Comparative Experimental Study Between Bupivacaine and Ropivacaine Regarding Efficacy in Third Molar Removal Surgery Under General Anesthesia
Phase: EARLY_PHASE1
Conditions: Third Molars Extraction
Sponsor: Henrique Tedesco

FEDERAL UNIVERSITY OF RIO GRANDE DO SUL 
INTEGRATED RESIDENCY IN ORAL HEALTH 
ORAL AND MAXILLOFACIAL SURGERY 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
COMPARATIVE EXPERIMENTAL STUDY BETWEEN BUPIVACAINE AND 
ROPIVACAINE REGARDING EFFICACY IN THIRD MOLAR REMOVAR 
SURGERY UNDER GENERAL ANESTHESIA 
 
 
 
 
 
 
 
Researcher: Henrique Tedesco de Oliveira 
          
 
   Identification: NCT07108465 
 
 
 
 
 
 
 
 
 
July 3rd, 2025 
 

 
ABSTRACT 
 
The removal of third molars is one of the most frequently performed procedures 
in dentistry, and can be carried out in a hospital setting under general anesthesia. In 
such cases, local anesthetics are often administered at the surgical site in addition to 
general anesthesia, to promote better hemostasis and postoperative analgesia. 
Bupivacaine is a local anesthetic commonly used in these situations. However, its 
known cardiotoxic and neurotoxic effects, as reported in the literature, have led to 
increased interest in safer alternatives, such as ropivacaine. Objective: to evaluate 
whether there is a significant difference between bupivacaine and ropivacaine in terms 
of postoperative analgesic efficacy, intraoperative hemostasis, and patient vital signs 
during the intraoperative period. Materials and Methods: This was a randomized, 
controlled, split-mouth clinical trial. The sample size was based on a similar previously 
published study and included 15 participants (n = 30). As this study also follows a split-
mouth design, each of the 15 patients underwent two tooth extractions. All patients had 
indications for the removal of both lower third molars under general anesthesia. 
Surgical extractions were performed in a single session, with bupivacaine (Group A) 
administered at one surgical site and ropivacaine (Group B) at the other. The 
procedures were carried out at the Hospital de Clínicas de Porto Alegre. Vital signs 
were continuously monitored by the same anesthesiology team, with data collected at 
the time of drug injection (before and immediately after), as well as one minute and five 
minutes post-injection. Intraoperative bleeding was measured by calculating the 
volume of blood aspirated into the collection vial, from the time of incision to the final 
suture, at each surgical site. To minimize systemic interference from the anesthetic 
agents, their administration was alternated between patients. Postoperative analgesia 
was self-reported by the patients using a Visual Analog Scale (VAS) for each side at 
various postoperative time points. A descriptive analysis will be conducted on the 
clinical data obtained through these measurements. 
Key-words: Third Molar; Anesthetics, Local; Surgery, Oral

SUMÁRIO 
SUMMARY. ................................................................................................................. 5 
1 INTRODUCTION ...................................................................................................... 6 
2 LITERATURE REVIEW ............................................................................................ 8 
3 OBJECTIVES ......................................................................................................... 10 
4 METHODOLOGY ................................................................................................... 11 
4.1 ETHINCAL ASPECTS ......................................................................................... 11 
4.2 TYPE OF STUDY ................................................................................................ 11 
4.3 LOCATION .......................................................................................................... 12 
4.4 SAMPLE .............................................................................................................. 12 
4.5 PREOPERATIVE CONDUCTS ............................................................................ 13 
4.6 SURGICAL TECHNIQUE .................................................................................... 13 
4.7 ASSESSMENT OF VITAL SIGNS DUREING THE OPERATIVE PERIOD..........14 
4.8 EVALUATION OF TRANSOPERATIVE BLEEDING............................................14 
4.9 EVALUATION OF POSTOPERATIVE ANALGESIA ........................................... 15 
4.10 DATA ANALYSIS .............................................................................................. 15 
5 TIMELINE .............................................................................................................. 15 
6 RESOURCES AND BUDGET ................................................................................ 16 
7 REFERENCES ....................................................................................................... 18 
8 APPENDIX ............................................................................................................. 21 

1 INTRODUCTION 
 
The search for painless surgical interventions was a highly controversial topic 
just a few centuries ago, often considered a utopia or the work of charlatans. This 
panorama began to change in the 18th century with the discovery of the anesthetic 
properties of nitrous oxide, known as "laughing gas," culminating in the first surgery 
performed under general anesthesia in October 1846.¹ Since then, new anesthetic 
agents have been developed and introduced into medical practice.² 
General anesthesia is an anesthetic technique in which a combination of drugs 
is used to induce analgesia, unconsciousness, immobility, and skeletal muscle 
relaxation, allowing procedures to be performed with greater safety and comfort for 
both professionals and patients.³ Currently, general anesthesia can be achieved using 
intravenous or inhaled agents, or a combination of both. Anesthetic agents widely used 
in Brazil include thiopental, propofol, etomidate, and midazolam (intravenous) and 
halothane, isoflurane, and sevoflurane (inhalation).4 
In dentistry, general anesthesia has several indications and can be used in 
cases of extensive or highly complex surgical procedures, in patients with 
odontophobia or extreme anxiety, in patients with special needs or children who cannot 
be managed in the office, and in patients allergic to local anesthetics, among other 
situations. Despite this, the use of general anesthesia in dentistry is not routine for most 
Brazilian dentists. On the other hand, local anesthetics are the most widely used and 
prevalent substances in dentistry, and their use is essential for adequate clinical 
practice.5 They are defined as substances capable of reversibly blocking nerve 
conduction by inhibiting the excitation and conduction processes of the nerve cell 
membrane, resulting in temporary impairment of thermal, pain, and tactile sensitivity 
without causing loss of consciousness.6 Currently, the use of local anesthetics in 
dentistry is considered quite safe, with substances that have low systemic toxicity, are 
non-irritating to tissues, and do not cause permanent nerve damage, ideally offering a 
short onset of action and sufficient duration for surgical procedures.7 
The most commonly used local anesthetics in dentistry are amide-type agents, 
including lidocaine, prilocaine, mepivacaine, articaine, bupivacaine, ropivacaine, and 
levobupivacaine.5,7 
Lidocaine hydrochloride, the most widely used amide-type local anesthetic in 
dentistry, is considered very safe for pregnant women, children, and heart patients. 

Commercial preparations containing lidocaine are diverse and may or may not be 
combined with vasoconstrictors such as epinephrine, norepinephrine, and 
phenylephrine.8 
Prilocaine hydrochloride has a structure very similar to lidocaine, but is less 
potent and less toxic. It is often found in commercial formulations combined with 
felypressin, exhibiting minimal cardiotoxicity. Its use is contraindicated in patients with 
methemoglobinemia, anemia, or hypoxic heart failure.9 Felypressin is contraindicated 
in pregnant women due to its potential to cause uterine contractions.10 
Mepivacaine hydrochloride is approximately twice as potent and toxic as 
lidocaine and is often used in combination with levonordefrin, norepinephrine, or 
epinephrine. However, unlike lidocaine, its use without an associated vasoconstrictor 
has clinical relevance, with an anesthetic effect lasting 20 to 40 minutes, significantly 
longer than the 5 minutes of lidocaine without a vasoconstrictor. It is an excellent choice 
for cases where the use of vasoconstrictors is contraindicated.11 
Articaine hydrochloride, the most widely used local anesthetic in countries such 
as Germany and the United States, is often found in combination with epinephrine. It 
has greater potency and less toxicity than lidocaine. It is contraindicated in patients 
with methemoglobinemia, anemia, or hypoxic heart failure.12 Despite reports of 
paresthesia associated with the use of articaine, there is no high-quality scientific 
evidence to support this relationship.13 
Bupivacaine hydrochloride provides long-lasting anesthesia, significantly 
contributing to the reduction of postoperative pain, and is the most widely used 
anesthetic in dental procedures under general anesthesia in hospital settings. Its 
potency is considerably greater than that of the other anesthetic agents mentioned 
above. However, its onset of action is slower, taking about 6 to 10 minutes to initiate 
analgesia. It can be used without vasoconstrictors or in combination with 
epinephrine.11,14 The cardiotoxicity of bupivacaine is well documented, with 
cardiovascular collapse being widely reported, especially when erroneously applied 
intravascularly, and it is difficult to reverse.15 
As a result, there has been a search for a new anesthetic substance that 
combines the advantages of bupivacaine (high potency and long duration) while 
minimizing its disadvantages (lower cardiac toxicity and arrhythmogenic properties). 
Among the substances found, levobupivacaine and ropivacaine stand out.16 
Levobupivacaine hydrochloride shares properties withracemic bupivacaine, but 

with lower cardiac toxicity. Its use is more common in the medical field, often combined 
with epinephrine. However, its use is not widespread in dentistry.17 
Ropivacaine hydrochloride also has properties similar to racemic bupivacaine, 
but with reduced cardiac toxicity. Furthermore, it has intrinsic vasoconstrictor 
properties, minimizing the need for additional vasoconstrictors during its 
administration. 16,18 
Among the main benefits of using local anesthetics are comfort, analgesia, 
vasoconstriction (when combined with vasoconstrictors) and reduce postoperative 
pain, what makes its use is recommended even during procedures under general 
anesthesia.19 Even with the proven greater safety of anesthetic agents such as 
levobupivacaine and ropivacaine, bupivacaine still dominates hospital dental practice, 
despite so much evidence against its use.20 Moreover, there is no protocol or 
commercial formulation for its use in anesthetic tubes, further hindering the use of 
these alternative anesthetic agents in dentistry. Therefore, this study aims to evaluate 
whether there is a significant difference between bupivacaine and ropivacaine in terms 
of postoperative analgesia, intraoperative hemostasis, and the patient's vital signs 
during the procedure.16 
 
2 LITERATURE REVIEW 
 
2.1 RACEMIC BUPIVACAINE 
 
Bupivacaine is a potent local anesthetic from the amide group, widely used in 
regional anesthesia, epidural anesthesia, spinal anesthesia, and local anesthesia. It is 
available in three different concentrations: 0.25%, 0.5%, and 0.75%.21 It is called 
racemic because it is an equimolar mixture of dextrorotatory and levorotatory 
isomers.22 Bupivacaine has a slow onset of action (6 to 10 minutes), a half-life of 2.7 
hours, and intrinsic vasodilatory potential. It is commonly used in more extensive 
procedures that require prolonged intraoperative and postoperative anesthesia.11 To 
reduce intraoperative bleeding, toxicity, and the required dose for anesthesia, 
vasoconstrictors are frequently added to bupivacaine, with epinephrine being one of 
the most commonly used substances.23 
Bupivacaine was first synthesized in 1957 and introduced to the market in the 
mid-1960s. As its use increased, so did reports of adverse effects, including toxicity to 
the central nervous system and cardiovascular system.24 Bupivacaine is closely 
associated with seizures, severe bradycardia, and cardiac arrest, which are often 

resistant to conventional cardiopulmonary resuscitation techniques. 25 These side 
effects are frequently linked with overdose or accidental intravascular injection. 26 
Duo to these concerns, several studies have been conducted to better 
understand the cause of bupivacaine's toxicity, ultimately leading to the exploration of 
isomers and the development of new anesthetic agents.27 
 
2.2 LEVOBUPIVACAÍNE 
 
Levobupivacaine is a long-acting anesthetic agent developed in response to 
reports of toxicity associated with bupivacaine in the 1970s.28 It is a pure enantiomer 
of bupivacaine, composed exclusively of levorotatory isomers, which explains its 
distinct physiological effects, despite the molecules being very similar.27 This local 
anesthetic has several properties that distinguish it from racemic bupivacaine, 
including less associated vasodilation, longer duration of action, lower potency, and 
reduced toxicity to the central nervous system and cardiovascular system.29 
 
2.3 ROPIVACAINE  
 
Ropivacaine was also developed in response to reports of toxicity associated 
with bupivacaine, becoming commercially available only in the mid-1990s.24 Although 
its name does not specifically mention levorotatory isomers, ropivacaine os, in fact, a 
pure levorotatory version, similar to levobupivacaine.27 
It is a long-acting amide-type local anesthetic with slightly lower potency and 
duration of action compared to bupivacaine, exhibiting rapid dissociation from sodium 
channels, which contributes to its reduced cardiotoxicity.30, 31, 32 Furthermore, animal 
studies show that resuscitation after local anesthetic-induced cardiovascular collapse 
was more easily achieved in the ropivacaine group compared with the bupivacaine 
group.33 
Studies indicate that higher doses of ropivacaine are required to trigger 
symptoms and initial signs of toxicity in the cardiovascular and nervous systems when 
compared with racemic bupivacaine.34 Unlike most local anesthetics, ropivacaine 
possesses intrinsic vasoconstrictor properties, which may be beneficial in surgical 
practice.35, 36 
 
3 OBJECTIVES 
 
3.1 GENERAL OBJECTIVE 
 

This study aims to evaluate whether there is a significant difference between 
0.5% bupivacaine with 0.2Ml of epinephrine and 0.75% ropivacaine with 0.2Ml of 
epinephrine in terms of postoperative analgesic capacity, intraoperative hemostasis 
and the patient's vital signs during the transoperative period. 
 
3.2 SPECIFIC OBJECTIVES 
 
 
- Measure the amount of intraoperative bleeding (in mL) during procedures 
performed with 0.5% bupivacaine with 0.2 mL of epinephrine and 0.75% ropivacaine 
with 0.2 mL of epinephrine. 
 
- Assess potential changes in patients vital signs during and after the 
administration of local anesthetics. 
 
- Compare the levels of postoperative discomfort associated with anesthetic 
agents using a visual analog scale (VAS). 
 
JUSTIFICATION 
Despite the well-known cardiotoxic and neurotoxic effects of bupivacaine, it 
continues to be widely used in oral and maxillofacial surgery. This study aims to 
compare and evaluate the feasibility of using a less toxic anesthetic agent in lower third 
molar removal surgeries under general anesthesia. 

4 MATERIAILS AND METHODS 
 
The study is designed as a randomized, controlled, split-mouth clinical trial. 
Patients receiving 0.5% bupivacaine with 0.2 mL of epinephrine are defined as group 
A (GA), while patients receiving 0.75% ropivacaine with 0.2 mL of epinephrine are 
classified as group B (GB).  
4.1 SAMPLE CALCULATION 
The sample size was determined for convenience, based on a similar study 
previously conducted37, which established a significance level of 5% (p < 0.05), a 
power of 80%, and a 5% margin of error for its calculation (n = 30). In the baseline 
study, a comparison was made between ropivacaine and lidocaine during implant 
placement, with procedures performed on 15 patients, as it was a split-mouth design. 
In the present study, procedures will be performed on 15 patients, yielding a total 
sample size of 30. 
 
4.1 ETHICAL ASPECTS 
 
The study will be conducted in accordance with the Guidelines and Regulatory 
Standards of the National Health Council (Resolution No. 466/12), which establishes 
the ethical guidelines for research involving human subjects in Brazil. 
The benefit of participating in the research is indirect, as the patient contributes 
to the discovery of scientific evidence that will serve as the foundation for safer and 
more effective treatment. 
Patient personal data, collected through direct contact with the participant during 
the study, will not be disclosed, and confidentiality will be ensured for all participants. 
This data will be stored in a Google Drive spreadsheet linked to the researchers 
institutional email address. 
Surgical procedures and the participant's participation in the project may 
present certain surgical and confidentiality risks inherent to participation, which are 
outlined in the Informed Consent Form (APPENDIX A). 
 
 
4.2 TYPE OF STUDY 
 
The study is a randomized, controlled, split-mouth clinical trial. 
 
 
4.3 LOCATION 
 
The surgeries will be performed at the Outpatient Surgery Center and Surgical 

Block of the Hospital de Clínicas de Porto Alegre, located at the address: Rua Ramiro 
Barcelos, 2350, Santa Cecília, Porto Alegre - RS, 90035-903. 
 
4.4 SAMPLE 
 
The sample selection will consist of patients referred to the Oral and 
Maxillofacial Surgery Unit at the Hospital de Clínicas de Porto Alegre. The selected 
patients require bilateral extraction of lower third molars under general anesthesia, 
either due to the complexity of the surgery or due to systemic conditions that 
contraindicate local anesthesia. Patients who meet these criteria will follow the routine 
care protocol adopted by the team. During outpatient consultations, laboratory tests 
(including blood count, PT, aPTT, glucose, AST, ALT, and creatinine), imaging (CT 
scan of the skull and facial bones), and pre-anesthetic evaluation will be requested. If 
the tests are normal and cleared by the Anesthesiology team, patients will be placed 
on the waiting list and contacted when surgery is available. There will be no change to 
the routine care for patients volunteeing in the study. The surgical procedures will be 
performed by the research team responsible for this study. The inclusion criteria will 
include patients aged 18 to 60, classified as ASA I or ASA II, who have impacted or 
semi-impacted lower third molars with similar positioning on both sides, according to 
the Pell and Gregory classification.38 
Patients who can undergo surgery under local anesthesia or who require 
additional procedures in the same surgical session, will be excluded from the sample. 
All patients, wheter participating in the study or not, will have the right to withdraw from 
the study at any time without penalty. 
Postoperative consultations will be conducted for follow-up, suture removal, and 
the evaluation and treatment ofany potential postoperative complications. 
Regarding general anesthesia, since this is a split-mouth study, both patients 
undergoing total intravenous anesthesia and general inhalational anesthesia will be 
included. Patients requiring additional intraoperative medications, which may interfere 
with the data, will be excluded. An example of this is patients receiving tranexamic acid 
during the procedure, as it could distort bleeding measurements between surgical 
sites. 
The selection of the control group and experimental groups will be determined 
by a simple randomization in the immediate preoperative period. One surgical site will 
recieve 0.5% bupivacaine + 0.2mL of epinephrine (GA) while the other site will recieve 
0.75% ropivacaine + 0.2mL epinephrine (GB). 

4.5 PREOPERATIVE CONDUCTS 
 
Each patient selected for the study will be required to complete an Informed 
Consent Form (APPENDIX A) prior to the clinical procedures. If any participant 
disagrees with the terms outlined in the form, they will not be included in the study. 
The patient's medical history will be taken during an outpatient appointment 
automatically scheduled via the GERCON system. During this appointment, the team 
will investigate the patient's current medical condition, other comorbidities, medication 
use, and known allergies. In addition to the physical examination, imaging tests 
(panoramic X-rays and/or CT scans) and laboratory tests will be requested. This 
consultation will also collect sociodemographic data from the sample, assess their 
health status, and identify any factors that may contraindicate their participation in the 
study. After the imaging and laboratory tests are completed at the Hospital de Clínicas 
de Porto Alegre, patients will be placed on the waiting list for surgery. Following the 
surgical procedure, patients will receive a postoperative care and instructions form 
(APPENDIX B), standardized medications, and medical notes, if necessary. The VAS 
(APPENDIX C) and instructions on how to use it will also be provided after the surgery.  
 
4.6 SURGICAL TECHNIQUE 
 
The procedure will be performed in a hospital setting, where patients undergo a 
single surgery for the extraction of the lower right and lower left third molars. 
Throughout the perioperative period, patients will be closely monitored, with their vital 
signs observed by both the surgical team and anesthesiology teams. As prophylaxis, 
patients will receive 900mg of clindamycin intravenously at the start of the procedure. 
The patient will be positioned supine on a hospital stretcher and placed under general 
anesthesia. Extra and intraoral antisepsis will be performed using a 0.12% 
chlorhexidine digluconate aqueous solution, and sterile surgical drapes will be used. 
Following these initial steps, one of the surgical sites (as selected) will be infiltrated 
with either 6 mL of 0.5% racemic bupivacaine + 0.2 mL of epinephrine or 4 mL of 0.75% 
ropivacaine with 0.2 mL of epinephrine, with approximately 25 mg of anesthetic 
injected. The surgical procedure will then begin. A Neumann incision with diverticulum 
will be made on the distal side of the adjacent mandibular second molar, followed by 
mucoperiosteal detachment, osteotomy, and odontosection (if necessary). The tooth 
will then be luxated and extracted using levers. The surgical wound will be cleaned  
and sutured with single or X-shaped stitches using 4-0 polyglactin sutures. Suture 
removal will take place between 7 and 10 days postoperatively. Before discharge, while 

still in the hospital, patients will receive intravenous administration of 2g of dipyrone 
every 6 hours, 40mg of tenoxicam once daily, 100mg of tramadol every 8 hours, 600mg 
of clindamycin every 6 hours, and 4mg of ondansetron every 8 hours. 
Postoperative instructions and necessary medications will be provided to 
patients both verbally and in writing, according to the protocol recommended by the 
hospital (APPENDIX B). Suture removal will be performed in an outpatient setting at 
the Hospital de Clínicas de Porto Alegre between 7 and 10 days postoperatively. 
 
4.7 ASSESSMENT OF VITAL SIGNS DURING THE OPERATIVE PERIOD 
 
Intraoperative vital signs will be assessed by the Anesthesiology and 
Perioperative Medicine Service of the Hospital de Clínicas de Porto Alegre, always led 
by the same care team. Heart rate, blood pressure, and oxygen saturation will be 
measured and recorded before, immediately after, 1 minute after, and 5 minutes after 
the injection of each anesthetic. Significant changes, such as hypo or hypertension, 
bradycardia or tachycardia, and hypoxia, will be recorded and presented in the results. 
 
4.8 EVALUATION OF TRANSOPERATIVE BLEEDING  
 
The intraoperative bleeding assessment will be quantitative, based on the blood 
collected in the collection bottle. The amount of distilled water used will be subtracted 
from the total aspirated volume. This value will be recorded at the time the suture is 
completed. 
To assess bleeding from the second surgical site, the measurement will be 
taken at the time the suture is completed. The amount of distilled water used, along 
with the volume present in the collection bottle prior to the incision at the second site, 
will be subtracted. These values will be recorded, compared, and presented in the 
results. 
 
4.9 EVALUATION OF POSTOPERATIVE ANALGESIA 
To assess postoperative analgesia, a VAS will be used, in which patients will 
rate their pain from zero (no pain) to ten (worst pain ever felt) at different postoperative 
time points: T0 (immediate postoperative period, as soon as the patient is lucid), T1 (1 
hour after T0), T2 (12 hours after T0), T3 (18 hours after T0), and T4 (24 hours after 
T0). Two scales will be used for each postoperative time point: one for the left side and 
one for the right side. These values will be recorded, compared, and presented in the 
results. 

4.10 DATA ANALYSIS 
 
A descriptive analysis will be performed on the changes in vital signs observed 
during the operation (if any). A direct comparison and calculation of the averages will 
be made beween the values observed in both the postoperative analgesia evaluation 
and the transoperative bleeding assessment.  
5 TIMELINE 
 
The mandibular third molar removal surgeries under general anesthesia will be 
performed based on availability at the Oral and Maxillofacial Surgery Unit of the 
Hospital de Clínicas de Porto Alegre. Currently, two surgeries per week are available, 
and these will be conducted until the sample size is reached. 
 
ACTIVITY/MONTH 
01 02 03 04 05 06 07 08 09 10 11 12 
BIBLIOGRAPHY 
REVIEW 
x 
x 
 
 
 
 
 
 
 
 
 
 
SURGICAL 
PROCEDURES 
x 
x 
x 
x 
 
 
 
 
DATA ANALYSIS 
x 
x 
COMPLEMENTAR
Y LITERATURE 
REVIEW 
x 
x 
PRESENTATION OF 
THE FINAL PAPER 
x 
x 
WRITING AND 
SUBMISSION OF 
THE SCIENTIFIC 
ARTICLE 
x 
6 RESOURCES AND BUDGET 
 
The transportation costs for research participants to attend their appointments 
will be covered by the researchers (including the cost of a municipal bus ticket for each 
appointment), as well as any other expenses incurred as a result o their participation 
in the study. 
All costs related to the surgical procedure will be covered by the Hospital de 
Clínicas de Porto Alegre, through the Unified Health System (SUS). Postoperative 
medications will be reimbursed through the Unified Health System (SUS). 

 
 
TYPE OF 
MATERIAL 
MATERIAL 
QUANTITY 
PRICE 
UNITARY 
TOTAL 
Bus ticket 
90 
R$ 4,80 
432  
Total 
R$ 432,00 
 
 
6.2 HUMAN RESOURCES 
 
The bibliographic review and construction of the project will be carried out by 
the research team, as well as the surgical procedures and data analysis. 
6.3 FINANCING SOURCES 
 
The expenses necessary for the execution of the research project will be paid 
with the responsible researcher’s own resources. 

7 REFERENCES 
 
1. 
ATKINSON, R. S.; BOULTON, T. B. The History of Anaesthesia. [s.l.] Royal 
Society of Medicine Press, 1989. 
2. 
REZENDE, J. M. À sombra do Plátano: crônicas de história da medicina. 
[s.l.] Editora Fap-Unifesp, 2009 
3. 
BARASH, P. G. Anestesia clínica. Éditeur: L’hospitalet Del Llobregat: Wolters 
Kluwer, 2018.  
4. 
NOCITE, J. R. Anestesia Geral e Condutiva em Cirurgia Ambulatorial. Rev 
Bras Anestesiol, v. 45, n. 1, p. 7–14, 1995.  
5. 
CARVALHO, B. et al. O emprego dos anestésicos locais em Odontologia: 
Revisão de Literatura. Revista Brasileira de Odontologia, v. 70, n. 2, p. 178–181, 1 
dez. 2013.  
6. 
CARVALHO, J. C. A. Farmacologia dos Anestésicos Locais. Rev Bras 
Anestesiol, v. 44, n.1, p. 75–82, 1994. 
7. 
L. C. A., P.; A. L., C. ANESTÉSICOS LOCAIS EM ODONTOLOGIA: UMA 
REVISÃO DE LITERATURA. Publicatio UEPG: Ciencias Biologicas e da Saude, v. 
11, n. 2, 2005. 
8. 
BRANDT, R. G. Et al. The Pulpar Anesthetic Efficacy of Articaine Versus 
Lidocaine in Dentistry: A Meta – Analysis. Smile Dental Journal, v. 9, n. 4, p.36-36, 
dez. 2014. 
9. 
MARRA, M. et al. Odontologia em Pacientes Portadores de Dispositivos 
Cardíacos Eletrônicos Implantáveis (DCEI). DOAJ (DOAJ: Directory of Open 
Access Journals), 1 out. 2009. 
10. 
KLEIN PARISE, G.; FERRANTI, K. N.; PIETROSKI GRANDO, C. Sais 
anestésicos utilizados na odontologia: revisão de literatura. Journal of Oral 
Investigations, v. 6, n. 1, p. 75, 4 ago. 2017. 
11. 
MALAMED, S. F. Handbook of local anesthesia. 7. ed. St. Louis, Missouri: 
Elsevier, 2020.Hassan AH. Pattern of third molar impaction in a Saudi population. Clin 
Cosmet Investig Dent. 2010;2:109–13. doi: 10.2147/cciden.s12394. 
12. 
YAPP, K. E.; HOPCRAFT, M. S.; PARASHOS, P. Articaine: a review of the 
literature. British Dental Journal, v. 210, n. 7, p. 323–329, abr. 2011. 
13. 
HOPMAN, A. J. G.; BAART, J. A.; BRAND, H. S. Articaine and neurotoxicity – 
a review. British Dental Journal, v. 223, n. 7, p. 501–506, 1 out. 2017. 
 
 

14. 
RANALI, J.; VOLPATO, M. C. Bupivacaína – anestésico local de longa duração: 
revisão sobre sua farmacologia e usoclínico em Odontologia. RBO, v. 47, n. 6, p. 36-
40, nov./dez. 1990. 
15. 
TORRES, M. L. A. Toxicidade dos anestésicos locais: o debate 
continua! Revista Brasileira de Anestesiologia, v. 56, n. 4, ago. 2006. 
16. 
DOS PRAZERES, M.; SIMONETTI, B.; TSA. Artigo de Revisão Ropivacaína: 
Estado Atual e Perspectivas Futuras*. Rev Bras Anestesiol, v. 45, n. 2, p. 131–140, 
1995. 
17. 
BERGAMASCHI, F. et al. Levobupivacaína versus bupivacaína em anestesia 
peridural 
para 
cesarianas: 
estudo 
comparativo. Revista 
Brasileira 
de 
Anestesiologia, v. 55, p. 606–613, 1 dez. 2005. 
18. 
EDNO MAGALHÃES; GOVÊIA, C. S.; OLIVEIRA, K. B. Bupivacaína racêmica, 
levobupivacaína e ropivacaína em anestesia loco-regional para oftalmologia: um 
estudo comparativo. Revista da Associação Médica Brasileira, v. 50, n. 2, p. 195–
198, 1 abr. 2004. 
19. 
SOARES, R. G. et al. Como escolher um adequado anestésico local para as 
diferentes situações na clínica odontológica diária. RSBO Revista Sul-Brasileira de 
Odontologia, v. 3, n. 1, p. 35–40, 1 jan. 2006. 
20. 
VEERING, B. T. Complications and local anaesthetic toxicity in regional 
anaesthesia. Current Opinion in Anaesthesiology, v. 16, n. 5, p. 455–459, out. 2003. 
21. SHAFIEI, F. T.; MCALLISTER, R. K.; LOPEZ, J. Bupivacaine. Disponível em: 
https://www.ncbi.nlm.nih.gov/books/NBK532883/ 
22. LIMA, V. L. E. Os fármacos e a quiralidade: uma breve abordagem. Química 
Nova, v. 20, n. 6, p. 657–663, 1997.  
23. 
GEORGE, M. et al. Avaliação da adição da epinefrina à bupivacaína intra-
articular no controle da dor aguda em pacientes submetidos a reconstrução do 
ligamento cruzado anterior. Revista Brasileira de Ortopedia, v. 57, n. 02, p. 257–
266, 19 abr. 2021. 
24. 
RUETSCH, Y. A.; BÖNI, T.; BORGEAT, A. From cocaine to ropivacaine: the 
history of local anesthetic drugs. Current Topics in Medicinal Chemistry, v. 1, n. 3, 
p. 175–182, 1 ago. 2001. 
25. NAGUIB, M. et al. Adverse Effects and Drug Interactions Associated with Local 
and Regional Anaesthesia. Drug Safety, v. 18, n. 4, p. 221–250, 1998. 
26. 
RYU, H. Y. et al. Bupivacaine Induced Cardiac Toxicity Mimicking an Acute Non-
ST Segment Elevation Myocardial Infarction. Yonsei Medical Journal, v. 48, n. 2, p. 
331–336, 30 abr. 2007. 

27. 
CASATI, A.; PUTZU, M. Bupivacaine, levobupivacaine and ropivacaine: are 
they clinically different? Best Practice & Research. Clinical Anaesthesiology, v. 19, 
n. 2, p. 247–268, 1 jun. 2005. 
28. HEPPOLETTE, C. A. A. et al. Clinical Pharmacokinetics and Pharmacodynamics 
of Levobupivacaine. Clinical Pharmacokinetics, 8 fev. 2020. 
29. 
DEMET GULEC et al. Intrathecal bupivacaine or levobupivacaine: Which should 
be used for elderly patients? Journal of International Medical Research, v. 42, n. 2, 
p. 376–385, 4 mar. 2014. 
30. 
MCCLURE, J. H. Ropivacaine. British Journal of Anaesthesia, v. 76, n. 2, p. 
300-307, fev. 1996. 
31. 
BRÄU, M. E. et al. Block of Neuronal Tetrodotoxin-Resistant Na+ Currents by 
Stereoisomers of Piperidine Local Anesthetics. Anesthesia & Analgesia, v. 91, n. 6, 
p. 1499–1505, 1 dez. 2000 
32. 
MORRISON, S. G. et al. A Comparison of the Electrocardiographic Cardiotoxic 
Effects of Racemic Bupivacaine, Levobupivacaine, and Ropivacaine in Anesthetized 
Swine. Anesthesia & Analgesia, v. 90, n. 6, p. 1308–1314, jun. 2000. 
33. 
GROBAN, L. et al. Cardiac Resuscitation After Incremental Overdosage with 
Lidocaine, Bupivacaine, Levobupivacaine, and Ropivacaine in Anesthetized 
Dogs. Anesthesia and Analgesia, p. 37–43, jan. 2001. 
34. 
SCOTT, D. et al. Acute Toxicity of Ropivacaine Compared with That of 
Bupivacaine. Anesthesia and Analgesia, v. 69, n. 5, p. 563–569, 1 nov. 1989. 
35. 
HIGUCHI, H. Spread of Epidural Anesthesia. The Journal of Japan Society 
for Clinical Anesthesia, v. 28, n. 1, p. 143–151, 1 jan. 2008. 
36. 
CEDERHOLM, I.; EVERS, H.; LÖFSTRÖM, J. B. Effect of intradermal injection 
of saline or a local anaesthetic agent on skin blood flow – a methodological study in 
man. Acta Anaesthesiologica Scandinavica, v. 35, n. 3, p. 208–215, abr. 1991.  
37. 
KALATH, R. N.; KULAL, R.; GOPINATH, S. Comparison of clinical efficacy of 
ropivacaine and lignocaine with adrenaline for implant surgery anesthesia: a split-
mouth randomized controlled clinical trial. Journal of Dental Anesthesia and Pain 
Medicine, v. 21, n. 4, p. 337, 2021. 
38. 
PELL, G. J.; GREGORY, B. T. Impacted mandibular thir molars classification 
and modified technique for removal. Dental Digest, v. 39, p. 330-338, 1933. 
 
 
 
 

APPENDIX A – FREE AND INFORMED CONSENT FORM 
 
 
CPPG OR CAAE PROJECT NUMBER: 89726325.2.0000.5327 
PROJECT TITLE: "COMPARIMENTAL STUDY BETWEEN BUPIVACAINE AND 
ROPIVACAINE REGARDING EFFICACY IN THIRD MOLAR REMOVAL SURGERY 
UNDER GENERAL ANESTHESIA" 
You are invited to participate in the research project "COMPARIMENTAL 
STUDY BETWEEN BUPIVACAINE AND ROPIVACAINE REGARDING EFFICACY IN 
THIRD MOLAR REMOVAL SURGERY UNDER GENERAL ANESTHESIA," which will 
be conducted at the Hospital de Clínicas de Porto Alegre. The main objective of this 
research is to compare the postoperative analgesic capacity, bleeding, and 
intraoperative signs of two anesthetic salts. The study is designed as a randomized, 
controlled, split-mouth clinical trial, with group A receiving 0.5% bupivacaine and 0.2 
mL of epinephrine, and group B receiving 0.5% ropivacaine and 0.2 mL of epinephrine. 
You may participate in this study if you have two lower third molars that require 
surgical removal under general anesthesia, either due to the complexity of the surgical 
technique or clinical management. If other procedures are required at the same time 
as the surgery, or if the procedure can be performed under local anesthesia, your 
participation will not be included in the study. If you agree to participate in the research, 
the procedure involved will be surgery to remove your lower third molars under general 
anesthesia. A local anesthetic (0.5% bupivacaine with 0.2mL of epinephrine) will be 
administered to one side and a local anesthetic (0.5% ropivacaine with 0.2mL of 
epinephrine) to the other side, selected randomly. The surgery will be performed under 
general anesthesia in a single session. 
Your participation in the research involves the collection of personal and health 
data during preoperative consultations, the surgical procedure, and postoperative 
appointments. This information is guaranteed confidentiality between the researchers 
and the patient. Furthermore, you, as a research participant, have the right not to 
answer any questions in the questionnaire that cause you embarrassment or 
discomfort, without needing to provide an explanation or justification. You may 
withdraw from the research at any time without any harm to yourself. 
 
Page: 1 de 5 
Heading:________ 

By participating in this research, you consent to undergo a tooth extraction 
procedure using two different anesthetic salts, both already established on the market. 
Furthermore, you agree to attend postoperative consultations. These 
consultations will take place 7 or 10 days after surgery, during which a physical and 
clinical examination will be performed, as well as suture removal and other 
postoperative measures, if necessary. The benefit you will receive from participating in 
this research is indirect, as you will contribute to the discovery of scientific knowledge 
that will serve as the basis for larger studies on this topic, which may create safer and 
more effective treatments for patients requiring third molar removal under general 
anesthesia. 
Surgical procedures and your participation in this research may present certain 
risks inherent to participation, such as: 
Regarding the surgical procedure, these risks are inherent to your participation 
in the research: risks of paresthesia (an abnormal and unpleasant sensation on the 
skin that takes various forms, including burning and numbness), mouth injuries, risk of 
infection of the fascial spaces, bleeding, and jaw fracture. These possible 
complications will be treated, if they occur, as follows: prescription of 
neuroregenerative medications, clinical management of mouth lesions, antibiotic 
prescription and immediate clinical management by the team, local hemostasis 
maneuvers, and immediate rigid internal fixation, all during the same surgical 
procedure. Furthermore, this document includes the cell phone number of the 
researcher in charge in case of complications beyond pre-scheduled postoperative 
appointments and the availability of the researchers for care at the Hospital de Clínicas 
de Porto Alegre and the UFRGS School of Dentistry.  
Regarding research participation: You will provide personal and health 
information that may cause embarrassment and/or discomfort. In this case, you may 
refuse to answer the questions without any need for justification. You should be aware 
that confidentiality may be breached in the following situations: when it is the last resort 
available, or in the event of an adverse event requiring care from other professionals. 
Therefore, to minimize this situation, only information relevant to the procedure to be 
performed will be disclosed after due consent. 
 
 
 
 
Page: 2 de 5 
Heading: ________ 

The researchers undertake to suspend the study in the event of any adverse 
reaction suspected to be related to the research procedure. If any, the treatment of 
these adverse reactions will be the sole responsibility of the lead researcher, without 
restriction. 
Participation in the study does not involve any financial gain for the participant, 
nor does it generate any costs to be paid by them. Transportation costs (the cost of a 
round-trip municipal bus ticket for each appointment) will be reimbursed, as well as 
any expenses incurred due to their participation in the study, with reimbursement being 
the responsibility of the lead researcher. 
The participant has the right to seek compensation for any damages arising from 
the study. Likewise, the participant may withdraw from the study at any time without 
needing to justify their decision, and without compromising the care provided at the 
Hospital de Clínicas de Porto Alegre. 
All patients will receive intravenous antibiotics (Clindamycin 900mg) from the 
researchers in the first 30 minutes of the surgical procedure, as a form of prophylaxis, 
reducing the risk of infection. During hospitalization, patients receive intravenous doses 
of 2g of dipyrone every 6 hours, 40mg of tenoxicam once daily, 100mg of tramadol 
every 8 hours, 600mg of clindamycin every 6 hours, and 4mg of ondansetron every 8 
hours. 
After the surgical procedure, patients will be prescribed 1g of paracetamol (take 
two 500mg tablets every 6 hours for 3 days), ketorolac tromethamine 10mg (place one 
10mg tablet under the tongue every 6 hours for 3 days), and 600mg of clindamycin 
(take two 300mg tablets every 6 hours for 7 days). In addition, an aqueous solution of 
chlorhexidine digluconate (150ml at 0.12%) will be prescribed for rinsing 10ml for 1 
minute, every 12 hours, for 7 days, to be started only 24 hours after the procedure. 
These medications should be used at home. The researchers undertake to 
disseminate the results to the research participants in an accessible format once the 
research is completed. 
Finally, it is important to emphasize that your data will be stored for at least 5 
years, and this Informed Consent Form must be signed and initialed on every page by 
the principal investigator and the participant in two copies. 
 
Page: 3 de 5 
Heading:________ 
 
 

 
It is important to emphasize that the project was evaluated by the CEP-UFRGS, 
a collegiate body with an advisory, deliberative, and educational nature, whose 
purpose is to evaluate, issue opinions, and monitor research projects involving human 
beings, in their ethical and methodological aspects, carried out within the institution. 
The CEP-UFRGS is located at Av. Paulo Gama, 110, Room 311, Annex Building I of 
the Rector's Office – Centro Campus, Porto Alegre, RS – Zip Code: 90040-060. Phone: 
+55 51 3308 3787. Email: etica@propesq.ufrgs.br. Opening hours: Monday to Friday, 
from 8:00 to 12:00 and from 13:30 to 17:30. 
 
Contacts: 
Researcher in Charge: Henrique Tedesco - (51) 99960-1939 
 
The participant declares having read and received information about the research, thus 
agreeing to participate in the study. 
Signatures: 
 
 
 
 
 
 
 
 
Reseacher 
Volunteer 
 
 
Date: 
/ 
/ 
. 
 
 
 
 
 
 
 
 
 
Page 4 de 4 
Heading:________ 

APPENDIX B – POSTOPERATIVE CARE PROTOCOL 
  
 
Bite firmly on a gauze pad for 20 minutes in case of delayed bleeding. 
 
Eat a soft, cold, or ice-cold liquid diet for 48 hours. Avoid grainy or bran-based 
foods until the suture is removed. 
 
Apply ice to the face over the surgical site for 20 minutes for the first 24 hours, 
followed by a 20-minute rest. 
 
Rest, keeping your head elevated above the rest of your body. 
 
Avoid strenuous physical activity and sun exposure for 7 days. 
 
Brush your teeth normally 24 hours after surgery. 
 
Gently brush the surgical site until the suture is removed. 
 
Do not rinse your mouth for 48 hours. 
 
Avoid spitting. 
 
Do not smoke until discharge from surgery. 
 
Medication: 
 
Paracetamol 1g, 2 tablets every 6 hours for three days. 
 
Ketorolac tromethamine 10mg, 1 tablet every 6 hours for three days. 
 
Clindamycin 300mg, 2 tablets every 6 hours for seven days. 
 
Rinse with 10mL of 0.12% chlorhexidine digluconate aqueous solution for 1 
minute every 12 hours for seven days, starting 24 hours after surgery. – see 
medications. 
 
In case of persistent bleeding, severe pain, or fever (temperature greater than or 
equal to 37.8°C), contact your doctor. 
  
 
 
 
 
 
 
 

APPENDIX C – VAS FOR ASSESSING POSTOPERATIVE 
                                                                                              
 
 
 
 
 
   No pain 
 
 
 
 
 
            
 
Unbearable pain  
 
A 10-cm visual analog scale is used to measure the patient's pain during the stipulated 
periods. It is used postoperatively for each operated side.