IJCBS, 23(1) (2023): 388-395
International Journal of Chemical and Biochemical Sciences
(ISSN 2226-9614)
Journal Home page: www.iscientific.org/Journal.html
© International Scientific Organization
A Comparison of Centbucridine and Lidocaine with Adrenaline as
Local Anesthetic Agents in Dental Procedures: A Randomized
Controlled Trial
Snehal Ingole1, Dhanashree Jadhav*2, Deepashree Meshram1, Anand Mohan Nikunj3,
Rushabh Rameshbhai Makwana4, Mohan Deshpande1
1
Department of Oral and Maxillofacial Surgery, Nair Hospital Dental College, Mumbai 400008, Maharashtra, India.
2
Dentistry Department, Bharat Ratna Atal Bihari Vajpayee Medical College, Pune, India.
3Department of Oral and Maxillofacial Surgery, Government Dental College and Hospital, Raipur, India.
4
Consultant Oral and Maxillofacial Surgeon, Anantaay Oral and Maxillofacial Surgery Clinic, Bharuch, Gujarat, India.
Abstract
Lidocaine with adrenaline is the most commonly used local anesthetic agent under routine clinical settings, However, its
use is contra-indicated in certain medically compromised patients. Hence, there is a need to develop safer alternatives to lidocaine
that is not much taxing on the cardiovascular system. A total of 50 participants requiring bilateral extraction of molars were injected
with lidocaine with adrenaline and Centbucridine on either side respectively. The onset, depth and duration of anesthesia, post-
operative bleeding, and pulse rate and blood pressure alterations were recorded at baseline and post-injection. A statistically
significant difference was observed in the onset, depth, and duration of anesthesia between the two agents with higher values in the
Centbucridine group (p<0.05). No significant difference was observed in the postoperative bleeding levels and no patients required
additional suturing to control the hemorrhage in either group. The average pulse rate reported before and after injection with lignocaine was
80.52 +_ 6.152 and 82.88 + 6.641 respectively while those before and after injection with centbucridine were 80.48 +6.370 and 84.52+_
6.152. The alteration in pulse rate was found to be statistically significantly higher in the patients injected with Centbucridine. The
onset of the anesthetic effect, its depth, and duration of Centbucridine are higher than lidocaine, indicating that the former is a more
potent local anesthetic agent. Further research is recommended before it can actually replace the currently used gold standard
anesthetic lidocaine.
Keywords: Anesthesia; Oral Surgery; Dental Extraction; Nerve Block
Full length article *Corresponding Author, e-mail: jadhavdhanashree88@gmail.com
1. Introduction
Perfusion of the drug, lidocaine is routinely used with a
Achieving adequate pain control with minimum vasoconstrictor such as epinephrine to decrease its absorption
systemic side effects during oral surgical procedures is of rate at the injection site and subsequently prolong the duration
paramount importance for dentists which significantly and depth of anesthesia. The use of vasoconstrictors may be
influences the patient acceptance of treatment, cooperation, contraindicated for a subset of medically compromised
and well-being. Lidocaine is the most commonly employed patients such as those with hypertension. Furthermore,
local anesthetic agent for dental procedures because its patients with cardiovascular problems may be sensitive to this
properties are closest to that of an ideal local anesthetic agent concentration of epinephrine in lidocaine [3]. The use of
[1]. Its rapid onset of action coupled with the intermediate lidocaine with epinephrine may be contraindicated in such
duration of action makes it suitable for surface, infiltration, patients. Thus, there has been a constant endeavor to develop
and block anesthesia in oral surgical procedures. equally effective but safer alternatives for the so-called ‘gold
While the incidence of allergic reactions is low following the standard anesthetic’ lidocaine.
use of lidocaine, its vasodilatory effect can lead to high levels
of the drug in the blood[2]. To avoid increased
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IJCBS, 23(1) (2023): 388-395
Centbucridine, a quinolone derivative, is one such alternative margin of the tongue. The time of onset of anesthesia and
local anesthetic agent with local anesthetic action. It has the subsequent systolic and diastolic blood pressure and heart
advantage of having an inherent vasoconstrictor property and rate after achieving the anesthetic effect was noted.
yet not affecting the cardiovascular system except when
administered at very large doses[4]. The Central Drug The depth of anesthesia was recorded using a visual analog
Research Institute of India concluded that Centbucridine has scale. Minimal mucoperiosteum reflection was done and the
a longer duration of action, better cardiovascular stability, extraction was carried out using appropriate dental extraction
and antihistaminic activity and is four to five times more forceps under standard aseptic precautions. An appropriately
potent as an anesthetic as compared to lidocaine[5]. sized pre-weighed cotton to serve as a pressure pack was
placed over the socket for 45 minutes and then weighed to
Not many studies have compared this relatively measure blood loss. The blood pressure and heart rate were
novel local anesthetic agent to the gold standard in dentistry. recorded again at this point in time.
In this context, the present study aimed to compare the In both groups, the duration of the anesthetic effect was
efficacy of 0.5% Centbucridine HCL to 2% lidocaine HCl marked by the return of pain sensation since the time of onset
with adrenaline as a local anesthetic agent for of the anesthetic effect was noted. Discomfort, adverse
dental extraction. The study has the objectives to analyze the effects, and any signs of an allergic reaction including itching,
various parameters associated with the local anesthetic effect redness, and localized edema during the procedure were
of Centbucridine such as the time required for the onset, recorded. Additional doses of LA, if required, were also
depth, and duration of the anesthetic effect, and its noted.
vasoconstriction ability, and compare it with those of All patients were discharged after ascertaining hemostasis 45
lidocaine. The study also has an objective to address the minutes post-extraction. They were instructed to avoid
safety concerns regarding the use of Centbucridine by rinsing for the next 24 hours, maintain good oral hygiene, and
analyzing its systemic effects, particularly on the take adequate rest. Mild analgesics and antibiotics were
cardiovascular system, toxicity, allergic reaction, and any prescribed over a 3-day course and the patients were asked to
other adverse effects produced by the use of the drug. report back in case of bleeding, pain, or discomfort. A review
was performed during the follow-up visit on the third-day
post-surgery to check for the healing of the socket.
2. Materials and methods
3. Results and Discussions
The present randomized clinical trial was conducted
from March 2014 to August 2015after due approval from the The age of the participants in the present study
institutional ethical committee. The study population ranged from 21 to 40 years with a mean age of 29.92 + 6.49
comprised a total of 50 patients (26 females and 24 males) years. The values for the onset and duration of the two
requiring bilateral extraction of erupted mandibular molars. respective local anesthetic agents are summarized in Table 1.
Only healthy subjects (according to ASA –I classification) of A statistically significant difference (p<0.05) was noted for
ages ranging from 18 to 60 years were included. Patients with the onset and duration of anesthesia of the two agents. p-value
systemic or mental conditions and pregnant females were for the t-test between the mean onset of anesthesia of the two
excluded from the study. Those having a history of recent agents was found to be less than 0.05 indicating that the onset
acute infection, radiotherapy to the jaws or hypersensitivity of anesthesia is significantly higher in 0.5% Centbucridine
reaction were also excluded. than that in 2% Lidocaine. The p-value for the t-test is less
Informed consent was obtained from the patients considered than that of 0.05 for the duration of anesthesia as indicated by
eligible for inclusion in the study following which their the time after which analgesia is required indicating that the
baseline systolic and diastolic blood pressures and heart rates duration of anesthesia is significantly more in Centbucridine
were recorded. For each patient, one quadrant was used as the than that of 2% Lidocaine. The depth of anesthesia of
control side where 2% Lidocaine Hydrochloride with 1: lidocaine was 2.48+ 0.544 and that of Centbucridine is 3.10+
200000 adrenaline (Makcur laboratories limited) was injected 0.647.The depth of anesthesia achieved was found to be
by pterygomandibular block type local anesthesia. The other statistically significantly more (p<0.05)by Centbucridine as
was used as the experimental side which was injected by the compared to Lignocaine. The mean values for depth of
same technique using 0.5% Centbucridine HCl (Anablock, anesthesia and post-extraction bleeding are tabularized in
Themis Medicare) each ml of which contained 5mg Table 2. A statistically non-significant difference was noted in
Centbucridine HCl. There was a minimum interval of one the post-operative bleeding levels achieved by the two
week between the two procedures. The selection process of anesthetic agents while none of the cases in either group
the participants in both study groups is depicted in Figure 1. required additional management of post-surgical hemorrhage
The effect of anesthesia was subjectively and objectively by sutures. The values for systolic and diastolic blood pressure
assessed over all three branches of the mandibular nerve before and after injection of the respective anesthetic agents
including the inferior alveolar nerve, lingual nerve, and the are comprehensively summarized in Table 3. A statistically
long buccal nerve. Objective confirmation of the effect was significant increase in systolic and diastolic blood pressure
confirmed by a pin-prick test using a 20-gauge sterile needle after the use of lidocaine with adrenaline (p<0.05).
which was applied over the attached gingiva of the molar
tooth to be extracted and probing buccal and lingual gingival
and mental foramen region. The onset of anesthesia was also
confirmed subjectively when the patient first described
numbness or a tingling sensation over the lower lip and lateral
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Figure 1: Flow diagram indicating the selection process of the participants in both groups in the present randomized controlled trial
There was a statistically non-significant difference
between the systolic as well as diastolic blood pressure of the
participants before injection indicating that the baseline
characteristics of the participants in the two respective groups
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were identical. The increase in blood pressure after injection al.[11] - 116.54 seconds, Gune and Katre [9] - 61.77 seconds].
was found to be statistically significantly higher (p<0.05) in The lower duration of onsets reported could be due to
the Centbucridine group. The average pulse rate reported before differences in the populations and techniques of anesthesia
injection with lidocaine plus adrenaline was 80.52 +6.152 and that across the various studies. While the onset of action was
before extraction was 82.88+ 6.641. Also, the average pulse rate slower for Centbucridine, a matter of a few seconds for the
before injection with Centbucridine reported was 80.48 +6.370, and onset of a local anesthetic agent does not make much of a
that before extraction was 84.52+_ 6.152. The change in difference in the real clinical situation. Earlier studies have
pulse rate was found to be significantly higher (p<0.05) in reported the duration of the anesthetic effect of Centbucridine
patients injected with Centbucridine as compared to those to range from 91 to 151 minutes [9-11]. In the present study
administered with lignocaine. No side effects were observed we found this value to be slightly higher with the average
in patients in the lidocaine group while only two patients in duration of the effect being about 163 minutes. This duration
the Centbucridine group experienced vomiting and dizziness was found to be significantly higher than that of lidocaine.
after injection; however, the difference was statistically non- Since unlike lidocaine, there is no adjunctive vasoconstrictor
significant. used along with Centbucridine, the prolonged duration can be
solely attributed to the chemical compound. The depth of
Small doses of lidocaine have a mild anesthesia was gauged by the use of a visual analog scale in
bronchodilating effect. Centbucridine is a novel anesthetic the present study which is a widely accepted scale for the
agent that has tetrahydroacridine as its basic chemical moiety subjective assessment of pain. In the present study, it was
instead of amides or esters that are generally present in other found that Centbucridine achieved a significantly greater
local anesthetic agents [4,5]. Owing to this difference in the depth of anesthesia as compared to lidocaine. This finding
basic chemical structures, it does not exhibit any danger of was in contrast to that from earlier studies that did not find
cross-sensitivity with available local anesthetic agents and any significant difference between the two chemicals in terms
also, no specific contraindications have been identified for its of depth of anesthesia [9-11]. While there were some issues
use. While most of the properties of lidocaine match that of concerning the depth of anesthesia in patients in the lidocaine
an ideal local anesthetic agent, it can have certain toxic effects group, the surgeon did not have any particular trouble in
on the cardiovascular system which are not recorded in the performing the surgical procedures in general. There was a
short-term duration of most of the studies including the mean rise in pulse rate by 2.36 after injection with lidocaine while the rise
present one. Furthermore, the chemical possesses inherent was 4.04 after injection with Centbucridine. Previous studies have
vasodilating properties which reduce the depth as well as the shown an increase in the pulse rate 10 minutes after
duration of the anesthesia. Consequently, a vasoconstrictor is administration of both drugs, however, the levels returned to
used in conjunction with lidocaine which is most commonly normal after 20 minutes and no significant difference was
adrenaline in a concentration of 1:80000 to 1:200000. While seen between both the drugs during the following assessment
the addition of a vasoconstrictor prolongs the duration of the intervals. At the end of one hour, both the drugs elicited a fall
anesthesia it has prominent adverse effects in certain sensitive in the pulse rate without much significant difference between
individuals or those suffering from systemic illnesses and its the two. The initial increase in the pulse rate after
use may, thus, be contraindicated [3]. Centbucridine, on the administration of lidocaine can be attributed to the
other hand, has been reported to elicit a pressor response sympathomimetic effect of the adrenaline added to lidocaine
endowing it with a vasoconstrictor ability[6]. This property [12]. On the other hand, a dose-dependent negative ionotropic
of Centbucridine fulfilled the existing need to develop a local effect has been demonstrated following the administration of
anesthetic agent that possessed inherent vasoconstrictive Centbucridine[6,13]. In the present study, systolic and
ability without affecting the stability of the cardiovascular diastolic blood pressure was measured before injection of
system. While varied concentrations of Centbucridine anesthesia and before extraction. Also in the present study, it
starting from as low as 0.0125% could be used for the purpose was found that there was a statistically significant increase in
of achieving local anesthesia, its effect is dose-dependent and systolic and diastolic blood pressure with Centbucridine. The
the optimal infiltration anesthetic effect has been reported results further showed that the change in systolic and diastolic
with the use of a concentration of 0.5% [7]. Further support BP is more with Centbucridine as compared to lidocaine.
of the statement was provided by a study conducted by Gupta Meiller et al[18]. in a study on normotensive and
et al. in 1989 which found that the depth and efficacy of hypertensive patients, determined that during local anesthesia
Centbucridine as a local anesthetic agent was significantly and tooth extraction, the blood pressure increased
better in a concentration of 0.5% as compared to continually, though without statistical significance.[18] Ezmek
0.25%[8].Therefore, a concentration of 0.5% Centbucridine et al.[19] performed a study comparing the hemodynamic
was used in the present study. The solution is stable in the effects of lidocaine, prilocaine, and mepivacaine in
solid form for more than 40 months at room temperature hypertensive patients and concluded that the systolic BP did
while the aqueous solution of 0.5% concentration remains not show statistically significant differences among the
viable for about 18 months. The onset of anesthesia was groups, but significant changes were observed in the
measured on the ipsilateral mental foramen region and the lidocaine and prilocaine groups in diastolic BP and mean
contralateral labial mucosa similar to the methodology arterial pressure, though not in an increasing fashion.
followed by an earlier study by Gune and Katre with similar
settings [9]. While in the present study, we observed an
average time of onset of the anesthetic effect to be 3.7 minutes
(223 seconds), earlier studies have reported the time to be less
than two minutes. [Mansuri et al.[10] - 162 seconds, Dugal et
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Table 1: Onset and duration of anesthetic effect of Lidocaine and Centbucridine
P value
Group Mean Std. Deviation
.001
Lidocaine 207.2 57.81
Onset
(in seconds)
Centbucridine 223.4 52.97
Lidocaine 138.2 19.97
Duration
0.00
(in Minutes)
Centbucridine 163.8 19.55
Table 2: Comparison of the depth of anesthesia and post-extraction bleeding between Lidocaine and Centbucridine
Mean Std. Deviation P value
Depth of anesthesia Lidocaine 0.001
2.48 .544
Centbucridine
3.10 .647
Post-extraction bleeding Lidocaine .687
7.41 .81891
Centbucridine
7.47 .67091
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Table 3: Comparison of Blood Pressure between Lidocaine and Centbucridine
Parameter Group Mean Std. Deviation P value
Before Injection Lidocaine 122.28 11.794
Systolic BP 0.212
Before Injection
122.00 11.321
Centbucridine
Before Injection Lidocaine 80.44 7.002
Diastolic BP 0.212
Before Injection
80.16 7.112
Centbucridine
After Injection Lidocaine 126.36 11.254
Systolic BP 0.003
After Injection Centbucridine 129.40 10.022
82.64 6.533
After Injection Lidocaine
Diastolic BP 0.001
After Injection Centbucridine 84.90 6.228
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They concluded that this may be due to the agents the latter is contraindicated. The onset of the anesthetic effect,
themselves or to the dental anxiety felt by the patients. In the its depth, and duration of Centbucridine were higher as
present study, postoperative hemostasis was evaluated 45 compared to lidocaine owing to its inherent vasoconstrictor
minutes after the procedure in both groups and it was found ability. While the safety concerns for the use of Centbucridine
that suturing of the extraction wound was never required to could not be completely addressed within the scope of the
control the hemorrhage. No case of reactionary or secondary present study, the drug can be safely used in regular dental
hemorrhage was reported in both groups. Furthermore, no clinical settings without any adverse effects. Further research
significant difference was observed between the post- is recommended before it can actually replace the currently
extraction bleeding of the two drugs. Lidocaine with used gold standard anesthetic lidocaine.
adrenaline has been the gold standard local anesthetic agent
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