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© 2020 Journal of Family Medicine and Primary Care | Published by Wolters Kluwer ‑ Medknow	 904
Introduction
The removal of impacted third molar is the most common
surgical procedure performed in oral surgery.[1]
The surgical
procedure causes trauma to the soft and bony tissues resulting
in pain, swelling, and trismus in the postoperative period, thereby
causing considerable distress to the patient. Postoperative swelling
and edema may be due in part to the conversion of phospholipids
into arachidonic acid by phospholipase A2, and the resultant
synthesis of prostaglandins, leukotrienes, or thromboxane‑related
Comparative evaluation of efficacy and latency of twin
mix vs 2% lignocaine HCL with 1:80000 epinephrine in
surgical removal of impacted mandibular third molar
Swati Sahu1
, Abhishek Patley1
, Vinay Kharsan1
, R. S. Madan2
, Manjula V3
,
Rahul Vinay Chandra Tiwari4
Department of 1
OMFS, 2
Oral and Maxillofacial Surgery, New Horizon Dental College and Research Institute, Bilaspur,
Chhattisgarh, 3
Department of OMFS, K.G.F College of Dental Sciences and Hospital, Kolar, Karnataka, 4
Department of Oral
and Maxillofacial Surgery, Sri Sai College of Dental Surgery, Vikarabad, Telangana, India
Abstract
Introduction: A  prospective randomized double‑blind controlled trial was conducted to evaluate the latency and duration of
pterygomandibular nerve block with a mixture of 1.8 ml 2% lignocaine with 1:80,000 epinephrine and 1 ml of 4 mg dexamethasone
and its impact on postoperative sequelae after surgical extraction of impacted mandibular third molars. Materials and Methods: This
study was conducted in 40 subjects referred to the department of oral and maxillofacial surgery; they were divided into 20 subjects
each in group A and B with the age range of 18–72 years planned for elective surgical removal of unilateral impacted mandibular third
molar. Each patient was randomly selected to receive anesthesia using 1.8 ml 2% lignocaine with 1:80,000 epinephrine in group A
or 2.8 ml twin mix (1.8 ml 2% lignocaine with 1:80,000 epinephrine + 1 ml 4 mg dexamethasone) in group B. After injection of the
anesthetic solution, the time to anesthetic effect, duration of anesthesia from initial patient perception of the anesthetic effect to
the time when the effect subsides, need to reanesthetize the surgical site were recorded, and 10‑point visual analog scale (VAS)
was used to subjectively assess the overall pain intensity while injecting the study drug, during surgery, and in the postoperative
period. Results: Mean VAS value for pain on local anesthetic injection was less in twin‑mix group. The time of onset of the local
anesthetic was significantly less for the study group T, 51.35 ± 7.15 s when compared with patients in study group C (P less than
0.0001). The duration of soft tissue anesthesia was longer for all the patients in the study group T. On comparative evaluation
between study group C and study group T, patients in the control group had more severe swelling and reduction in mouth opening
in the postoperative period. Conclusion : The addition of dexamethasone to lignocaine and its administration as an intraspace
injection significantly shortens the latency and prolongs the duration of the soft tissue anesthesia, with improved quality of life in
the postoperative period after surgical extraction of mandibular third molars.
Keywords: Dexamethasone, impacted tooth, lignocaine, twin mix
Original Article
Access this article online
Quick Response Code:
Website:
www.jfmpc.com
DOI:
10.4103/jfmpc.jfmpc_998_19
Address for correspondence: Dr. Vinay Kharsan,
Department of OMFS, New Horizon Dental College and Research
Institute, Bilaspur ‑ 495 001, Chhattisgarh, India.
E‑mail: kharsan@rediffmail.com
How to cite this article: Sahu S, Patley A, Kharsan V, Madan RS,
Manjula V, Tiwari RV. Comparative evaluation of efficacy and latency
of twin mix vs 2% lignocaine HCL with 1:80000 epinephrine in surgical
removal of impacted mandibular third molar. J Family Med Prim Care
2020;9:904-8.
This is an open access journal, and articles are distributed under the terms of the Creative
Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to
remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is
given and the new creations are licensed under the identical terms.
For reprints contact: reprints@medknow.com
Received: 11-11-2019		 Revised: 27-12-2019
Accepted: 08-01-2020		 Published: 28-02-2020
[Downloaded free from http://www.jfmpc.com on Tuesday, March 3, 2020, IP: 183.83.106.191]
Sahu, et al.: Efficacy and latency of twin mix vs 2% lignocaine HCL in surgical removal of impacted M3
Journal of Family Medicine and Primary Care	 905	 Volume 9 : Issue 2 : February 2020
substances which act as mediators of the inflammatory response.
These symptoms are not observed immediately after surgery
but rather begin gradually, peaking 2 days after the procedure.
Apart from nonsteroidal antiinflammatory drugs, corticosteroids
have been widely used in a number of clinical trials as an aid to
improve the post‑surgical sequelae.[2]
Steroids prevent diapedesis,
the initial leakage of fluids from the capillaries, and stabilize the
membranes of the cellular lysosomes which hold large quantities
of hydrolytic enzymes. There is also a decrease in the formation
of bradykinin, a powerful vasodilating substance, thereby
reducing the postoperative swelling.[3]
However even with ample
clinical trials, clinicians remain uncertain about the preferred
route of administration of steroids.[4]
This study compares
the effectiveness of pterygomandibular nerve block using 2%
lignocaine HCL with 1:80,000 adrenaline to twin mix (4 mg of
dexamethasone mixed with 2% lignocaine Hcl with 1:80,000
adrenaline) on postoperative discomfort after mandibular third
molar surgery.
Materials and Methods
Patient selection and anesthesia
This study was conducted with kind approval from the
institutional ethical committee (20-12-2017) with proper
signed informed consent being taken from the patients before
the procedure.[5]
The study containing 40 subjects, referred
to the department of oral and maxillofacial surgery, were
divided into 20 subjects each in group A (control group) and
group B (twin‑mix group). Patients within the age range of
18–60 years planned for elective surgical removal of unilateral
impacted mandibular third molar and fulfilling the inclusion
criteria were selected for the study. All patients were of Indian
origin. The inclusion criterion was ASA Class I subjects
presenting with unilaterally impacted mandibular third molar
with similar difficulty indices. The exclusion criteria were
the presence of acute infection and/or swelling and pain at
the time of surgery, medically compromised patients, any
history of allergy to local anesthetic drugs, and refusal of
informed consent. Each patient was randomly selected to
receive anesthesia using 1.8 ml 2% lignocaine with 1:80,000
epinephrine in group A or 2.8 ml twin mix (1.8 ml 2% lignocaine
with 1:80,000 epinephrine + 1 ml 4 mg dexamethasone) in
group B. Preparation of twin mix was done by mixing 1.8 ml
of 2% lignocaine with 1:80,000 epinephrine with 1 ml of 4 mg
dexamethasone immediately before dispensing.[6]
The same
operator performed all inferior alveolar nerve block injections
in a standardized manner. Two plane aspiration was done and
the solution was deposited at the rate of 1 ml/min. After
injecting the anesthetic solution, the time to anesthetic effect
was recorded (defined as the time elapsed from full needle
withdrawal until the onset of subjective signs of anesthesia),
also the duration of anesthesia was recorded from initial patient
perception of the anesthetic effect to the time when the effect
subsides. The need to reanesthetize the surgical site was also
recorded. A 10‑point visual analog scale (VAS) was used to
subjectively assess the overall pain intensity while injecting the
study drug, during surgery, and in the postoperative period. All
the findings were carefully recorded and statistically analyzed.
Surgical procedure
All the patients received antibiotics (amoxicillin + clavulanic acid
625 mg) 1 h prior to surgery. Surgical access to the mandibular
third molars was achieved using wards or modified ward’s incision
depending upon the difficulty level of impaction, mucoperiosteal
flap was raised, and bone removal was done with a 702 surgical
carbide tapered fissure bur (SS White) using straight surgical
micro‑motor/hand piece under copious normal saline irrigation.
The impacted tooth was removed in toto or after odontectomy
as desired, based on the type of impaction and root pattern.
Surgical site was thoroughly irrigated and sutured with 3–0
silk sutures. The time required for each surgical procedure was
recorded from incision to the placement of the last suture.
Postoperative instructions were given to the patients. All the
patients were prescribed tablets amoxicillin + clavulanic acid
625 mg and diclofenac potassium 50 mg tablet twice for 5 days.
Each patient was evaluated for postoperative pain, facial swelling,
and maximal mouth opening on the first, third, and seventh
postoperative day. Pain was recorded using 10‑point VAS scale;
facial swelling using measurements between tragus to angle
of mouth, menton, and angle of mandible, and postoperative
maximal mouth opening interincisally using vernier caliper.[7]
Results
All the 20 nerve blocks in group B (twin‑mix group)
were successful, not requiring reanesthesia, whereas, in
group A (control group), 05 out of 20 subjects required
the need for reanesthesia. The mean time recorded for the
surgical procedure was 26.9 ± 4.12 min for study group A
and 29.8 ± 4.18 min for study group B, showing no statistical
difference (t = 0–2.206, P = 0–0.73). Mean VAS value for the
pain/sting on local anesthetic injection/block was 1.05 ± 0.68 for
study group B which was comparatively less than study group A,
i.e. 1.70 ± 1.08 [Table 1]. Time of onset of local anesthesia was
51.35 ± 7.15 s for study group B which was significantly less as
compared to 80.85 ± 10.00 s for study group A, showing the much
faster onset of anesthesia in case of twin‑mix group. The mean
duration of soft tissue anesthesia was clinically and statistically
much longer for study group B (250.85 ± 37.86 min) than study
group A (142.10 ± 36.84 min) Table 2. Intraoperative VAS
scores did not show any statistical difference between the study
group B (0.75 ± 0.85) and the control group A (1.75 ± 0.91).
Postoperative mean visual analog scale scores for group B were
Table 1: Mean VAS value for the pain/sting on local
anesthetic injection/block
Solution Mean (±SD) VAS value for the pain/
sting on local anesthetic injection/block
2% Lignocaine with
1:200,000 Epinephrine
1.7000±1.08
Twin mix 1.0500±0.68
[Downloaded free from http://www.jfmpc.com on Tuesday, March 3, 2020, IP: 183.83.106.191]
Sahu, et al.: Efficacy and latency of twin mix vs 2% lignocaine HCL in surgical removal of impacted M3
Journal of Family Medicine and Primary Care	 906	 Volume 9 : Issue 2 : February 2020
lower in the first, third, and seventh postoperative day [Table 3].
On the first postoperative day, in the control group A, there was
a gradual increase in the facial swelling from the first to third
postoperative day followed by the reduction in the swelling till
seventh postoperative day. In the study group B, facial swelling
was maximum on the first postoperative day followed by a
reduction in the swelling till seventh postoperative day. Mean
reduction in mouth opening in group B was significantly lower
on the first, third, and seventh postoperative day. On comparative
evaluation between study group A and study group B, patients
in the control group had more severe swelling and reduction in
mouth opening in the postoperative period. Recovery from the
local anesthetic was complete, without any residual deficit in all
the patients in both the study groups.
Discussion
Every oral surgeon encounters problems of pain, swelling,
and trismus associated with third molar surgery.[3]
Steroids
are added to local anesthetic agents in order to prolong the
duration of anesthesia and improve the quality of pain relief.
This combination provides both neuroaxial route and peripheral
nerve blocks.[8‑10]
Dexamethasone exerts potent antiinflammatory
action by inducing the synthesis of endogenous proteins, which
acts by blocking the enzymatic activation of phospholipase
A2.[11]
Dionne et al. stated that glucocorticoids act as potential
suppressor agents of multiple signaling pathways involved in the
inflammatory response causing decreased levels of inflammatory
mediators at the site of injury, and therefore, corticosteroids
are used as the drug of choice used after surgical procedures to
suppress acute inflammatory manifestations.[12]
Bhargava et al. in their prospective study used dexamethasone as
an intraspace injection in surgical removal of mandibular third
molars and found that addition of dexamethasone to lignocaine
and its administration as an intraspace injection significantly
shortens the latency and prolongs the duration of the soft
tissue anesthesia, thereby improving the quality of life in the
postoperative period.[11]
In our study, 1 ml (4 mg) dexamethasone with 2% lignocaine
is used as an intraspace injection prior to third molar surgery.
All the patients in group T showed a mean latency of
51.3500 ± 7.15 s and longer duration of soft tissue anesthesia
(mean 250.8500 ± 37.86 s).
Grossi et al.[13]
concluded that corticosteroids are primarily
used after surgical procedures for suppressing tissue mediators
of inflammation, thereby reducing transudation of fluids and
lessening edema. Although some reduction of postoperative pain
generally accompanies a reduction of edema, steroids alone do
not have a clinically significant analgesic effect.
In our study, patients in study group T showed a significant
reduction in VAS score on the first, third, and seventh
postoperative day.
In a well‑conducted trial with patients serving as their own
control, Graziani et al.[14]
investigated the effect of submucosal
injection of dexamethasone 4 mg in 43 subjects undergoing
bilateral surgical extraction of lower third molars. With regard to
the edema analysis, each treatment subgroup showed a reduced
postoperative degree of edema compared with the control
group, as highly significant on the second postoperative day as
after 1 week.
In agreement with Graziani et al.,[14]
our data shows that the
intraspace administration of dexamethasone 4 mg resulted in a
highly significant decrease in edema on the third postoperative
day.
Bhargava et al.[15]
in their study concluded that twin‑mix
administration did reduce the severity of trismus in the study
patients when seen in comparison to the control group. The
reduction of trismus may be attributed to the suppression of fluid
transudation and relatively lesser edema in the twin‑mix group.
In our study, patients in study group T showed a significant
reduction in postoperative trismus in the first, third, and seventh
day.
Berrada et al. reported in their study that alkalinization of local
anesthetic agents may shorten the onset time and lengthen the
duration of action and, hence, increases its clinical effectiveness,
and makes its injection more comfortable.[16]
Local anesthetics
exist in equilibrium between the basic uncharged (nonionized)
form, which is lipid‑soluble, and the charged (ionized) cationic
form, which is water‑soluble. Lipid soluble, nonionized form
of the local anesthetic penetrates the neural sheath and nerve
membrane. The ionized form of the local anesthetic binds with
the sodium channel and prevents the propagating of nerve
Table 2: Mean latency and duration of the soft tissue
anesthesia in the study groups
Study group Mean latency in sec (±SD) Mean duration in min (±SD)
Group C 80.8500±10.00 142.1000±36.84
Group T 51.3500±7.15 250.8500±37.86
‘t’ ‑10.728 9.206
Table 3: Mean operative and postoperative visual analog scale scores
Study
group
Mean visual analog scale scores (± SD)
Surgical Procedure First postoperative day Third postoperative day Seventh postoperative day
Group C 1.7500±0.91047 2.7500±1.16416 2.1000±1.02084 0.9000±0.91191
Group T 0.7500±0.85070 1.2000±0.76777 0.6000±0.68056 0.2000±0.41039
[Downloaded free from http://www.jfmpc.com on Tuesday, March 3, 2020, IP: 183.83.106.191]
Sahu, et al.: Efficacy and latency of twin mix vs 2% lignocaine HCL in surgical removal of impacted M3
Journal of Family Medicine and Primary Care	 907	 Volume 9 : Issue 2 : February 2020
impulses. Altering the pH to a more basic solution tends to
increase the amount of nonionized form compared to ionized
form which will speed the onset of action. Increasing the pH
of lidocaine decreases the pain associated with its infiltration.[17]
This study utilized 2.8 ml study solutions for pterygomandibular
nerve blocks to maintain volume parameter consistent in
twin‑mix groups, 1 ml more than the standard inferior alveolar
block. Steroid induces shorter onset and prolonged duration,
apart from change in pH, which may also be due to the property
of vasoconstriction of dexamethasone, or by an increase in the
activity of the inhibitory potassium channels on nociceptive
C‑fibers (via glucocorticoid receptors), thus decreasing their
activity.[18,19]
Addition of dexamethasone increases the pH,
thereby increases the amount of free base of the local anesthetic,
decreases the time required for onset of the anesthetic, decreases
pain during injection, and improves overall patients postoperative
comfort and quality of life as demonstrated by the postoperative
VAS scores and measurements for the facial swelling and
reduction in mouth opening.
In this study, patients in group T showed a significantly faster
onset of anesthesia (mean: 51.35 ± 7.15 s). Pain during injection
for both groups C and T does not show much statistical
difference, whereas VAS score for group T shows a significant
decrease in pain on postoperative first, third, and seventh day.
Facial swelling for patients of group T shows a significant
decrease in the postoperative first, third, and seventh day with
the peak level on the third postoperative day. Patients of group T
does not show much decrease in mouth opening as compared
to group C.
Conclusion
Clinical anesthetic efficacy of twin mix offers the advantage
of single prick co‑administration of dexamethasone with
local anesthetic, lesser sting of local anesthetic injection,
shorter aesthetic latency, and prolonged duration of the
soft tissue anesthesia and a decrease in postoperative
discomfort after the oral surgical procedure. A long‑term
stability study is mandated to assess the compatibility of
the mixture components for its production, storage, and
shelf‑life assessment.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient
consent forms. In the form, the patients have given their consent
for their images and other clinical information to be reported in
the journal. The patients understand that their names and initials
will not be published and due efforts will be made to conceal
their identity, but anonymity cannot be guaranteed.
Financial support and  sponsorship
Nil.
Conflicts of  interest
There are no conflicts of interest.
References
1.	 Grossi GB, Maiorana C, Garramone AR, Borgonovo A,
Creminelli L, Santoro F, et al. Assessing postoperative
discomfort after third molar surgery: A prospective study.
J Oral MaxillofacSurg 2007;65:901‑17.
2.	 Markiewicz MR, Brady MF, Ding EL, Dodson TB.
Corticosteroids reduce postoperative morbidity after
third molar surgery: A systematic review and meta‑analysis.
J Oral MaxillofacSurg 2008;66:1881‑94.
3.	 Dhanavelu PR, Gapriyan S, Ebenezer V, Balakrishnan EM.
Dexamethasone for third molar surgery—A review. Int J
Pharma Bio Sci 2013;4:9‑13.
4.	 Ruta DA, Bissias E, Ogston S, Ogden GR. Assessing
health outcomes after extraction of third molars: The
postoperative symptom severity (PoSSe) scale. Br J Oral
Maxillofac Surg 2000;38:480‑7.
5.	 Bhargava D, Deshpande A. Twin‑mix anesthesia as
pterygomandibular nerve block for surgical removal of
impacted mandibular third molars. J Stomat Occ Med.
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6.	 Bhargava D, Sreekumar K, Rastogi S, Deshpande A,
Chakravorty N. A prospective randomized double‑blind
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lignocaine with 1: 200,000 epinephrine in surgical removal
of impacted mandibular third molars: A pilot study. Oral
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7.	 Sreekumar K, Bhargava D. A prospective randomized
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8.	 Shrestha BR, Maharjan SK, Tabedar S. Supraclavicular
brachial plexus block with and without dexamethasone—A
comparative study. Kathmandu Univ Med J 2003;1:158‑60.
9.	 Banaszkiewicz PA, Kader D, Wardlaw D. The role of caudal
epidural injections in the management of low back pain.
Bull Hosp Jt Dis 2003;61:127‑31.
10.	 Bansal S, Turtle MJ. Inadvertent subdural spread
complicating cervical epidural steroid injection with local
anaesthetic agent. Anaesth Intensive Care 2003;31:570‑2.
11.	 Bhargava D, Sreekumar K, Deshpande A. Effects of intra‑space
injection of twin mix versus intraoral‑submucosal,
intramuscular, intravenous and per‑oral administration of
dexamethasone on post‑operative sequelae after mandibular
impacted third molar surgery: A preliminary clinical
comparative study. Oral Maxillofac Surg 2014;18:293‑6.
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Dexamethasone suppresses peripheral prostanoid levels
without analgesia in a clinical model of acute inflammation.
J Oral Maxillofac Surg 2003;61:997‑1003.
13.	 Grossi GB, Maiorana C, Garramone RA, Borgonovo A,
Beretta M, Farronato D, et al. Effect of submucosal injection
of dexamethasone on postoperative discomfort after third
molar surgery: A prospective study. J Oral Maxillofac Surg
2007;65:2218‑26.
14.	 Graziani F, D’Aiuto F, Arduino PG, Tonelli M, Gabriele M.
Perioperative dexamethasonereduces post‑surgical sequelae
of wisdom tooth removal. A split‑mouth randomized
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Sahu, et al.: Efficacy and latency of twin mix vs 2% lignocaine HCL in surgical removal of impacted M3
Journal of Family Medicine and Primary Care	 908	 Volume 9 : Issue 2 : February 2020
double‑masked clinical trial. Int J Oral Maxillofac Surg
2006;35:241‑6.
15.	 Bhargava D, Deshpande A, Khare P, Pandey SP, Thakur N.
Validation of data on the use of twin mix in minor oral
surgery: Comparative evaluation of efficacy of twin mix versus
2% lignocaine with 1: 200000 epinephrine based on power
analysis and an UV spectrometry study for chemical stability
of the mixture. Oral Maxillofac Surgery 2015;19:37‑41.
16.	 Berrada R, Chassard D, Bryssine S, Berthier S, Bryssine B,
Boulétreau P. In vitro effects of the alkalinization of
0.25% bupivacaine and 2% lidocaine. Anne Fr Anesth
Reanim 1994;13:165‑8
17.	 Malamend SF. Buffering local anesthetics in dentistry. Pulse
2011;4:8‑9.
18.	 Cummings KC 3rd
, Napierkowski DE, Parra‑Sanchez I, Kurz A,
Dalton JE, Brems JJ, et al. Effect of dexamethasone on the
duration of interscalene nerve blocks with ropivacaine or
bupivacaine. Br J Anaesth 2011;107:446‑53.
19.	 Tandoc MN, Fan L, Kolesnikov S, Kruglov A, Nader ND.
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155th publication jfmpc- 6th name

  • 1. © 2020 Journal of Family Medicine and Primary Care | Published by Wolters Kluwer ‑ Medknow 904 Introduction The removal of impacted third molar is the most common surgical procedure performed in oral surgery.[1] The surgical procedure causes trauma to the soft and bony tissues resulting in pain, swelling, and trismus in the postoperative period, thereby causing considerable distress to the patient. Postoperative swelling and edema may be due in part to the conversion of phospholipids into arachidonic acid by phospholipase A2, and the resultant synthesis of prostaglandins, leukotrienes, or thromboxane‑related Comparative evaluation of efficacy and latency of twin mix vs 2% lignocaine HCL with 1:80000 epinephrine in surgical removal of impacted mandibular third molar Swati Sahu1 , Abhishek Patley1 , Vinay Kharsan1 , R. S. Madan2 , Manjula V3 , Rahul Vinay Chandra Tiwari4 Department of 1 OMFS, 2 Oral and Maxillofacial Surgery, New Horizon Dental College and Research Institute, Bilaspur, Chhattisgarh, 3 Department of OMFS, K.G.F College of Dental Sciences and Hospital, Kolar, Karnataka, 4 Department of Oral and Maxillofacial Surgery, Sri Sai College of Dental Surgery, Vikarabad, Telangana, India Abstract Introduction: A  prospective randomized double‑blind controlled trial was conducted to evaluate the latency and duration of pterygomandibular nerve block with a mixture of 1.8 ml 2% lignocaine with 1:80,000 epinephrine and 1 ml of 4 mg dexamethasone and its impact on postoperative sequelae after surgical extraction of impacted mandibular third molars. Materials and Methods: This study was conducted in 40 subjects referred to the department of oral and maxillofacial surgery; they were divided into 20 subjects each in group A and B with the age range of 18–72 years planned for elective surgical removal of unilateral impacted mandibular third molar. Each patient was randomly selected to receive anesthesia using 1.8 ml 2% lignocaine with 1:80,000 epinephrine in group A or 2.8 ml twin mix (1.8 ml 2% lignocaine with 1:80,000 epinephrine + 1 ml 4 mg dexamethasone) in group B. After injection of the anesthetic solution, the time to anesthetic effect, duration of anesthesia from initial patient perception of the anesthetic effect to the time when the effect subsides, need to reanesthetize the surgical site were recorded, and 10‑point visual analog scale (VAS) was used to subjectively assess the overall pain intensity while injecting the study drug, during surgery, and in the postoperative period. Results: Mean VAS value for pain on local anesthetic injection was less in twin‑mix group. The time of onset of the local anesthetic was significantly less for the study group T, 51.35 ± 7.15 s when compared with patients in study group C (P less than 0.0001). The duration of soft tissue anesthesia was longer for all the patients in the study group T. On comparative evaluation between study group C and study group T, patients in the control group had more severe swelling and reduction in mouth opening in the postoperative period. Conclusion : The addition of dexamethasone to lignocaine and its administration as an intraspace injection significantly shortens the latency and prolongs the duration of the soft tissue anesthesia, with improved quality of life in the postoperative period after surgical extraction of mandibular third molars. Keywords: Dexamethasone, impacted tooth, lignocaine, twin mix Original Article Access this article online Quick Response Code: Website: www.jfmpc.com DOI: 10.4103/jfmpc.jfmpc_998_19 Address for correspondence: Dr. Vinay Kharsan, Department of OMFS, New Horizon Dental College and Research Institute, Bilaspur ‑ 495 001, Chhattisgarh, India. E‑mail: kharsan@rediffmail.com How to cite this article: Sahu S, Patley A, Kharsan V, Madan RS, Manjula V, Tiwari RV. Comparative evaluation of efficacy and latency of twin mix vs 2% lignocaine HCL with 1:80000 epinephrine in surgical removal of impacted mandibular third molar. J Family Med Prim Care 2020;9:904-8. This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution‑NonCommercial‑ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non‑commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. For reprints contact: reprints@medknow.com Received: 11-11-2019 Revised: 27-12-2019 Accepted: 08-01-2020 Published: 28-02-2020 [Downloaded free from http://www.jfmpc.com on Tuesday, March 3, 2020, IP: 183.83.106.191]
  • 2. Sahu, et al.: Efficacy and latency of twin mix vs 2% lignocaine HCL in surgical removal of impacted M3 Journal of Family Medicine and Primary Care 905 Volume 9 : Issue 2 : February 2020 substances which act as mediators of the inflammatory response. These symptoms are not observed immediately after surgery but rather begin gradually, peaking 2 days after the procedure. Apart from nonsteroidal antiinflammatory drugs, corticosteroids have been widely used in a number of clinical trials as an aid to improve the post‑surgical sequelae.[2] Steroids prevent diapedesis, the initial leakage of fluids from the capillaries, and stabilize the membranes of the cellular lysosomes which hold large quantities of hydrolytic enzymes. There is also a decrease in the formation of bradykinin, a powerful vasodilating substance, thereby reducing the postoperative swelling.[3] However even with ample clinical trials, clinicians remain uncertain about the preferred route of administration of steroids.[4] This study compares the effectiveness of pterygomandibular nerve block using 2% lignocaine HCL with 1:80,000 adrenaline to twin mix (4 mg of dexamethasone mixed with 2% lignocaine Hcl with 1:80,000 adrenaline) on postoperative discomfort after mandibular third molar surgery. Materials and Methods Patient selection and anesthesia This study was conducted with kind approval from the institutional ethical committee (20-12-2017) with proper signed informed consent being taken from the patients before the procedure.[5] The study containing 40 subjects, referred to the department of oral and maxillofacial surgery, were divided into 20 subjects each in group A (control group) and group B (twin‑mix group). Patients within the age range of 18–60 years planned for elective surgical removal of unilateral impacted mandibular third molar and fulfilling the inclusion criteria were selected for the study. All patients were of Indian origin. The inclusion criterion was ASA Class I subjects presenting with unilaterally impacted mandibular third molar with similar difficulty indices. The exclusion criteria were the presence of acute infection and/or swelling and pain at the time of surgery, medically compromised patients, any history of allergy to local anesthetic drugs, and refusal of informed consent. Each patient was randomly selected to receive anesthesia using 1.8 ml 2% lignocaine with 1:80,000 epinephrine in group A or 2.8 ml twin mix (1.8 ml 2% lignocaine with 1:80,000 epinephrine + 1 ml 4 mg dexamethasone) in group B. Preparation of twin mix was done by mixing 1.8 ml of 2% lignocaine with 1:80,000 epinephrine with 1 ml of 4 mg dexamethasone immediately before dispensing.[6] The same operator performed all inferior alveolar nerve block injections in a standardized manner. Two plane aspiration was done and the solution was deposited at the rate of 1 ml/min. After injecting the anesthetic solution, the time to anesthetic effect was recorded (defined as the time elapsed from full needle withdrawal until the onset of subjective signs of anesthesia), also the duration of anesthesia was recorded from initial patient perception of the anesthetic effect to the time when the effect subsides. The need to reanesthetize the surgical site was also recorded. A 10‑point visual analog scale (VAS) was used to subjectively assess the overall pain intensity while injecting the study drug, during surgery, and in the postoperative period. All the findings were carefully recorded and statistically analyzed. Surgical procedure All the patients received antibiotics (amoxicillin + clavulanic acid 625 mg) 1 h prior to surgery. Surgical access to the mandibular third molars was achieved using wards or modified ward’s incision depending upon the difficulty level of impaction, mucoperiosteal flap was raised, and bone removal was done with a 702 surgical carbide tapered fissure bur (SS White) using straight surgical micro‑motor/hand piece under copious normal saline irrigation. The impacted tooth was removed in toto or after odontectomy as desired, based on the type of impaction and root pattern. Surgical site was thoroughly irrigated and sutured with 3–0 silk sutures. The time required for each surgical procedure was recorded from incision to the placement of the last suture. Postoperative instructions were given to the patients. All the patients were prescribed tablets amoxicillin + clavulanic acid 625 mg and diclofenac potassium 50 mg tablet twice for 5 days. Each patient was evaluated for postoperative pain, facial swelling, and maximal mouth opening on the first, third, and seventh postoperative day. Pain was recorded using 10‑point VAS scale; facial swelling using measurements between tragus to angle of mouth, menton, and angle of mandible, and postoperative maximal mouth opening interincisally using vernier caliper.[7] Results All the 20 nerve blocks in group B (twin‑mix group) were successful, not requiring reanesthesia, whereas, in group A (control group), 05 out of 20 subjects required the need for reanesthesia. The mean time recorded for the surgical procedure was 26.9 ± 4.12 min for study group A and 29.8 ± 4.18 min for study group B, showing no statistical difference (t = 0–2.206, P = 0–0.73). Mean VAS value for the pain/sting on local anesthetic injection/block was 1.05 ± 0.68 for study group B which was comparatively less than study group A, i.e. 1.70 ± 1.08 [Table 1]. Time of onset of local anesthesia was 51.35 ± 7.15 s for study group B which was significantly less as compared to 80.85 ± 10.00 s for study group A, showing the much faster onset of anesthesia in case of twin‑mix group. The mean duration of soft tissue anesthesia was clinically and statistically much longer for study group B (250.85 ± 37.86 min) than study group A (142.10 ± 36.84 min) Table 2. Intraoperative VAS scores did not show any statistical difference between the study group B (0.75 ± 0.85) and the control group A (1.75 ± 0.91). Postoperative mean visual analog scale scores for group B were Table 1: Mean VAS value for the pain/sting on local anesthetic injection/block Solution Mean (±SD) VAS value for the pain/ sting on local anesthetic injection/block 2% Lignocaine with 1:200,000 Epinephrine 1.7000±1.08 Twin mix 1.0500±0.68 [Downloaded free from http://www.jfmpc.com on Tuesday, March 3, 2020, IP: 183.83.106.191]
  • 3. Sahu, et al.: Efficacy and latency of twin mix vs 2% lignocaine HCL in surgical removal of impacted M3 Journal of Family Medicine and Primary Care 906 Volume 9 : Issue 2 : February 2020 lower in the first, third, and seventh postoperative day [Table 3]. On the first postoperative day, in the control group A, there was a gradual increase in the facial swelling from the first to third postoperative day followed by the reduction in the swelling till seventh postoperative day. In the study group B, facial swelling was maximum on the first postoperative day followed by a reduction in the swelling till seventh postoperative day. Mean reduction in mouth opening in group B was significantly lower on the first, third, and seventh postoperative day. On comparative evaluation between study group A and study group B, patients in the control group had more severe swelling and reduction in mouth opening in the postoperative period. Recovery from the local anesthetic was complete, without any residual deficit in all the patients in both the study groups. Discussion Every oral surgeon encounters problems of pain, swelling, and trismus associated with third molar surgery.[3] Steroids are added to local anesthetic agents in order to prolong the duration of anesthesia and improve the quality of pain relief. This combination provides both neuroaxial route and peripheral nerve blocks.[8‑10] Dexamethasone exerts potent antiinflammatory action by inducing the synthesis of endogenous proteins, which acts by blocking the enzymatic activation of phospholipase A2.[11] Dionne et al. stated that glucocorticoids act as potential suppressor agents of multiple signaling pathways involved in the inflammatory response causing decreased levels of inflammatory mediators at the site of injury, and therefore, corticosteroids are used as the drug of choice used after surgical procedures to suppress acute inflammatory manifestations.[12] Bhargava et al. in their prospective study used dexamethasone as an intraspace injection in surgical removal of mandibular third molars and found that addition of dexamethasone to lignocaine and its administration as an intraspace injection significantly shortens the latency and prolongs the duration of the soft tissue anesthesia, thereby improving the quality of life in the postoperative period.[11] In our study, 1 ml (4 mg) dexamethasone with 2% lignocaine is used as an intraspace injection prior to third molar surgery. All the patients in group T showed a mean latency of 51.3500 ± 7.15 s and longer duration of soft tissue anesthesia (mean 250.8500 ± 37.86 s). Grossi et al.[13] concluded that corticosteroids are primarily used after surgical procedures for suppressing tissue mediators of inflammation, thereby reducing transudation of fluids and lessening edema. Although some reduction of postoperative pain generally accompanies a reduction of edema, steroids alone do not have a clinically significant analgesic effect. In our study, patients in study group T showed a significant reduction in VAS score on the first, third, and seventh postoperative day. In a well‑conducted trial with patients serving as their own control, Graziani et al.[14] investigated the effect of submucosal injection of dexamethasone 4 mg in 43 subjects undergoing bilateral surgical extraction of lower third molars. With regard to the edema analysis, each treatment subgroup showed a reduced postoperative degree of edema compared with the control group, as highly significant on the second postoperative day as after 1 week. In agreement with Graziani et al.,[14] our data shows that the intraspace administration of dexamethasone 4 mg resulted in a highly significant decrease in edema on the third postoperative day. Bhargava et al.[15] in their study concluded that twin‑mix administration did reduce the severity of trismus in the study patients when seen in comparison to the control group. The reduction of trismus may be attributed to the suppression of fluid transudation and relatively lesser edema in the twin‑mix group. In our study, patients in study group T showed a significant reduction in postoperative trismus in the first, third, and seventh day. Berrada et al. reported in their study that alkalinization of local anesthetic agents may shorten the onset time and lengthen the duration of action and, hence, increases its clinical effectiveness, and makes its injection more comfortable.[16] Local anesthetics exist in equilibrium between the basic uncharged (nonionized) form, which is lipid‑soluble, and the charged (ionized) cationic form, which is water‑soluble. Lipid soluble, nonionized form of the local anesthetic penetrates the neural sheath and nerve membrane. The ionized form of the local anesthetic binds with the sodium channel and prevents the propagating of nerve Table 2: Mean latency and duration of the soft tissue anesthesia in the study groups Study group Mean latency in sec (±SD) Mean duration in min (±SD) Group C 80.8500±10.00 142.1000±36.84 Group T 51.3500±7.15 250.8500±37.86 ‘t’ ‑10.728 9.206 Table 3: Mean operative and postoperative visual analog scale scores Study group Mean visual analog scale scores (± SD) Surgical Procedure First postoperative day Third postoperative day Seventh postoperative day Group C 1.7500±0.91047 2.7500±1.16416 2.1000±1.02084 0.9000±0.91191 Group T 0.7500±0.85070 1.2000±0.76777 0.6000±0.68056 0.2000±0.41039 [Downloaded free from http://www.jfmpc.com on Tuesday, March 3, 2020, IP: 183.83.106.191]
  • 4. Sahu, et al.: Efficacy and latency of twin mix vs 2% lignocaine HCL in surgical removal of impacted M3 Journal of Family Medicine and Primary Care 907 Volume 9 : Issue 2 : February 2020 impulses. Altering the pH to a more basic solution tends to increase the amount of nonionized form compared to ionized form which will speed the onset of action. Increasing the pH of lidocaine decreases the pain associated with its infiltration.[17] This study utilized 2.8 ml study solutions for pterygomandibular nerve blocks to maintain volume parameter consistent in twin‑mix groups, 1 ml more than the standard inferior alveolar block. Steroid induces shorter onset and prolonged duration, apart from change in pH, which may also be due to the property of vasoconstriction of dexamethasone, or by an increase in the activity of the inhibitory potassium channels on nociceptive C‑fibers (via glucocorticoid receptors), thus decreasing their activity.[18,19] Addition of dexamethasone increases the pH, thereby increases the amount of free base of the local anesthetic, decreases the time required for onset of the anesthetic, decreases pain during injection, and improves overall patients postoperative comfort and quality of life as demonstrated by the postoperative VAS scores and measurements for the facial swelling and reduction in mouth opening. In this study, patients in group T showed a significantly faster onset of anesthesia (mean: 51.35 ± 7.15 s). Pain during injection for both groups C and T does not show much statistical difference, whereas VAS score for group T shows a significant decrease in pain on postoperative first, third, and seventh day. Facial swelling for patients of group T shows a significant decrease in the postoperative first, third, and seventh day with the peak level on the third postoperative day. Patients of group T does not show much decrease in mouth opening as compared to group C. Conclusion Clinical anesthetic efficacy of twin mix offers the advantage of single prick co‑administration of dexamethasone with local anesthetic, lesser sting of local anesthetic injection, shorter aesthetic latency, and prolonged duration of the soft tissue anesthesia and a decrease in postoperative discomfort after the oral surgical procedure. A long‑term stability study is mandated to assess the compatibility of the mixture components for its production, storage, and shelf‑life assessment. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and  sponsorship Nil. Conflicts of  interest There are no conflicts of interest. References 1. Grossi GB, Maiorana C, Garramone AR, Borgonovo A, Creminelli L, Santoro F, et al. Assessing postoperative discomfort after third molar surgery: A prospective study. J Oral MaxillofacSurg 2007;65:901‑17. 2. Markiewicz MR, Brady MF, Ding EL, Dodson TB. Corticosteroids reduce postoperative morbidity after third molar surgery: A systematic review and meta‑analysis. J Oral MaxillofacSurg 2008;66:1881‑94. 3. Dhanavelu PR, Gapriyan S, Ebenezer V, Balakrishnan EM. Dexamethasone for third molar surgery—A review. Int J Pharma Bio Sci 2013;4:9‑13. 4. Ruta DA, Bissias E, Ogston S, Ogden GR. Assessing health outcomes after extraction of third molars: The postoperative symptom severity (PoSSe) scale. Br J Oral Maxillofac Surg 2000;38:480‑7. 5. Bhargava D, Deshpande A. Twin‑mix anesthesia as pterygomandibular nerve block for surgical removal of impacted mandibular third molars. J Stomat Occ Med. 2015;8:29‑32. 6. Bhargava D, Sreekumar K, Rastogi S, Deshpande A, Chakravorty N. A prospective randomized double‑blind study to assess the latency and efficacy of Twin‑mix and 2% lignocaine with 1: 200,000 epinephrine in surgical removal of impacted mandibular third molars: A pilot study. Oral Maxillofac Surg 2013;17:275‑80. 7. Sreekumar K, Bhargava D. A prospective randomized double‑blind study to assess the latency and efficacy of articaine and lignocaine in surgical removal of impacted mandibular third molars in Indian patients. J StomatOcc Med 2012;5:10‑4. 8. Shrestha BR, Maharjan SK, Tabedar S. Supraclavicular brachial plexus block with and without dexamethasone—A comparative study. Kathmandu Univ Med J 2003;1:158‑60. 9. Banaszkiewicz PA, Kader D, Wardlaw D. The role of caudal epidural injections in the management of low back pain. Bull Hosp Jt Dis 2003;61:127‑31. 10. Bansal S, Turtle MJ. Inadvertent subdural spread complicating cervical epidural steroid injection with local anaesthetic agent. Anaesth Intensive Care 2003;31:570‑2. 11. Bhargava D, Sreekumar K, Deshpande A. Effects of intra‑space injection of twin mix versus intraoral‑submucosal, intramuscular, intravenous and per‑oral administration of dexamethasone on post‑operative sequelae after mandibular impacted third molar surgery: A preliminary clinical comparative study. Oral Maxillofac Surg 2014;18:293‑6. 12. Dionne RA, Gordon SM, Rowan J, Kent A, Brahim JS. Dexamethasone suppresses peripheral prostanoid levels without analgesia in a clinical model of acute inflammation. J Oral Maxillofac Surg 2003;61:997‑1003. 13. Grossi GB, Maiorana C, Garramone RA, Borgonovo A, Beretta M, Farronato D, et al. Effect of submucosal injection of dexamethasone on postoperative discomfort after third molar surgery: A prospective study. J Oral Maxillofac Surg 2007;65:2218‑26. 14. Graziani F, D’Aiuto F, Arduino PG, Tonelli M, Gabriele M. Perioperative dexamethasonereduces post‑surgical sequelae of wisdom tooth removal. A split‑mouth randomized [Downloaded free from http://www.jfmpc.com on Tuesday, March 3, 2020, IP: 183.83.106.191]
  • 5. Sahu, et al.: Efficacy and latency of twin mix vs 2% lignocaine HCL in surgical removal of impacted M3 Journal of Family Medicine and Primary Care 908 Volume 9 : Issue 2 : February 2020 double‑masked clinical trial. Int J Oral Maxillofac Surg 2006;35:241‑6. 15. Bhargava D, Deshpande A, Khare P, Pandey SP, Thakur N. Validation of data on the use of twin mix in minor oral surgery: Comparative evaluation of efficacy of twin mix versus 2% lignocaine with 1: 200000 epinephrine based on power analysis and an UV spectrometry study for chemical stability of the mixture. Oral Maxillofac Surgery 2015;19:37‑41. 16. Berrada R, Chassard D, Bryssine S, Berthier S, Bryssine B, Boulétreau P. In vitro effects of the alkalinization of 0.25% bupivacaine and 2% lidocaine. Anne Fr Anesth Reanim 1994;13:165‑8 17. Malamend SF. Buffering local anesthetics in dentistry. Pulse 2011;4:8‑9. 18. Cummings KC 3rd , Napierkowski DE, Parra‑Sanchez I, Kurz A, Dalton JE, Brems JJ, et al. Effect of dexamethasone on the duration of interscalene nerve blocks with ropivacaine or bupivacaine. Br J Anaesth 2011;107:446‑53. 19. Tandoc MN, Fan L, Kolesnikov S, Kruglov A, Nader ND. Adjuvant dexamethasone with bupivacaine prolongs the duration of interscalene block: A prospective randomized trial. J Anesth 2011;25:704‑9. [Downloaded free from http://www.jfmpc.com on Tuesday, March 3, 2020, IP: 183.83.106.191]