articaine when used as an an-
BupivacaineArticaine
Chemical structureAmide Amide with ester group (thiophene ring)
PotencyHigh High
Onset Intermediate Rapid
Duration of actionLong Moderate
Side effects Cardiotoxic Similar to other local anesthetics
Table 1. Characteristics of bupivacaine and articaine.

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Med Oral Patol Oral Cir Bucal. 2011 May 1;16 (3):e390-6. Comparative study of bupivacaine and articaine
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esthetic for the extraction of mandibular third molars.
The following secondary objectives were established:
- Within the comparison of the efficacy, collect infor-
mation on postoperative pain and inflammation.
- Within the comparison of safety, measuring patients’
vital signs and bleeding during surgery, as well as veri-
fying the postoperative complications possibly related
to these drugs.
- Assess the patient’s preference for one or the other lo-
cal anesthetic.
Materials and Methods
In this study we compared bupivacaine 0.5% and ar-
ticaine 4%, both with an epinephrine concentration of
1:200,000 in a crossover design model of extraction of
bilaterally symmetrical mandibular third molars.
Patients were selected from among those who attended
the surgical department of the Faculty of Dentistry,
Universidad Complutense de Madrid, for the extraction
of bilateral mandibular third molars between October
2008 and March 2009. We carried out a non-probabil-
istic sampling of consecutive cases and selected 35 pa-
tients ASA I or ASA II.
We included those patients who were to undergo extrac-
tion of bilaterally symmetrical mandibular third molars
when both were of similar surgical difficulty and simi-
lar estimated duration of the intervention. If the patient
also required upper third molar extraction, these had to
be of similar surgical difficulty and estimated duration
of the intervention. In the subsequent analysis, only the
mandibular molars were taken into account. Patients
had to sign a consent form for surgery and inclusion in
the study.
We excluded patients who had allergy or hypersensi-
tivity to the local anesthetics, antibiotics or analgesics
used, pregnant patients, patients with cardiovascular,
liver or renal disease, hyperthyroidism, diabetes mel-
litus, immunosuppression or chronic pain, and patients
who had taken drugs (except oral contraceptives) .
Each patient underwent two surgical procedures, per-
formed by the same surgeon and separated a minimum
of two weeks. Anesthesia was administered by block-
ing the inferior alveolar nerve, accompanied by lingual
and buccal nerve block with carpule-type syringes and
anesthetic in dental cartridges. The manufacturer’s in-
structions were followed for the administration of the
anesthetic, and the dose was the one that the surgeon
deemed necessary for surgery, usually two cartridges,
one for the anesthesia of the inferior alveolar and lingual
nerves, and one for the buccal nerve. The patients were
randomly administered one of the two local anesthetics
in the first surgery, and the other one in the following.
The anesthetic used was unknown for the patient and
the observer who performed the measurements. At the
time of the surgery this information was only known
by the surgeon who administered the anesthesia and
the surgeon who assisted him, who recorded the anes-
thetic and dose in the patient’s medical history and a
collection sheet in an opaque envelope, which were not
consulted until the data analysis. After the surgical pro-
cedure, all patients were prescribed the same antibiotic
(750mg amoxicillin every 8 hours for 7 days) and anti-
inflammatory (600mg ibuprofen, maximum once every
6 hours in case of pain).
The study variables were measured and collected dur-
ing surgery, as well as in the postsurgical and final
questionnaires.
To evaluate the efficacy, we assessed those variables that
gave information about the action of the anesthetic, both
those measured during surgery (time of onset, need for
reinforcement), and the data collected in the following
questionnaire (duration of soft tissue anesthesia, dura-
tion of residual analgesia, postoperative pain, analgesic
intake and decrease in mouth opening) (Table 2).
For the evaluation of safety, we analyzed the patients’
vital signs measured with a blood pressure monitor and
a pulse oximeter, bleeding during surgery and postop-
erative complications reported by patients (Table 2).
We evaluated patient preference for either anesthetic
(Table 2).
-Statistical analysis
For the statistical analysis the following analyses were
performed with SPSS:
- T-test to compare quantitative variables in related sam-
ples, when criteria of normal distribution were met.
- Wilcoxon signed-rank test to compare quantitative
variables in related samples where the distribution did
not meet criteria of normal distribution.
- Pearson’s correlation coefficient to assess the correla-
tion between surgical time and postoperative pain.
- McNemar’s test for comparison of the need for rein-
forcement.
The results are given as mean ± standard deviation.
Results
Of the thirty-five patients selected, nineteen were in-
cluded in the study. The mean age was 24.47 years, with
31.6% male and 68.4% women.
In the evaluation of the efficacy of the anesthetics, no
statistically significant differences were found for time
of onset (inferior alveolar nerve: bupivacaine 3.68 ±
3.11 minutes and articaine 2.81 ± 1.92 minutes; buc-
cal nerve: bupivacaine 1.95 ± 1.25 minutes and artic-
aine 1.63 ± 1.14 minutes), the need for reinforcement
(articaine 47.4% and bupivacaine 31.6%), the duration
of residual analgesia (bupivacaine 5.11 ± 4.45 hours and
articaine 4.61 ± 3.77 hours), analgesic intake or decrease
in mouth opening.
Statistically significant differences were found between
the duration of soft tissue anesthesia, this being 8.20 ±

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Med Oral Patol Oral Cir Bucal. 2011 May 1;16 (3):e390-6. Comparative study of bupivacaine and articaine
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Fig. 1. Postoperative pain with bupivacaine and articaine.
0
1
2
3
4
5
6 1224 48
Pain
Hours
Bupivacaine
Articaine
EVALUATION?OF?EFFICACY?
Time?of?onset?
Time?between?anesthetic?administration?and?the?onset?of?anesthesia:?
?
Inferior?alveolar?nerve:?lip?numbness.?
?
Buccal?nerve:?sensitivity?in?the?vestibular?gum?innervated?by?the?
buccal?nerve.?
Need?for?reinforcement?Need?to?administrate?additional?anesthesia.?
Duration?of?soft?tissue?
anesthesia?
Time?between?onset?of?anesthesia?and?stop?of?soft?tissue?numbness?and?
paresthesia.?
Duration?of?residual?
analgesia?
Time?between?onset?of?anesthesia?and?onset?of?pain?(information?obtained?
in?the?postoperative?questionnaire).?
Postoperative?pain? Assessment?with?visual?analogue?scale?(VAS)?at?6,?12,?24?and?48?hours.?
Analgesic?intake?
Number?of?doses?of?analgesic?and?time?when?they?were?taken?during?the?
postoperative?week.?
Distance?between?incisal?edge?of?upper?incisors?and?incisal?edge?of?lower?
incisors?at?maximum?opening.?Difference?between?measurement?before?
surgery?and?one?week?after?surgery.?
Before?anesthesia,?after?anesthesia?and?after?surgery:??
?
Blood?pressure:?with?digital?wrist?blood?pressure?monitor?(AIRIS?
TS001).?
?
Pulse?and?oxygen?saturation:?with?a?pulse?oximeter?
(OhmedaTuffSat®).?
Decrease?in?mouth?opening?
SAFETY?ASSESMENT?
Measurement?of?vital?signs?
Bleeding?during?surgery?
Subjective?scale?0?3,?with?0?being?the?absence?of?bleeding,?1?mild?bleeding,?
2?moderate?bleeding?and?3?heavy?bleeding.?From?November?2008.?
Postoperativecomplications?
Postoperative?discomforts?considered?related?with?surgery?or?anesthesia?by?
the?patient.?
PREFERENCE?
Preference?Patient?described?and?compared?his?experience?with?both?anesthetics.?
Table 2. Characteristics of bupivacaine and articaine.

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Med Oral Patol Oral Cir Bucal. 2011 May 1;16 (3):e390-6. Comparative study of bupivacaine and articaine
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4.54 hours in the case of bupivacaine, and 5.32 ± 2.16
hours in the case of articaine.
Postoperative pain was significantly lower at 6 and 12
hours in procedures performed with articaine as anes-
thetic (Fig. 1). In addition it was found that there was
a correlation between pain and surgical time for bupi-
vacaine at 6, 12, 24 and 48 hours, but not for articaine.
Within the safety assessment of the anesthetics, no sta-
tistically significant differences were found for blood
pressure, pulse or bleeding during surgery.
For the oxygen saturation, the only significant differ-
ences were found in the initial and final measurements,
but not between the ones made after the administration
of anesthesia or changes in oxygen saturation.
Regarding postoperative complications reported by
patients in the postoperative questionnaires, 42.1% of
patients considered to have had at least one. Among
the complications reported by patients after the sur-
gery performed with bupivacaine as an anesthetic, were
postoperative swelling, infection and bleeding, cramps
in the hemimandible where the surgical procedure was
performed, headache, bruising, pain at the injection
site, dizziness and vomiting. In the case of articaine the
complications reported were postoperative swelling,
infection and bleeding, ulcers, heat sensation, temporo-
mandibular joint pain, lip droop and sleepiness. It gave
the same percentage of patients without postoperative
complications, patients with infection, inflammation
and bleeding after the surgery for both anesthetics.
Within the patient preference, 63.2% of the patients
chose articaine, 26.3% bupivacaine and 10.5% neither.
Those who chose the surgical procedure carried out
with articaine as the least painful gave as main reasons
for this choice the more postoperative pain and swelling
after the interventions with bupivacaine.
Discussion
As the extraction of third molars is very frequent in oral
surgery and postoperative discomfort is usually associ-
ated, it would be interesting to have an anesthetic that
produced residual analgesia for some time, reducing the
consumption of analgesics and improving the patient’s
postoperative experience. Several authors have sug-
gested that bupivacaine could achieve this effect (3-5,
11-13).
The study followed a bilateral crossover design, which
has the advantage that each patient acts as his own
control. Thus, the individual characteristics of each
patient and their subjective assessment of pain do not
influence the results of the study. The double-blind con-
tributed to avoid bias, as the observer and the patient
ignored the anesthetic used in each surgery. To avoid
differences between surgeons and their subjective as-
sessment of bleeding influencing the data collected, the
same surgeon performed both interventions in each pa-
tient. Likewise, efforts were made for the time between
surgeries to be the least possible to make it easier for
the patient to compare the interventions and prevent the
increasing experience of surgeons from influencing the
study results.
To date, we only have knowledge of another study that
compares bupivacaine 0.5% with 1:200 000 epine-
phrine, with articaine 4% with 1:200 000 epinephrine
in oral surgery (14).
For the evaluation of efficacy we took into account the
time of onset, the need for reinforcement, the duration
of soft tissue anesthesia, the duration of residual anal-
gesia, postoperative pain, analgesic intake and decrease
in mouth opening.
In our study, the time of onset of bupivacaine was great-
er than that of articaine, but the differences were not
statistically significant. However, Gregorio et al. (14)
did find statistically significant differences.
Regarding the administration of reinforcement, al-
though it was necessary more frequently in the inter-
ventions with articaine, the difference was not signifi-
cant. In the study by Gregorio et al. (14), reinforcement
was necessary in 14% of surgeries performed with
bupivacaine and 2% of those performed with articaine,
this difference was significant. It has been shown that
bupivacaine is less effective in infiltrative techniques,
due to its high lipid solubility which also makes the po-
sition of the needle key (4, 6, 11). This could explain the
difference found in the work by Gregorio et al. (14). The
high percentage of interventions that needed additional
anesthesia in our study may be more related to anatomi-
cal variations or anesthetic technique since the surgery
was performed by postgraduate students and not by ex-
perienced surgeons, than with the anesthetics.
The values of duration of soft tissue anesthesia reported
for bupivacaine were similar to those of other authors,
whereas the values for articaine were somewhat higher
(Table 3). The differences were statistically significant,
like those found by Gregorio et al. (14). The longer dura-
tion of soft tissue anesthesia of bupivacaine is explained
by its higher protein binding and pKa of 8.1 (6). The
longer duration of the anesthesia could be unpleasant
for patients and could cause difficulty eating, speaking,
and a greater risk of soft tissue trauma (11, 16, 17).
The duration of residual analgesia was higher for bupi-
vacaine, although the difference was not statistically
significant. The study of Gregorio et al. (14) obtained
similar results.
Several authors have advocated for the analgesic effect
of bupivacaine, with consequent lower perception of
pain and less analgesic intake by the patient, compared
with other anesthetics such as lidocaine or mepivacaine
(3, 5, 11, 12). However, in our study, postoperative pain
scores were higher for bupivacaine than for articaine,
and this difference was statistically significant at 6 and