ANESTHETIC EFFICACY OF 3% MEPIVACAINE PLUS
2% LIDOCAINE WITH 1:100,000 EPINEPHRINE FOR
INFERIOR ALVEOLAR NERVE BLOCKS
A Thesis
Presented in Partial Fulfillment of the Requirements for the Degree of Master of Science
in the Graduate School of The Ohio State University
By
Emily Theresa Lammers, D.D.S.
Graduate Program in Dentistry
The Ohio State University
2013
Master’s Examination Committee:
John Nusstein, D.D.S., M.S., Advisor
Al Reader, D.D.S., M.S.
Melissa Drum, D.D.S., M.S.
F. Michael Beck, D.D.S., M.A.
Copyright by
Emily Theresa Lammers, D.D.S.
2013
ABSTRACT
Introduction: Combinations of anesthetics are used clinically to potentially increase the
success of pulpal anesthesia and decrease the pain of injection. The purpose of this study
was to evaluate the combination of mepivacaine and lidocaine when used for inferior
alveolar nerve blocks.
Materials and Methods: One hundred asymptomatic subjects were given 1.8 mL 3%
mepivacaine plus 1.8 mL 2% lidocaine with 1:100,000 epinephrine or two injections of
1.8 mL 2% lidocaine with 1:100,000 epinephrine for the IANB at two separate
appointments spaced at least one week apart. Subjects rated the pain of needle insertion,
needle placement, and solution deposition on a Heft-Parker VAS. The first and second
molars, first and second premolars, and incisors were tested with an EPT every 4 minutes
for 56 minutes post-injection for pulpal anesthesia. Anesthetic success was considered to
occur when the subject achieved two consecutive 80 readings within 15 minutes of
injection and sustained the 80 reading for the remainder of the testing period.
Results: Mean injection pain was in the mild pain range for both anesthetic
combinations, with the exception of needle placement pain in females, which was
moderate. No significant differences in injection pain were seen between the two groups.
Anesthetic success was not significantly different between the anesthetic groups in any of
the teeth tested.
Summary and Conclusions: The combination of 3% mepivacaine and 2% lidocaine
with 1:100,000 epinephrine is equivalent to 2% lidocaine with 1:100,000 epinephrine in
terms of injection pain and pulpal anesthetic success for the IANB .
ii
DEDICATION
To Maxwell- you are a beautiful child, inside and out. You have changed my life in so
many ways. You are the reason for everything that I do, and I can’t wait to see what life
has in store for you.
To Philip- you are my best friend, a wonderful husband, and an amazing father. Thank
you for your constant support, and for loving me unconditionally.
To my parents- you were my first teachers. Thank you for instilling me with a love of
learning, and for always supporting me.
I love you all.
iii
ACKNOWLEDGEMENTS
Dr. Nusstein- It has been a pleasure working with you for the past three years. Thank you
for your constant encouragement and guidance. You have been a wonderful mentor, and
your dedication to this department is apparent in all of the hard work that you do. You
have certainly earned that golden squirrel!
Dr. Reader- Thank you for welcoming me to your endo family, and for always making
me laugh! I feel so lucky to have learned from the best. You are the reason that Ohio
State Endodontics has such an outstanding reputation.
Dr. Drum- Not only are you an amazing teacher, but a great friend. Thank you for sharing
your knowledge and for always being there. I hope you know how special you are to this
program.
Dr. Beck- Thank you for making the world of statistics a little less confusing! I’m sure I
couldn’t have completed this project without your help. It was a pleasure getting to know
you.
Dr. Fowler- I am so happy that you have found your niche in education! You are a
wonderful teacher, and this program is lucky to have you. Thank you for all of your
advice and for your friendship.
To my co-residents: Brett, Shayne, and Vivian- Thank you for two years of friendship,
laughter, and of course, tacos. I wish you all the best in your careers and in life.
Thank you to all of the dental students, especially: Chase, Jeff, Tommy, Sahar, Brandon,
Jason, and Kurt. Without you, I would probably still be pulp testing.
iv
VITA
July 22, 1985………………………………………. Born: Lima, Ohio
2003-2006…………………………………………..The Ohio State University
College of Arts and Sciences
2010…………………………………………………Doctor of Dental Surgery,
The Ohio State University
Columbus, Ohio
2013…………………………………………………Master of Science &
Specialization in Endodontics
Post-Doctoral Certificate,
The Ohio State University,
Columbus, Ohio
FIELD OF STUDY
Major Field: Dentistry
Specialization: Endodontics
v
TABLE OF CONTENTS
Page
Abstract……………………………………………………………………………………ii
Dedication……………………………………………………………………………...…iii
Acknowledgements……………………………………………………………………….iv
Vita…………………………………………………………………………………….…..v
Table of Contents………………………………………………………………………...vi
List of Tables…………………………………………………………………….............vii
List of Figures………………………………………………………………………….....ix
Chapters:
1. Introduction……………………………………………………………..1
2. Literature Review……………………………………………………….3
3. Materials and Methods………………………………………………..58
4. Results…………………………………………………………………64
5. Discussion……………………………………………………………..69
6. Summary and Conclusions…………………………………………..104
Appendices:
A. Tables………………………………………………………………..106
B. Figures…………………………………………………………….....125
C. Medical History Form………………………………………….……132
D. Consent Form…………………………………………………..……135
E. HIPAA Privacy Form……………………………………..…………142
F. Heft-Parker VAS Form…………………………………………..…..146
G. Electric Pulp Testing Form…………………………………...……..148
H. Raw Data……………………………………………………...……..152
References………………………………………………………………………………243
vi
LIST OF TABLES
Table
Page
5-1.
Needle insertion pain reported by category………………………….………..…74
5-2.
Needle placement pain reported by category………………………….…….…..76
5-3.
Solution deposition pain reported by category………………………………..…82
5-4.
Mean onset times for pulpal anesthesia of IANB……………………………..…94
5-5.
Incidence of anesthesia of slow onset for IANB…………………………….......98
5-6.
Incidence of non-continuous anesthesia for IANB…………………….……..….99
5-7.
Incidence of anesthesia of short duration with IANB……………….………….100
A-1.
Biographical data for all subjects…………………………………..………..….107
A-2.
Mean pain ratings for first injection………………………………………….....108
A-3.
Mean pain ratings for second injection………………………….………..…….109
A-4.
Injection pain (first injection)………………………………………..…………110
A-5.
Injection pain (second injection)……………………………..…………………111
A-6.
Anesthetic success………………………………………..………………..…...112
A-7.
Anesthetic failure……………………………………………..…………….......113
A-8.
Central incisors 80/80 pulp tester readings…………………………..……..….114
A-9.
Lateral incisors 80/80 pulp tester readings…………………………………..…115
A-10. First premolars 80/80 pulp tester readings…………………………..............…116
A-11. Second premolars 80/80 pulp tester readings………………………………..…117
A-12. First molars 80/80 pulp tester readings………………………………………....118
A-13. Second molars 80/80 pulp tester readings………………………………...…....119
A-14. Onset of anesthesia………………………………………………………......…120
A-15. Duration of anesthesia………………………..…………………………..……..121
A-16. pH of anesthetic solutions………………………..…………………………......122
vii
A-17. Pulpal anesthesia success rates with 2% lidocaine with 1:100,000 epinephrine and
with 3% mepivacaine for IANB……………………………………………………123
A-18. Pulpal anesthesia failure rates with 2% lidocaine with 1:100,000 epinephrine and
with 3% mepivacaine for IANB…………………………………………………....124
viii
LIST OF FIGURES
Figure
Page
1. Pulpal anesthesia by time for central incisor……………………………………....126
2. Pulpal anesthesia by time for lateral incisor……………………………………….127
3. Pulpal anesthesia by time for first premolar……………………………………….128
4. Pulpal anesthesia by time for second premolar…………………………………....129
5. Pulpal anesthesia by time for first molar…………………………………………..130
6. Pulpal anesthesia by time for second molar………………………………………..131
ix
INTRODUCTION
The inferior alveolar nerve (IAN) block is the most frequently used injection
technique for achieving local anesthesia for mandibular restorative and surgical
procedures. However, the IAN block does not always result in successful pulpal
anesthesia (1). Failure rates of 10% to 39% have been reported in experimental studies
(1). Clinical studies in endodontics (2-14) have found success with the IAN block
occurring between 15% and 57% of the time. Therefore, it would be advantageous to
improve the success rate of the inferior alveolar nerve block.
Some clinicians combine 3% mepivacaine plain with 2% lidocaine with
1:100,000 epinephrine for IAN blocks (15). The thought is that 3% mepivacaine has
more anesthetic molecules than 2% lidocaine because of its higher concentration and that
it also has a higher pH because it does not contain epinephrine. Both of these concepts
would supposedly provide more of the base molecules for the IAN block initially –
therefore potentiating the effect of administration of the second cartridge of 2% lidocaine
with 1:100,000 epinephrine. Two studies found that 3% mepivacaine was equivalent to
2% lidocaine with 1:100,000 epinephrine for an inferior alveolar nerve block (4,16).
Rood and coauthors (17) found there was no potentiation of lidocaine with epinephrine
by adding 4% prilocaine plain for dental extractions.
1
No objective study has combined 3% mepivacaine and 2% lidocaine with
1:100,000 epinephrine for inferior alveolar nerve blocks. Therefore, the purpose of this
prospective, randomized, double-blind study is to compare the degree of pulpal
anesthesia obtained with a combination 3% mepivacaine/2% lidocaine with 1:100,000
epinephrine formulation versus 2% lidocaine with 1:100,000 epinephrine/2% lidocaine
with 1:100,000 epinephrine formulation in inferior alveolar nerve blocks. Additionally,
we will study injection pain of the two sets of IAN blocks.
2
LITERATURE REVIEW
Local Anesthetics
MECHANISM OF ACTION OF LOCAL ANESTHETICS
The primary function of a local anesthetic is to reversibly block the initiation and
conduction of a nerve impulse (18, 19). The nerve impulse is dependent on the
concentration of specific electrolytes in the intracellular and extracellular fluid spaces, as
well as the permeability of the nerve membrane to these electrolytes (19). While the
membrane is freely permeable to potassium and chloride ions, it is only slightly
permeable to sodium ions. The resting potential of the membrane is maintained at -90
mV due to the high concentrations of K+ within the cell and Na+ outside the cell (18-21).
Stimulation or excitation of the nerve causes a transient widening of
transmembrane channels which allow sodium ions to pass through. This results in a
decrease in the negative transmembrane potential. If the potential change is great enough
to reach the firing threshold of -55 mV, membrane permeability to sodium increases
dramatically and a large influx of sodium ions occurs. This results in a reversed electrical
potential of +40 mV across the membrane (19-24). This process, known as
depolarization, takes approximately 0.3 milliseconds (20).
At this point the permeability of the membrane to K+ increases, resulting in the
efflux of potassium ions. The transmembrane channels enter an inactive state in which
3
they are unable to respond to another stimulus. This is known as the absolute refractory
period. By the time the membrane returns to a resting potential of -60 to -90 mV, the
channels have returned to a closed resting form (20, 22). This process of repolarization
occurs in approximately 0.7 milliseconds (20).
After the membrane has returned to its resting potential, a slight excess of sodium
exists within the nerve cell, and a slight excess of potassium exists extracellularly. The
sodium pump actively transfers sodium ions out of the cell using energy from the
oxidative metabolism of adenosine triphosphate (19, 20, 23). The electrical imbalance
that is created disrupts the resting equilibrium of the adjacent area of the nerve, causing
cycles of depolarization and repolarization that propagate an impulse along the nerve.
Due to the refractory period of each nerve segment, the conduction of the impulse can
only proceed in one direction (20).
Local anesthetics affect the nerve by reducing the passage of sodium into the cell
(18-20, 24-27). The specific action of local anesthetics on the nerve membrane has not
been clearly established (22-24, 28); however, there are currently two theories that may
explain the mechanism (20, 24, 28). The membrane expansion theory states that local
anesthetic molecules prevent an increase in membrane permeability to sodium ions by
diffusing into critical areas of the membrane and decreasing the diameter of sodium
channels. This is hypothesized to occur due to the distortion or expansion of membrane
proteins, leading to the inhibition of sodium passage and therefore, neural excitation (20,
23, 25). The specific receptor theory, which is more widely accepted, states that local
anesthetics bind to specific receptors on the internal surface of the open sodium channel.
4
This either blocks the sodium channels or causes them to close, resulting in
impermeability of the membrane to sodium ions (19, 20, 24, 27-29). Biotoxins, such as
tetrodotoxin and saxitoxin, support this theory as they have been shown to irreversibly
bind at a receptor site on the external surface of the nerve membrane (19, 27, 29-32).
PHARMACOLOGY OF LOCAL ANESTHETICS
The local anesthetic molecule consists of three components: a lipophilic aromatic
ring, an intermediate hydrocarbon chain, and a hydrophilic terminal amine group (19, 20,
22, 26). The aromatic ring makes the molecule lipid soluble, and can be enhanced by
aliphatic substitutions. Lipid solubility promotes diffusion through the nerve sheath and
allows more molecules to enter the neuron; therefore, greater lipid solubility makes the
local anesthetic more potent (26).
The intermediate chain contains either an ester or an amide linkage, and thus the
molecule is classified an amino-ester or an amino-amide anesthetic (20). Amino-ester
anesthetics, with the exception of topical benzocaine, are rarely used clinically today
(26). These compounds are hydrolyzed by plasma esterases to form para-aminobenzoic
acid, or PABA, which has been implicated in causing allergic reactions. Amino-amide
anesthetics, such as lidocaine and mepivacaine, are biotransformed in the liver and
excreted in the urine. PABA is not formed from amide anesthetics so allergic reactions
are extremely rare (19). Articaine is a unique amide anesthetic as it contains a thiophene
ring which allows the molecule to better diffuse through the lipid-rich nerve membrane,
5
and an ester group which facilitates hydrolyzation in the plasma before excretion by the
kidneys (26, 33).
The terminal amine group exists in either a tertiary or quaternary form, which
allows the local anesthetic to conform to a lipid-soluble or water-soluble state (26).
Alone, local anesthetics are weakly basic compounds which are insoluble in water (20).
To increase solubility and stability, they are formulated as hydrochloride salts (20, 26).
The majority of injectable local anesthetics are tertiary amines (18, 20). In solution, the
local anesthetic salt exists in two forms: the quaternary cation form which is positively
charged and therefore water soluble, and the tertiary base form which is uncharged and
lipid soluble (18, 19, 26, 27). The balance between the two forms is dependent on the
environmental pH (29). The pKa, or dissociation constant, is the pH at which 50% of
each form is present (19, 26, 27). Each local anesthetic has a specific pKa, and for most
anesthetic solutions it is between 7.5 and 9 (22, 27). When exposed to physiologic pH of
7.4, more of the uncharged base form of the anesthetic will be present and this form is
able to diffuse through the nerve sheath (19, 26). Once inside the nerve, equilibrium
between the two forms reoccurs and the charged cation form binds to the receptor site on
the nerve membrane to cause local anesthesia (19, 29).
SAFETY OF LOCAL ANESTHETICS
Many adverse reactions associated with local anesthetics are not due to the drugs
themselves (formulation), but to the drug concentration or the act of drug administration
(34, 35). Local complications, such as post-injection neuropathy or paresthesia, trismus,
6
hematoma, facial nerve paralysis, and soft tissue injury have been reported following
injections (34). In a study by Garisto et al. (35), 94.5% of reported adverse anesthetic
events were associated with mandibular nerve blocks; this trend has been reported by
other studies as well (36, 37).
Paresthesias may manifest as total loss of sensation, burning or tingling feeling, or
pain in response to normal stimuli (38). It is speculated that the incidence of non-surgical
paresthesia in dentistry occurs in 1:785,000 to 1:26,000 patients, but the actual number is
unknown (34, 36, 39). While the exact cause of paresthesia is unknown, it appears to be
associated with local anesthetic administration and is almost exclusively related to the
inferior alveolar nerve block injection (34, 36). Current hypotheses include direct trauma
to the nerve from the needle, hemorrhage into the neural sheath, and neurotoxicity
associated with a local anesthetic (34, 38). Some authors have concluded that the
incidence of paresthesia is associated with higher concentrations of local anesthetic (35,
38). Approximately 85-94% of paresthesias resolve spontaneously within 8 weeks, but
two-thirds of those who do not recover quickly may never recover (39).
Trismus and soft tissue injury may occur following the inferior alveolar nerve
(IAN) block injection; this can be caused by hematoma formation subsequent to damage
to the inferior alveolar artery or vein, multiple injections or intramuscular injection
causing damage to the muscle fibers, or excessive volume of local anesthetics (40, 41).
Facial nerve paralysis has been reported in patients when local anesthetic was deposited
into the parotid gland; this resolved as the anesthetic was redistributed (40).
7
A true allergic reaction to amide local anesthetics is extremely rare, as these
reactions are mainly seen with ester anesthetics or anesthetics stored in multi-dose vials
with paraben preservatives (40-42). The most common sign of an allergic reaction is a
skin reaction; however, bronchospasm and anaphylaxis can occur (40). Adverse reactions
such as fear and anxiety, intravascular injection, toxic overdose, and sensitivity to
epinephrine are often mistaken for a true allergy (41). Some patients may have an allergic
reaction caused by sulfite preservatives in anesthetic solutions that contain epinephrine
(40, 41). Mild allergic reactions can be treated with antihistamines, while acute reactions
necessitate activation of an emergency response system (41).
Toxicity from local anesthetics can be seen following excessive dosing,
intravascular injection, or with rapid systemic absorption due to the absence of a
vasoconstrictor (41). Symptoms are dose-dependent and include drowsiness, numbness of
the lips and tongue, metallic taste in the mouth, double vision, nystagmus, tremors, and
eventual grand mal convulsions and impaired circulation due to anesthetic-induced
cardiovascular depression (42). Mepivacaine and prilocaine are commonly associated
with toxicity due to the higher concentration of anesthetic and lack of epinephrine;
however, toxicity can result from an overdose with any anesthetic (20, 41). Overdosage is
reported more often in children when doses are not adjusted to the child’s weight, or
when an anesthetic without a vasoconstrictor is selected and multiple injections are given
due to the short duration of these anesthetics. In adults, the maximum recommended dose
of lidocaine is 500 mg (6.6 mg/kg), mepivacaine is 400 mg (6.6 mg/kg), and articaine is
500 mg (7.0 mg/kg) (20).
8
Vasoconstrictors, such as epinephrine, are added to local anesthetics to improve
efficacy, increase the duration of anesthesia, and lessen systemic toxicity (28, 40, 42).
Epinephrine stimulates alpha-1 and alpha-2 receptors in the walls of arterioles causing
them to constrict, which decreases blood flow locally (43). While this is beneficial in
slowing the absorption of local anesthetic, it can be dangerous in patients with reduced
cardiovascular function as epinephrine also stimulates beta-1 receptors causing increased
heart rate and contractility (40, 43, 44). It is recommended that a local anesthetic
containing epinephrine be limited to two 1.8 mL cartridges in patients with
cardiovascular disease (40). In patients taking non-selective beta blockers, epinephrine
administration may result in a significant increase of blood pressure. Drug interactions
may also be seen in patients taking tri-cyclic antidepressants (43). Adverse effects of
epinephrine include tachycardia, tremor, palpitations, arrhythmia, anxiety, headache, and
hypertension (40).
Pregnancy is a relative contraindication to elective dental care; however, local
anesthetics and vasopressors may be administered during any trimester (20). All local
anesthetics are able to cross the placental barrier by passive diffusion (45). Lidocaine is
listed as a Category B drug by the FDA, which states “Animal studies show no risk or
adverse fetal effects but controlled human first trimester studies not available/do not
confirm; no evidence of second or third trimester risk; fetal harm possible but unlikely”.
Mepivacaine is classified as Category C, and its use is recommended with caution (20).
Possible complications of mepivacaine include fetal bradycardia. The use of benzocaine
is also cautioned in pregnant patients due to the risk of methemoglobinemia and possible
9
hypoxemia in both the mother and fetus. High amounts of vasoconstrictors can decrease
uterine blood flow, but up to 0.1 mg of epinephrine can be used safely in healthy
pregnant patients (45).
INFERIOR ALVEOLAR NERVE BLOCK
The most common injection for obtaining mandibular anesthesia is the inferior
alveolar nerve block (20). The site of injection is the soft tissue overlying the medial
surface of the ramus, lateral to the pterygomandibular raphe, at a height determined by
the coronoid notch on the anterior border of the ramus. Once the subject’s mouth is wide
open, the thumb of the non-injecting hand is placed over the pterygomandibular triangle
and then pulled laterally until a depression in the anterior border of the ramus is felt. The
posterior portion of the ramus is palpated with the first or second finger of the noninjecting hand until a slight depression is located. The vertical height of the injection site
is determined by the line between the thumb and the finger. The direction of the needle
insertion is from the contralateral mandibular premolars and aligned parallel to the
occlusal plane (46). The needle is advanced until bone is sounded, then retracted 1 mm
before aspiration and injection into the pterygomandibular space (20). The conventional
inferior alveolar nerve block will anesthetize the inferior alveolar nerve, mental nerve,
and the lingual nerve. This would include pulpal anesthesia of mandibular molars,
premolars, and incisors on the injected side, as well as the associated supporting bony and
periodontal structures to the midline. It would also anesthetize the buccal and labial soft
10
tissues and chin to the midline, and the contralateral anterior two-thirds of the tongue
(20).
INJECTION PAIN
Local anesthetics are the most important and most frequently used drugs in a
dental practice. While their use leads to a relatively painless dental procedure, the
administration of anesthetics can be a source of anxiety and pain for many patients (4749). Different methods have been studied in an attempt to reduce pain during each stage
of an injection: insertion of the needle into the mucosa, placement of the needle to the
target site, and deposition of the local anesthetic solution.
NEEDLE INSERTION
The use of topical anesthetics has been studied to determine their effect on needle
insertion pain for the inferior alveolar nerve block (IANB) injection. Nusstein and Beck
(47) evaluated the effectiveness of 20% benzocaine as a topical anesthetic in a
retrospective study. One thousand six hundred and thirty-five IANB injections were
given; 470 of these received topical anesthetic, whereas 1165 did not. While 14-22% of
subjects reported moderate-to-severe pain to needle insertion, there was no significant
difference between the two groups for the IANB injection.
The following studies evaluated needle insertion pain for IANB injections
utilizing 2% lidocaine with 1:100,000 epinephrine. The type of anesthetic being injected
should not have an impact on needle insertion pain. Factors that must be considered when
11
evaluating needle insertion pain include needle gauge, use of topical anesthetic, operator
differences, and gender of the subject.
Childers (50) studied the anesthetic efficacy of the periodontal ligament (PDL)
injection after an IANB injection. Forty asymptomatic subjects recorded pain of needle
insertion with a 27-gauge needle during the IANB injection on a four-point scale (0= no
pain, 1= mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic was used in
this study. No pain during needle insertion was reported in 25% of injections, mild pain
in 58.75%, moderate pain in 13.75%, and severe pain in 2.5% of injections.
Dunbar (51) evaluated the anesthetic efficacy of the intraosseous injection
following an IANB injection. Forty asymptomatic subjects recorded pain of needle
insertion with a 27-gauge needle during the IANB injection on a four-point scale (0= no
pain, 1= mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic was used in
this study. No pain during needle insertion was reported in 43% of injections, mild pain
in 53%, moderate pain in 5%, and severe pain in 0% of injections.
Reitz (52) evaluated the anesthetic efficacy of the intraosseous injection following
an IANB injection. Thirty-eight asymptomatic subjects recorded pain of needle insertion
with a 27-gauge needle during the IANB injection on a four-point scale (0= no pain, 1=
mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic was used in the study.
No pain during needle insertion was reported in 32% of injections, mild pain in 58%,
moderate pain in 10%, and severe pain in 0% of injections.
Clark (53) evaluated the anesthetic efficacy of the mylohyoid nerve (MN) block
and the combination IANB/MN block. Thirty asymptomatic subjects recorded pain of
12
needle insertion with a 27-gauge needle during the IANB injection utilizing a four-point
scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic
was used in this study. No pain during needle insertion was reported in 28.8% of
injections, mild pain in 53.1%, moderate pain in 14.4%, and severe pain in 3.8% of
injections.
Willett (54) studied the anesthetic efficacy of diphenhydramine and the
combination diphenhydramine/lidocaine for the IANB injection. Thirty asymptomatic
subjects recorded pain of needle insertion with a 27-gauge needle on a four-point scale
(0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic was
used in this study. No pain during needle insertion was reported in 29% of injections,
mild pain in 58%, moderate pain in 12%, and severe pain in 1% of injections.
Whitcomb and coauthors (55) evaluated the anesthetic efficacy of sodium
bicarbonate buffered 2% lidocaine with 1:100,000 epinephrine versus a non-buffered
solution for IANB injections. No topical anesthetic was used in this study. Subjects were
asked to rate the discomfort of needle insertion with a 27-gauge needle on a 4-point scale
(0= no pain, 1= mild, 2= moderate, 3= severe). Patients reported no pain to needle
insertion in 40% of injections, mild pain in 55%, moderate pain in 5%, and severe pain in
0% of injections.
Simon and coauthors (56) evaluated the anesthetic efficacy of the IANB
administered with a peripheral nerve stimulator. Forty-six asymptomatic patients each
received a conventional IANB with a 22-gauge needle, and an IANB administered with
the help of a peripheral nerve stimulator and a 22-gauge needle. No topical anesthetic
13
was used in this study. Immediately after the injections, the subjects rated the pain of
needle insertion on a 4-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3=
severe pain). Needle insertion pain with the conventional IANB was rated as no pain by
16% of subjects, mild pain by 53%, moderate pain by 29%, and severe pain by 3%.
Wolf (57) evaluated the anesthetic efficacy of mannitol and lidocaine with
epinephrine in IANB injections with a 27-gauge needle. Forty asymptomatic subjects
rated the pain of needle insertion on a 4-point scale (0= no pain, 1= mild pain, 2=
moderate pain, 3= severe pain). No topical anesthetic was used in this study. No pain to
needle insertion was reported in 31% of injections, mild pain in 55%, moderate pain in
14%, and severe pain in 0% of injections.
Guglielmo (58) evaluated the anesthetic efficacy of a supplemental intraosseous
injection following an IANB injection with a 27-gauge needle. Forty asymptomatic
subjects recorded the pain of needle insertion during the IANB injection on a 4-point
scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). No topical anesthetic
was used in this study. No pain to needle insertion was reported in 7% of injections, mild
pain in 67%, moderate pain in 26%, and severe pain in 0% of injections.
Mikesell (59) evaluated the anesthetic efficacy of articaine and lidocaine for
IANB injections. Fifty-seven asymptomatic subjects recorded the pain of needle insertion
with a 27-gauge needle during the IANB injection on a 170-mm Heft-Parker VAS form.
Topical anesthetic gel (20% benzocaine) was placed at the injection site for 60 seconds.
No pain was reported in 6% of injections, mild pain in 65%, moderate pain in 29%, and
14
severe pain in 0% of injections. The mean VAS score was 38.7 mm, which was in the
mild range.
Goodman (60) evaluated the anesthetic efficacy of lidocaine and meperidine for
IAN blocks. Fifty-two asymptomatic subjects recorded the pain of needle insertion with a
27-gauge needle during the IANB injection on a 170-mm Heft-Parker VAS form. Topical
anesthetic gel (20% benzocaine) was placed at the injection site for 60 seconds. No pain
during needle insertion was reported in 4% of injections, mild pain in 84%, moderate
pain in 11%, and severe pain in 1% of injections. The mean VAS score was 37.5 mm,
which was in the mild range.
Steinkruger (61) evaluated the significance of needle bevel orientation in
achieving a successful IAN block. Fifty-one asymptomatic subjects each recorded the
pain of needle insertion with a 27-gauge needle during the IANB injection on a 170-mm
Heft-Parker VAS form. Topical anesthetic gel (20% benzocaine) was placed at the
injection site for 60 seconds. Regarding the one-stage injection, no pain during needle
insertion was reported in 7.8% of injections, mild pain in 84.3%, moderate pain in 7.8%,
and severe pain in 0% of injections. The mean VAS score was 34 mm, which was in the
mild range.
Elmore (62) evaluated the anesthetic reversal agent, Oraverse™, following an
IANB injection. Ninety asymptomatic subjects rated the pain of needle insertion with a
27-gauge needle on a 170-mm Heft Parker VAS form. Topical anesthetic (20%
benzocaine) was placed at the injection site for 60 seconds. The mean VAS score was 44
15
mm, which was in the mild range. Subjects reported none-to-mild pain in 64% of
insertions, and moderate-to-severe pain in 36% of insertions.
Vreeland and coauthors (63) evaluated the anesthetic efficacy of different
volumes and concentrations of lidocaine in the IAN block. Thirty asymptomatic subjects
each received an IANB injections of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine,
3.6 mL of 2% lidocaine with 1:200,000 epinephrine, and 1.8 mL of 4% lidocaine with
1:100,000 epinephrine at 3 separate appointments. Topical anesthetic (20% benzocaine)
was placed at the injection site for 30 seconds. Each subject was asked to rate the pain of
needle insertion with a 27-gauge needle on a three-point scale (1= no-to-mild pain, 2=
moderate pain, 3= severe pain). Although the phases of needle insertion and needle
placement were not separated in this study, 63.3% of subjects reported no-to-mild pain,
31.1% reported moderate pain, and 5.5% reported severe pain.
Hinkley (64) evaluated 4% prilocaine with 1:200,000 epinephrine, 2%
mepivacaine with 1:20,000 levonordefrin, and 2% lidocaine with 1:100,000 epinephrine
for the IANB injection. Thirty asymptomatic subjects rated the pain of needle insertion
with a 27-gauge needle a 4-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3=
severe pain); however, there was no distinction between needle insertion and needle
placement in this study. No topical anesthetic was used in this study. No pain to needle
insertion was reported in 21% of injections, mild pain in 67%, moderate pain in 11%, and
severe pain in 1% of injections.
McLean (65) evaluated the efficacy of 4% prilocaine, 3% mepivacaine, and 2%
lidocaine solutions for the IANB injection. Thirty asymptomatic subjects recorded the
16
pain of needle insertion with a 27-gauge needle on a 4-point scale (0= no pain, 1= mild
pain, 2= moderate pain, 3= severe pain); however, there was no distinction between
needle insertion and needle placement in this study. No topical anesthetic was used. No
pain to needle insertion was reported in 9% of injections, mild pain in 50%, moderate
pain in 34%, and severe pain in 7% of injections.
Yonchak (66) studied the anesthetic efficacy of unilateral and bilateral IAN
blocks to determine cross innervation in anterior teeth. Forty asymptomatic subjects
recorded the pain of needle insertion with a 27-gauge needle on a 4-point scale (0= no
pain, 1= mild pain, 2= moderate pain, 3= severe pain); however, there was no distinction
between needle insertion and needle placement in this study. No topical anesthetic was
used in this study. No pain to needle insertion was reported in 6% of injections, mild pain
in 49%, moderate pain in 40%, and severe pain in 5% of injections.
Goldberg and coauthors (67) compared the conventional inferior alveolar, GowGates, and Vazirani-Akinosi techniques for mandibular anesthesia. Forty asymptomatic
subjects recorded the pain of needle insertion with a 27-gauge needle on a 4-point scale
(0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain); however, there was no
distinction between needle insertion and needle placement in this study. Topical
anesthetic gel (20% benzocaine) was placed at the injection site for 60 seconds. Needle
insertion for the IANB was reported as none-to-mild pain in 77%, moderate pain in 22%,
and severe pain in 0% of injections.
In the studies reviewed, no significant difference was seen with the use of topical
anesthetic to reduce the pain of needle insertion. Although there were some operator
17
differences, a majority of subjects reported no-to-mild pain. Only one study analyzed the
effect of gender on pain reported, but no difference was seen in the pain reported between
males and females (62). A 27-gauge needle was used in all of the above studies;
therefore, no differences were seen regarding needle gauge.
NEEDLE PLACEMENT
Studies have looked at the pain of needle placement to the injection target site.
The main method attempted to reduce pain during this phase of an IANB injection has
been to deposit anesthetic solution as the needle is moved through the soft tissues. A twostage injection technique has also been studied in an attempt to reduce the pain of needle
placement during an IANB injection. The following studies looked at the pain of needle
placement during an IANB injection.
Childers (50) studied the anesthetic efficacy of the periodontal ligament (PDL)
injection after an IANB. Forty asymptomatic subjects recorded pain of needle placement
during an IANB injection on a four-point scale (0= no pain, 1= mild pain, 2= moderate
pain, 3= severe pain). No anesthetic was deposited until the target site was reached. No
pain during needle placement was reported in 17.5% of injections, mild pain in 47.5%,
moderate pain in 35%, and severe pain in 0% of injections.
Dunbar (51) evaluated the anesthetic efficacy of the intraosseous injection
following an IAN block. Forty asymptomatic subjects recorded pain of needle placement
during a conventional IANB injection on a four-point scale (0= no pain, 1= mild pain, 2=
moderate pain, 3= severe pain). No anesthetic was deposited until the target site was
18
reached. No pain during needle placement was reported in 14% of injections, mild pain in
63%, moderate pain in 23%, and severe pain in 1% of injections.
Reitz (52) evaluated the anesthetic efficacy of the intraosseous injection following
an IANB injection. Thirty-eight asymptomatic subjects recorded pain of needle
placement during a conventional IANB injection on a four-point scale (0= no pain, 1=
mild pain, 2= moderate pain, 3= severe pain). No anesthetic was deposited until the target
site was reached. No pain during needle placement was reported in 40% of injections,
mild pain in 45%, moderate pain in 15%, and severe pain in 0% of injections.
Clark (53) evaluated the anesthetic efficacy of the mylohyoid nerve (MN) block
and the combination IANB/MN block. Thirty asymptomatic subjects recorded pain of
needle placement during a conventional IANB injection on a four-point scale (0= no pain,
1= mild pain, 2= moderate pain, 3= severe pain). No anesthetic was deposited until the
target site was reached. No pain during needle placement was reported in 26% of
injections, mild pain in 36%, moderate pain in 27%, and severe pain in 11% of injections.
Willett (54) studied the anesthetic efficacy of lidocaine, diphenhydramine, and the
combination of diphenhydramine/lidocaine for the IANB injection. Thirty asymptomatic
subjects recorded pain of needle placement on a four-point scale (0= no pain, 1= mild
pain, 2= moderate pain, 3= severe pain). No anesthetic was deposited until the target site
was reached. No pain during needle placement was reported in 12.9% of injections, mild
pain in 42.6%, moderate pain in 38.6%, and severe pain in 5.9% of injections.
Simon and coauthors (56) evaluated the anesthetic efficacy of the IANB
administered with the aid of a peripheral nerve stimulator. Forty-six asymptomatic
19
patients each received a conventional IANB and an IANB administered with the aid of a
peripheral nerve stimulator. No anesthetic was deposited until the target site was reached.
Immediately after the injection, the subject rated the pain of needle placement on a 4point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). Needle
placement pain with the conventional IANB was rated as no pain by 11% of subjects,
mild pain by 58%, moderate pain by 32%, and severe pain by 0%.
Guglielmo (58) evaluated the anesthetic efficacy of a supplemental intraosseous
injection following an IANB injection. Forty asymptomatic subjects recorded the pain of
needle placement during an IANB injection on a 4-point scale (0= no pain, 1= mild pain,
2= moderate pain, 3= severe pain). No anesthetic was deposited until the target site was
reached. No pain to needle placement was reported in 27% of injections, mild pain in
51%, moderate pain in 22%, and severe pain in 0% of injections.
Elmore (62) evaluated the anesthetic reversal agent, Oraverse™, following an
IANB injection. Ninety asymptomatic subjects rated the pain of needle placement with a
on a 170-mm Heft-Parker VAS form. No anesthetic was deposited until the target site
was reached. Subjects reported none-to-mild pain in 51% of needle placements, and
moderate-to-severe pain in 49% of needle placements. The mean VAS score was 54.3
mm, which is in the moderate pain range.
Mikesell (59) evaluated the anesthetic efficacy of articaine and lidocaine for
IANB injections. Fifty-seven asymptomatic subjects recorded the pain of needle
placement during the IANB injection on a 170-mm Heft-Parker VAS form. While
advancing the needle, 0.2 mL of the anesthetic solution was deposited. Using 2%
20
lidocaine with 1:100,000 epinephrine, no pain during needle placement was reported in
0% of injections, mild pain in 40.4%, moderate pain in 54.4%, and severe pain in 5.3% of
injections. The mean VAS score was 60.6 mm, which was in the moderate pain range.
Goodman (60) evaluated the anesthetic efficacy of lidocaine and meperidine for
IAN blocks. Fifty-two asymptomatic subjects recorded the pain of needle placement
during the IANB injection on a 170-mm Heft-Parker VAS form. While advancing the
needle, 0.2 mL of the anesthetic solution was deposited. Using 2% lidocaine with
1:100,000 epinephrine, no pain during needle placement was reported in 7% of
injections, mild pain in 64%, moderate pain in 24%, and severe pain in 5% of injections.
The mean VAS score was 47.5 mm, which was in the mild pain range.
Whitcomb and coauthors (55) evaluated the anesthetic efficacy of sodium
bicarbonate buffered 2% lidocaine with 1:100,000 epinephrine versus a non-buffered
solution for IANB injections. While advancing the needle to the target site, 0.2 mL of the
solution was deposited. Subjects were asked to rate the discomfort of needle placement
on a 4-point scale (0= no pain, 1= mild, 2= moderate, 3= severe). No pain from needle
placement was reported by 28% of subjects, while mild pain was reported by 50%,
moderate pain by 20%, and severe pain by 2%.
Wolf (57) evaluated the anesthetic efficacy of 1.8 mL of 2% lidocaine with
1:100,000 epinephrine, 2.84 mL of 2% lidocaine with 1:100,000 epinephrine with 0.5M
mannitol, and 5 mL of 2% lidocaine with 1:100,000 epinephrine with 0.5M mannitol in
IANB injections. Forty asymptomatic subjects rated the pain of needle placement on a 4point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). As the needle
21
was advanced to the target site, 0.2 mL of anesthetic solution was deposited. Regarding
the lidocaine solution, no pain to needle placement was reported in 30% of injections,
mild pain in 52.5%, moderate pain in 17.5%, and severe pain in 0% of injections.
Regarding the 2.84 mL lidocaine plus mannitol solution, no pain to needle placement was
reported by 30% of subjects, mild pain by 50%, moderate pain by 20%, and severe pain
by 0%. Regarding the 5 mL lidocaine plus mannitol solution, no pain was reported by
22.5% of subjects, mild pain by 50%, moderate pain by 25%, and severe pain by 2.5% of
subjects. There were no significant differences in needle placement pain between the
three solutions.
Nusstein and coauthors (68) evaluated the effects of a 2-stage injection technique
on IANB injection pain. Fifty-one asymptomatic subjects were each given an injection of
2.2 mL of 2% lidocaine with 1:100,000 epinephrine at two separate appointments in a
crossover design. A traditional one-stage IANB injection was given with 0.4 mL of
anesthetic deposited over 10 seconds during needle placement, and the remaining 1.8 mL
of solution deposited at target site over 1 minute. A 2-stage IANB injection was given
with 0.4 mL of anesthetic deposited over 1 minute after initial penetration of 2-3 mm.
After waiting 5 minutes, the needle was then reinserted and the remaining 1.8 mL of
solution was deposited at the target site over 1 minute. Subjects were asked to rate the
pain of needle placement on a 170-mm Heft-Parker VAS. Needle placement pain for the
one-stage injection was reported as no pain by 0% of subjects, mild pain by 64.7%,
moderate pain by 33.3%, and severe pain by 2% of subjects. The mean VAS score for the
one-stage injection was 53 mm, which was in the mild range. Needle placement pain for
22
the two-stage injection was reported as no pain by 27.5% of subjects, mild pain by 51%,
moderate pain by 21.6%, and severe pain by 0% of subjects. The mean VAS score for the
two-stage injection was 33 mm, which was in the mild range. No significant difference
was noted between techniques, except needle placement for women was rated as
significantly less painful with the 2-stage technique.
Pain during needle placement is reported as none-to-mild by a majority of patients
receiving the IANB injection. It appears that this stage of injection is slightly more
painful than needle insertion. A two-stage injection technique resulted in significantly
less needle placement pain for women (68); however, injecting a small amount of
anesthetic during needle placement did not result in a less painful injection (55, 57, 59,
60). Elmore (62) evaluated the effect of gender on reported pain during needle placement
in his study and found no difference. One potential confounding factor appears to be the
operator- the person giving the injection. If all variables in the above-listed studies are
controlled (ex- needle size, injection type, injection technique, etc.) operator appears to
have a large impact; that is, some operators appear to have caused more moderate-tosevere pain during needle insertion than others. Further research needs to be conducted to
look at this aspect.
SOLUTION DEPOSITION
Several factors could affect the pain reported with anesthetic solution deposition
for the IANB injection. These include the speed of the solution deposition, the type of
anesthetic utilized, the volume of anesthetic injected, the presence or absence of a
23
vasoconstrictor, the scale used to record pain, any alterations or additives to the solution,
and even the gender of the subject. In reviewing the literature for data on this subject, one
must take all of these factors into consideration when attempting to compare results
between studies.
Vreeland and coauthors (63) evaluated the anesthetic efficacy of different
volumes and concentrations of lidocaine in the IAN block. Thirty asymptomatic subjects
each received an IANB injections of A: 1.8 mL of 2% lidocaine with 1:100,000
epinephrine, B: 3.6 mL of 2% lidocaine with 1:200,000 epinephrine, and C: 1.8 mL of
4% lidocaine with 1:100,000 epinephrine at 3 separate appointments. The entire
anesthetic solution was deposited over 2 minutes, regardless of volume. Each subject was
asked to rate the pain of injection of the solution on a three-point scale (1= none-to-mild
pain, 2= moderate pain, 3= severe pain). Regarding Solution A, 66.7% of subjects
reported no to mild pain, 26.7% reported moderate pain, and 6.7% reported severe pain.
Regarding Solution B, 63.3% of subjects reported none-to-mild pain, 30% reported
moderate pain, and 6.7% reported severe pain. Regarding Solution C, 60% of subjects
reported none-to-mild pain, 33.3% reported moderate pain, and 6.7% reported severe
pain. The authors concluded that there were no significant differences in pain of solution
deposition between any of the three anesthetic solutions.
Hinkley (64) evaluated anesthetic efficacy of 4% prilocaine with 1:200,000
epinephrine, 2% mepivacaine with 1:20,000 levonordefrin, and 2% lidocaine with
1:100,000 epinephrine for the IAN block. Thirty asymptomatic subjects were given an
IANB injection with 1.8 mL of one of the anesthetic solutions at a rate of 1 mL per
24
minute at each appointment. Subjects recorded the pain of solution injection on a fourpoint scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). With the
prilocaine solution, no pain was reported by 46.7% of subjects, mild pain by 43.3%,
moderate pain by 10%, and severe pain by 0% of subjects. With the mepivacaine
solution, no pain was reported by 46.7% of subjects, mild pain by 40%, moderate pain by
13.3%, and severe pain by 0% of subjects. With the lidocaine solution, no pain was
reported by 56.7% of subjects, mild pain by 33.3%, moderate pain by 10%, and severe
pain by 0% of subjects. There were no significant differences in pain of solution
deposition found between the three solutions.
Nist and coauthors (69) evaluated the anesthetic efficacy of the incisive nerve
(IN) block and combination IANB/IN blocks. An IANB injection of 3.6 mL of 2%
lidocaine with 1:100,000 epinephrine was given over 2 minutes. Forty subjects recorded
the pain of solution injection on a four-point scale (0= no pain, 1= mild pain, 2=
moderate pain, 3= severe pain). No pain was reported by 19% of subjects, 56% reported
mild pain, 23% reported moderate pain, and 2% reported severe pain.
McLean (65) evaluated the efficacy of prilocaine, mepivacaine, and lidocaine
solutions for the IAN block. Thirty asymptomatic subjects were given IANB injections of
1.8 mL of 4% prilocaine plain, 3% mepivacaine plain, and 2% lidocaine with 1:100,000
epinephrine at three successive appointments. The anesthetic solution was given at a rate
of 1 mL per minute. Thirty subjects recorded the pain of solution injection on a four-point
scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). With the prilocaine
solution, no pain was reported by 43.4% of subjects, mild pain by 30%, moderate pain by
25
23.3%, and severe pain by 3.3% of subjects. With the mepivacaine solution, no pain was
reported by 33.3% of subjects, mild pain by 40%, moderate pain by 20%, and severe pain
by 6.7% of subjects. With the lidocaine solution, no pain was reported by 33.3% of
subjects, mild pain by 36.7%, moderate pain by 20%, and severe pain by 10% of subjects.
There were no significant differences in the pain of injection for the three solutions.
Childers (50) studied the anesthetic efficacy of the periodontal ligament (PDL)
injection after an IAN block. For each IANB injection, 1.8 mL of 2% lidocaine with
1:100,000 epinephrine was deposited over a period of 2 minutes. Forty asymptomatic
subjects recorded the pain of solution deposition on a four-point scale (0= no pain, 1=
mild pain, 2= moderate pain, 3= severe pain). No pain was reported by 35% of subjects,
mild pain by 47.5%, moderate pain by 17.5%, and severe pain by 0% of subjects.
Dunbar (51) evaluated the anesthetic efficacy of the intraosseous injection after an
IAN block. Forty asymptomatic subjects were given an IANB injection with 1.8 mL of
2% lidocaine with 1:100,000 epinephrine over a period of 2 minutes. Subjects were asked
to record the pain of solution deposition on a four-point scale (0= no pain, 1= mild pain,
2= moderate pain, 3= severe pain). No pain was reported in 34% of injections, mild pain
in 45%, moderate pain in 21%, and severe pain in 0% of subjects.
Reitz (52) evaluated the anesthetic efficacy of the intraosseous injection following
an IANB injection. For each IANB injection, 1.8 mL of 2% lidocaine with 1:100,000
epinephrine was deposited over one minute. Thirty-eight asymptomatic subjects recorded
pain of solution deposition on a four-point scale (0= no pain, 1= mild pain, 2= moderate
26
pain, 3= severe pain). No pain during solution deposition was reported in 82% of
injections, mild pain in 17%, moderate pain in 1%, and severe pain in 0% of injections.
Clark (53) evaluated the anesthetic efficacy of the mylohyoid nerve (MN) block
and the combination IANB/MN block. Each IANB injection was given with 3.6 mL of
2% lidocaine with 1:100,000 epinephrine deposited over a period of 2 minutes. Thirty
asymptomatic subjects recorded pain of solution deposition on a four-point scale (0= no
pain, 1= mild pain, 2= moderate pain, 3= severe pain). No pain was reported by 17% of
subjects, mild pain by 41%, moderate pain by 27%, and severe pain by 15% of subjects.
Yonchak (66) studied the anesthetic efficacy of unilateral and bilateral IAN
blocks to determine cross innervation in anterior teeth. Forty asymptomatic subjects were
given an IANB injection with 3.6 mL of 2% lidocaine with 1:100,000 epinephrine, which
was deposited over 2 minutes. Subjects were asked to record the pain of solution
deposition on a four-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe
pain). No pain was reported by 39.2% of subjects, mild pain by 54.2%, moderate pain by
7.5%, and severe pain by 0% of subjects.
Mikesell (59) evaluated the anesthetic efficacy of 2% lidocaine with 1:100,000
epinephrine and 4% articaine with 1:100,000 epinephrine for IAN blocks. Each IANB
injection used 1.8 mL of anesthetic solution and was given over a period of 1 minute.
Immediately following the injection, subjects rated the pain of solution deposition on a
170-mm Heft-Parker VAS form. Regarding the lidocaine solution, no pain was reported
by 9% of subjects, mild pain by 72%, moderate pain by 18%, and severe pain by 2% of
subjects. The mean VAS score with lidocaine was 31.5 mm, which was in the mild range.
27
Regarding the articaine solution, no pain was reported by 12% of subjects, mild pain by
54%, moderate pain by 30%, and severe pain by 4%. The mean VAS score with articaine
was 39.1 mm, which was in the mild range. There were no significant differences in pain
from solution deposition between the two anesthetics.
Goodman (60) evaluated the anesthetic efficacy of lidocaine and meperidine for
IAN blocks. Fifty-two asymptomatic subjects randomly received an IANB injection of
either 1.8 mL of 2% lidocaine with 1:100,000 epinephrine or 3.6 mL of 2% lidocaine
with 1:100,000 epinephrine plus 36 mg of meperidine at two separate appointments. The
anesthetic solution was deposited over 2 minutes regardless of volume. Immediately
following the injection, each subject rated the pain for solution deposition on a 170-mm
Heft-Parker VAS form. Regarding the lidocaine solution, no pain was rated by 8% of
subjects, mild pain by 75%, moderate pain by 12%, and severe pain by 6% of subjects.
The mean VAS score with lidocaine was 40.3 mm, which was in the mild range.
Regarding the lidocaine/meperidine solution, no pain was rated by 4% of subjects, mild
pain by 60%, moderate pain by 25%, and severe pain by 12% of subjects. The mean VAS
score with the lidocaine/meperidine combination was 55.4 mm, which was in the
moderate range. The pain of solution deposition for lidocaine was significantly less than
that of the lidocaine/meperidine combination injection.
Kanaa and coauthors (70) evaluated the influence of the speed of injection on
anesthetic efficacy of the IAN block. Thirty-eight asymptomatic subjects received IANB
injections of 2 mL 2% lidocaine with 1:80,000 epinephrine at two separate appointments.
The subjects were randomly assigned to groups in which a fast injection was deposited
28
over 15 seconds, and a slow injection was deposited over 60 seconds. Subjects were
asked to record the pain of local anesthetic deposition on a 100-mm VAS form.
Regarding the slow injection, discomfort ranged from 0-65 mm with a mean of 20.9 mm.
During the fast injection, reported pain ranged from 3-73 mm with a mean of 30.5 mm.
The fast injection was determined to be significantly more painful to subjects.
Steinkruger (61) evaluated the significance of needle bevel orientation in
achieving a successful IAN block. Fifty-one asymptomatic subjects each received an
IANB injection with 2.2 mL of 2% lidocaine with 1:100,000 epinephrine. During the
one-stage injection, the clinician injected 0.4 mL of anesthetic over a 10-second period
while advancing the needle, then deposited the remaining 1.8 mL of anesthetic over one
minute. Subjects rated no pain in 15.7% of injections, mild pain in 68.6%, moderate pain
in 15.7%, and severe pain in 0% of one-stage injections. The mean VAS score for the
one-stage injection was 33 mm, which was in the mild range. During the two-stage
injection, 0.4 mL of anesthetic was deposited over one minute after initial penetration of
2-3 mm. After waiting 5 minutes, the needle was then reinserted and the remaining 1.8
mL of solution was deposited at the target site over one minute. Subjects rated no pain in
15.7% of injections, mild pain in 70.6%, moderate pain in 13.7%, and severe pain in 0%
of two-stage injections. The mean VAS score for the two-stage injection was 35 mm,
which was in the mild range. No significant differences in solution deposition pain were
found between the two groups.
Goldberg and coauthors (67) compared the anesthetic efficacy of the conventional
inferior alveolar, Gow-Gates, and Vazirani-Akinosi techniques for mandibular
29
anesthesia. Forty asymptomatic subjects were injected with 3.6 mL of 2% lidocaine with
1:100,000 epinephrine over a period of 2 minutes. Immediately after the nerve block,
each subject rated the pain for solution deposition of the anesthetic on a 4-point scale (0=
no pain, 1= mild pain, 2= moderate pain, 3= severe pain). Solution deposition for the
IANB was rated as no pain in 38%, mild pain in 48%, moderate pain in 15%, and severe
pain in 0% of injections.
Willett (54) studied the anesthetic efficacy of diphenhydramine and the
combination diphenhydramine/lidocaine for the IAN block. Thirty asymptomatic subjects
were each given 1.8 mL of 2% lidocaine with 1:100,000 epinephrine, 1.8 mL of 1%
diphenhydramine with 1:100,000 epinephrine, and 3.6 mL of a combination of 1.8 mL of
2% lidocaine with 1:100,000 epinephrine and 1.8 mL of 1% diphenhydramine with
1:100,000 epinephrine at three separate appointments in a double-blind, crossover design.
Each IANB injection was deposited at a rate of 1.8 mL per minute. Subjects were asked
to rate the pain of solution deposition on a four-point scale (0= no pain, 1= mild pain, 2=
moderate pain, 3= severe pain). Regarding the lidocaine solution, no pain was reported by
24%, mild pain by 40%, moderate pain by 32%, and severe pain by 4% of subjects.
Regarding the diphenhydramine solution, no pain was reported by 0% of subjects, mild
pain by 10%, moderate pain by 40%, and severe pain by 50% of subjects. Regarding the
lidocaine/diphenhydramine combination solution, no pain was reported by 16% of
subjects, mild pain by 28%, moderate pain by 40%, and severe pain by 16% of subjects.
The authors concluded that although deposition of the diphenhydramine solution was
30
significantly more painful, there was no significant difference between the lidocaine
solution and the lidocaine/diphenhydramine combination solution.
A review of medical literature by Davies (71) found that buffering local
anesthetics with sodium bicarbonate significantly reduced injection pain. However, the
usefulness of this technique in dentistry has been debated. Only a few studies have
evaluated the effects of a buffered anesthetic solution on the deposition pain of IAN
blocks.
Whitcomb and coauthors (55) evaluated the anesthetic efficacy of 0.17 mEq/mL
sodium bicarbonate buffered 2% lidocaine with 1:100,000 epinephrine verses a nonbuffered solution for IANB injections. At two separate appointments, 3.6 mL of one of
the solutions was deposited at the target site over 2 minutes. Forty asymptomatic subjects
were asked to rate the discomfort of solution deposition on a 4-point scale (0= no pain,
1= mild, 2= moderate, 3= severe). The pH of the non-buffered solution was reported as
6.4, while the buffered solution had a pH of 7.5. Regarding the non-buffered lidocaine
solution, no pain to solution deposition was reported by 58% of subjects, mild pain by
35%, moderate pain by 8%, and severe pain by 0% of subjects. With the buffered
solution, no pain was reported by 72% of subjects, mild pain by 25%, moderate pain by
2%, and severe pain by 0% of subjects. There was no significant difference in pain
between the buffered and non-buffered solutions.
Kashyap and coauthors (72) evaluated the effect of alkalinization of lidocaine on
the pain of injection during intraoral block injections. One hundred healthy subjects were
given IANB, lingual nerve, and long buccal nerve blocks with a maximum of 2.5 mL of
31
anesthetic solutions. The control group received 2% lidocaine with 1:80,000 epinephrine,
and the study group received the same lidocaine solution with a 1/10 dilution of 8.4%
sodium bicarbonate. Pain during injection was assessed on a 4-point scale (0 = no pain, 1
= mild pain, 2 = moderate pain, 3 = severe pain), and was defined as pain that was
described by the patient during injection of the solution. The pH of the lidocaine solution
was measured to be 3.05, and the pH of the buffered lidocaine solution was 7.38. Of the
50 subjects in the control group, 11 reported no pain, 31 reported mild pain, 8 reported
moderate pain, and 0 reported severe pain during the injection. All patients in the study
group reported no pain. The authors concluded that buffering an anesthetic solution is
effective in reducing the pain of injection.
Ridenour and coauthors (73) evaluated the combination of hyaluronidase and
buffered lidocaine with epinephrine in IAN blocks. The control group received an IANB
injection of a 1.8 mL solution containing 24 mg lidocaine and 12 µg epinephrine buffered
with 0.33 mEq/mL sodium bicarbonate deposited over one minute. Subjects were asked
to rate the pain of solution deposition on a 4-point scale (0 = no pain, 1 = mild pain, 2 =
moderate pain, 3 = severe pain). Subjects reported no pain to solution deposition in 27%
of injections, mild pain in 53%, moderate pain in 13%, and severe pain in 7% of
injections.
Wolf (57) evaluated the anesthetic efficacy of 1.8 mL of 2% lidocaine with
1:100,000 epinephrine, 2.84 mL of 2% lidocaine with 1:100,000 epinephrine with 0.5M
mannitol, and 5 mL of 2% lidocaine with 1:100,000 epinephrine with 0.5M mannitol in
IANB injections. Forty asymptomatic subjects rated the pain of solution deposition on a
32
4-point scale (0= no pain, 1= mild pain, 2= moderate pain, 3= severe pain). The
anesthetic was deposited over one minute, regardless of volume. Regarding the lidocaine
solution, no pain to solution deposition was reported in 17% of injections, mild pain in
50%, moderate pain in 30%, and severe pain in 3% of injections. Regarding the 2.84 mL
lidocaine plus mannitol solution, no pain to solution deposition was reported by 12% of
subjects, mild pain by 45%, moderate pain by 40%, and severe pain by 3%. Regarding
the 5 mL lidocaine plus mannitol solution, no pain to solution deposition was reported by
7% of subjects, mild pain by 55%, moderate pain by 35%, and severe pain by 3% of
subjects. There were no significant differences in solution deposition pain between the
three solutions.
Elmore (62) evaluated the anesthetic reversal agent, Oraverse™, following an
IANB injection. Ninety asymptomatic subjects received IANB injections with 1.8 mL of
2% lidocaine with 1:100,000 epinephrine deposited over one minute. Subjects were asked
to rate the pain of solution deposition on a 170-mm Heft-Parker VAS form. The mean
VAS rating was 55.9 mm which was in the moderate range. Subjects reported none-tomild pain in 48% of injections, and moderate-to-severe pain in 52% of injections.
Guglielmo (58) evaluated the anesthetic efficacy of a supplemental intraosseous
injection following an IANB injection. Forty asymptomatic subjects were given an IANB
injection of 1.8 mL of 3% mepivacaine deposited over one minute. Forty asymptomatic
subjects were asked to rate the discomfort of solution deposition during the IANB
injection on a 4-point scale (0= no pain, 1= mild, 2= moderate, 3= severe). No pain was
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reported by 58% of subjects, mild pain by 35%, moderate pain by 6%, and severe pain by
2% of subjects.
Kramp and coauthors (48) evaluated prilocaine for the reduction of pain
associated with the intraoral administration of local anesthesia. This study compared 2%
mepivacaine with 1:20,000 levonordefrin, 2% lidocaine with 1:100,000 epinephrine, and
4% prilocaine plain in asymptomatic patients. No topical anesthetic was used. A 1.8 mL
solution was injected with a 30-gauge needle for the IANB injection in 36 subjects.
Following the injection, each patient was asked to describe the level of discomfort
associated with the injection by marking the appropriate number on a 10-point VAS
form. The phases of injection were not separated in this study. Mean scores for each
solution were as follows: mepivacaine = 3.0, lidocaine = 2.6 and prilocaine = 2.0. The
authors concluded that the injection of prilocaine resulted in significantly less pain, with
no difference between lidocaine and mepivacaine. They hypothesize that this difference
is due to the pH of the anesthetic solutions, which were recorded as follows: lidocaine =
4.12; mepivacaine = 3.05; prilocaine = 6.28.
Wahl, Schmitt, and Overton (74) evaluated injection pain of 4% prilocaine plain,
3% mepivacaine plain, 4% articaine with 1:100,000 epinephrine, and 2% lidocaine with
1:100,000 epinephrine in patients undergoing routine dental procedures. Topical
anesthetic (Benzo-Jel) was placed at the injection site for 10 seconds. A 25-gauge needle
was used to given an IANB injection of 1.8 mL of anesthetic. Subjects were asked to rate
the pain of injection on a ten point scale where 1 = no pain and 10 = unbearable pain. The
phases of injection were not separated in this study. For the IANB, 609 subjects reported
34
the following mean pain scores: articaine = 3.33, lidocaine = 3.14, mepivacaine = 3.12
and prilocaine = 2.66. Authors concluded that prilocaine was significantly less painful,
and hypothesized that this may be associated with the higher pH of the solution. The pHs
of the anesthetic solutions as measured by the authors were recorded as follows:
prilocaine = 5.5-6.5; lidocaine = 4.0-4.5; articaine = 3.5-4.5; mepivacaine = 4.5-5.5.
Wahl and coauthors (49) evaluated pain of injection between 4% prilocaine plain
and 2% lidocaine with 1:100,000 epinephrine in patients undergoing routine dental
procedures. Topical anesthetic (20% benzocaine) was placed at the injection site for an
unspecified amount of time preceding the injection. A 25-gauge needle was used to give
an IANB injection of 1.8 mL of anesthetic solution. Immediately following the injection,
145 patients were asked to rate the pain of injection on a 6-point scale (0= no pain, 1=
mild, 2= moderate, 3= distressing, 4= horrible, 5= unbearable). The phases of injection
were not separated in this study. Mean scores for the IANB injections were 0.63 for
prilocaine, and 0.72 for the lidocaine solution. No significant difference was found
between the two solutions.
Sumer et al. (75) compared the injection pain of 4% articaine with 1:200,000
epinephrine, 3% prilocaine with 1.08 µg phenylpressin, and 2% lidocaine with 1:100,000
epinephrine. Three hundred eighteen asymptomatic subjects received an IANB injection
with one of the three solutions. Topical anesthetic was applied to the injection site for 5
to 10 seconds, and an unspecified amount of anesthetic was injected slowly (time not
specified). Subjects who received more than one injection were excluded from the study.
Immediately after the injection, subjects were asked to rate their injection pain on a 6-
35
point scale (0 = no pain, 1 = mild pain, 2 = moderate pain, 3 = distressing pain, 4 =
horrible pain, 5 = unbearable pain). The phases of injection were not separated in this
study. Subjects reported none-to-mild pain for 75.4% of injections. The authors
concluded that there were no significant differences among the anesthetic solutions for
injection pain, although the results were not analyzed by location of injection.
Kanaa and coauthors (76) gave subjects an IANB injection of 2 mL of 2%
lidocaine with 1:80,000 epinephrine over one minute at each appointment. Immediately
after needle withdrawal, subjects were asked to rate the discomfort associated with the
injection on a 100 mm visual analogue scale (VAS). The phases of injection were not
separated in this study. VAS scores for the IANB injection with lidocaine ranged from 781 mm, with a mean of 32.2 mm and 34.7 mm at each appointment.
In the studies reviewed, subjects reported moderate-to-severe pain during solution
deposition in approximately 24% of injections. While it has been hypothesized that the
injection of an anesthetic solution with a higher pH (due to anesthetic selection or
buffering) is less painful, there is currently not enough evidence to support this theory.
Giving an injection slowly; however, does seem to be less painful than a fast injection
(70). The effect of gender was analyzed in one study, and no significant difference was
found in terms of pain reported during solution deposition (62).
SUMMARY OF INJECTION PAIN
Although the scales used to measure pain in these studies differed (VAS vs.
ordinal scale), Kreimer (77) showed a high correlation between subject responses using a
36
4-point scale and a 170-mm Heft-Parker VAS. Overall, subjects rated the least pain
during needle insertion, but ¼ to 1/3 of subjects reported moderate-to-severe pain during
needle placement and solution deposition. In the studies that didn’t separate the phases of
needle insertion and needle placement, reported pain levels were similar to needle
placement values of the studies that analyzed needle placement individually. No
difference in pain has been reported regarding gender with the conventional IANB
injection, although a two-stage technique resulted in significantly less pain during needle
placement in females (68). Further evaluation or research may be warranted to look into
the gender effect.
ANESTHETIC SUCCESS RATES
The traditional method for determining the success of the IANB is lip numbness,
which usually occurs within 4.5 to 6 minutes of injection (16, 63, 78, 79). Studies
confirm that although this clinical sign determines that the injection has been given
accurately, pulpal anesthesia may not have been obtained (1, 16, 55, 56, 62, 63, 67, 69,
70, 73, 76, 78-99). The onset of pulpal anesthesia, which can be defined as two
consecutive 80/80 readings on an electric pulp tester, generally occurs within 5-19
minutes of local anesthetic administration (16, 63, 67, 78, 79, 89, 91). Successful
mandibular pulpal anesthesia, which has been defined in some studies as pulp numb
within fifteen minutes and continuously numb for one hour, tends to be more frequent in
molars (32-92%) and premolars (38-92%) than in incisors (2-67%) (1, 16, 55, 56, 62, 63,
67, 69, 70, 73, 76, 78-99). Although there is an abundance of information on anesthetic
37
success, this section will focus solely on studies looking at the success rates of 2%
lidocaine with 1:100,000 epinephrine and 3% mepivacaine with the IAN block.
LIDOCAINE
Vreeland and coauthors (63) evaluated the anesthetic efficacy of different
volumes and concentrations of lidocaine with the IAN block. Thirty asymptomatic
subjects each received IANB injections of A: 1.8 mL of 2% lidocaine with 1:100,000
epinephrine, B: 3.6 mL of 2% lidocaine with 1:200,000 epinephrine, and C: 1.8 mL 4%
lidocaine with 1:100,000 epinephrine at three separate appointments. The first molar,
canine, lateral incisor, and contralateral canine (control) were tested with an electric pulp
tester (EPT) every 3 minutes for 55 minutes. Anesthesia was considered to be successful
if an 80 reading was obtained within 16 minutes of injection and continuously sustained
for the remainder of the testing period. Successful anesthesia using Solution A occurred
in 63.3% of first molars, and in 33.3% of lateral incisors. With solution B, success
occurred in 63.3% of first molars and 43.3% of lateral incisors. With solution C, success
occurred in 53.3% of first molars and 43.3% of lateral incisors. The authors concluded
that there were no significant differences in successful pulpal anesthesia between the
solutions.
Hinkley et al. (78) evaluated 4% prilocaine with 1:200,000 epinephrine, 2%
mepivacaine with 1:20,000 levonordefrin, and 2% lidocaine with 1:100,000 epinephrine
for the IAN block. Thirty asymptomatic subjects were given an IANB injection with 1.8
mL of one of the anesthetic solutions at each appointment. The first molar, first premolar,
38
lateral incisor, and contralateral canine (control) were then tested with an EPT every 3
minutes for 50 minutes. Anesthesia was considered to be successful if an 80 reading was
achieved within 16 minutes of injection and sustained for the remainder of the 50-minute
test period. Anesthetic success with lidocaine was 54% in the first molar, 50% in the first
premolar, and 36% in the lateral incisor. Anesthetic success with mepivacaine was 57%
in the first molar, 54% in the first premolar, and 36% in the lateral incisor. There were no
significant differences in anesthetic success found between any of the solutions.
Chaney and coauthors (79) evaluated lidocaine hydrocarbonate compared with
lidocaine hydrochloride for IAN blocks. Thirty asymptomatic subjects received 1.8 mL
injections of 2.2% lidocaine hydrocarbonate, 2.2% lidocaine hydrocarbonate with
1:100,000 epinephrine, and 2% lidocaine with 1:100,000 epinephrine at three separate
appointments. The first molar, first premolar, and lateral incisor were tested with an EPT
every 3 minutes for 60 minutes. Anesthesia was considered successful when an 80
reading was obtained within 16 minutes of injection and sustained for the remainder of
the test period. Anesthetic success with 2% lidocaine with 1:100,000 epinephrine was
seen in 57% of first molars, 63% of first premolars, and 43% of lateral incisors.
Nist and coauthors (69) studied the combination of the inferior alveolar nerve and
incisive nerve blocks in mandibular anesthesia. Forty asymptomatic subjects with vital
teeth were given an IANB injection with 3.6 mL of 2% lidocaine with 1:100,000
epinephrine. The first and second molars, first and second premolars, central and lateral
incisors, and contralateral canine (control) were then tested with an EPT every 4 minutes
for 60 minutes. Anesthesia was considered to be successful when an 80 reading was
39
obtained within 15 minutes of injection and sustained for 60 minutes. Anesthetic success
of the IANB alone was 15% in the central incisor, 35% in the lateral incisor, 70% in the
first premolar, 52% in the second premolar, 43% in the first molar, and 50% in the
second molar.
McLean et al. (16) evaluated the efficacy of 4% prilocaine, 3% mepivacaine, and
2% lidocaine solutions for the IAN block. Thirty asymptomatic subjects were given
IANB injections of 1.8 mL of 4% prilocaine, 3% mepivacaine, and 2% lidocaine with
1:100,000 epinephrine at three successive appointments. Following the injection, the first
molar, first premolar, lateral incisor, and contralateral canine (control) were tested with
an EPT every 3 minutes for 50 minutes. Anesthesia was considered successful if an 80
reading was achieved within 16 minutes of injection and sustained for the remainder of
the 50 minutes of the test. Anesthetic success with lidocaine was 63% in the first molar,
67% in the first premolar, and 30% in the lateral incisor. Anesthetic success with
mepivacaine was 43% in the first molar, 57% in the first premolar, and 30% in the lateral
incisor. There were no statistically significant differences found between any of the three
anesthetic solutions.
Childers and coauthors (80) studied the anesthetic efficacy of the periodontal
ligament (PDL) injection after an IAN block. Forty asymptomatic subjects received an
IANB injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The first and
second molars, second premolar, and contralateral canine (control) were tested with an
EPT every 2 minutes for 60 minutes. Anesthesia was considered successful when an 80
reading was obtained within 15 minutes and sustained for the remainder of the test
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period. Anesthetic success of the IANB alone was 63% in the first molar, 73% in the
second molar, and 60% in the second premolar.
Dunbar and coauthors (81) evaluated the anesthetic efficacy of the intraosseous
injection after an IANB injection. Forty asymptomatic subjects were given an IANB
injection with 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The first and second
molars, the second premolar, and the contralateral canine (control) were tested with an
EPT every 2 minutes for 60 minutes. Anesthesia was considered successful when an 80
reading was obtained within 15 minutes, and sustained for the remainder of the test
period. Anesthetic success of the IANB alone was 42% in the first molar, 45% in the
second molar, and 38% in the second premolar.
Dagher and coauthors (82) evaluated 2% lidocaine with different concentrations
of epinephrine for the IAN block. Thirty asymptomatic subjects were each given three
IANB injections at successive appointments: 1.8 mL of 2% lidocaine with 1:50,000
epinephrine, 1.8 mL 2% lidocaine with 1:80,000 epinephrine, and 1.8 mL 2% lidocaine
with 1:100,000 epinephrine. The first molar, first premolar, lateral incisor, and
contralateral canine (control) were tested with an EPT every 3 minutes for 50 minutes.
Anesthesia was considered successful if an 80 reading was achieved within 16 minutes
and sustained for the remainder of the 50-minute test period. Anesthetic success with the
1:100,000 epinephrine formulation was 47% in the first molar, 43% in the first premolar,
and 50% in the lateral incisor. The authors concluded that anesthetic success was not
significantly different among the three solutions.
41
Yared and Dagher (83) evaluated lidocaine with different concentrations of
epinephrine with larger volumes of anesthetic for the IAN block. Thirty asymptomatic
subjects were each given 3.6 mL of 2% lidocaine with 1:50,000 epinephrine, 3.6 mL of
2% lidocaine with 1:80,000 epinephrine, and 3.6 mL of 2% lidocaine with 1:100,000
epinephrine at three separate appointments in a double-blind, repeated measures design.
The first molar, first premolar, lateral incisor, and contralateral canine (control) were
tested with an EPT every 3 minutes for 50 minutes. Anesthesia was considered successful
if an 80 reading was obtained within 16 minutes and sustained for the remainder of the
50-minute testing period. Anesthetic success with 2% lidocaine with 1:100,000
epinephrine was 77% for the first molar, 80% for the first premolar, and 67% for the
lateral incisor. The authors concluded that the concentration of epinephrine did not
influence the degree of pulpal anesthesia when utilizing 3.6 mL of anesthetic.
Reitz and co-authors (84) studied the augmentation of an IAN block with an
intraosseous injection of 0.9 mL of 2% lidocaine with 1:100,000 epinephrine. Thirtyeight asymptomatic subjects with vital teeth were given an IANB injection with 1.8 mL
of 2% lidocaine with 1:100,000 epinephrine. The first and second molars, the second
premolar and the contralateral canine (control) were then tested with an EPT every 2
minutes for 120 minutes. Anesthesia was considered successful when 2 consecutive 80
readings were obtained. Percentages of anesthetic success for the IANB alone were 60%
in the second premolar, 71% in the first molar, and 74% in the second molar.
Clark and coauthors (85) evaluated the anesthetic efficacy of the mylohyoid nerve
(MN) block and the combination IANB/MN block. Each IANB consisted of 3.6 mL of
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2% lidocaine with 1:100,000 epinephrine. The first and second molars, first and second
premolars, central and lateral incisors, and contralateral canine (control) were tested with
an EPT every 4 minutes for 60 minutes. Anesthesia was considered successful when 2
consecutive 80 readings were recorded. Anesthetic success for the IANB was 87% in the
second molar, 73% in the first molar, 90% in the second premolar, 87% in the first
premolar, 50% in the lateral incisor, and 33% in the central incisor.
Hannan and coauthors (86) evaluated the use of ultrasound for guiding needle
placement for IAN blocks. Forty asymptomatic subjects received an ultrasound-assisted
IANB and a conventional IANB at 2 separate appointments. For each injection, 1.8 mL
of 2% lidocaine with 1:100,000 epinephrine was deposited. The first and second molars,
first and second premolars, central and lateral incisors, and contralateral canine (control)
were tested with an EPT every 4 minutes for 60 minutes. Anesthesia was considered
successful when 2 consecutive 80 readings were obtained. Anesthetic success with the
ultrasound IANB was 92% in the second molar, 78% in the first molar, 92% in the
second premolar, 88% in the first premolar, 65% in the lateral incisor, and 38% in the
central incisor. Anesthetic success with the conventional IANB was 92% in the second
molar, 85% in the first molar, 90% in the second premolar, 90% in the first premolar,
65% in the lateral incisor, and 38% in the central incisor. The authors concluded that
there were no significant differences in anesthetic success between the two techniques.
Yonchak and coauthors (87) studied the anesthetic efficacy of unilateral and
bilateral IAN blocks to determine cross innervation in anterior teeth. Forty asymptomatic
subjects with vital teeth were given a unilateral IANB injection with 3.6 mL of 2%
43
lidocaine with 1:100,000 epinephrine. The ipsilateral lateral incisor, central incisor, and
canine, were then tested with an EPT every 4 minutes for 60 minutes. Anesthesia was
considered successful when 2 consecutive 80 readings were obtained. Success rates of the
unilateral IANB were 39% in the central incisor, 50% in the lateral incisor, and 68% in
the canine.
Mikesell and coauthors (88) compared the anesthetic efficacy of articaine and
lidocaine for IAN blocks. Fifty-seven asymptomatic subjects were given 1.8 mL of 2%
lidocaine with 1:100,000 epinephrine. The first and second molars, first and second
premolars, central and lateral incisors, and contralateral canine (control) were then tested
with an EPT every 4 minutes for 60 minutes. Anesthesia was considered to be successful
when 2 consecutive 80 readings were obtained within 15 minutes and continuously
sustained for 60 minutes. Anesthetic success with lidocaine was 48% in the second
molar, 32% in the first molar, 29% in the second premolar, 42% in the first premolar,
14% in the lateral incisor, and 2% in the central incisor.
Fernandez et al. (89) compared the anesthetic efficacy of bupivacaine and
lidocaine for IAN blocks. Thirty-nine asymptomatic subjects were given an IAN block
injection with 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The first and second
molars, first and second premolars, lateral incisor, and contralateral canine (control) were
then tested with an Analytic Technology pulp tester every 3 minutes for the first 2 hours
and testing continued for 5 hours or until at least two consecutive readings of less than 80
were recorded on 3 of the 5 experimental teeth. Anesthesia was considered successful if
an 80 reading was achieved within 15 minutes and continuously sustained for 60 minutes.
44
Anesthetic success with lidocaine was observed in 77% of second molars, 54% of first
molars, 74% of second premolars, 84% of first premolars, and 54% of lateral incisors.
Goodman and coauthors (90) evaluated the anesthetic efficacy of lidocaine and
meperidine for IAN blocks. Fifty-two asymptomatic subjects randomly received an
IANB injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The first and
second molars, first and second premolars, central and lateral incisors, and contralateral
canine (control) were tested with an EPT every 4 minutes for 60 minutes. Anesthesia was
considered successful when 2 consecutive 80 readings were obtained within 15 minutes
and the 80 reading was continuously sustained for 60 minutes. Anesthetic success was
58% in the second molar, 44% in the first molar, 48% in the second premolar, 51% in the
first premolar, 23% in the lateral incisor, and 8% in the central incisor.
Kanaa and coauthors (70) evaluated the influence of the speed of injection on
anesthetic efficacy of the IAN block. Thirty-eight asymptomatic subjects received IANB
injections of 2 mL 2% lidocaine with 1:80,000 epinephrine at two separate appointments,
with a fast injection (deposited over 15 seconds), and a slow injection (deposited over 60
seconds). The mandibular first molar, first or second premolar, and lateral incisor were
tested with an EPT every 2 minutes for the first 10 minutes following the injection, then
every 5 minutes for the remainder of the 55-minute testing period. The anesthetic efficacy
was evaluated by comparing the number of 80 readings obtained by all subjects (total
pulpal anesthesia) throughout the testing period and separating the results by tooth (532
readings per tooth). Regarding the slow injection; 80 readings were seen in 220 cases for
molars, 253 cases for premolars, and 119 cases for lateral incisors. Regarding the fast
45
injection; 80 readings were seen in 159, 216, and 99 cases, respectively. The authors
concluded that a slow IANB injection may result in improved anesthetic efficacy in
asymptomatic patients.
Steinkruger and coauthors (91) evaluated the significance of needle bevel
orientation in achieving a successful IAN block. Fifty-one asymptomatic subjects each
received an IANB injection with the needle bevel oriented away from the mandibular
ramus and an IANB injection with the needle bevel oriented toward the mandibular
ramus at two separate appointments. Each IANB injection was given with 2.2 mL of 2%
lidocaine with 1:100,000 epinephrine. The first and second molars, first and second
premolars, central and lateral incisors, and contralateral canine (control) were tested with
an EPT every 4 minutes for 60 minutes. Anesthesia was considered to be successful if
two consecutive 80 readings were obtained within 15 minutes and continuously sustained
for the remainder of the testing period. When the needle bevel was oriented away from
the ramus, anesthetic success was found in 90% of second molars, 76% of first molars,
78% of second premolars, 80% of first premolars, 43% of lateral incisors, and 24% of
central incisors. When the needle bevel was oriented toward the ramus, anesthetic success
was found in 92% of second molars, 73% of first molars, 78% of second premolars, 73%
of first premolars, 33% of lateral incisors, and 14% of central incisors. The authors
concluded that there were no significant differences between the two needle bevel
orientations.
Foster and coauthors (92) studied the anesthetic efficacy of buccal and lingual
infiltrations of lidocaine following an IAN block in mandibular posterior teeth. Forty-
46
nine asymptomatic subjects were given an IANB plus mock buccal infiltration and mock
lingual infiltration of the first mandibular molar. Each IANB injection used 3.6 mL of 2%
lidocaine with 1:100,000 epinephrine. The first and second molars, first and second
premolars, and contralateral canine (control) were then tested with an EPT. Anesthesia
was considered successful when 2 consecutive 80 readings were obtained within 15
minutes, and continuously sustained for 60 minutes. Anesthetic success of the IANB
alone was 74% in the second molar, 53% in the first molar, 66% in the second premolar,
and 56% in the first premolar.
Goldberg and coauthors (67) compared the anesthetic efficacy of the conventional
IANB, Gow-Gates, and Vazirani-Akinosi techniques for mandibular anesthesia. Forty
asymptomatic subjects were given 3 injections at separate appointments using 3.6 mL of
2% lidocaine with 1:100,000 epinephrine. The first molar, first premolar, lateral incisor,
and contralateral canine (control) were tested with an EPT every 3 minutes for 60
minutes. Anesthesia was considered successful when 2 consecutive 80 readings were
obtained within 15 minutes of the injection and the 80 reading was continuously
sustained for the remainder of the 60-minute testing period. Anesthetic success for the
IANB was 53% in the first molar, 62% in the first premolar, and 25% in the lateral
incisor.
Willett and coauthors (93) studied the anesthetic efficacy of diphenhydramine and
the combination diphenhydramine/lidocaine for the IAN block. Thirty asymptomatic
subjects were each given 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The first
and second molars, first and second premolars, lateral and central incisors, and
47
contralateral canine (control) were tested with an EPT every 4 minutes for 60 minutes.
Anesthesia was considered successful when two consecutive 80 readings were obtained
within 15 minutes and continuously sustained through the entire testing period.
Anesthetic success with lidocaine alone was 84% for the second molar, 52% for the first
molar, 52% for the second premolar, 68% for the first premolar, 36% for the lateral
incisor, and 12% for the central incisor.
Kanaa and coauthors (76) studied the buccal infiltration of articaine following an
IANB with lidocaine. Thirty-six asymptomatic subjects were given an IANB injection of
2 mL of 2% lidocaine with 1:80,000 epinephrine. This was followed by either a buccal
injection of 4% articaine solution, or a mock buccal injection. The first molar, first
premolar (or second premolar if the first premolar was removed for orthodontic
treatment), and lateral incisor were tested with an EPT every 2 minutes for 10 minutes,
then every 5 minutes for the remainder of the 45 minute testing period. Anesthesia was
considered successful if there was no response to maximum stimulation with two or more
consecutive readings. Anesthetic success for the IANB alone was 55.6% in the first
molar, 66.7% in the premolars, and 19.4% in the lateral incisors.
Whitcomb and coauthors (55) evaluated the anesthetic efficacy of sodium
bicarbonate buffered 2% lidocaine with 1:100,000 epinephrine verses a non-buffered
solution for IANB injections. Forty asymptomatic subjects were given 3.6 mL of local
anesthetic solution. The first and second molars, first and second premolars, lateral and
central incisors, and contralateral canine (control) were tested with an EPT every 4
minutes for 60 minutes. Anesthesia was considered successful when two consecutive 80
48
readings were obtained within 15 minutes and continuously sustained for the entire
testing period. Anesthetic success was seen in 65% of second molars, 58% of first
molars, 68% of second premolars, 71% of first premolars, 35% of lateral incisors, and
10% of central incisors.
Simon and coauthors (56) evaluated the anesthetic efficacy of the IANB
administered with the aid of a peripheral nerve stimulator. Forty-six asymptomatic
patients each received a conventional IANB and an IANB administered utilizing a
peripheral nerve stimulator to localize the inferior alveolar nerve at two separate
appointments. Each IANB injection was given with 1.8 mL 2% lidocaine with 1:100,000
epinephrine. The first molar, first premolar, lateral incisor, and contralateral canine
(control) were tested with an EPT every 2 minutes for 60 minutes. Anesthesia was
considered successful when 2 consecutive 80 readings were obtained within 15 minutes
and continuously sustained for the entire testing period. Anesthetic success of the
conventional IANB was found to be 45% in the first molar, 42% in the first premolar, and
32% in the lateral incisor. The authors concluded that there was no significant difference
in anesthetic success between the two IANB techniques.
Wali and coauthors (94) evaluated the anesthetic efficacy of 1.8 and 3.6 mL of
2% lidocaine with 1:50,000 epinephrine versus 1.8 mL 2% lidocaine with 1:100,000
epinephrine for the IAN block. Thirty asymptomatic subjects each received an IANB
injection of 1.8 mL of 2% lidocaine with 1:100,000 epinephrine. The first molar, first
premolar, lateral incisor, and contralateral canine (control) were tested with an EPT every
3 minutes for 60 minutes. Anesthesia was considered to be successful when 2 consecutive
49
80 readings were obtained within 15 minutes and continuously sustained for the
remainder of the testing period. Successful anesthesia occurred in 43% of first molars,
60% of first premolars, and 40% of lateral incisors.
Hutchison and coauthors (95) evaluated the anesthetic efficacy of frequencydependent conduction blockade of the inferior alveolar nerve. Eighty asymptomatic
subjects randomly received an IANB injection of 1.8 mL 2% lidocaine with 1:100,000
epinephrine at two separate appointments. Subjects then received continuous electrical
stimulation or mock electrical stimulation of the first molar or lateral incisor for six
cycles of three minutes each. An EPT was used to test the teeth for pulpal anesthesia
between stimulation cycles for a total of 64 minutes. Anesthesia was considered to be
successful when two consecutive 80 readings were obtained within 15 minutes and the 80
reading was sustained for the remainder of the 64-minute testing period. Regarding the
group that received electrical stimulation, anesthetic success was seen in 35% of lateral
incisors and 48% of first molars. Regarding the mock-stimulation group, anesthetic
success was seen in 18% of lateral incisors and 62% of first molars. The authors
concluded that there were no significant differences between the two groups, and that
continuous electrical stimulation did not result in greater anesthetic success with the IAN
block.
Wolf et al. (96) evaluated the anesthetic efficacy of 1.8 mL of 2% lidocaine with
1:100,000 epinephrine, 2.84 mL of 2% lidocaine with 1:100,000 epinephrine with 0.5M
mannitol, and 5 mL of 2% lidocaine with 1:100,000 epinephrine with 0.5M mannitol in
IANB injections. Forty asymptomatic subjects each received IANB injections with these
50
anesthetic solutions. The first and second molars, first and second premolars, and lateral
and central incisors were tested with an EPT every 4 minutes for 60 minutes. Mean total
pulpal anesthesia was defined as the total of all the times of pulpal anesthesia (80
readings) over the 60-minute testing period. Regarding the 1.8 mL solution; mean total
pulpal anesthesia was seen in second molars 75% of the time, first molars 48%, second
premolars 54%, first premolars 50%, lateral incisors 27%, and central incisors 12% of the
time.
MEPIVACAINE
Guglielmo and coauthors (97) evaluated the anesthetic efficacy of a supplemental
intraosseous injection following an IANB injection. Forty asymptomatic subjects were
given an IANB injection of 1.8 mL of 3% mepivacaine. The first and second molars,
second premolar, and contralateral canine (control) were tested with an EPT every 2
minutes for 60 minutes. Anesthesia was considered to be successful when two
consecutive 80 readings were obtained. Anesthetic success for the IANB was 80% for the
first molar, 90% for the second molar, and 77% for the second premolar.
Gallatin and coauthors (98) evaluated the anesthetic efficacy and heart rate effects
of the intraosseous injection of 3% mepivacaine after an IAN block. Forty-eight
asymptomatic subjects were given an IANB injection of 1.8 mL of 3% mepivacaine. The
first molar and contralateral canine (control) were tested with an EPT every 2 minutes for
60 minutes. Anesthesia was considered to be successful when two consecutive 80
51
readings were obtained. Regarding the IANB + mock IO injections, anesthetic success in
the first molar was 81%.
Stabile and coauthors (99) evaluated the anesthetic efficacy and heart rate effects
of the intraosseous (IO) injection of 1.5% etidocaine with 1:200,000 epinephrine
following an IAN block. Forty-eight asymptomatic subjects received an IANB injection
of 1.8 mL of 3% mepivacaine. The first molar was tested with an EPT every 2 minutes
for 60 minutes. Anesthesia was considered to be successful when two consecutive 80
readings were obtained. Regarding the IANB + mock IO injections, anesthetic success in
the first molar was 81%.
McLean and coauthors (16) evaluated the efficacy of 4% prilocaine, 3%
mepivacaine, and 2% lidocaine solutions for the IAN block, as previously described.
Anesthetic success with mepivacaine was 43% in the first molar, 57% in the first
premolar, and 30% in the lateral incisor. There were no statistically significant
differences found between any of the three anesthetic solutions.
IMPACT OF VOLUME OF ANESTHETICS ON SUCCESS WITH IANB
Research on the impact of the volume of anesthetic injected for the IANB has
been conducted to see if an increase in success can occur when the volume injected
increases. Nusstein and coauthors (1) evaluated the anesthetic efficacy of different
volumes of lidocaine with epinephrine for IAN blocks. In this retrospective study, four
hundred sixty-two asymptomatic subjects were given an IANB injection of either 1.8 mL
or 3.6 mL of 2% lidocaine with 1:100,000 epinephrine. The first molar, first premolar,
52
lateral incisor, and contralateral canine (control) were tested with an EPT at 3-4 minute
cycles for 55-60 minutes. Anesthesia was considered successful when two consecutive 80
readings were obtained within 15-16 minutes and continuously sustained for the entire
testing period. Anesthetic success with 1.8 mL occurred in 53% of first molars, 61% of
first premolars, and 35% of lateral incisors. Anesthetic success with 3.6 mL occurred in
44% of first molars, 67% of first premolars, and 32% of lateral incisors. The authors
concluded that there was no significant difference in successful pulpal anesthesia
between the two volumes of anesthetic.
In the study previously mentioned by Vreeland (63), the authors concluded that
there were no significant differences in successful pulpal anesthesia between anesthetic
solutions, regardless of volume. However, a retrospective evaluation by Yared and
Dagher (83) states a significant difference in the anesthetic success of first molars and
first premolars when doubling the volume of the anesthetic solution, independent of
epinephrine concentration.
INCIDENCE AND TYPES OF ANESTHETIC FAILURE
Anesthetic failure in asymptomatic patients in a study setting has been defined as
the percentage of patients who never achieve two consecutive 80 EPT readings during a
defined testing period. Clinically, anesthetic failure represents a patient who would feel
pain during a dental procedure. Studies have shown that pulpal anesthetic failure occurs
with the IANB in 17-58% of asymptomatic patients, and has been shown to be even
higher in cases of irreversible pulpitis (1, 4, 15, 16, 63, 69, 78-88). Slow onset of
53
anesthesia is a subset of failure that occurs when patients achieve pulpal anesthesia
greater than 15 minutes post-injection. Non-continuous anesthesia is considered to have
occurred when the subject achieved two consecutive 80 readings, lost the 80 reading,
then regained the 80 reading. Anesthesia of short duration has also been seen when a
subject achieved two consecutive 80 readings, but lost the 80 reading before the end of
the testing period. These definitions tend to be used when more specific, time-related
definitions of anesthetic success are utilized.
A retrospective study by Nusstein et al. (1) reviewed failures by volume of
anesthetic. When using 1.8 mL of 2% lidocaine with 1:100,000 epinephrine, anesthetic
failure occurred in 17% of first molars, 11% of first premolars, and 32% of lateral
incisors. Regarding 3.6 mL of the same solution, anesthetic failure was observed in 21%
of first molars, 10% of first premolars, and 39% of lateral incisors. No significant
differences were found between the two volumes for any of the types of failure.
REASONS for FAILURE
While the cause of anesthetic failure remains undetermined, there are several
hypotheses as to why this phenomenon occurs. Traditionally, it has been assumed that
anatomic variation has led to inadequate nerve blockade (100); however, Hannan et al.
(86), Simon et al. (56), and Steinkruger et al. (91) have shown that even an accurate
injection can result in failure of pulpal anesthesia. Another theory is that accessory nerve
innervation may prevent mandibular pulpal anesthesia when only the inferior alveolar
nerve is blocked. The chief nerve that is considered is the mylohyoid nerve which
54
branches from the IAN prior to its entry into the mandibular canal. The mylohyoid nerve
runs downward and along the mylohyoid groove on the medial surface of the ramus (20).
A study by Clark et al. (85) showed no improvement in pulpal anesthesia when adding
the mylohyoid nerve block to the IANB. Also implicated is the retromolar canal, which
may contain accessory innervation to the mandibular teeth. Von Arx et al. (101) recently
showed a 25% incidence of this canal that branches off from the mandibular canal behind
the third molar and travels to the retromolar foramen in the retromolar fossa. Failure and
low success rates in mandibular anterior teeth have been associated with IAN crossinnervation. Yonchak et al. (87) attempted to achieve pulpal anesthesia in mandibular
anterior teeth utilizing bilateral mandibular blocks, and although this technique was
slightly more successful than a unilateral block, anesthetic failure was still observed in
mandibular incisors.
It has been hypothesized that a lower pH due to inflammation at the site of
injection or solution pH may result in ion trapping as the charged acid form is unable to
cross the cell membrane; however, the actual pH change may not be large enough to
produce substantial ion trapping and with the IANB the site of injection is not inflamed
(100). Buffering an anesthetic with sodium bicarbonate causes CO 2 to enter cell and
decrease intracellular pH, which favors the passage of the ionized form of an anesthetic
to pass through the cell membrane. Whitcomb et al. (55) studied this theory in
asymptomatic patients, but no difference was seen in anesthetic success between buffered
and non-buffered anesthetics for the IANB injection.
55
Perhaps the most widely accepted theory for anesthetic failure in asymptomatic
patients is the central core theory. This theory states that the fibers on the outside of the
nerve bundle, which are the first to be anesthetized, supply the molars while the fibers in
the center of the nerve bundle, which are the last to be anesthetized, supply the anterior
teeth (15, 24, 102). While this theory may explain higher experimental failure rates in
anterior teeth, it does not address anesthetic failure in molars or premolars (15).
SUMMARY OF SUCCESS - LIDOCAINE VS. MEPIVACAINE
Many studies have evaluated the anesthetic efficacy of 2% lidocaine with
1:100,000 epinephrine for IAN blocks. While this anesthetic has become the standard to
which many other anesthetics are compared, success rates range from 32-92% in molars,
38-92% in premolars, and 2-67% in incisors. In the limited studies evaluating 3%
mepivacaine plain, success rates range from 43-90% in molars, 54-77% in premolars, and
30-36% in incisors. Although the success rates of these two anesthetic formulations are
similar, there remains room for improvement.
Some clinicians combine 3% mepivacaine plain with 2% lidocaine with
1:100,000 epinephrine for IAN blocks. The thought behind this is that 3% mepivacaine
has more anesthetic molecules available to block sodium channels due to its higher
concentration, and that it also has a higher pH (pH = 6.6) because it does not contain
epinephrine. Both of these concepts may provide more of the base form of the anesthetic
for the IANB initially, therefore potentiating the anesthetic effect after administration of
lidocaine. Rood and coauthors (17) reported on the potential benefits of using prilocaine
56
and lidocaine in combination, but it was determined that there was no potentiation of the
anesthetic effect.
Another potential benefit of using mepivacaine is that it may lessen the pain of
injection. Many practitioners feel that the higher pH of the solution, as compared to
lidocaine (pH = 4.2), results in less pain during solution deposition. McLean et al. (16)
showed no difference when comparing pain of solution deposition utilizing 3%
mepivacaine and 2% lidocaine with 1:100,000 epinephrine; however, other studies have
shown that the injection of a solution with a higher pH is less painful (48, 74). Guglielmo
and coauthors (97) reported moderate-to-severe pain in only 8% of subjects during
solution deposition of 3% mepivacaine.
While studies have shown that 3% mepivacaine was equivalent to 2% lidocaine
with 1:100,000 epinephrine for an IAN block (4,16), no clinical trial has evaluated the
combination of 3% mepivacaine and 2% lidocaine with 1:100,000 epinephrine for IAN
blocks. Therefore, the purpose of this prospective, randomized, double-blind study is to
compare the degree of pulpal anesthesia obtained with a combination 3%
mepivacaine/2% lidocaine with 1:100,000 epinephrine formulation versus 2% lidocaine
with 1:100,000 epinephrine/2% lidocaine with 1:100,000 epinephrine formulation in
inferior alveolar nerve blocks, and to study the injection pain of the two sets of IAN
blocks.
57
MATERIALS AND METHODS
One hundred adult subjects (50 males, 50 females) participated in this study. The
subjects were in good health as determined by a written health history and oral
questioning. Exclusion criteria were as follows: younger than 18 or older than 65 years of
age; ASA Classification of III or greater; allergy to local anesthetics or sulfites; taking
any medications (analgesics, alcohol, anti-depressant or anti-anxiety medications) that
would alter perception of pain or metabolism of anesthetics within the last 48 hours;
inability to give informed consent. Females were questioned regarding pregnancy and
were not allowed to participate if pregnant, suspected a pregnancy, trying to become
pregnant, or lactating. If a pregnancy was suspected, female subjects were required to
take a urine pregnancy test (Osom®, Genzyme Diagnostics Corp, San Diego, CA) before
participation in the appointment was allowed. The Ohio State University Human Subjects
Review Committee approved the study and written informed consent was obtained from
each subject. Subjects were also asked to fill out a Health Insurance Portability and
Accountability Act (HIPAA) release form (APPENDIX E).
The 100 blinded subjects randomly received two sets of IAN blocks: either a
cartridge of 3% mepivacaine (Carbocaine, Dentsply Pharmaceutical, York, PA) followed
by a cartridge of 2% lidocaine with 1:100,000 epinephrine (Xylocaine, Dentsply
Pharmaceutical, York, PA) or a cartridge of 2% lidocaine with 1:100,000 epinephrine
58
followed by a second cartridge of 2% lidocaine with 1:100,000 epinephrine, at two
separate appointments spaced at least one week apart, in a crossover design. With the
crossover design, there were 200 sets of IAN blocks administered and each subject served
as his or her own control. An equal number of sets of IAN blocks were administered on
the right side and the left side. The same side randomly chosen for the first set of
injections was used again for the second set of injections. The test teeth chosen for the
experiment were the first and second molars, first and second premolars, and central and
lateral incisors. The contralateral canine was used as the unanesthetized control to ensure
that the pulp tester was operating properly and that the subject was responding
appropriately during each experimental portion of the study. Clinical examinations were
done prior to subject inclusion to ensure that all teeth were free of caries, large
restorations, and periodontal disease; no patients had a history of trauma or sensitivity.
Before the experiment, the two sets of IAN blocks were randomly assigned sixdigit numbers from a random number table. Each subject was randomly assigned to one
of the two sets of IAN blocks to determine which set would be administered at each
appointment. The anesthetic solutions administered were blinded by removing the labels
from each of the cartridges, and the cartridges were then labeled with the six-digit
numbers. The colors of the cartridge tips and rubber stoppers were identical for both
types of anesthetics. The expiration dates on the cartridges were checked before the
labels were removed. Only the random numbers were recorded on the data collection
sheets to blind the experiment. Only the principal investigator and co-investigator had
access to the master list.
59
At the beginning of each appointment and before any injections were given, the
experimental teeth and control contralateral canine were tested three times with the
electric pulp tester (Kerr, Analytic Technology Corp., Redmond, WA) to record baseline
vitality. After the tooth to be tested was isolated with cotton rolls and dried with gauze,
toothpaste (Crest Cavity Protection®, Procter & Gamble, Cincinnati, OH) was applied to
the probe tip, which was placed half way between the gingival margin and the occlusal or
incisal edge of the tooth. The patient held a grounding wire to complete the circuit. The
current rate was set at 25 seconds to increase from no output (0) to the maximum output
(80). The number associated with the initial sensation was recorded. If the patient had no
sensation, testing was stopped and a value of 80 was recorded. Trained research
personnel performed all pre-injection and post-injection tests. The trained research
assistants were dental or hygiene students specifically trained in conducting this clinical
trial.
Before the IAN block injection, each subject was informed of the pain rating for
injection pain and shown the visual analog scale (VAS). A Heft-Parker VAS (103)
(APPENDIX F) was used in this study. The VAS was a 170-mm line with various
descriptive terms. Immediately after each IAN block, each subject rated the pain for
needle insertion, needle placement and solution deposition on the VAS by placing a mark
on the scale where it best described their pain level. To interpret the data, the VAS was
divided into the following four categories. No pain corresponds to 0 mm on the scale.
Mild pain was defined as greater than 0 mm and less than or equal to 54 mm. Mild pain
included the descriptors of “faint”, “weak”, and “mild” pain. Moderate pain was defined
60
as greater than 54 mm and less than 114 mm and included the descriptor of “moderate”
pain. Severe pain was defined as equal to or greater than 114 mm. Severe pain included
the descriptors of “strong”, “intense”, and “maximum possible” pain.
Topical anesthetic gel (0.2 mL) (20% benzocaine, Benco Dental, Pittston, PA)
was passively placed at the dried IAN block injection site for 60 seconds using a cotton
tip applicator. A standard IAN block (46) was administered with a 27-gauge 1½-inch
needle (Monoject; Sherwood Medical, St. Louis, MO) attached to a standard aspirating
syringe. With the subject’s mouth wide open, the thumb of the non-injecting hand was
placed over the pterygomandibular triangle and then pulled laterally until a depression in
the anterior border of the ramus was felt. The posterior portion of the ramus was palpated
with the first or second finger of the non-injecting hand until a slight depression was
located. The vertical height of the injection site was determined by the line between the
thumb and the finger. The direction of the needle insertion was from the contralateral
mandibular premolars and aligned parallel to the occlusal plane. The needle was
advanced until bone was sounded, then retracted 1 mm. After the block target area was
reached and aspiration performed, 1.8 mL of anesthetic solution (either 3% mepivacaine
or 2% lidocaine with 1:100,000 epinephrine) was deposited over a 1½ minute (90 sec.)
time period. The mouth was then rinsed with water and aspirated, and the subject rated
the pain from the first injection on the first VAS. One minute following the first injection,
a second cartridge (1.8 mL) of anesthetic solution (2% lidocaine with 1:100,000
epinephrine) was administered as described above. The subject then rated the pain of the
second injection on a second VAS. All injections were given by one operator (EL).
61
During the first 15 minutes of testing, each subject was asked if his or her
lip/tongue were numb every minute. If profound lip numbness was not recorded within
15 minutes, the block was considered unsuccessful; the subject was then reappointed.
At 1 minute after the second IAN block, the first and second molars were tested
with the electric pulp tester. At 2 minutes, the first and second premolars were tested. At
three minutes, the lateral and central incisors were tested. At 4 minutes, the control
canine was tested. This cycle of testing was repeated every 4 minutes. At every third
cycle the control tooth, the contralateral canine, was tested by a pulp tester tip that was
not connected to the unit to test the reliability of the subject. Unreliable subjects were
disqualified from the study. All testing was stopped at 56 minutes post-injection.
No response from the subject at the maximum output (80 reading) of the pulp
tester was used as the criterion for pulpal anesthesia. Anesthesia was considered
successful when the first of two consecutive 80 readings was obtained by the fifth testing
period (17 minutes) and the 80 reading was continuously sustained for 56 minutes.
Anesthesia was considered a failure if the subject never achieved two consecutive 80
readings during the 56 minutes, or if the anesthesia was defined as slow onset, noncontinuous, or short duration. Onset of pulpal anesthesia was recorded at the time of the
first of two consecutive 80 readings. Anesthesia of slow onset was defined as the subject
achieving two consecutive 80 readings later than 17 minutes following the second IAN
block injection. Non-continuous anesthesia was defined as onset of anesthesia which was
not continuously sustained for 56 minutes. Anesthesia of short duration was defined as
onset of anesthesia which was not sustained for the full 56 minutes.
62
Comparisons between the sets of anesthetic solutions for anesthetic success,
failure, slow onset and incidence of pulpal anesthesia (percentage of 80 readings across
time) were analyzed nonparametrically using Exact McNemar tests with p-values
adjusted using the Step-down Bonferroni method of Holm. Between-anesthetic solution
differences in pain ratings for needle insertion, needle placement and solution deposition
were analyzed using multiple Wilcoxon matched-pairs, signed ranks tests with p-values
adjusted using the Step-down Bonferroni method of Holm. Between-gender pain
comparisons were assessed using multiple Mann-Whitney-Wilcoxon tests and the Stepdown Bonferroni method of Holm. Comparisons were considered significant at p<0.05.
With a non-directional alpha risk of 0.05 and assuming a total proportion of
discordant pairs of 0.5, a sample size of 100 subjects was required to demonstrate a
difference of ±20 percentage points in anesthetic success with a power of 0.82. With a
non-directional alpha risk of 0.05 and assuming a standard deviation of 27.4, a sample
size of 100 subjects provided a power of 0.82 to demonstrate a difference ± 10 points on
the visual analogue scale.
The pH of each anesthetic solution was tested. Three random samples of 3%
mepivacaine and 2% lidocaine with 1:100,000 epinephrine were subjected to three
readings each with the Orion Star AIII pH meter (Thermo Scientific, Beverly, MA). The
pH tester was calibrated with pH buffers (NIST Traceable Solution, OAKTON®, Vernon
Hills, IL) prior to testing.
63
RESULTS
One hundred subjects (50 males, 50 females) were included in this study. Subjects
ranged in age from 18 to 38 with a mean age of 25.6 years (Table A-1). All subjects were
classified as ASA I or II as indicated on a health history (Appendix C) filled out by the
subject and oral questioning.
Subjects rated each phase of anesthetic injection (insertion, deposition,
placement) on a 170-mm Heft-Parker VAS form (Appendix F). Table A-2 shows the
mean pain ratings for each phase of the first injection and for each anesthetic
combination.
For the first injection, the mean VAS pain ratings for needle insertion were as
follows: mepivacaine 42.7 mm, lidocaine 43.5 mm. There was no significant difference
between the two anesthetics regarding needle insertion pain (p>0.05). While females
reported more pain than males, no significant differences in insertion pain were seen
between subject genders. The means for both anesthetics were in the “mild” category on
the VAS.
The mean VAS pain ratings for needle placement during the first injection were
as follows: mepivacaine 55.6 mm, lidocaine 57.1 mm. There was no significant
difference between the two anesthetics regarding needle placement pain (p>0.05). The
means for both anesthetics were in the “moderate” category on the VAS. Subject gender
64
did not have a significant effect on needle placement pain reported, although females
reported more pain than males.
Regarding the first injection, the mean VAS pain ratings for solution deposition
were as follows: mepivacaine 41.2 mm, lidocaine 39.1 mm. There was no significant
difference between the two anesthetics regarding solution deposition (p>0.05). The
means for both anesthetics were in the “mild” category on the VAS. Females rated
solution deposition of mepivacaine significantly (p=0.0001) more painful than males.
The summary of injection pain ratings from the first injection can be found in
Table A-4. Utilizing lidocaine, subjects reported none-to-mild pain in 80% of needle
insertions, 62% of needle placements, and 84% of solution depositions. With
mepivacaine, subjects reported none-to-mild pain in 83% of needle insertions, 62% of
needle placements, and 78% of solution depositions.
Table A-3 shows the mean pain ratings during each phase of the second injection.
The summary of these ratings can be found in Table A-5. As the patient was partially
anesthetized from the first injection, one would expect the reported pain from the second
injection to be lower; therefore, no analysis of this data was completed.
In both anesthetic groups needle placement during the first injection had the
highest mean pain ratings of the three phases of injection, but there were no significant
differences between the solutions used. Females rated solution deposition of mepivacaine
significantly more painful than lidocaine (Table A-2), but both anesthetics were rated in
the “mild” category. Females reported more pain during all phases of injection (Table A2) versus males, although these differences were smaller for the second injection.
65
Anesthetic success was defined as achieving the first of two consecutive 80/80
(maximum) readings with the electric pulp tester by the fifth testing period (17 minutes
post-injection) and sustaining that reading for the remainder of the 56 minute testing
period. All subjects that were included had profound lip numbness at this time. Six
subjects were reappointed because they did not have lip numbness at 15 minutes postinjection (4 lidocaine/lidocaine, 2 mepivacaine/lidocaine). One subject was disqualified
due to unreliable pulp testing responses. Success rates for mepivacaine/lidocaine and
lidocaine/lidocaine, respectively are as follows: second molar (51.5%, 56.6%), first molar
(44.0%, 40.0%), second premolar (44.7%, 40.4%), first premolar (52.6%, 49.5%), lateral
incisor (30.0%, 27.0%), and central incisor (10.1%, 10.0%). The highest success was
seen in second molars, and the lowest success was in the central incisor. The
mepivacaine/lidocaine combination group generally had a higher success rate, with the
exception of the second molar; however, there were no significant differences between
the two anesthetic groups for any of the teeth tested. It should be noted that some subjects
had teeth previously extracted for orthodontic considerations (mandibular first and
second premolars, mandibular second molars) resulting in N<100 (Table A-6).
Anesthetic failure was defined as the absence of two consecutive 80/80
(maximum) readings with the pulp tester throughout the entire testing period. Failure was
seen in the mepivacaine/lidocaine and lidocaine/lidocaine groups as follows: second
molar (13.1%, 12.1%), first molar (30.0%, 28.0%), second premolar (22.6%, 26.9%),
first premolar (13.4%, 21.6%), lateral incisor (52.0%, 54.0%), and central incisor (72.0%,
75.0%). The lidocaine/lidocaine group generally had a higher failure rate in premolars
66
and incisors, while the mepivacaine/lidocaine group had a higher failure rate in the
molars. The failure rate generally increased from posterior to anterior, with the exception
of the first molar having a higher failure rate than the premolars. The central incisor had
the highest failure rate. No significant difference was seen for failure between the two
anesthetic groups for the teeth tested (Table A-7).
It should be noted that the percentages of success and failure do not add up to
100%. This is due to a group of teeth that fell into neither category. These teeth can be
classified into the following categories: anesthesia of slow onset (two consecutive 80/80
readings obtained after the fourth testing period), anesthesia of short duration (80/80
readings were obtained but lost before the end of the testing period), and/or noncontinuous anesthesia (80/80 readings were obtained, lost, and re-obtained). Clinically,
anesthesia of these teeth would not be considered successful.
Comparisons of pulpal anesthesia over time can be seen in Tables A-9 through A14 and Figures 1-6. No significant differences were seen between the two anesthetics for
any tooth.
Tables A-14 and A-15 show times for onset and duration of anesthesia. Generally,
posterior teeth were numb before anterior teeth. The mean onset times for the
mepivacaine/lidocaine group ranged from 6.9 to 16.2 minutes, while mean onset times
ranged from 6.0 to 12.2 minutes for the lidocaine/lidocaine group. Duration of anesthesia
ranged from 4 to 52 minutes in both groups. No differences in onset or duration were
seen between the two anesthetics.
67
The mean pH of mepivacaine was registered as 6.69, and the mean pH of
lidocaine was 4.28. The difference in pH was significant (p<0.0001) (Table A-16).
68
DISCUSSION
One hundred asymptomatic adult subjects (50 males, 50 females) volunteered to
participate in this study. Subjects ranged in age from 18 to 38 years with a mean age of
25.6 years (Table A-1). Inclusion criteria required subjects to be between the ages of 18
and 65 years. No minors (<18 years) were allowed to participate as they are unable to
provide consent. Nordenram and Danielsson (104) found that local infiltration injections
were more effective in elderly patients versus a younger age group. The authors
speculated that this may be due to a higher pain threshold in the elderly. For this reason,
subjects greater than 65 years of age were excluded from this study.
Subjects were required to be in good health as determined by a written health
history and oral questioning. Exclusion criteria were as follows: history of significant
medical issues (ASA Classification of III or greater), allergy to local anesthetics or
sulfites, or taking any medications (analgesics, alcohol, anti-depressant or anti-anxiety
medications) that would alter perception of pain or metabolism of anesthetics. Opioid
analgesics act at central and peripheral sites and influence the response to a painful
stimulus (105), and while the main action of non-steroidal anti-inflammatory drugs
(NSAIDs) is in response to peripheral inflammation, NSAIDs have also demonstrated
central effects (106, 107). Consumption of ethanol has an inhibitory effect on the CNS,
69
which causes anxiolysis and anesthesia (105). Tricyclic antidepressants (TCAs) inhibit
the neuronal uptake of catecholamines which results in an increased catecholamine
concentration at the sympathetic neuroeffector junction (43, 108). Boakes et al. (109)
noted a 2-4 fold potentiation of cardiovascular effects with subsequent administration of
imipramine and adrenaline, and suggested that the interaction of TCAs and local
anesthetics used in dentistry could be hazardous. TCAs also have analgesic action, as
they are often effective in the treatment of neuropathic pain (105). Anti-anxiety
medications also have CNS depressant effects, which may affect interpretation of pain
(105). These exclusion criteria were intended to eliminate any potential confounding
factors that may affect the results of this study.
Female subjects were questioned regarding pregnancy and were not allowed to
participate if pregnant, suspected a pregnancy, trying to become pregnant, or lactating. If
a pregnancy was suspected, female subjects were required to take a urine pregnancy test
before each appointment. Local anesthetics and vasoconstrictors used in dentistry are
considered to be safe to administer in the pregnant patient (20, 110); however, pregnant
patients were eliminated from this study due to medico-legal reasons. Congenital
anomalies occur naturally in 3% of the general population, yet the cause cannot be
determined in over 50% of these cases (111). The risks of associating such an event with
this study were deemed to be too high; therefore, pregnant subjects were not allowed to
participate.
Females have been shown to report higher levels of pain, more frequent pain, and
pain of longer duration versus males (112). Liddell and Locker found that women report
70
higher levels of dental anxiety, and that they are less accepting of pain versus males
(113). Keogh et al. showed that females are less tolerant to cold pressor pain than males
(114). Fillingim et al. (115) suggested that due to these gender differences, experimental
pain responses may be more clinically relevant for females than males. Unbalanced
gender groups in the current study could have resulted in higher or lower reported
injection pain scores that may mistakenly be attributed to the effect of the anesthetic
solution. For these reasons, males and females were balanced and also separately
evaluated regarding injection pain.
Prior to injection, each subject was informed how to rate injection pain and shown
the visual analog scale (VAS) which was used to record any pain. The VAS is considered
to be the most sensitive method for measuring pain as compared to simple descriptive,
nominal, and nonverbal methods (116). A Heft-Parker VAS was used in this study. Heft
and Parker (103) showed that pain categories should not be equally spaced on a VAS, and
that it is important for the verbal descriptors used (faint, weak, mild, moderate, strong,
intense, severe) to correspond with their location on the scale. The Heft-Parker VAS
combines a graphic rating scale with a visual analog scale, yet allows subjects the ability
to mark any point along the line. It has been noted, however, that subject responses tend
to be grouped around the verbal descriptors (103). Although a four-point scale was used
in many of the previously reviewed studies, Kreimer et al. (77) showed that the category
of rated pain corresponded well when comparing a four-point scale to the Heft-Parker
VAS. Subjects in the current study were instructed to rate the pain experienced during
injection phases of needle insertion, needle placement, and solution deposition.
71
Injection Pain
Needle Insertion
Needle insertion pain was measured in this study. Regarding the first injection,
80% of subjects (88% of males, 72% of females) reported none-to-mild pain during
needle insertion in the lidocaine/lidocaine group, while 83% of subjects (86% of males,
80% of females) reported none-to-mild pain during needle insertion in the
mepivacaine/lidocaine group (Table A-4). When comparing to the range of pain scores
from previous studies (Table 5-1), our results fall somewhere near the middle. No
differences between the two groups were seen, which is expected as the type of anesthetic
used would not have an impact at this stage of injection. Although not statistically
significant, females reported higher levels of pain during needle insertion regardless of
anesthetic group (Table A-2).
Factors influencing the pain of needle insertion may include needle gauge, use of
topical anesthetic, subject gender, and operator differences (20, 47, 112, 117-121).
Flanagan and coauthors evaluated 25- and 27-gauge needles for inferior alveolar nerve
block (IANB) injections (117). They determined that there was no difference in reported
injection pain between the different needle gauges. Brownbill et al. (118) found no
difference of injection pain between 25- and 30-gauge needles in children during the
IANB. A study by Fuller, Menke, and Meyers showed no differences in the perception of
pain produced by penetrations of 25-, 27-, and 30-gauge needles in the retromolar fossa
(119). These studies indicate that it is unlikely that needle gauge has a large impact on
needle insertion pain. The most commonly used needle in dentistry is the 27-gauge long
72
needle (20). As many other anesthetic studies evaluating injection pain during the IANB
have used a 27-gauge needle, it was determined that it should also be used in the current
study so that our results are directly comparable.
The usefulness of topical anesthetic for the IANB has been widely debated. Gill
and Orr (122) found that topical anesthetic had no effect on palatal injection pain;
however, Rosa et al. (123) found a significant decrease in pain with 20% benzocaine and
5% lidocaine versus placebo in the palate. Rosivack et al. (124) concluded that 20%
benzocaine and 5% lidocaine significantly reduced pain during needle insertion versus
placebo in the mucobuccal fold above the maxillary canine. Mikesell (125) found that
injection pain was significantly reduced when using topical anesthetic versus placebo in
maxillary infiltrations. However, none of these studies evaluated the use of topical with
the IANB injection, and injection discomfort can be affected by the area of the mouth that
is injected (126).
The effectiveness of 20% benzocaine as a topical anesthetic was evaluated in a
retrospective study by Nusstein and Beck (47). Moderate-to-severe pain to needle
insertion was reported by 14-22% of subjects during the IANB, whether or not they
received topical anesthetic prior to needle insertion, and there was no significant
difference reported between the two groups. Nakanishi et al. (120) found that while
topical 20% benzocaine reduced injection pain in the anterior mandibular mucobuccal
fold, it was not effective for the IANB injection. Nist (127) found no difference in needle
insertion pain between the topical application of 20% benzocaine, Vaseline, or no
treatment prior to an IANB injection. The results of these studies make it reasonable for
73
one to conclude that topical anesthetic may be of no benefit to patients receiving the
IANB; however, Martin and coauthors (121) suggested that psychologic factors may play
a more important role when topical anesthesia is used to reduce the pain of dental
injections, and Meit et al. (128) found that 93.4% of dentists use topical anesthetic.
Acknowledging that there is some potential benefit to using topical anesthetic, it was
utilized in the current study.
The percentage of asymptomatic subjects in previously reviewed studies reporting
none-to-mild pain during the needle insertion phase of an IANB injection can be
referenced in the following table:
Author
Childers (50)
Dunbar (51)
Reitz (52)
Clark (53)
Willett (54)
Whitcomb et al. (55)
Wolf (57)
Guglielmo (58)
Mikesell (59)*
Goodman (60)*
Steinkruger (61)*
Elmore (62)*
None-to-mild pain
84%
96%
90%
82%
87%
95%
86%
74%
71%
88%
92%
64%
Moderate-to-severe pain
16%
5%
10%
18%
13%
5%
14%
26%
29%
12%
8%
36%
*topical anesthetic was used.
Table 5-1. Needle insertion pain reported by category.
All of the preceding studies used a 27-gauge needle, similar to this study. Mean pain
scores for needle insertion pain during both injections in the current study were in the
mild category (Tables A-2 and A-3). While our study does not show any improvement
over the referenced studies, it is certainly consistent with previous results.
74
Needle Placement
Pain experienced during needle placement may be influenced by the injection
technique, gender, or operator differences (20, 55, 57, 59, 60, 68, 112). Some clinicians
have deposited a small amount of anesthetic solution during needle placement in the hope
that an immediate anesthetic effect would result in less pain for the patient (55, 57, 59,
60, 68); however, it does not appear that this technique has reduced the pain reported.
Nusstein and coauthors evaluated the effects of a 2-stage injection technique on IANB
injection pain (68). Females reported significantly less pain during needle placement with
the two-stage injection versus a conventional injection.
In the current study, needle placement was the most painful stage of injection for
both anesthetic groups and for both genders. Regarding the first injection, 62% of
subjects (74% of males, 50% of females) reported none-to-mild pain during needle
placement in the lidocaine/lidocaine group, while 62% of subjects (68% of males, 56% of
females) reported none-to-mild pain during needle placement in the
mepivacaine/lidocaine group (Table A-4). These results are within the range found in
previous studies, although the number of subjects reporting none-to-mild pain is on the
lower end. This may be due to operator differences. No differences between the two
anesthetic groups were seen, which is expected as the type of anesthetic used would not
have an impact at this stage of injection. Although not statistically significant, females
reported higher levels of pain versus males during needle placement regardless of
anesthetic group (Table A-2). The mean pain scores on the VAS for females during
needle placement were 63.8 mm (lidocaine/lidocaine group) and 62.4 mm
75
(mepivacaine/lidocaine group). While these scores were not statistically higher than in
males (50.5 mm for lidocaine/lidocaine, 48.7 mm for mepivacaine/lidocaine- both in the
mild range), they were within the moderate pain range, which may have some clinical
significance.
Although needle placement pain is reported as none-to-mild by a majority of
patients receiving the IANB injection, it appears to be slightly more painful than needle
insertion as a higher percentage of subjects have reported moderate-to-severe pain during
this phase. Results from previous studies utilizing the conventional IANB technique in
asymptomatic subjects can be seen below:
Author
Childers (50)
Dunbar (51)
Reitz (52)
Clark (53)
Willett (54)
Guglielmo (58)
Elmore (62)
Mikesell (59)*
Goodman (60)*
Whitcomb et al. (55)*
Wolf (57)*
Nusstein et al. (68)*
Nusstein et al. (68)†
None-to-mild
Moderate-to-severe
65%
77%
85%
62%
56%
78%
51%
40%
71%
78%
83%
65%
79%
35%
24%
15%
38%
45%
22%
49%
60%
29%
22%
18%
35%
22%
* anesthetic was deposited as the needle was advanced to the target site.
† 2-stage injection technique.
Table 5-2. Needle placement pain reported by category.
Gender was not evaluated separately in any of the preceding studies, except for Elmore
(62) who found no difference during needle placement. With mean pain scores for
females in the moderate range during needle placement in the current study, the gender
effect certainly warrants further research. It is also obvious when looking at these studies
76
that operator differences can greatly influence pain reported. While our results fall within
the range of previous studies, we showed fewer subjects reporting none-to-mild pain
during needle placement than a majority of authors. More research evaluating operator
differences could also be helpful in reducing the pain of needle placement.
Solution Deposition
Subjects recorded the pain of solution deposition in this study. Factors influencing
the pain of solution deposition may include: speed of injection, volume of anesthetic
injected, type of anesthetic, presence/absence of a vasoconstrictor or other additives, and
subject gender (48, 49, 54, 55, 57-60, 63, 65, 70-72, 74, 75, 112, 129-131). Kanaa and
coauthors (70) showed that a slow (60 seconds) IANB injection of 2.0 mL 2% lidocaine
with 1:80,000 epinephrine was significantly less painful than a fast injection (15
seconds). This is likely due to the higher tissue pressure that is caused from the fast
injection of anesthetic. Kudo (129) measured injection pressure during fast and slow
injections and assessed the pain and anxiety of male subjects. A significant correlation
was noted between injection pressure and pain, and between injection pressure and
anxiety. While this same phenomenon might be expected with the injection of a larger
volume of anesthetic solution, Vreeland et al. (63) found no significant difference in
solution deposition pain when comparing 1.8 mL and 3.6 mL solutions deposited over
two minutes with the IANB injection.
The type of anesthetic used has been suggested to have an effect on pain during
solution deposition (20, 48, 49, 74). In general, solutions containing a vasoconstrictor
77
have a lower pH than plain solutions because they are acidified with an antioxidant by the
manufacturer to prolong the shelf life. Sodium bisulfite is commonly added to slow the
oxidation of epinephrine in commercially prepared solutions; it reacts with oxygen to
form sodium bisulfate which has an even lower pH. It has been suggested that injection
of plain anesthetic solutions should be more comfortable due to their higher pH (20). This
may be because it takes the body less time to buffer tissue fluids to normal levels. A
review of the medical literature shows that buffering local anesthetics with sodium
bicarbonate closer to physiologic pH (7.4) significantly reduces the pain of injection (71),
but this same effect has been debated in the dental field. Whitcomb et al. (55) showed no
difference in solution deposition pain between lidocaine buffered with sodium
bicarbonate and non-buffered lidocaine solutions for the IANB injection. Ridenour et al.
(73) reported 80% of subjects experienced none-to-mild pain during IANB injection of a
sodium bicarbonate-buffered solution, which is similar to the results of our study with
non-buffered anesthetics (Table 4). In a study by Kashyap et al. (72), it was reported that
84% of subjects experienced none-to-mild pain with a non-buffered anesthetic solution
and 100% of subjects experienced no pain during injection of a sodium bicarbonatebuffered anesthetic solution. In that study; however, pain was not recorded by the subject
but was assessed by the operator based on the subject’s response to questioning and
behavioral signs. While the operators were blinded to the anesthetic used, it is possible
that there was some operator bias in this study or a failure to properly recognize all
patient signs.
78
In the current study, each first injection consisted of 1.8 mL of either 2%
lidocaine with 1:100,000 epinephrine or 3% mepivacaine deposited over 90 seconds.
None-to-mild pain when utilizing mepivacaine and lidocaine was reported during 78%
and 84% of injections, respectively (Table A-4). Mean pain scores with mepivacaine
(41.2 mm) and lidocaine (39.1 mm) were both in the mild pain range (Table A-2). While
no significant differences between the two solutions were seen overall, analyzing genders
separately showed that females found solution deposition of mepivacaine significantly
more painful than lidocaine (mean VAS = 53.2 mm vs. 43.9 mm, p=0.0001) (Table A-2).
Females also reported significantly more pain to solution deposition than males (Table A2). The pH of the solutions used in the current study were recorded as lidocaine = 4.28
and mepivacaine = 6.69 (Table 16). Under the assumption that a significant difference in
solution pH should result in a significant difference in pain during solution deposition,
one would expect that the injection of mepivacaine would be less painful than lidocaine.
However, our results indicate no difference between the two solutions with a tendency of
less pain with the lidocaine solution. This is the opposite of what we expected to find.
A study by Kramp and coauthors (48) concluded that the use of 4% prilocaine
plain for IANB injections resulted in significantly less pain than the other solutions
tested, with no difference between 2% lidocaine with 1:100,000 epinephrine and 2%
mepivacaine with 1:20,000 levonordefrin. They hypothesized that this difference is due
to the pH difference of the anesthetic solutions, which were recorded as follows:
lidocaine = 4.12; mepivacaine = 3.05; prilocaine = 6.28. It should be noted that the
lidocaine and mepivacaine each had a lower pH due to the presence of the
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vasoconstrictor. All mean pain scores were in the mild range, so these results may not be
clinically significant.
Wahl, Schmitt, and Overton (74) evaluated injection pain of 4% prilocaine plain,
3% mepivacaine plain, 4% articaine with 1:100,000 epinephrine, and 2% lidocaine with
1:100,000 epinephrine in patients undergoing routine dental procedures. For the IANB,
609 subjects reported the following mean pain scores on a ten-point scale: articaine =
3.33 (56.6 mm on a 170-mm VAS), lidocaine = 3.14 (53.4 mm on a 170-mm VAS),
mepivacaine = 3.12 (53.0 mm on a 170-mm VAS) and prilocaine = 2.66 (45.2 mm on a
170-mm VAS). The authors concluded that prilocaine was significantly less painful
(p<0.001), and hypothesized that this may be associated with the higher pH of the
solution. The pHs of the anesthetic solutions, as measured by the authors, were recorded
as follows: prilocaine = 5.5-6.5; lidocaine = 4.0-4.5; articaine = 3.5-4.5; mepivacaine =
4.5-5.5. While there was a statistically significant finding, it is difficult to say whether
this was clinically significant or not. With a VAS difference of less than 10 mm
(converted to the 170-mm VAS) and three of the four solutions reported in the mild pain
range, patients may not experience noticeably less pain with the injection of a higher pH
solution.
Wahl and coauthors (49) evaluated pain of injection between 4% prilocaine plain
and 2% lidocaine with 1:100,000 epinephrine in patients receiving the IANB prior to
undergoing routine dental procedures. No significant difference was found between the
two solutions. The mean pain scores were in the none-to-mild range. Sumer et al. (sumer)
found no differences in the injection pain of 4% articaine with 1:200,000 epinephrine, 3%
80
prilocaine with 1.08 µg phenylpressin, and 2% lidocaine with 1:100,000 epinephrine.
Subjects reported none-to-mild pain for 75.4% of injections.
Morris et al. (130) evaluated the pain of intradermal and subcutaneous injection of
different local anesthetic solutions and found that 1% mepivacaine was significantly
more painful than 1% lidocaine. The authors stated that the mechanism of pain produced
by local anesthetics is unknown; however, it appears to be unrelated to the formulation of
the anesthetic solutions. That is, the components of the anesthetic solution may not be as
important to injection pain as the chemical structure of the anesthetic molecule. McKay et
al. (131) found that while increasing the pH of a particular anesthetic with sodium
bicarbonate may decrease the pain of injection, the cause of pain is complex and likely
depends on factors other than pH alone. The effect of pH does not appear to be relevant
when comparing different agents (130).
Mikesell (59) found no difference in solution deposition pain between 2%
lidocaine with 1:100,000 epinephrine and 4% articaine with 1:100,000 epinephrine for
IANB injections. McLean (65) reported no significant difference in solution deposition
pain during the IANB between 2% lidocaine with 1:100,000 epinephrine and 3%
mepivacaine, with 70-73% of subjects reporting none-to-mild pain. Ninety-three percent
of subjects in a study by Guglielmo (58) reported none-to-mild pain during solution
deposition of 3% mepivacaine for the IANB. Even with these clinical findings, many
practitioners use a combination of mepivacaine and lidocaine because they believe it
results in less pain for their patients. In theory, the higher pH of mepivacaine should
result in a less painful injection than lidocaine, and one would expect this difference to be
81
evident during the stage of solution deposition. Results of previous studies on
asymptomatic subjects involving these two anesthetics for IANB can be found below:
Author
Anesthetic
Vreeland et al. (63)
Hinkley (64)
Nist (69)
McLean (65)
McLean (65)
Childers (50)
Dunbar (51)
Reitz (52)
Clark (53)
Yonchak (66)
Mikesell (59)
Goodman (60)
Steinkruger (61)
Goldberg et al. (67)
Willett (54)
Whitcomb et al. (55)
Wolf (57)
Elmore (62)
Guglielmo (58)
Volume Speed None/mild
2% Lidocaine
2% Lidocaine
2% Lidocaine
3% Mepivacaine
2% Lidocaine
2% Lidocaine
2% Lidocaine
2% Lidocaine
2% Lidocaine
2% Lidocaine
2% Lidocaine
2% Lidocaine
2% Lidocaine
2% Lidocaine
2% Lidocaine
2% Lidocaine
2% Lidocaine
2% Lidocaine
3% Mepivacaine
1.8 mL
1.8 mL
3.6 mL
1.8 mL
1.8 mL
1.8 mL
1.8 mL
1.8 mL
3.6 mL
3.6 mL
1.8 mL
1.8 mL
1.8 mL
3.6 mL
1.8 mL
3.6 mL
1.8 mL
1.8 mL
1.8 mL
2 minutes
1 mL/min
2 minutes
1 mL/min
1 mL/min
2 minutes
2 minutes
1 minute
2 minutes
2 minutes
1 minute
2 minutes
1 minute
2 minutes
1 minute
2 minutes
1 minute
1 minute
1 minute
67%
90%
75%
73%
70%
83%
79%
99%
58%
93%
81%
83%
84-86%
86%
64%
93%
67%
48%
93%
Moderate/severe
33%
10%
25%
27%
30%
18%
21%
1%
42%
8%
20%
18%
14-16%
15%
36%
8%
33%
52%
8%
Table 5-3. Solution deposition pain reported by category.
Pain reported during solution deposition in our study is consistent with results of previous
studies utilizing these anesthetics. It should be noted, however, that direct comparison
can only be made to the studies utilizing 1.8 mL of 2% lidocaine with 1:100,000
epinephrine (50-52, 54, 57, 59-65) or 3% mepivacaine (58, 65).
Other additives to the anesthetic solution may also influence the pain of solution
deposition. In a study by Willett (54), 50% of subjects reported severe pain when injected
with diphenhydramine for the IANB, but no difference was seen between lidocaine and a
combination of lidocaine and diphenhydramine. Wolf (57) showed no difference in
solution deposition pain during the IANB with the addition of mannitol to lidocaine. The
addition of meperidine to lidocaine in a study by Goodman (60), resulted in subjects
82
reporting significantly more pain during the IANB (as compared to a regular solution of
lidocaine) even though the pHs of the solutions were similar, with the mean VAS score in
the moderate pain category (55.4 mm). Again, this suggests that pain during solution
deposition when comparing different anesthetics is not likely due to pH.
No difference in pain has been reported regarding gender with the conventional
IANB injection, although a two-stage technique resulted in significantly less pain during
needle placement in females (68). Of the studies reviewed, only Elmore (62) evaluated
the effects of subject gender on injection pain during the IANB, but no differences were
found. Further evaluation or research may be warranted to look into the gender effect.
Females have been shown to report higher levels of pain, more frequent pain, and pain of
longer duration versus males (112). Liddell and Locker found that women report higher
levels of dental anxiety, and that they are less accepting of pain versus males (113).
Keogh et al. showed that females are less tolerant to cold pressor pain than males (114).
Fillingim et al. (115) suggested that due to these gender differences, experimental pain
responses may be more clinically relevant for females than males. In the current study,
gender groups were balanced and analyzed separately regarding injection pain to
eliminate gender as a confounder when evaluating the effect of the anesthetic solution on
injection pain.
In our study, females reported higher levels of pain in all phases of injection as
compared to males (Table 2). During the phases of needle insertion, needle placement,
and solution deposition, males reported mean pain ratings of 37.6-39.3 mm, 48.7-50.5
mm, and 29.1-34.3 mm, respectively. Females reported mean pain ratings of 46.0-49.3
83
mm, 62.4-63.8 mm, and 43.9-53.2 mm, respectively. The only difference that was
significant between genders was during solution deposition of mepivacaine (p=0.0001).
One other potential confounding factor appears to be the operator- the person giving the
injection. If all variables in the above-listed studies are controlled (ex- needle size,
injection type, injection technique, anesthetic type, etc.) operator appears to have a large
impact; that is, some operators appear to have caused more moderate-to-severe pain
during injection than others, or the patient population sampled reported more pain (53,
54, 59, 62). Further research needs to be conducted to look at this aspect. Operator
technique differences influence the pain experienced by subjects during all phases of
injection. This was not a confounder of the current study, however, as all injections were
given by a single operator (EL).
Each second injection in our study consisted of 1.8 mL of 2% lidocaine with
1:100,000 epinephrine deposited over 90 seconds. Mean pain ratings were recorded for
this injection (Table A-3) and are summarized in Table A-5. As the patient was partially
anesthetized from the first injection, one would expect the reported pain from the second
injection to be lower; therefore, no analysis of this data was completed. However, pain
ratings were noted to be much lower during the second injection versus the first, and the
difference between genders was smaller although females still tended to report more pain
than males.
While we were hopeful that the combination of mepivacaine and lidocaine would
result in a less painful injection experience for patients, we were unable to show a
difference in solution deposition pain between the two anesthetics. As suggested by
84
Morris et al. (130), it appears that pH is not a significant factor in injection pain when
comparing two different solutions. More research is needed in this area to determine what
components of an anesthetic solution are related to solution deposition pain.
Pulpal Anesthesia
Anesthetic Success
The ability of the anesthetic combinations to provide successful pulpal anesthesia
was also evaluated. The experimental teeth selected for this study were the mandibular
first and second molars, first and second premolars, and central and lateral incisors. The
contralateral canine was used as the unanesthetized control to ensure that the electric pulp
tester (EPT) was operating properly and that the subject was responding appropriately
during each experimental portion of the study. This study used a Kerr (Analytic
Technology Corp., Redmond, WA) EPT. Vital, asymptomatic pulps were evaluated in
virgin or minimally restored teeth. All experimental teeth were determined to be vital by
a positive response to testing with the EPT two times at the beginning of each
appointment. Lundy and Stanley (132) determined that there was no correlation between
the pulpal status and the EPT value, but that a negative (80/80) reading indicated a
necrotic pulp. All pulp testing was done by the principal investigator or a trained research
assistant, both of whom were blinded to the anesthetic combination used. Two
consecutive 80/80 readings on any tooth, teeth exhibiting active caries, periodontal
disease, extensive restorations, history of trauma or symptoms, or teeth missing for
reasons other than orthodontic considerations resulted in the disqualification of that
85
particular quadrant of the subject’s mouth. Eleven subjects had teeth previously extracted
for orthodontic reasons resulting in N<100 (Table A-6). One subject was dismissed from
the study due to unreliable responses during pulp testing.
An electric pulp tester (EPT) was used to measure pulpal anesthesia in this study.
Certosimo and Archer (133) evaluated the level of local anesthesia experienced by
patients undergoing operative dental procedures. Readings were taken with an EPT
before and after injection of anesthetic. Teeth were then prepared for restoration, and
subjects rated their level of anesthesia on a VAS form. EPT readings of less than 80/80
resulted in pain during the procedure. Their results indicated that the EPT is a valuable
tool in predicting pulpal anesthesia in asymptomatic carious teeth. Dreven and coauthors
(134) evaluated the pulpal anesthesia of teeth in symptomatic and asymptomatic subjects
presenting for endodontic treatment. They showed that with an 80/80 reading, profound
anesthesia during endodontic treatment occurred in 100% of asymptomatic patients and
73% of subjects with symptomatic irreversible pulpitis. Modaresi et al. (135) confirmed
that EPT can be an accurate device in determining pulpal anesthesia in asymptomatic
teeth.
The traditional definition of anesthetic success for an IANB injection is numb
within 15 minutes of injection and sustaining anesthesia for 60 minutes. This definition is
used because it is clinically practical: dentists want patients to obtain anesthesia within a
reasonable amount of time and maintain anesthesia during the entire dental procedure.
This definition of success was used in the current study and is used in most studies
referenced in this discussion unless otherwise noted.
86
The current study is the first to evaluate the combination of 3% mepivacaine plain
and 2% lidocaine with 1:100,000 epinephrine in human subjects. Some clinicians use
these anesthetics together for IAN blocks. The thought behind this is that 3%
mepivacaine has more anesthetic molecules available to block sodium channels due to its
higher concentration and that it also has a higher pH (pH = 6.69) because it does not
contain epinephrine. Both of these conditions may provide more of the base form of the
anesthetic for the IANB initially, therefore potentiating the anesthetic effect after
administration of lidocaine.
Local anesthetics are prepared as salts, which are water soluble, and exist
simultaneously as uncharged base molecules and positively charged cations. The
Henderson-Hasselbalch equation [log(base/acid)=pH-pKa] shows that when the pH is
equal to the pKa of the anesthetic, 50% of the drug exists in each form. Physiologic pH is
7.4, and while the tissues tend to maintain a normal pH, it takes longer to buffer a more
acidic anesthetic solution. Solutions with a lower pH due to a vasoconstrictor (see
Discussion, page 78), such as lidocaine, may have a longer onset time while the tissues
neutralize the solution to normal pH. Lidocaine, with a pKa of 7.9, has less available
uncharged base-form molecules available to diffuse through the nerve sheath versus
mepivacaine, with a pKa of 7.6. This may not only affect success of anesthesia, but may
result in slower onset of lidocaine versus mepivacaine (20). McLean et al. (16) showed
no difference in success or onset of anesthesia when comparing lidocaine and
mepivacaine. The current study was done in the hope that this combination of anesthetics
might have a synergistic effect and result in increased pulpal anesthesia success rates
87
with the IANB. Rood and coauthors (17) reported on the potential benefits of using
prilocaine and lidocaine in combination, but it was determined that there was no
potentiation of the anesthetic effect.
In our study, anesthetic success was defined as the first of two consecutive 80/80
readings within the first five testing periods (17 minutes post-injection), with the 80/80
reading sustained through the remainder of the 56-minute testing period. All subjects
were required to have profound lip numbness within 15 minutes of receiving the second
IANB injection. The absence of lip numbness indicated a failed IANB, and this occurred
in six subjects who were reappointed. It is important to note that these six subjects all had
profound lip numbness at their other two appointments. The pH of each solution was
measured as follows: 6.69 (mepivacaine) and 4.28 (lidocaine) (Table A-16).
Success rates for mepivacaine/lidocaine and lidocaine/lidocaine, respectively,
were as follows: second molar (51.5%, 56.6%), first molar (44.0%, 40.0%), second
premolar (44.7%, 40.4%), first premolar (52.6%, 49.5%), lateral incisor (30.0%, 27.0%),
and central incisor (10.1%, 10.0%) (Table A-6, Figures 1-6). No significant differences
were noted between the two anesthetic groups for any tooth. It should be noted that direct
comparisons to the control group can only be made by the referenced studies that utilized
3.6 mL of 2% lidocaine with 1:100,000 epinephrine and used the same definition of
success as the current study (55, 67, 69, 83, 92). Our success rates are slightly lower than
those of previous studies, but fairly similar to results by Nist et al. (69). This may be due
to the population sampled. Unfortunately, no improvement of pulpal anesthetic success
was found with the combination of mepivacaine and lidocaine.
88
Factors that may influence pulpal anesthetic success also include the speed of
injection (70), presence of a vasoconstrictor (20), volume or concentration of anesthetic
(1, 63, 83, 94), additives to the solution (55, 79, 90, 93, 96), accuracy of the injection (56,
86, 91), and anesthetic type (16, 88, 89). Kanaa et al. (70) found that total pulpal
anesthesia was greater in subjects receiving the IANB over 60 seconds versus 15 seconds
in asymptomatic subjects. They suggest this is due to deeper penetration of the nerve
trunk by the anesthetic with a slow injection as discussed by Rucci et al. (136).
The presence of a vasoconstrictor may affect anesthetic success. An IANB
injection of 2% lidocaine without a vasoconstrictor may only last for 10-20 minutes (20);
when 1:100,000 epinephrine is added, the duration of pulpal anesthesia is likely to be
greater than 60 minutes (16, 55, 56, 63, 67, 69, 78-83, 85-95, 97). With the definition
used in this study, shorter duration of an anesthetic without a vasoconstrictor would most
likely cause it to be classified as a failure. Anesthetics such as mepivacaine and
prilocaine have less vasodilatory effects; therefore, a vasoconstrictor is not needed to
extend the duration of these drugs (20). The concentration of vasoconstrictor does not
appear to affect pulpal anesthetic success. Wali et al. (94), Yared and Dagher (83), and
Dagher et al. (82) all showed no difference in success when altering the concentration of
epinephrine in a lidocaine solution for the IANB.
It has been suggested that increasing the volume or concentration of anesthetic
administered may increase the success of pulpal anesthesia with the IANB injection (1,
63, 83, 94). Studies have shown success rates utilizing 3.6 mL 2% lidocaine with
1:100,000 epinephrine ranging over the following percentages: second molar 50-87%,
89
first molar 43-77%, second premolar 52-90%, first premolar 56-80%, lateral incisor 2567%, and central incisor 10-39% (55, 63, 67, 69, 83, 85, 87, 92) (Table A-17). In studies
utilizing 1.8 mL of 2% lidocaine with 1:100,000 epinephrine, success ranged from:
second molar 45-92%, first molar 32-85%, second premolar 29-92%, first premolar 4290%, lateral incisor 14-65%, and central incisor 2-38% (16, 56, 63, 78-82, 84, 86, 88-91,
93-95) (Table A-17). A retrospective evaluation of these studies by Nusstein (1) showed
no difference in pulpal anesthetic success related to the volume of the anesthetic solution
deposited. Although a retrospective evaluation by Yared and Dagher (83) showed higher
pulpal anesthesia success rates with a greater volume of anesthetic, this trend was not
seen in studies by Vreeland et al. (63) and Wali et al. (94). Therefore, it is assumed that
volume of anesthetic solution does not influence pulpal anesthetic success. In the current
study it was decided to use 3.6 mL of lidocaine because clinicians combining
mepivacaine and lidocaine would use 1.8 mL cartridges of these anesthetics (resulting in
a total volume of 3.6 mL), and by utilizing 3.6 mL of lidocaine the volume of the control
group and experimental group were the same.
Other studies aiming to increase the success of the IANB have included using
lidocaine hydrocarbonate (79), changing the concentration of epinephrine in the
anesthetic (82, 83, 94), using a higher concentration of anesthetic (63), adding meperidine
(90) or diphenhydramine (93), buffering the anesthetic solution with sodium bicarbonate
(55), and a frequency-dependent conduction blockade (95). Unfortunately, none of these
methods has increased the success of the IANB. Wolf et al. (96) attempted to increase
success of the IANB with the utilization of mannitol. Mannitol is a six-carbon sugar
90
alcohol that opens the perineural membrane and is commonly used in medicine to enable
chemotherapeutic agents to cross the blood-brain barrier (137). The addition of mannitol
to lidocaine was shown to increase total pulpal anesthesia 9-16%, but this method is
clinically impractical to use and success was still not at an acceptable level (96).
Attempts to improve the accuracy of the IANB injection have included
ultrasound-guided placement (86), evaluation of needle bevel direction utilizing the
directional and bi-directional techniques (91), and the use of a peripheral nerve stimulator
(56). These studies showed that even with an accurate injection, the IANB success rate
did not improve over the conventional technique. This may be because anesthetic
solutions move in the path of least resistance, and even if the anesthetic is deposited in
the pterygomandibular space it may move away from the nerve (15, 138, 139).
Supplemental injections such as the incisive nerve block (69), PDL (80), intraosseous
(81, 84), mylohyoid (85), bilateral IANB (87), and buccal and lingual infiltrations (76,
92) have been studied in an attempt to improve the success of the IANB with mixed
success.
Different anesthetic solutions have been used for the IANB in an attempt to
increase the incidence of successful pulpal anesthesia. Mikesell et al. (88) evaluated the
anesthetic efficacy of articaine and lidocaine for the IANB injection and found no
significant difference between the two anesthetics. Fernandez et al. (89) compared
lidocaine and bupivacaine and found that lidocaine had higher success rates in all study
teeth except first molars. It has been shown that 3% mepivacaine is equivalent to 2%
lidocaine with 1:100,000 epinephrine in terms of anesthetic success with the IANB (16).
91
The pulpal anesthetic success rates of previous studies utilizing mepivacaine or lidocaine
in asymptomatic patients can be found in the Table A-17.
Figures 1-6 show the percentage of pulpal anesthesia throughout the 56-minute
testing period. The curves on each figure are nearly identical when comparing the two
anesthetic groups. Most teeth showed a dramatic increase in pulpal anesthesia through 17
minutes, then sustained anesthesia or gradually increased for the remainder of the testing
period. Clinically, this indicates that both anesthetic groups behave similarly, and that if
pulpal anesthesia is obtained it will likely be sustained for at least 56 minutes. Neither
anesthetic combination in our study was able to provide successful pulpal anesthesia in
all patients.
Anesthetic Onset
The onset of anesthesia is determined by the pKa of the anesthetic solution (20),
and may be affected by the concentration of anesthetic, additives to the solution, or by
utilizing a combination of drugs. When the pKa of a solution is close to physiologic pH
of 7.4, a higher percentage of base form molecules are available to diffuse across the
nerve sheath; therefore, the time to onset is dependent on the number of anesthetic
molecules available. Theoretically, with a higher concentration of anesthetic, more base
molecules should also be available to diffuse through the nerve sheath to bind at the
receptor site in the ion channel and produce anesthesia. However, Vreeland et al. (63)
found no difference in onset times between 2% lidocaine and 4% lidocaine solutions in
the first molar and lateral incisor. McLean et al. (16) showed no difference between 4%
92
prilocaine, 3% mepivacaine, and 2% lidocaine solutions regarding mean onset time of
pulpal anesthesia for any of the teeth tested. Therefore, anesthetic concentration may not
be as critical of a factor.
It has been suggested that adjusting the pH of an anesthetic solution with sodium
bicarbonate may result in faster onset of anesthesia (20). While this buffering technique
has proven to have some success in medicine (140-142), it has yet to show a decrease in
anesthetic onset times with the IANB. Whitcomb et al. (55) evaluated the time to
anesthetic onset with buffered and non-buffered 2% lidocaine solutions and found no
difference for any of the teeth tested. Mean onset times for pulpal anesthesia in previous
IANB studies on asymptomatic subjects can be found in Table 5-4:
93
Author (anesthetic)
Tooth
Mean Onset (minutes)
Steinkruger et al. (91)
(2% lidocaine)
Second molar
First molar
Second premolar
First premolar
Lateral incisor
Central incisor
Second molar
First molar
Second premolar
First premolar
Lateral incisor
Central incisor
Second molar
First molar
Second premolar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
Lateral incisor
First molar
Premolars
Lateral incisors
5.3 ± 5.6, 3.9 ± 4.7
8.8 ± 7.8, 9.2 ± 8.5
10.2 ± 11.5, 10.3 ± 10.0
11.1 ± 10.0, 10.8 ± 9.7
17.1 ± 17.6, 13.0 ± 13.9
19.1 ± 11.1, 19.4 ± 14.0
5 ± 6.6
5 ± 6.0
7 ± 7.3
7 ± 6.7
11 ± 6.3
12 ± 9.3
6.4 ± 1.09
10.7 ± 2.17
8.1 ± 1.12
7.7 ± 1.16
12.0 ± 1.75
10.8 ± 2.0
11.8 ± 1.9
17.2 ± 2.9
8.2 ± 2.0
10.0 ± 1.7
14.6 ± 3.3
13.3 ± 2.7
12.5 ± 2.5
11.6 ± 2.8
8.8 ± 1.8
10.6 ± 1.6
12.3 ± 1.9
8.44 ± 1.85
13.20 ± 2.35
6.8 ± 5.8
8.9 ± 7.9
10.9 ± 11.3
Whitcomb et al. (55)
(2% lidocaine)
Fernandez et al. (89)
(2% lidocaine)
McLean et al. (16)
(2% lidocaine)
McLean et al. (16)
(3% mepivacaine)
Wali et al. (94)
(2% lidocaine)
Hinkley et al. (78)
(2% lidocaine)
Vreeland et al. (63)
(2% lidocaine)
Kanaa et al. (76)
(2% lidocaine)
Table 5-4. Mean onset times for pulpal anesthesia of IANB.
The current study hypothesized that there may be a faster time to onset with the
combination of anesthetics due to the lower pKa and higher concentration of
mepivacaine, and that there may be some potentiation of lidocaine when given as a
second injection. The pH of each solution was measured and found to be the following:
6.69 (mepivacaine), and 4.28 (lidocaine) (Table A-16). In our study, mean times for onset
94
of anesthesia (in minutes) for mepivacaine/lidocaine and lidocaine/lidocaine,
respectively, were the following: second molar (6.9 ±8.9, 6.0 ± 8.2), first molar (8.1 ±
8.3, 7.6 ± 10.0), second premolar (8.1 ± 7.6, 10.8 ± 11.2), first premolar (10.3 ± 11.5, 9.4
± 8.6), lateral incisor (10.2 ± 10.8, 12.2 ± 10.7), central incisor (16.2 ± 14.7, 12.2 ± 8.9)
(Table A-14). These times are very similar to onset times in the previously reviewed
studies. No improvement was noted with the mepivacaine/lidocaine combination. No
significant differences were seen between the two anesthetic groups. One weakness of
our study is that onset times could only be calculated according to the testing time
periods (4-minute intervals). This allows for large standard deviations and a much less
accurate determination of time to onset of pulpal anesthesia. Ideally, onset time could be
measured more accurately by testing the same tooth every 30 seconds, but this would
result in data for only that tooth and this method would be impractical in a research
setting.
Anesthetic Duration
The mean anesthetic duration times ranged from 35.2-44.5 minutes in our study
(Table A-15). However, these numbers do not reflect an accurate model in determining
anesthetic duration. They only take into account the subjects who achieved anesthetic
onset, and measured anesthesia only through the 56-minute testing period. Peak incidence
of anesthesia ranged from 17-53 minutes with mepivacaine/lidocaine, and 25-53 minutes
with lidocaine/lidocaine (Tables A-8 through A-13, Figures 1-6). In general, anterior
teeth had a later peak incidence of anesthesia. Fernandez et al. (89) evaluated the
95
anesthetic duration of 1.8 mL 2% lidocaine with 1:100,000 epinephrine and found that
pulpal anesthesia decreased the most between 2 and 2.5 hours. Most of the other
reviewed studies (16, 55, 56, 63, 67, 69, 78-83, 85-88, 90-95, 97) also measured pulpal
anesthesia only for 50-60 minutes, as success is commonly defined within these
parameters.
Factors that may influence anesthetic duration include volume of anesthetic, type
of anesthetic, and additives to the solution. While maxillary anesthetic studies have
shown increased duration of anesthesia with a greater volume of anesthetic (143-145), no
one has evaluated the effect of volume on duration of anesthesia in the mandible. This
may be due to the fact that duration of anesthesia generally tends to be longer in the
mandible versus the maxilla (15), so this is not a common clinical problem. In other
words, most patients who obtain pulpal anesthesia are able to sustain it for the remainder
of the procedure. Short duration of anesthesia will be discussed later. More research
could be done to compare the relationship of anesthetic volume to duration with the
IANB.
Long-acting anesthetics can greatly increase the duration of pulpal anesthesia.
Fernandez et al. (89) showed that bupivacaine had a significantly longer duration than
lidocaine when used for the IANB. Success rates within the first hour, however, were
significantly higher with lidocaine. Malamed (20) has suggested that a hydrocarbonated
solution should provide a longer duration of anesthesia, as the intracellular pH is
decreased by CO 2 and the charged cation form of the anesthetic is “trapped” within the
nerve trunk. Chaney et al. (79) showed no difference in onset or peak incidence of
96
anesthesia in the first molar and first premolar when comparing lidocaine hydrocarbonate
and lidocaine hydrochloride solutions, but since testing was stopped at 60 minutes
postinjection it is impossible to evaluate the full duration of the anesthetics in this study.
Mepivacaine has only mild vasodilating properties and therefore can provide longer
duration of anesthesia than most other local anesthetics without the addition of a
vasoconstrictor (20). No significant differences in duration were found between 3%
mepivacaine and 2% lidocaine with 1:100,000 epinephrine in the current study (Table
15).
Anesthetic Failure
Anesthetic failure was defined as the absence of two consecutive 80/80 readings
during the testing period. Previous studies utilizing lidocaine or mepivacaine have shown
the failure rates that can be found in Table A-18.
In the current study, anesthetic failure was observed in mepivacaine/lidocaine and
lidocaine/lidocaine groups at the following rates: second molar (13.1%, 12.1%), first
molar (30.0%, 28.0%), second premolar (22.6%, 26.9%), first premolar (13.4%, 21.6%),
lateral incisor (52.0%, 54.0%), and central incisor (72.0%, 75.0%) (Table A-7). With the
exception of the premolars, failure seemed to increase from posterior to anterior. It
should be noted that direct comparisons to the control group can only be made by the
referenced studies that utilized 3.6 mL of 2% lidocaine with 1:100,000 epinephrine (69,
83, 85). The failure rates in this study are consistent with previous studies using
mepivacaine or lidocaine, and the combination of the two anesthetic solutions did not
97
decrease the failure rate for any of the teeth tested. Reasons for anesthetic failure can be
found later in this discussion.
Subsets of failure include slow onset of anesthesia, non-continuous anesthesia,
and anesthesia of short duration. These are problems occasionally encountered clinically,
and as a result, they have been defined and evaluated during anesthetic studies. Slow
onset of anesthesia is considered to occur when the subject experiences the onset of
pulpal anesthesia (two consecutive 80 readings) greater than 15 minutes post-injection.
The incidence of slow onset anesthesia in asymptomatic subjects following the IANB, as
found in previous studies, can be seen below:
Author
Anesthetic
Mikesell et al. (88)
2% lidocaine
McLean et al. (16)
McLean et al. (16)
Nusstein et al. (1)
Hinkley et al. (78)
Dagher et al. (82)
Yared et al. (83)
Vreeland et al. (63)
Tooth
Second molar
First molar
Second premolar
First premolar
Lateral incisor
Central incisor
2% lidocaine
First molar
First premolar
Lateral incisor
3% mepivacaine First molar
First premolar
Lateral incisor
2% lidocaine
First molar
First premolar
Lateral incisor
2% lidocaine
First molar
First premolar
Lateral incisor
2% lidocaine
First molar
First premolar
Lateral incisor
2% lidocaine
First molar
First premolar
Lateral incisor
2% lidocaine
First molar
Lateral incisor
Incidence (%)
14%
19%
16%
23%
19%
16%
13%
23%
30%
17%
20%
20%
19-22%
19-27%
22-27%
11%
21%
14%
10%
17%
23%
17%
3%
10%
3.3%
16.7%
Table 5-5. Incidence of anesthesia of slow onset for IANB.
98
The current study found the following percentages of anesthesia of slow onset
utilizing mepivacaine/lidocaine and lidocaine/lidocaine, respectively: second molars
(12.8%, 14.0%), first molars (20.3%, 18.3%), second premolars (20.5%, 29.0%), first
premolars (22.9%, 18.7%), lateral incisors (22.4%, 36.2%), central incisors (32.1%,
46.2%). Slow onset of anesthesia was seen more frequently in anterior versus posterior
teeth, with no difference found between the two anesthetic groups. Our results were
similar to those of previous studies in the posterior teeth, although we found a higher
incidence of slow onset in lateral and central incisors. This may be due to the population
sampled.
Non-continuous anesthesia is considered to occur when onset of pulpal anesthesia
is achieved within 15 minutes, but the 80 reading is lost and then regained during the
testing period. The incidence of non-continuous anesthesia in asymptomatic subjects, as
found in previous IANB studies, can be seen below:
Author
Anesthetic
Tooth
Incidence (%)
McLean et al. (16)
2% Lidocaine
McLean et al. (16)
3% Mepivacaine
Nusstein et al. (1)
2% Lidocaine
Dagher et al. (82)
2% Lidocaine
Yared et al. (83)
2% Lidocaine
First molar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
Lateral incisor
20%
3%
10%
30%
20%
17%
20%
8-12%
13-15%
20%
27%
27%
0%
0%
0%
20.0%
10.0%
Vreeland et al. (63)
2% Lidocaine
Table 5-6. Incidence of non-continuous anesthesia for IANB.
99
The incidence of non-continuous anesthesia in our study was found in the
following percentages when utilizing mepivacaine/lidocaine and lidocaine/lidocaine,
respectively: second molar (26.7%, 19.8%), first molar (18.8%, 29.6%), second premolar
(24.7%, 26.1%), first premolar (22.9%, 22.7%), lateral incisor (18.4%, 25.5%), central
incisor (39.3%, 30.8%). No significant differences were noted between the two anesthetic
groups, although the incidence of non-continuous anesthesia is slightly higher in our
study as compared to previous studies. This could be due to the population sampled.
Anesthesia is of short duration if the subject achieves two consecutive 80
readings, but loses the 80 reading prior to the end of testing (60 minutes) and it is not
regained during the testing period. Previous studies have shown the following incidence
of anesthesia of short duration in asymptomatic subjects with the IANB:
Author
Anesthetic
Volume
McLean et al. (16)
2% lidocaine
1.8 mL
McLean et al.(16)
3% mepivacaine
1.8 mL
Nusstein et al. (1)
2% lidocaine
1.8-3.6 mL
Hinkley et al. (78)
2% lidocaine
1.8 mL
Dagher et al. (82)
2% lidocaine
1.8 mL
Yared et al. (83)
2% lidocaine
3.6 mL
Vreeland et al. (63)
2% lidocaine
1.8 mL
Tooth
First molar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
First premolar
Lateral incisor
First molar
Lateral incisor
Table 5-7. Incidence of anesthesia of short duration with IANB.
100
Incidence (%)
10%
7%
0%
17%
17%
17%
8-12%
6-7%
7-8%
4%
4%
0%
13%
20%
17%
10%
20%
10%
3.3%
10.0%
Our study found the following incidence of anesthesia of short duration when
utilizing mepivacaine/lidocaine and lidocaine/lidocaine, respectively: second molar
(18.6%, 23.3%), first molar (21.7%, 18.3%), second premolar (13.7%, 8.7%), first
premolar (12.0%, 5.3%), lateral incisor (18.4%, 6.4%), central incisor (32.1%, 3.8%). No
significant differences were noted between the two anesthetic groups; however, with the
exception of the second molar, the incidence of anesthesia of short duration was higher in
the mepivacaine/lidocaine group for all other teeth. Both groups have a high incidence of
anesthesia of short duration when comparing to previous studies; this may be due to the
population sampled.
While the cause of anesthetic failure remains undetermined, there are several
hypotheses as to why this phenomenon occurs. Traditionally, it has been assumed that
anatomic variation has led to inadequate nerve blockade (100); however, Hannan et al.
(86), Simon et al. (56), and Steinkruger et al. (91) have shown that even an accurate
injection can result in failure of pulpal anesthesia. Another theory is that accessory nerve
innervation may prevent mandibular pulpal anesthesia when only the inferior alveolar
nerve is blocked. The chief nerve that is considered or blamed is the mylohyoid nerve
which branches from the inferior alveolar nerve prior to its entry into the mandibular
canal. The mylohyoid nerve runs downward and along the mylohyoid groove on the
medial surface of the ramus (20). A study by Clark et al. (85) showed no improvement in
pulpal anesthesia when adding a mylohyoid nerve block to the IANB. Also implicated is
the retromolar canal, which may contain accessory innervation to the mandibular teeth.
Von Arx et al. (101) recently showed a 25% incidence of this canal that branches off
101
from the mandibular canal behind the third molar and travels to the retromolar foramen in
the retromolar fossa. No study has looked at giving a supplemental injection to
anesthetize this nerve. Failure and low success rates in mandibular anterior teeth have
been associated with inferior alveolar nerve cross-innervation. Yonchak et al. (87)
attempted to achieve pulpal anesthesia in mandibular anterior teeth utilizing bilateral
mandibular blocks, and although this technique was slightly more successful than a
unilateral block, anesthetic failure was still observed in mandibular incisors.
The effects of pH have been blamed for anesthetic failure. Solutions with a lower
pH generally have fewer base molecules available to diffuse through the nerve sheath,
which may result in slower onset and lower success rates. Buffering an anesthetic with
sodium bicarbonate or using a hydrocarbonated solution causes CO 2 to enter the cell and
decrease intracellular pH, which favors the passage of the ionized form of an anesthetic
to pass through the cell membrane (20). Whitcomb et al. (55) and Chaney et al. (79)
studied these theories in asymptomatic patients, but no difference was seen in anesthetic
success using buffered or hydrocarbonated anesthetics for the IANB injection, and
anesthetic failure was significantly greater in hydrocarbonated solutions lacking
epinephrine (79).
Perhaps the more widely accepted theory for anesthetic failure in asymptomatic
patients is the central core theory. This theory states that the fibers on the outside of the
nerve bundle, which are the first to be anesthetized, supply the molars while the fibers in
the center of the nerve bundle, which are the last to be anesthetized, supply the anterior
102
teeth (15, 24, 102). While this theory may explain higher experimental failure rates in
anterior teeth, it does not address anesthetic failure in molars or premolars (15).
Although our study was unable to find an improvement of anesthetic success with
the combination of mepivacaine and lidocaine for the IANB, it is clear that more research
needs to be done in this area. The IANB is the most frequently administered mandibular
injection (20), and it is imperative that we improve success rates if our aim is to provide
painless dentistry. Until we find a method to do so, supplemental injections such as the
periodontal ligament injection (80), intraosseous injection (81, 84), and mandibular
buccal infiltration injection (76, 92) currently seem to be the best way to achieve pulpal
anesthesia when used in combination with the IANB.
103
SUMMARY AND CONCLUSIONS
The purpose of this prospective, randomized, double-blind study was to compare
the degree of pulpal anesthesia obtained with a combination 3% mepivacaine/2%
lidocaine with 1:100,000 epinephrine formulation versus 2% lidocaine with 1:100,000
epinephrine/2% lidocaine with 1:100,000 epinephrine formulation in inferior alveolar
nerve (IAN) blocks, and to study the injection pain of the two sets of IAN blocks.
One hundred asymptomatic subjects (50 males, 50 females) volunteered to
participate in this study. The experimental teeth tested were mandibular first and second
molars, first and second premolars, and lateral and central incisors. Prior to injection,
pulp vitality was confirmed with an electric pulp tester (EPT). Subjects were instructed to
report the pain of needle insertion, needle placement, and solution deposition on a HeftParker VAS form.
Inferior alveolar nerve block (IANB) injections of 1.8 mL 3% mepivacaine plus
1.8 mL 2% lidocaine with 1:100,000 epinephrine and two injections of 1.8 mL 2%
lidocaine with 1:100,000 epinephrine were administered at two separate appointments
spaced at least one week apart. The experimental teeth were pulp tested every 4 minutes
for 56 minutes post-injection. No subject response at maximum output of the EPT (80
reading) was the criterion for pulpal anesthesia. Anesthesia was considered successful
when the subject achieved two consecutive 80 readings within 17 minutes post-injection
104
and continuously sustained the 80 reading for the remainder of the testing period. The pH
of each anesthetic solution was also measured.
Mean injection pain scores for the first injection were in the mild pain range, with
the exception of needle placement pain in females, which was rated as moderate. No
significant differences in needle insertion and needle placement pain were noted between
the anesthetic groups. While a significant pH difference was found between the two
anesthetic solutions (p<0.0001), no significant difference in solution deposition pain was
seen between the two groups (p>0.05). No statistical analysis of the second injection was
completed, although injection pain was noted to be less than during the first injection.
Anesthetic success was not significantly different between the anesthetic groups in any of
the teeth tested. The combination of 1.8 mL 3% mepivacaine and 1.8 mL 2% lidocaine
with 1:100,000 epinephrine is not different than two injections of 1.8 mL 2% lidocaine
with 1:100,000 epinephrine in regard to injection pain and pulpal anesthetic success for
the IANB.
105
APPENDIX A
TABLES
106
Males
Females
Total
# of
subjects
Age range
(years)
Mean age
(years)
Standard
Deviation
50
50
100
21-32
18-38
18-38
25.8
25.4
25.6
±2.53
±3.60
±3.10
Table A-1. Biographical data for all subjects.
107
Total
(N=100)
Male (N=50)
Female (N=50)
p-value†
p-value adj‡
Mepivacaine/
Lidocaine
42.7 ± 24.1
39.3 ± 23.4
46.0 ± 24.5
0.1281
0.2013
Lidocaine/
Lidocaine
43.5 ± 24.2
37.6 ± 18.3
49.3 ± 27.8
0.0227
0.0909
Needle Placement
Total
(N=100)
Male (N=50)
Female (N=50)
p-value†
p-value adj‡
55.6 ± 28.9
48.7 ± 26.1
62.4 ± 30.3
0.0438
0.1315
57.1 ± 28.2
50.5 ± 26.9
63.8 ± 28.1
0.0161
0.0804
Solution Deposition
Total
(N=100)
Male (N=50)
Female (N=50)
p-value†
p-value adj‡
41.2 ± 27.0
29.1 ± 18.1
53.2 ± 29.1
<0.0001
0.0001
39.1 ± 24.7
34.3 ± 22.3
43.9 ± 26.3
0.1007
0.2013
Needle Insertion
p-value*
p-adj‡
0.9060
0.4003
1.0000
0.8006
0.6893
0.6859
1.0000
0.8006
0.0714
0.0065
0.2143
0.0194
† Multiple Mann-Whitney-Wilcoxon tests.
* Multiple Wilcoxon matched-pairs, signed ranks tests.
‡ Corrected with step-down Bonferroni method of Holm x 6.
Table A-2. Mean pain ratings for first injection as measured on 170-mm VAS (in
mm).
108
Needle
Insertion
Total (N=100)
Male (N=50)
Female (N=50)
Mepivacaine/
Lidocaine
24.4 ± 24.6
22.2 ± 22.0
26.6 ± 27.1
Lidocaine/
Lidocaine
27.3 ± 23.8
25.8 ± 25.5
28.8 ± 22.1
Needle
Placement
Total (N=100)
Male (N=50)
Female (N=50)
21.6 ± 24.8
20.6 ± 24.5
22.6 ± 25.4
27.8 ± 27.1
26.0 ± 27.1
29.6 ± 27.3
Solution
Deposition
Total (N=100)
Male (N=50)
Female (N=50)
12.0 ± 18.5
11.5 ± 15.7
12.5 ± 21.0
16.7 ± 19.6
16.3 ± 16.0
17.1 ± 22.9
Table A-3. Mean pain ratings for second injection as measured on 170-mm VAS (in
mm).
109
Mepivacaine/Lidocaine
Female (N=50)
Insertion
Placement
Deposition
Male (N=50)
Insertion
Placement
Deposition
None
Mild
Moderate
Severe
0
1 (2%)
0
40 (80%)
27 (54%)
31 (62%)
9 (18%)
20 (40%)
19 (38%)
1 (2%)
2 (4%)
0
0
1 (2%)
3 (6%)
43 (86%)
33 (66%)
44 (88%)
7 (14%)
16 (32%)
3 (6%)
0
0
0
1 (2%)
0
0
35 (70%)
25 (50%)
39 (78%)
12 (24%)
23 (46%)
11 (22%)
2 (4%)
2 (4%)
0
0
2 (4%)
3 (6%)
44 (88%)
35 (70%)
42 (84%)
6 (12%)
13 (26%)
5 (10%)
0
0
0
Lidocaine/Lidocaine
Female (N=50)
Insertion
Placement
Deposition
Male (N=50)
Insertion
Placement
Deposition
Table A-4. Injection pain (first injection) utilizing 4-point scale.
110
Mepivacaine/Lidocaine
Female (N=50)
Insertion
Placement
Deposition
Male (N=50)
Insertion
Placement
Deposition
None
Mild
Moderate
Severe
12 (24%)
14 (28%)
24 (48%)
31 (62%)
32 (64%)
23 (46%)
7 (14%)
3 (6%)
3 (6%)
0
1 (2%)
0
12 (24%)
16 (32%)
22 (44%)
35 (70%)
30 (60%)
27 (54%)
3 (6%)
4 (8%)
1 (2%)
0
0
0
9 (18%)
9 (18%)
17 (34%)
37 (74%)
34 (68%)
31 (62%)
4 (8%)
6 (12%)
2 (4%)
0
1 (2%)
0
12 (24%)
14 (28%)
15 (30%)
33 (66%)
31 (62%)
34 (68%)
5 (10%)
5 (10%)
1 (2%)
0
0
0
Lidocaine/Lidocaine
Female (N=50)
Insertion
Placement
Deposition
Male (N=50)
Insertion
Placement
Deposition
Table A-5. Injection pain (second injection) utilizing 4-point scale.
111
Tooth
Second Molar
First Molar
Second Premolar
First Premolar
Lateral Incisor
Central Incisor
N
99
100
93
97
100
100
Mepivacaine/
Lidocaine
51 (51.5%)
44 (44.0%)
42 (44.7%)
51 (52.6%)
30 (30.0%)
10 (10.1%)
Lidocaine/
Lidocaine
56 (56.6%)
40 (40.0%)
38 (40.4%)
48 (49.5%)
27 (27.0%)
10 (10.0%)
* Multiple McNemar tests.
† Corrected with Step-down Bonferroni method of Holm.
Table A-6. Anesthetic success.
112
p-value*
p-adj†
0.4869
0.5413
0.5413
0.7283
0.6072
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
Tooth
Second Molar
First Molar
Second Premolar
First Premolar
Lateral Incisor
Central Incisor
N
99
100
93
97
100
100
Mepivacaine/
Lidocaine
14 (13.1%)
30 (30.0%)
28 (22.6%)
16 (13.4%)
52 (52.0%)
72 (72.0%)
Lidocaine/
Lidocaine
13 (12.1%)
28 (28.0%)
32 (26.9%)
24 (21.6%)
54 (54.0%)
75 (75.0%)
* Multiple McNemar tests.
† Corrected with Step-down Bonferroni method of Holm.
Table A-7. Anesthetic failure.
113
p-value*
p-adj†
1.0000
0.8555
0.5235
0.1153
0.8145
0.6072
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
Time
(minutes)
1
5
9
13
17
21
25
29
33
37
41
45
49
53
Mepivacaine/ Lidocaine/
Lidocaine
Lidocaine
(%)
(%)
6.0%
5.0%
12.0%
7.0%
14.0%
13.0%
17.0%
12.0%
18.0%
15.0%
19.0%
17.0%
19.0%
17.0%
16.0%
17.0%
17.0%
20.0%
22.0%
19.0%
20.0%
21.0%
21.0%
25.0%
22.0%
22.0%
21.0%
27.0%
p-value†
p-adj‡
0.7905
0.0755
0.8555
0.0755
0.3616
0.5413
0.4545
0.8145
0.2863
0.3269
0.8642
0.2430
1.0000
0.0357
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
† Multiple McNemar tests.
‡ Corrected with Step-down Bonferroni method of Holm.
Table A-8. Central incisors 80/80 pulp tester readings (N=100).
114
Time
(minutes)
1
5
9
13
17
21
25
29
33
37
41
45
49
53
Mepivacaine/
Lidocaine
(%)
8.0%
26.0%
34.0%
37.0%
41.0%
38.0%
41.0%
42.0%
41.0%
37.0%
40.0%
42.0%
42.0%
41.0%
Lidocaine/
Lidocaine
(%)
12.0%
14.0%
26.0%
28.0%
36.0%
34.0%
34.0%
35.0%
39.0%
41.0%
35.0%
39.0%
39.0%
45.0%
p-value†
0.1516
0.0012
0.0365
0.0079
0.1215
0.2430
0.0436
0.0436
0.5966
0.2430
0.1215
0.3616
0.3915
0.2430
p-adj‡
1.0000
0.1004
1.0000
0.6491
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
† Multiple McNemar tests.
‡ Corrected with Step-down Bonferroni method of Holm.
Table A-9. Lateral incisors 80/80 pulp tester readings (N=100).
115
Time
(minutes)
1
5
9
13
17
21
25
29
33
37
41
45
49
53
Mepivacaine/
Lidocaine
(%)
17.5%
45.4%
51.5%
62.9%
74.2%
74.2%
71.1%
75.3%
74.2%
76.3%
74.2%
75.3%
78.4%
77.3%
Lidocaine/
Lidocaine
(%)
18.6%
33.0%
51.5%
64.9%
66.0%
69.1%
73.2%
72.2%
72.2%
70.1%
69.1%
77.3%
74.2%
74.2%
p-value†
p-adj‡
0.8830
0.0018
1.0000
0.6989
0.0441
0.2203
0.6655
0.4966
0.6889
0.1550
0.2529
0.6655
0.3123
0.4966
1.0000
0.1529
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
† Multiple McNemar tests.
‡ Corrected with Step-down Bonferroni method of Holm.
Table A-10. First premolars 80/80 pulp tester readings (N=97).
116
Time
(minutes)
1
5
9
13
17
21
25
29
33
37
41
45
49
53
Mepivacaine/
Lidocaine
(%)
25.8%
43.0%
52.7%
62.4%
68.8%
60.2%
68.8%
67.7%
65.6%
63.4%
68.8%
65.6%
68.8%
72.0%
Lidocaine/
Lidocaine
(%)
24.7%
34.4%
51.6%
51.6%
59.1%
63.4%
65.6%
66.7%
64.5%
67.7%
67.7%
71.0%
68.8%
68.8%
p-value†
p-adj‡
0.8957
0.0441
0.8877
0.0135
0.0154
0.4966
0.5118
0.8957
0.8957
0.3497
0.8957
0.1839
1.0000
0.4966
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
† Multiple McNemar tests.
‡ Corrected with Step-down Bonferroni method of Holm.
Table A-11. Second premolars 80/80 pulp tester readings (N=93).
117
Time
(minutes)
1
5
9
13
17
21
25
29
33
37
41
45
49
53
Mepivacaine/
Lidocaine
(%)
26.0%
41.0%
49.0%
58.0%
60.0%
61.0%
61.0%
62.0%
55.0%
61.0%
58.0%
56.0%
56.0%
59.0%
Lidocaine/
Lidocaine
(%)
26.0%
50.0%
47.0%
55.0%
57.0%
55.0%
63.0%
61.0%
63.0%
60.0%
57.0%
62.0%
59.0%
65.0%
p-value†
p-adj‡
1.0000
0.0356
0.7080
0.4966
0.5258
0.1550
0.6989
0.8919
0.0681
0.8957
0.8957
0.1409
0.5118
0.2067
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
† Multiple McNemar tests.
‡ Corrected with Step-down Bonferroni method of Holm.
Table A-12. First molars 80/80 pulp tester readings (N=100).
118
Time
(minutes)
1
5
9
13
17
21
25
29
33
37
41
45
49
53
Mepivacaine/
Lidocaine
(%)
51.5%
61.6%
68.7%
71.7%
77.8%
73.7%
74.7%
73.7%
74.7%
74.7%
74.7%
73.7%
66.7%
72.7%
Lidocaine/
Lidocaine
(%)
44.4%
65.7%
70.7%
73.7%
71.7%
76.8%
78.8%
75.8%
74.7%
77.8%
75.8%
76.8%
72.7%
69.7%
p-value†
p-adj‡
0.1702
0.4222
0.7240
0.6889
0.0807
0.4177
0.3497
0.6889
1.0000
0.4408
0.8919
0.4799
0.1818
0.5118
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
† Multiple McNemar tests.
‡ Corrected with Step-down Bonferroni method of Holm.
Table A-13. Second molars 80/80 pulp tester readings (N=99).
119
N
Central incisor
Lateral incisor
First premolar
Second premolar
First molar
Second molar
19
38
70
59
56
78
Mean
Range
Mepi/
Lido/
Mepi/ Lido/
p-value† p-adj‡
Lido
Lido
Lido Lido
16.2 ± 14.7 12.2 ± 8.9
1-45 1-33
0.4898 1.0000
10.2 ± 10.8 12.2 ± 10.7 1-49 1-49
0.1465 1.0000
10.3 ± 11.5
9.4 ± 8.6
1-49 1-45
0.9413 1.0000
8.1 ± 7.6
10.8 ± 11.2 1-29 1-41
0.1175 1.0000
8.1 ± 8.3
7.6 ± 10.0
1-37 1-49
0.8207 1.0000
6.9 ± 8.9
6.0 ± 8.2
1-41 1-41
0.3337 1.0000
† Multiple Wilcoxon matched-pairs, signed-ranks tests.
‡ Corrected with Step-down Bonferroni method of Holm.
Mepi=Mepivacaine.
Lido=Lidocaine.
Table A-14. Onset of anesthesia (minutes).
120
Mean
N
Central incisor
Lateral incisor
First premolar
Second premolar
First molar
Second molar
19
38
70
59
56
78
Mepi/
Lido
35.2 ± 16.3
42.2 ± 11.1
41.5 ± 12.7
43.3 ± 10.0
42.6 ± 12.7
43.1 ± 12.9
Lido/
Lido
40.8 ± 8.9
40.9 ± 10.3
42.9 ± 9.7
41.6 ± 11.8
42.7 ± 12.3
44.5 ± 11.8
Range
Mepi/ Lido/
Lido Lido
4-52 20-52
4-52
8-52
4-52
4-52
4-52
4-52
4-52
4-52
4-52
4-52
† Multiple Wilcoxon matched-pairs, signed-ranks tests.
‡ Corrected with Step-down Bonferroni method of Holm.
Mepi=Mepivacaine.
Lido=Lidocaine.
Table A-15. Duration of anesthesia (minutes).
121
pvalue†
0.2980
0.2679
0.6501
0.3752
0.8387
0.3706
p-adj‡
1.0000
1.0000
1.0000
1.0000
1.0000
1.0000
Mepivacaine
Lidocaine
N
3
3
Mean
6.69 ± 0.06
4.28 ± 0.16
p-value
<0.0001
Table A-16. pH of anesthetic solutions.
122
2nd
Molar
1st
Molar
2nd
Premolar
1st
Premolar
Lateral
Incisor
Study
Solution
Volume
Vreeland et al. (63)
2% lido
1.8 mL
63.30%
Hinkley et al. (78)
2% lido
1.8 mL
54%
50%
36%
Chaney et al. (79)
2% lido
1.8 mL
57%
63%
43%
Nist et al. (69)
2% lido
3.6 mL
70%
35%
67%
30%
43%
50%
80%
67%
50%
43%
Central
Incisor
33.30%
52%
63%
McLean et al. (16)
2% lido
1.8 mL
Childers et al. (80)
2% lido
1.8 mL
73%
63%
60%
Dunbar et al. (81)
2% lido
1.8 mL
45%
42%
38%
Dagher et al. (82)
2% lido
1.8 mL
47%
77%
15%
Yared, Dagher (83)
2% lido
3.6 mL
Reitz et al.*(84)
2% lido
1.8 mL
74%
71%
60%
Clark et al. *(85)
2% lido
3.6 mL
87%
73%
90%
87%
50%
33%
Hannan et al.*(86)
2% lido
1.8 mL
92%
78-85%
90-92%
88-90%
65%
38%
Yonchak et al.* (87)
2% lido
3.6 mL
50%
39%
Mikesell et al. (88)
2% lido
1.8 mL
48%
32%
29%
42%
14%
2%
Fernandez et al. (89)
2% lido
1.8 mL
77%
54%
74%
84%
54%
Goodman et al. (90)
2% lido
1.8 mL
58%
44%
48%
51%
23%
8%
33-43%
14-24%
Steinkruger et al. (91)
2% lido
1.8 mL
90-92%
73-76%
78%
73-80%
Foster et al. (92)
2% lido
3.6 mL
74%
53%
66%
56%
Goldberg et al. (67)
2% lido
3.6 mL
Willett et al. (93)
2% lido
1.8 mL
84%
Whitcomb et al. (55)
2% lido
3.6 mL
65%
Simon et al. (56)
2% lido
1.8 mL
45%
Wali et al. (94)
2% lido
1.8 mL
43%
60%
40%
Hutchison et al. (95)
2% lido
1.8 mL
48-62%
Wolf et al.†(96)
2% lido
1.8 mL
McLean et al. (16)
3% mepi
1.8 mL
Guglielmo et al.* (97)
3% mepi
1.8 mL
Gallatin et al.* (98)
3% mepi
1.8 mL
81%
Stabile et al.* (99)
3% mepi
1.8 mL
81%
53%
75%
52%
52%
58%
68%
48%
80%
25%
68%
36%
12%
71%
35%
10%
42%
32%
18-35%
54%
43%
90%
62%
50%
27%
57%
30%
77%
*success = 2 consecutive 80 readings with EPT.
†total pulpal anesthesia.
Table A-17. Pulpal anesthesia success rates with 2% lidocaine with 1:100,000
epinephrine and with 3% mepivacaine for IANB.
123
2nd
Molar
1st
Molar
2nd
Premolar
Study
Solution
Volume
Vreeland et al. (63)
2% lido
1.8 mL
16.70%
Hinkley et al. (78)
2% lido
1.8 mL
32%
Nist et al. (69)
2% lido
3.6 mL
McLean et al. (16)
2% lido
1.8 mL
Childers et al. (80)
2% lido
1.8 mL
Dagher et al. (66)
2% lido
1.8 mL
Yared, Dagher (83)
2% lido
3.6 mL
Clark et al. (85)
2% lido
3.6 mL
13%
27%
Hannan et al. (86)
2% lido
1.8 mL
8%
15-22%
Mikesell et al. (88)
2% lido
1.8 mL
7%
18%
20%
McLean et al. (16)
3% mepi
1.8 mL
Guglielmo et al. (97)
3% mepi
1.8 mL
Gallatin et al. (98)
3% mepi
1.8 mL
19%
Stabile et al. (99)
3% mepi
1.8 mL
19%
22%
Central
Incisor
25%
46%
5%
45%
10%
37%
10%
10%
27%
10%
3%
13%
10%
13%
50%
67%
8-10%
10-12%
35%
62%
19%
44%
72%
0%
40%
25%
30%
3%
20%
23%
Table A-18. Pulpal anesthesia failure rates with 2% lidocaine with 1:100,000
epinephrine and with 3% mepivacaine for IANB.
124
68%
8%
10%
10%
Lateral
Incisor
33.30%
10%
15%
1st
Premolar
APPENDIX B
FIGURES
125
100
90
% Pulpal Anesthesia
80
70
Mepivacaine/Lidocaine
60
Lidocaine/Lidocaine
50
40
30
20
10
0
1
5
9
13
17
21
25
29
33
37
41
45
49
53
Time (minutes)
Figure 1. Percentage of pulpal anesthesia by time (minutes) for the central incisor.
126
100
90
% Pulpal Anesthesia
80
Mepivacaine/Lidocaine
70
Lidocaine/Lidocaine
60
50
40
30
20
10
0
1
5
9
13
17
21
25
29
33
37
41
45
49
53
Time (minutes)
Figure 2. Percentage of pulpal anesthesia by time (minutes) for the lateral incisor.
127
100
90
% Pulpal Anesthesias
80
70
60
50
40
Mepivacaine/Lidocaine
30
Lidocaine/Lidocaine
20
10
0
1
5
9
13
17
21
25
29
33
37
41
45
49
53
Time (minutes)
Figure 3. Percentage of pulpal anesthesia by time (minutes) for the first premolar.
128
100
90
% Pulpal Anesthesia
80
70
60
50
40
Mepivacaine/Lidocaine
30
Lidocaine/Lidocaine
20
10
0
1
5
9
13
17
21
25
29
33
37
41
45
49
53
Time (minutes)
Figure 4. Percentage of pulpal anesthesia by time (minutes) for the second premolar.
129
100
90
% Pulpal Anesthesia
80
70
60
50
40
Mepivacaine/Lidocaine
30
Lidocaine/Lidocaine
20
10
0
1
5
9
13
17
21
25
29
33
37
41
45
49
53
Time (minutes)
Figure 5. Percentage of pulpal anesthesia by time (minutes) for the first molar.
130
100
90
% Pulpal Anesthesia
80
70
60
50
Mepivacaine/Lidocaine
40
Lidocaine/Lidocaine
30
20
10
0
1
5
9
13
17
21
25
29
33
37
41
45
49
53
Time (minutes)
Figure 6. Percentage of pulpal anesthesia by time (minutes) for the second molar.
131
APPENDIX C
MEDICAL HISTORY FORM
132
133
134
APPENDIX D
CONSENT FORM
135
The Ohio State University Consent to Participate in Research
Study Title:
A prospective, randomized, double-blind study of the
anesthetic efficacy of 3% mepivacaine plus 2% lidocaine with
1:100,000 epinephrine for inferior alveolar nerve blocks
Principal
Investigator:
John Nusstein, DDS, MS
Sponsor:
•
This is a consent form for research participation. It contains important
information about this study and what to expect if you decide to participate. Please
consider the information carefully. Feel free to discuss the study with your friends
and family and to ask questions before making your decision whether or not to
participate.
•
Your participation is voluntary. You may refuse to participate in this study. If you
decide to take part in the study, you may leave the study at any time. No matter what
decision you make, there will be no penalty to you and you will not lose any of your
usual benefits. Your decision will not affect your future relationship with The Ohio
State University. If you are a student or employee at Ohio State, your decision will
not affect your grades or employment status.
•
You may or may not benefit as a result of participating in this study. Also, as
explained below, your participation may result in unintended or harmful effects for
you that may be minor or may be serious depending on the nature of the research.
•
You will be provided with any new information that develops during the study
that may affect your decision whether or not to continue to participate. If you
decide to participate, you will be asked to sign this form and will receive a copy of
the form. You are being asked to consider participating in this study for the reasons
explained below.
1. Why is this study being done?
Lidocaine and mepivacaine are numbing solutions approved by the FDA for routine use
in the dental office (like “novocaine”). The purpose of this study is to see if the
combination of the two solutions is better at making your teeth numb for a dental
procedure. This combination may also be less painful when you receive the injection
(shot).
2. How many people will take part in this study?
One hundred (100) people will take part in this study.
136
3. What will happen if I take part in this study?
You will receive injections (shots) of mepivacaine and lidocaine with epinephrine
(numbing solutions like “novocaine”) in the back of your lower jaw. These numbing
solutions are not experimental. They are routinely used in the dental office and have
been approved by the FDA for dental use. Prior to the first injection, you will be required
to complete a medical history questionnaire. A device called an electric pulp tester will
be used to test your teeth for numbness. The electric pulp tester is a battery operated
device that delivers a very small amount of current to the tooth resulting in a tingling
sensation that might be uncomfortable or cause pain in the tooth being tested and which
may last up to one second. It will be used on your teeth before the injections of numbing
solution. Six of your lower teeth as well as a tooth on the opposite side (control tooth)
will be tested with the electric pulp tester to be sure that your teeth respond (the nerves
are alive and the teeth have not had root canal treatment). This will take about 6 minutes.
You will have two appointments spaced at least two weeks apart. You will receive two
injections (shots) at each appointment. After topical numbing anesthetic (20%
Benzocaine), a gel that numbs the gum tissue, has been applied to the injection (shot) site
for one minute, you will receive 1.8 mL (a little more than one third of a teaspoon) of
either 3% mepivacaine or 2% lidocaine with 1:100,000 epinephrine. Whether you receive
the mepivacaine or lidocaine will be determined at random (by chance, like flipping a
coin). You will not know which injection you will receive. Your doctor will not know
which injection you receive. You will then receive 1.8 mL 2% lidocaine with 1:100,000
epinephrine. Your teeth will be pulp tested every 4 minutes for a total of 60 minutes to
determine how well the injection (shot) gets your teeth numb. In addition, the electric
pulp tester will be used on one of your teeth on the opposite side (where you are not
numb). Teeth that are not numb or are being used as a control will experience a tingling
sensation or discomfort at which time the device will be removed immediately. You will
be asked to rate the amount of pain you feel when the injections are being given. You will
do this by marking your pain experience on a line graph with a pen.
4. How long will I be in the study?
You are aware that you will have two appointments, each will last approximately 70
minutes - 10 minutes for baseline pulp testing and filling out health information and
receiving the initial injection. Your teeth will be pulp tested for a total of 60 minutes.
5. Can I stop being in the study?
You may leave the study at any time. If you decide to stop participating in the study,
there will be no penalty to you, and you will not lose any benefits to which you are
otherwise entitled. Your decision will not affect your future relationship with The Ohio
State University.
If you are a student or staff member at OSU and choose not to participate in this study,
your grades and/or employment will not be affected.
137
6. What risks, side effects or discomforts can I expect from being in the
study?
You may have pain associated with the local anesthetic (numbing solution) or soreness at
the site of the injections (shots) for approximately two days. Where you receive the
injections, you may have swelling (hematoma-a collection of blood in my mouth) or a
bruise may develop. You may experience a feeling of anxiety, lightheadedness or
fainting, and or a temporary increase in your heart rate. The tingling sensation and/or
slight discomfort (pain) produced by the pulp tester may be uncomfortable to you. You
may have an allergic reaction to the local anesthetic (itching or hives, very rare), or have
an unexpected infection (rare) which could result in permanent nerve damage. You may
have soreness of your gum tissue for a few days or a possible altered sensation of your lip
or tongue that may last up to a few weeks. Your tooth may feel sore to bite on for a few
days.
If you are a woman able to have children, you will be questioned regarding pregnancy or
suspected pregnancy and will not be allowed to participate if pregnant, suspect a
pregnancy, trying to become pregnant, or nursing. Additionally, you will be required to
take a urine pregnancy test before you can start this study. If you are a woman, you must
also be using a reliable method of contraception (oral contraceptives, condoms,
diaphragm, or abstinence) during the next 24 hours. The reason for excluding pregnant
or potentially pregnant women is an attempt to minimize this population in the study
because the potential risks to the fetus and nursing baby are unknown. There are no
adequate and well-controlled studies of mepivacaine in pregnant women. This test will
be paid for by the investigator.
7. What benefits can I expect from being in the study?
You will not directly benefit from this study. Society may benefit if the combination of
mepivacaine and lidocaine is better at making your teeth numb, and if the injections
(shots) are less painful than with lidocaine alone.
8. What other choices do I have if I do not take part in the study?
You may choose not to participate without penalty or loss of benefits to which you are
otherwise entitled.
If you are a student or staff member at OSU and choose not to participate in this study,
your grades and/or employment will not be affected.
There are no other choices other than to participate or not participate in the study.
9. Will my study-related information be kept confidential?
Efforts will be made to keep your study-related information confidential. However, there
may be circumstances where this information must be released. For example, personal
information regarding your participation in this study may be disclosed if required by
state law.
138
Also, your records may be reviewed by the following groups (as applicable to the
research):
•
Office for Human Research Protections or other federal, state, or international
regulatory agencies;
•
U.S. Food and Drug Administration;
•
The Ohio State University Institutional Review Board or Office of Responsible
Research Practices;
•
The sponsor supporting the study, their agents or study monitors; and
•
Your insurance company (if charges are billed to insurance).
You may also be asked to sign a separate Health Insurance Portability and
Accountability Act (HIPAA) research authorization form if the study involves the use
of your protected health information.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov,
as required by U.S. law. This website will not include information that can identify
you. At most, the website will include a summary of the results. You can search the
website at any time.
10. What are the costs of taking part in this study?
The study will pay for the cost of the study drugs (mepivacaine and lidocaine) and the
urine pregnancy test.
11. Will I be paid for taking part in this study?
Yes, you will be paid $75 for your participation. You will receive $75.00 for completing
all aspects of the study. If you are unable or unwilling to complete both sessions of the
study, you will be paid a pro-rated $30.00 per session. Payment is to compensate you for
time and travel expenses. By law, payments to subjects are considered taxable income.
12. What happens if I am injured because I took part in this study?
If you suffer an injury from participating in this study, you should notify the researcher or
study doctor immediately, who will determine if you should obtain medical treatment at
The Ohio State University Medical Center.
The cost for this treatment will be billed to you or your medical or hospital insurance.
The Ohio State University has no funds set aside for the payment of health care expenses
for this study.
13. What are my rights if I take part in this study?
If you choose to participate in the study, you may discontinue participation at any time
without penalty or loss of benefits. By signing this form, you do not give up any personal
legal rights you may have as a participant in this study.
139
You will be provided with any new information that develops during the course of the
research that may affect your decision whether or not to continue participation in the
study.
You may refuse to participate in this study without penalty or loss of benefits to which
you are otherwise entitled.
An Institutional Review Board responsible for human subjects research at The Ohio State
University reviewed this research project and found it to be acceptable, according to
applicable state and federal regulations and University policies designed to protect the
rights and welfare of participants in research.
14. Who can answer my questions about the study?
For questions, concerns, or complaints about the study you may contact Dr. John
Nusstein or Dr. Emily Lammers at 614 – 292-5399.
For questions about your rights as a participant in this study or to discuss other studyrelated concerns or complaints with someone who is not part of the research team, you
may contact Ms. Sandra Meadows in the Office of Responsible Research Practices at 1800-678-6251.
If you are injured as a result of participating in this study or for questions about a studyrelated injury, you may contact Dr. John Nusstein or Dr. Emily Lammers at 614 – 2925399.
140
Signing the consent form
I have read (or someone has read to me) this form and I am aware that I am being asked
to participate in a research study. I have had the opportunity to ask questions and have
had them answered to my satisfaction. I voluntarily agree to participate in this study.
I am not giving up any legal rights by signing this form. I will be given a copy of this
form.
Printed name of subject
Signature of subject
AM/PM
Date and time
Printed name of person authorized to consent for
subject (when applicable)
Signature of person authorized to consent for subject
(when applicable)
Relationship to the subject
Date and time
AM/PM
Investigator/Research Staff
I have explained the research to the participant or his/her representative before requesting
the signature(s) above. There are no blanks in this document. A copy of this form has
been given to the participant or his/her representative.
Printed name of person obtaining consent
Signature of person obtaining consent
AM/PM
Date and time
Witness(es) - May be left blank if not required by the IRB
Printed name of witness
Signature of witness
AM/PM
Date and time
Printed name of witness
Signature of witness
AM/PM
Date and time
141
APPENDIX E
HIPAA PRIVACY FORM
142
THE OHIO STATE UNIVERSITY
AUTHORIZATION TO USE
PERSONAL HEALTH INFORMATION IN RESEARCH
Title of the Study: A prospective, randomized, double-blind study of the anesthetic efficacy of 3%
mepivacaine plus 2% lidocaine with 1:100,000 epinephrine for inferior alveolar nerve blocks
OSU Protocol Number: 2012H0001
Principal Investigator: Dr. John Nusstein, DDS, MS
Subject Name__________________________________________________________
Before researchers use or share any health information about you as part of this study, The Ohio
State University is required to obtain your authorization. This helps explain to you how this
information will be used or shared with others involved in the study.
•
The Ohio State University and its hospitals, clinics, health-care providers and researchers are
required to protect the privacy of your health information.
•
You should have received a Notice of Privacy Practices when you received health care
services here. If not, let us know and a copy will be given to you. Please carefully review
this information. Ask if you have any questions or do not understand any parts of this notice.
•
If you agree to take part in this study your health information will be used and shared with
others involved in this study. Also, any new health information about you that comes from
tests or other parts of this study will be shared with those involved in this study.
•
Health information about you that will be used or shared with others involved in this study
may include your research record and any health care records at the Ohio State University.
For example, this may include your medical records, x-ray or laboratory results.
Psychotherapy notes in your health records (if any) will not, however, be shared or used. Use
of these notes requires a separate, signed authorization.
Please read the information carefully before signing this form. Please ask if you have any
questions about this authorization, the University’s Notice of Privacy Practices or the study
before signing this form.
Initials/Date: _______________
Page 1 of 3
143
Those Who May Use, Share And Receive Your Information As Part Of This Study
•
Researchers and staff at The Ohio State University will use, share and receive your personal
health information for this research study. Authorized Ohio State University staff not
involved in the study may be aware that you are participating in a research study and have
access to your information. If this study is related to your medical care, your study-related
information may be placed in your permanent hospital, clinic or physician’s office records.
•
Those who oversee the study will have access to your information, including:
•
•
Members and staff of the Ohio State University’s Institutional Review Boards,
including the Western Institutional Review Board
•
The Office for Responsible Research Practices
•
University data safety monitoring committees
•
The Ohio State University Research Foundation
Your health information may also be shared with federal and state agencies that have
oversight of the study or to whom access is required under the law. These may include:
•
The Food and Drug Administration
•
The Office for Human Research Protections
•
The National Institutes of Health
•
The Ohio Department of Job and Family Services
These researchers, companies and/or organization(s) outside of The Ohio State University may
also use, share and receive your health information in connection with this study:
•
None
The information that is shared with those listed above may no longer be protected by federal
privacy rules.
Initials/Date_________
Page 2 of 3
144
Authorization Period
This authorization will not expire unless you change your mind and revoke it in writing. There is
no set date at which your information will be destroyed or no longer used. This is because the
information used and created during the study may be analyzed for many years, and it is not
possible to know when this will be complete.
Signing the Authorization
•
You have the right to refuse to sign this authorization. Your health care outside of the study,
payment for your health care, and your health care benefits will not be affected if you choose
not to sign this form.
•
You will not be able to take part in this study and will not receive any study treatments if you
do not sign this form.
•
If you sign this authorization, you may change your mind at any time. Researchers may
continue to use information collected up until the time that you formally changed your mind.
If you change your mind, your authorization must be revoked in writing. To revoke your
authorization, please write to:
Dr. John Nusstein at the College of Dentistry, 305 W. 12th Avenue, The Ohio State
University, Columbus, Ohio 43210 or Dr. Henry Fischbach at the College of Dentistry, 305 W.
12th Avenue, The Ohio State University, Columbus, Ohio 43210
•
Signing this authorization also means that you will not be able to see or copy your studyrelated information until the study is completed. This includes any portion of your medical
records that describes study treatment.
Contacts for Questions
•
If you have any questions relating to your privacy rights, please contact Dr. Henry Fischbach
at the College of Dentistry, 305 W. 12th Avenue, The Ohio State University, Columbus, Ohio
43210.
•
If you have any questions relating to the research, please contact Dr. John Nusstein at the
College of Dentistry, 305 W. 12th Avenue, The Ohio State University, Columbus, Ohio
43210.
Signature
I have read (or someone has read to me) this form and have been able to ask questions. All of my
questions about this form have been answered to my satisfaction. By signing below, I permit Dr.
John Nusstein and the others listed on this form to use and share my personal health information
for this study. I will be given a copy of this signed form.
Signature________________________________________________________
(Subject or Legally Authorized Representative)
Name _____________________________________________________________
(Print name above)
(If legal representative, also print relationship to subject.)
Date___________ Time __________ AM / PM
145
APPENDIX F
HEFT-PARKER VAS FORM
146
INJECTION INFORMATION SHEET
Name: _____________________
Patient #: _________
Date: _________
Side: ____
Code #: __________
Injection # 1 or 2
1.
None
Needle Insertion
When advised by the doctor, please place an “X” on the line below to rank the level of pain felt during needle insertion.
Faint
Weak
Mild
Moderate
Strong
Intense
Maximum
Possible
147
2.
None
3.
None
Needle Placement
When advised by the doctor, please place an “X” on the line below to rank the level of pain felt during needle placement.
Faint
Weak
Mild
Moderate
Strong
Intense
Maximum
Possible
Solution Deposition
When advised by the doctor, please place an “X” on the line below to rank the level of pain felt during solution deposition.
Faint
Weak
Mild
Moderate
Strong
Intense
Maximum
Possible
APPENDIX G
ELECTRIC PULP TESTING FORM
148
EPT Values
Date:__________
Patient # _______________
Sex:
Patient Age: ___________
M
F
2nd
molar
1st
molar
2nd
premolar
1st
premolar
Side:_________________
Lateral
incisor
Central
incisor
Contralateral
canine
Lateral
Incisor
Central
Incisor
Contralateral
Canine
Min. Pre-test
Min. Pre-test
Base-line
* Indicates tooth will be tested with a mock electrode
2nd
Molar
1st
Molar
2nd
Premolar
1st
Premolar
Numbness
Lip / Tongue
1
2
3
4
5
Y
N
/
Y
N
Y
N
/
Y
N
Y
N
/
Y
N
6
7
8
9
10
11
12
13
14
15
16
149
17
18
19
20
*
Y
N
/
Y
N
Y
N
/
Y
N
Y
N
/
Y
N
Y
N
/
Y
N
Y
N
/
Y
N
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
*
37
38
39
40
150
41
42
43
44
45
Y
N
/
Y
N
Y
N
/
Y
N
Y
N
/
Y
N
Y
N
/
Y
N
46
47
48
*
49
50
51
52
53
54
55
56
57
58
59
60
*
151
APPENDIX H
RAW DATA
152
SUB
#
1
1
1
1
1
1
2
2
2
2
2
2
3
3
3
3
3
3
4
4
4
4
4
4
5
5
5
5
5
5
6
6
6
6
6
6
7
7
7
7
7
7
AGE
yrs
SEX
0=female
1=male
24
24
24
24
24
24
28
28
28
28
28
28
27
27
27
27
27
27
23
23
23
23
23
23
26
26
26
26
26
26
26
26
26
26
26
26
24
24
24
24
24
24
SIDE
0=rt
1=lt
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
LINS1
VAS
SCORE
L=LIDO
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
37
37
37
37
37
37
115
115
115
115
115
115
83
83
83
83
83
83
21
21
21
21
21
21
24
24
24
24
24
24
59
59
59
59
59
59
37
37
37
37
37
37
153
LPLC1
VAS
SCORE
53
53
53
53
53
53
85
85
85
85
85
85
54
54
54
54
54
54
20
20
20
20
20
20
24
24
24
24
24
24
87
87
87
87
87
87
54
54
54
54
54
54
LDEP1
VAS
SCORE
19
19
19
19
19
19
53
53
53
53
53
53
54
54
54
54
54
54
22
22
22
22
22
22
32
32
32
32
32
32
52
52
52
52
52
52
54
54
54
54
54
54
LINS2
VAS
SCORE
0
0
0
0
0
0
37
37
37
37
37
37
0
0
0
0
0
0
21
21
21
21
21
21
15
15
15
15
15
15
58
58
58
58
58
58
0
0
0
0
0
0
SUB
#
8
8
8
8
8
8
9
9
9
9
9
9
10
10
10
10
10
10
11
11
11
11
11
11
12
12
12
12
12
12
13
13
13
13
13
13
14
14
14
14
14
14
AGE
yrs
SEX
0=female
1=male
26
26
26
26
26
26
24
24
24
24
24
24
24
24
24
24
24
24
25
25
25
25
25
25
27
27
27
27
27
27
25
25
25
25
25
25
27
27
27
27
27
27
SIDE
0=rt
1=lt
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
LINS1
VAS
SCORE
L=LIDO
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
15
15
15
15
15
15
21
21
21
21
21
21
30
30
30
30
30
30
54
54
54
54
54
54
37
37
37
37
37
37
37
37
37
37
37
37
57
57
57
57
57
57
154
LPLC1
VAS
SCORE
24
24
24
24
24
24
54
54
54
54
54
54
95
95
95
95
95
95
83
83
83
83
83
83
37
37
37
37
37
37
54
54
54
54
54
54
79
79
79
79
79
79
LDEP1
VAS
SCORE
5
5
5
5
5
5
21
21
21
21
21
21
95
95
95
95
95
95
37
37
37
37
37
37
37
37
37
37
37
37
54
54
54
54
54
54
62
62
62
62
62
62
LINS2
VAS
SCORE
0
0
0
0
0
0
21
21
21
21
21
21
68
68
68
68
68
68
21
21
21
21
21
21
0
0
0
0
0
0
0
0
0
0
0
0
51
51
51
51
51
51
SUB
#
15
15
15
15
15
15
16
16
16
16
16
16
17
17
17
17
17
17
18
18
18
18
18
18
19
19
19
19
19
19
20
20
20
20
20
20
21
21
21
21
21
21
AGE
yrs
SEX
0=female
1=male
24
24
24
24
24
24
29
29
29
29
29
29
26
26
26
26
26
26
25
25
25
25
25
25
28
28
28
28
28
28
29
29
29
29
29
29
29
29
29
29
29
29
SIDE
0=rt
1=lt
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
LINS1
VAS
SCORE
L=LIDO
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
21
21
21
21
21
21
37
37
37
37
37
37
50
50
50
50
50
50
21
21
21
21
21
21
41
41
41
41
41
41
38
38
38
38
38
38
37
37
37
37
37
37
155
LPLC1
VAS
SCORE
54
54
54
54
54
54
37
37
37
37
37
37
90
90
90
90
90
90
0
0
0
0
0
0
52
52
52
52
52
52
54
54
54
54
54
54
54
54
54
54
54
54
LDEP1
VAS
SCORE
21
21
21
21
21
21
37
37
37
37
37
37
56
56
56
56
56
56
37
37
37
37
37
37
52
52
52
52
52
52
38
38
38
38
38
38
54
54
54
54
54
54
LINS2
VAS
SCORE
21
21
21
21
21
21
0
0
0
0
0
0
63
63
63
63
63
63
0
0
0
0
0
0
11
11
11
11
11
11
53
53
53
53
53
53
3
3
3
3
3
3
SUB
#
22
22
22
22
22
22
23
23
23
23
23
23
24
24
24
24
24
24
25
25
25
25
25
25
26
26
26
26
26
26
27
27
27
27
27
27
28
28
28
28
28
28
AGE
yrs
SEX
0=female
1=male
23
23
23
23
23
23
23
23
23
23
23
23
29
29
29
29
29
29
24
24
24
24
24
24
25
25
25
25
25
25
23
23
23
23
23
23
24
24
24
24
24
24
SIDE
0=rt
1=lt
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
LINS1
VAS
SCORE
L=LIDO
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
14
14
14
14
14
14
37
37
37
37
37
37
83
83
83
83
83
83
69
69
69
69
69
69
45
45
45
45
45
45
54
54
54
54
54
54
37
37
37
37
37
37
156
LPLC1
VAS
SCORE
45
45
45
45
45
45
83
83
83
83
83
83
83
83
83
83
83
83
65
65
65
65
65
65
60
60
60
60
60
60
83
83
83
83
83
83
54
54
54
54
54
54
LDEP1
VAS
SCORE
29
29
29
29
29
29
37
37
37
37
37
37
21
21
21
21
21
21
27
27
27
27
27
27
30
30
30
30
30
30
0
0
0
0
0
0
54
54
54
54
54
54
LINS2
VAS
SCORE
15
15
15
15
15
15
37
37
37
37
37
37
21
21
21
21
21
21
31
31
31
31
31
31
0
0
0
0
0
0
37
37
37
37
37
37
21
21
21
21
21
21
SUB
#
29
29
29
29
29
29
30
30
30
30
30
30
31
31
31
31
31
31
32
32
32
32
32
32
33
33
33
33
33
33
34
34
34
34
34
34
35
35
35
35
35
35
AGE
yrs
SEX
0=female
1=male
24
24
24
24
24
24
27
27
27
27
27
27
26
26
26
26
26
26
22
22
22
22
22
22
31
31
31
31
31
31
24
24
24
24
24
24
24
24
24
24
24
24
SIDE
0=rt
1=lt
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
LINS1
VAS
SCORE
L=LIDO
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
54
54
54
54
54
54
17
17
17
17
17
17
60
60
60
60
60
60
21
21
21
21
21
21
6
6
6
6
6
6
54
54
54
54
54
54
29
29
29
29
29
29
157
LPLC1
VAS
SCORE
74
74
74
74
74
74
100
100
100
100
100
100
78
78
78
78
78
78
37
37
37
37
37
37
26
26
26
26
26
26
83
83
83
83
83
83
52
52
52
52
52
52
LDEP1
VAS
SCORE
54
54
54
54
54
54
109
109
109
109
109
109
58
58
58
58
58
58
54
54
54
54
54
54
42
42
42
42
42
42
37
37
37
37
37
37
47
47
47
47
47
47
LINS2
VAS
SCORE
75
75
75
75
75
75
26
26
26
26
26
26
77
77
77
77
77
77
0
0
0
0
0
0
0
0
0
0
0
0
21
21
21
21
21
21
3
3
3
3
3
3
SUB
#
36
36
36
36
36
36
37
37
37
37
37
37
38
38
38
38
38
38
39
39
39
39
39
39
40
40
40
40
40
40
41
41
41
41
41
41
42
42
42
42
42
42
AGE
yrs
SEX
0=female
1=male
29
29
29
29
29
29
23
23
23
23
23
23
25
25
25
25
25
25
26
26
26
26
26
26
37
37
37
37
37
37
24
24
24
24
24
24
24
24
24
24
24
24
SIDE
0=rt
1=lt
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
LINS1
VAS
SCORE
L=LIDO
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
54
54
54
54
54
54
32
32
32
32
32
32
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
5
5
5
5
5
5
34
34
34
34
34
34
158
LPLC1
VAS
SCORE
54
54
54
54
54
54
35
35
35
35
35
35
21
21
21
21
21
21
83
83
83
83
83
83
54
54
54
54
54
54
73
73
73
73
73
73
42
42
42
42
42
42
LDEP1
VAS
SCORE
83
83
83
83
83
83
25
25
25
25
25
25
21
21
21
21
21
21
83
83
83
83
83
83
54
54
54
54
54
54
21
21
21
21
21
21
29
29
29
29
29
29
LINS2
VAS
SCORE
54
54
54
54
54
54
5
5
5
5
5
5
21
21
21
21
21
21
54
54
54
54
54
54
0
0
0
0
0
0
0
0
0
0
0
0
29
29
29
29
29
29
SUB
#
43
43
43
43
43
43
44
44
44
44
44
44
45
45
45
45
45
45
46
46
46
46
46
46
47
47
47
47
47
47
48
48
48
48
48
48
49
49
49
49
49
49
AGE
yrs
SEX
0=female
1=male
23
23
23
23
23
23
23
23
23
23
23
23
27
27
27
27
27
27
25
25
25
25
25
25
22
22
22
22
22
22
24
24
24
24
24
24
25
25
25
25
25
25
SIDE
0=rt
1=lt
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
LINS1
VAS
SCORE
L=LIDO
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
21
21
21
21
21
21
83
83
83
83
83
83
142
142
142
142
142
142
37
37
37
37
37
37
9
9
9
9
9
9
37
37
37
37
37
37
27
27
27
27
27
27
159
LPLC1
VAS
SCORE
54
54
54
54
54
54
114
114
114
114
114
114
142
142
142
142
142
142
54
54
54
54
54
54
12
12
12
12
12
12
37
37
37
37
37
37
39
39
39
39
39
39
LDEP1
VAS
SCORE
39
39
39
39
39
39
21
21
21
21
21
21
113
113
113
113
113
113
21
21
21
21
21
21
23
23
23
23
23
23
37
37
37
37
37
37
21
21
21
21
21
21
LINS2
VAS
SCORE
0
0
0
0
0
0
83
83
83
83
83
83
54
54
54
54
54
54
54
54
54
54
54
54
16
16
16
16
16
16
37
37
37
37
37
37
7
7
7
7
7
7
SUB
#
50
50
50
50
50
50
51
51
51
51
51
51
52
52
52
52
52
52
53
53
53
53
53
53
54
54
54
54
54
54
55
55
55
55
55
55
56
56
56
56
56
56
AGE
yrs
SEX
0=female
1=male
24
24
24
24
24
24
27
27
27
27
27
27
28
28
28
28
28
28
32
32
32
32
32
32
24
24
24
24
24
24
34
34
34
34
34
34
26
26
26
26
26
26
SIDE
0=rt
1=lt
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
LINS1
VAS
SCORE
L=LIDO
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
41
41
41
41
41
41
54
54
54
54
54
54
21
21
21
21
21
21
52
52
52
52
52
52
30
30
30
30
30
30
54
54
54
54
54
54
21
21
21
21
21
21
160
LPLC1
VAS
SCORE
119
119
119
119
119
119
83
83
83
83
83
83
0
0
0
0
0
0
77
77
77
77
77
77
68
68
68
68
68
68
83
83
83
83
83
83
21
21
21
21
21
21
LDEP1
VAS
SCORE
88
88
88
88
88
88
54
54
54
54
54
54
0
0
0
0
0
0
57
57
57
57
57
57
29
29
29
29
29
29
37
37
37
37
37
37
21
21
21
21
21
21
LINS2
VAS
SCORE
40
40
40
40
40
40
83
83
83
83
83
83
21
21
21
21
21
21
35
35
35
35
35
35
12
12
12
12
12
12
0
0
0
0
0
0
0
0
0
0
0
0
SUB
#
57
57
57
57
57
57
58
58
58
58
58
58
59
59
59
59
59
59
60
60
60
60
60
60
61
61
61
61
61
61
62
62
62
62
62
62
63
63
63
63
63
63
AGE
yrs
SEX
0=female
1=male
24
24
24
24
24
24
25
25
25
25
25
25
30
30
30
30
30
30
26
26
26
26
26
26
25
25
25
25
25
25
27
27
27
27
27
27
30
30
30
30
30
30
SIDE
0=rt
1=lt
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
LINS1
VAS
SCORE
L=LIDO
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
37
37
37
37
37
37
0
0
0
0
0
0
58
58
58
58
58
58
21
21
21
21
21
21
87
87
87
87
87
87
21
21
21
21
21
21
60
60
60
60
60
60
161
LPLC1
VAS
SCORE
41
41
41
41
41
41
113
113
113
113
113
113
50
50
50
50
50
50
21
21
21
21
21
21
40
40
40
40
40
40
79
79
79
79
79
79
42
42
42
42
42
42
LDEP1
VAS
SCORE
4
4
4
4
4
4
83
83
83
83
83
83
28
28
28
28
28
28
9
9
9
9
9
9
3
3
3
3
3
3
13
13
13
13
13
13
42
42
42
42
42
42
LINS2
VAS
SCORE
21
21
21
21
21
21
0
0
0
0
0
0
19
19
19
19
19
19
12
12
12
12
12
12
35
35
35
35
35
35
17
17
17
17
17
17
35
35
35
35
35
35
SUB
#
64
64
64
64
64
64
65
65
65
65
65
65
66
66
66
66
66
66
67
67
67
67
67
67
68
68
68
68
68
68
69
69
69
69
69
69
70
70
70
70
70
70
AGE
yrs
SEX
0=female
1=male
25
25
25
25
25
25
28
28
28
28
28
28
26
26
26
26
26
26
24
24
24
24
24
24
24
24
24
24
24
24
23
23
23
23
23
23
25
25
25
25
25
25
SIDE
0=rt
1=lt
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
LINS1
VAS
SCORE
L=LIDO
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
54
54
54
54
54
54
35
35
35
35
35
35
37
37
37
37
37
37
53
53
53
53
53
53
21
21
21
21
21
21
30
30
30
30
30
30
21
21
21
21
21
21
162
LPLC1
VAS
SCORE
37
37
37
37
37
37
48
48
48
48
48
48
54
54
54
54
54
54
83
83
83
83
83
83
37
37
37
37
37
37
26
26
26
26
26
26
83
83
83
83
83
83
LDEP1
VAS
SCORE
21
21
21
21
21
21
6
6
6
6
6
6
83
83
83
83
83
83
54
54
54
54
54
54
21
21
21
21
21
21
10
10
10
10
10
10
83
83
83
83
83
83
LINS2
VAS
SCORE
21
21
21
21
21
21
11
11
11
11
11
11
21
21
21
21
21
21
37
37
37
37
37
37
19
19
19
19
19
19
17
17
17
17
17
17
21
21
21
21
21
21
SUB
#
71
71
71
71
71
71
72
72
72
72
72
72
73
73
73
73
73
73
74
74
74
74
74
74
75
75
75
75
75
75
76
76
76
76
76
76
77
77
77
77
77
77
AGE
yrs
SEX
0=female
1=male
20
20
20
20
20
20
24
24
24
24
24
24
23
23
23
23
23
23
24
24
24
24
24
24
24
24
24
24
24
24
30
30
30
30
30
30
29
29
29
29
29
29
SIDE
0=rt
1=lt
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
LINS1
VAS
SCORE
L=LIDO
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
83
83
83
83
83
83
21
21
21
21
21
21
21
21
21
21
21
21
54
54
54
54
54
54
83
83
83
83
83
83
11
11
11
11
11
11
70
70
70
70
70
70
163
LPLC1
VAS
SCORE
83
83
83
83
83
83
37
37
37
37
37
37
37
37
37
37
37
37
83
83
83
83
83
83
113
113
113
113
113
113
3
3
3
3
3
3
66
66
66
66
66
66
LDEP1
VAS
SCORE
54
54
54
54
54
54
68
68
68
68
68
68
37
37
37
37
37
37
37
37
37
37
37
37
0
0
0
0
0
0
3
3
3
3
3
3
36
36
36
36
36
36
LINS2
VAS
SCORE
54
54
54
54
54
54
22
22
22
22
22
22
0
0
0
0
0
0
54
54
54
54
54
54
54
54
54
54
54
54
16
16
16
16
16
16
35
35
35
35
35
35
SUB
#
78
78
78
78
78
78
79
79
79
79
79
79
80
80
80
80
80
80
81
81
81
81
81
81
82
82
82
82
82
82
83
83
83
83
83
83
84
84
84
84
84
84
AGE
yrs
SEX
0=female
1=male
21
21
21
21
21
21
24
24
24
24
24
24
22
22
22
22
22
22
25
25
25
25
25
25
32
32
32
32
32
32
23
23
23
23
23
23
22
22
22
22
22
22
SIDE
0=rt
1=lt
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
LINS1
VAS
SCORE
L=LIDO
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
23
23
23
23
23
23
66
66
66
66
66
66
51
51
51
51
51
51
21
21
21
21
21
21
54
54
54
54
54
54
83
83
83
83
83
83
54
54
54
54
54
54
164
LPLC1
VAS
SCORE
32
32
32
32
32
32
54
54
54
54
54
54
59
59
59
59
59
59
54
54
54
54
54
54
83
83
83
83
83
83
54
54
54
54
54
54
37
37
37
37
37
37
LDEP1
VAS
SCORE
59
59
59
59
59
59
46
46
46
46
46
46
27
27
27
27
27
27
21
21
21
21
21
21
37
37
37
37
37
37
21
21
21
21
21
21
21
21
21
21
21
21
LINS2
VAS
SCORE
18
18
18
18
18
18
50
50
50
50
50
50
25
25
25
25
25
25
39
39
39
39
39
39
114
114
114
114
114
114
21
21
21
21
21
21
54
54
54
54
54
54
SUB
#
85
85
85
85
85
85
86
86
86
86
86
86
87
87
87
87
87
87
88
88
88
88
88
88
89
89
89
89
89
89
90
90
90
90
90
90
91
91
91
91
91
91
AGE
yrs
SEX
0=female
1=male
24
24
24
24
24
24
23
23
23
23
23
23
23
23
23
23
23
23
24
24
24
24
24
24
27
27
27
27
27
27
25
25
25
25
25
25
27
27
27
27
27
27
SIDE
0=rt
1=lt
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
LINS1
VAS
SCORE
L=LIDO
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
37
37
37
37
37
37
21
21
21
21
21
21
61
61
61
61
61
61
37
37
37
37
37
37
21
21
21
21
21
21
114
114
114
114
114
114
54
54
54
54
54
54
165
LPLC1
VAS
SCORE
83
83
83
83
83
83
21
21
21
21
21
21
49
49
49
49
49
49
54
54
54
54
54
54
21
21
21
21
21
21
114
114
114
114
114
114
54
54
54
54
54
54
LDEP1
VAS
SCORE
54
54
54
54
54
54
54
54
54
54
54
54
31
31
31
31
31
31
37
37
37
37
37
37
21
21
21
21
21
21
114
114
114
114
114
114
21
21
21
21
21
21
LINS2
VAS
SCORE
83
83
83
83
83
83
37
37
37
37
37
37
42
42
42
42
42
42
0
0
0
0
0
0
21
21
21
21
21
21
37
37
37
37
37
37
37
37
37
37
37
37
SUB
#
92
92
92
92
92
92
93
93
93
93
93
93
94
94
94
94
94
94
95
95
95
95
95
95
96
96
96
96
96
96
97
97
97
97
97
97
98
98
98
98
98
98
AGE
yrs
SEX
0=female
1=male
28
28
28
28
28
28
26
26
26
26
26
26
25
25
25
25
25
25
25
25
25
25
25
25
38
38
38
38
38
38
25
25
25
25
25
25
18
18
18
18
18
18
SIDE
0=rt
1=lt
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
LINS1
VAS
SCORE
L=LIDO
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
37
37
37
37
37
37
54
54
54
54
54
54
54
54
54
54
54
54
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
54
54
54
54
54
54
166
LPLC1
VAS
SCORE
114
114
114
114
114
114
21
21
21
21
21
21
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
54
54
54
54
54
54
LDEP1
VAS
SCORE
54
54
54
54
54
54
37
37
37
37
37
37
21
21
21
21
21
21
37
37
37
37
37
37
37
37
37
37
37
37
21
21
21
21
21
21
54
54
54
54
54
54
LINS2
VAS
SCORE
54
54
54
54
54
54
37
37
37
37
37
37
0
0
0
0
0
0
0
0
0
0
0
0
37
37
37
37
37
37
21
21
21
21
21
21
21
21
21
21
21
21
SUB
#
99
99
99
99
99
99
100
100
100
100
100
100
AGE
yrs
SEX
0=female
1=male
25
25
25
25
25
25
24
24
24
24
24
24
SIDE
0=rt
1=lt
0
0
0
0
0
0
0
0
0
0
0
0
LINS1
VAS
SCORE
L=LIDO
0
0
0
0
0
0
1
1
1
1
1
1
37
37
37
37
37
37
55
55
55
55
55
55
167
LPLC1
VAS
SCORE
37
37
37
37
37
37
62
62
62
62
62
62
LDEP1
VAS
SCORE
21
21
21
21
21
21
5
5
5
5
5
5
LINS2
VAS
SCORE
37
37
37
37
37
37
13
13
13
13
13
13
SUB
#
1
1
1
1
1
1
2
2
2
2
2
2
3
3
3
3
3
3
4
4
4
4
4
4
5
5
5
5
5
5
6
6
6
6
6
6
7
7
7
7
7
7
LPLC2
VAS
SCORE
0
0
0
0
0
0
39
39
39
39
39
39
0
0
0
0
0
0
0
0
0
0
0
0
12
12
12
12
12
12
50
50
50
50
50
50
0
0
0
0
0
0
LDEP2
VAS
SCORE
0
0
0
0
0
0
114
114
114
114
114
114
0
0
0
0
0
0
19
19
19
19
19
19
10
10
10
10
10
10
19
19
19
19
19
19
0
0
0
0
0
0
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
38
38
38
38
38
38
84
84
84
84
84
84
37
37
37
37
37
37
21
21
21
21
21
21
42
42
42
42
42
42
70
70
70
70
70
70
21
21
21
21
21
21
56
56
56
56
56
56
83
83
83
83
83
83
21
21
21
21
21
21
38
38
38
38
38
38
53
53
53
53
53
53
67
67
67
67
67
67
37
37
37
37
37
37
168
CDEP1
VAS
SCORE
38
38
38
38
38
38
112
112
112
112
112
112
37
37
37
37
37
37
21
21
21
21
21
21
18
18
18
18
18
18
18
18
18
18
18
18
21
21
21
21
21
21
CINS2
VAS
SCORE
38
38
38
38
38
38
54
54
54
54
54
54
0
0
0
0
0
0
0
0
0
0
0
0
31
31
31
31
31
31
74
74
74
74
74
74
0
0
0
0
0
0
CPLC2
VAS
SCORE
20
20
20
20
20
20
55
55
55
55
55
55
0
0
0
0
0
0
1
1
1
1
1
1
18
18
18
18
18
18
96
96
96
96
96
96
0
0
0
0
0
0
CDEP2
VAS
SCORE
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
4
4
4
4
4
4
9
9
9
9
9
9
0
0
0
0
0
0
SUB
#
8
8
8
8
8
8
9
9
9
9
9
9
10
10
10
10
10
10
11
11
11
11
11
11
12
12
12
12
12
12
13
13
13
13
13
13
14
14
14
14
14
14
LPLC2
VAS
SCORE
0
0
0
0
0
0
21
21
21
21
21
21
5
5
5
5
5
5
21
21
21
21
21
21
0
0
0
0
0
0
37
37
37
37
37
37
23
23
23
23
23
23
LDEP2
VAS
SCORE
6
6
6
6
6
6
0
0
0
0
0
0
5
5
5
5
5
5
0
0
0
0
0
0
0
0
0
0
0
0
37
37
37
37
37
37
1
1
1
1
1
1
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
43
43
43
43
43
43
54
54
54
54
54
54
37
37
37
37
37
37
108
108
108
108
108
108
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
52
52
52
52
52
52
169
CDEP1
VAS
SCORE
21
21
21
21
21
21
37
37
37
37
37
37
88
88
88
88
88
88
83
83
83
83
83
83
37
37
37
37
37
37
54
54
54
54
54
54
24
24
24
24
24
24
CINS2
VAS
SCORE
0
0
0
0
0
0
21
21
21
21
21
21
6
6
6
6
6
6
54
54
54
54
54
54
21
21
21
21
21
21
41
41
41
41
41
41
34
34
34
34
34
34
CPLC2
VAS
SCORE
21
21
21
21
21
21
21
21
21
21
21
21
34
34
34
34
34
34
37
37
37
37
37
37
37
37
37
37
37
37
42
42
42
42
42
42
26
26
26
26
26
26
CDEP2
VAS
SCORE
21
21
21
21
21
21
0
0
0
0
0
0
60
60
60
60
60
60
21
21
21
21
21
21
0
0
0
0
0
0
0
0
0
0
0
0
4
4
4
4
4
4
SUB
#
15
15
15
15
15
15
16
16
16
16
16
16
17
17
17
17
17
17
18
18
18
18
18
18
19
19
19
19
19
19
20
20
20
20
20
20
21
21
21
21
21
21
LPLC2
VAS
SCORE
54
54
54
54
54
54
0
0
0
0
0
0
84
84
84
84
84
84
21
21
21
21
21
21
25
25
25
25
25
25
38
38
38
38
38
38
2
2
2
2
2
2
LDEP2
VAS
SCORE
0
0
0
0
0
0
0
0
0
0
0
0
55
55
55
55
55
55
21
21
21
21
21
21
21
21
21
21
21
21
24
24
24
24
24
24
21
21
21
21
21
21
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
37
37
37
37
37
37
21
21
21
21
21
21
24
24
24
24
24
24
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
45
45
45
45
45
45
55
55
55
55
55
55
21
21
21
21
21
21
79
79
79
79
79
79
37
37
37
37
37
37
51
51
51
51
51
51
83
83
83
83
83
83
54
54
54
54
54
54
170
CDEP1
VAS
SCORE
21
21
21
21
21
21
37
37
37
37
37
37
71
71
71
71
71
71
2
2
2
2
2
2
34
34
34
34
34
34
21
21
21
21
21
21
42
42
42
42
42
42
CINS2
VAS
SCORE
37
37
37
37
37
37
0
0
0
0
0
0
38
38
38
38
38
38
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
29
29
29
29
29
29
CPLC2
VAS
SCORE
37
37
37
37
37
37
0
0
0
0
0
0
78
78
78
78
78
78
0
0
0
0
0
0
1
1
1
1
1
1
20
20
20
20
20
20
0
0
0
0
0
0
CDEP2
VAS
SCORE
21
21
21
21
21
21
0
0
0
0
0
0
80
80
80
80
80
80
0
0
0
0
0
0
0
0
0
0
0
0
21
21
21
21
21
21
0
0
0
0
0
0
SUB
#
22
22
22
22
22
22
23
23
23
23
23
23
24
24
24
24
24
24
25
25
25
25
25
25
26
26
26
26
26
26
27
27
27
27
27
27
28
28
28
28
28
28
LPLC2
VAS
SCORE
12
12
12
12
12
12
21
21
21
21
21
21
21
21
21
21
21
21
28
28
28
28
28
28
0
0
0
0
0
0
37
37
37
37
37
37
0
0
0
0
0
0
LDEP2
VAS
SCORE
30
30
30
30
30
30
21
21
21
21
21
21
0
0
0
0
0
0
17
17
17
17
17
17
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
47
47
47
47
47
47
37
37
37
37
37
37
37
37
37
37
37
37
86
86
86
86
86
86
15
15
15
15
15
15
54
54
54
54
54
54
21
21
21
21
21
21
29
29
29
29
29
29
54
54
54
54
54
54
54
54
54
54
54
54
86
86
86
86
86
86
97
97
97
97
97
97
83
83
83
83
83
83
84
84
84
84
84
84
171
CDEP1
VAS
SCORE
46
46
46
46
46
46
21
21
21
21
21
21
54
54
54
54
54
54
58
58
58
58
58
58
15
15
15
15
15
15
37
37
37
37
37
37
21
21
21
21
21
21
CINS2
VAS
SCORE
12
12
12
12
12
12
37
37
37
37
37
37
0
0
0
0
0
0
57
57
57
57
57
57
0
0
0
0
0
0
21
21
21
21
21
21
0
0
0
0
0
0
CPLC2
VAS
SCORE
9
9
9
9
9
9
37
37
37
37
37
37
0
0
0
0
0
0
43
43
43
43
43
43
0
0
0
0
0
0
21
21
21
21
21
21
21
21
21
21
21
21
CDEP2
VAS
SCORE
9
9
9
9
9
9
21
21
21
21
21
21
21
21
21
21
21
21
40
40
40
40
40
40
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
SUB
#
29
29
29
29
29
29
30
30
30
30
30
30
31
31
31
31
31
31
32
32
32
32
32
32
33
33
33
33
33
33
34
34
34
34
34
34
35
35
35
35
35
35
LPLC2
VAS
SCORE
54
54
54
54
54
54
30
30
30
30
30
30
60
60
60
60
60
60
0
0
0
0
0
0
0
0
0
0
0
0
37
37
37
37
37
37
4
4
4
4
4
4
LDEP2
VAS
SCORE
54
54
54
54
54
54
32
32
32
32
32
32
12
12
12
12
12
12
0
0
0
0
0
0
6
6
6
6
6
6
0
0
0
0
0
0
4
4
4
4
4
4
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
74
74
74
74
74
74
31
31
31
31
31
31
11
11
11
11
11
11
37
37
37
37
37
37
14
14
14
14
14
14
44
44
44
44
44
44
26
26
26
26
26
26
74
74
74
74
74
74
30
30
30
30
30
30
57
57
57
57
57
57
37
37
37
37
37
37
22
22
22
22
22
22
83
83
83
83
83
83
47
47
47
47
47
47
172
CDEP1
VAS
SCORE
97
97
97
97
97
97
15
15
15
15
15
15
76
76
76
76
76
76
54
54
54
54
54
54
3
3
3
3
3
3
46
46
46
46
46
46
31
31
31
31
31
31
CINS2
VAS
SCORE
59
59
59
59
59
59
17
17
17
17
17
17
2
2
2
2
2
2
0
0
0
0
0
0
2
2
2
2
2
2
21
21
21
21
21
21
2
2
2
2
2
2
CPLC2
VAS
SCORE
59
59
59
59
59
59
17
17
17
17
17
17
2
2
2
2
2
2
0
0
0
0
0
0
13
13
13
13
13
13
54
54
54
54
54
54
1
1
1
1
1
1
CDEP2
VAS
SCORE
77
77
77
77
77
77
16
16
16
16
16
16
17
17
17
17
17
17
21
21
21
21
21
21
2
2
2
2
2
2
0
0
0
0
0
0
11
11
11
11
11
11
SUB
#
36
36
36
36
36
36
37
37
37
37
37
37
38
38
38
38
38
38
39
39
39
39
39
39
40
40
40
40
40
40
41
41
41
41
41
41
42
42
42
42
42
42
LPLC2
VAS
SCORE
54
54
54
54
54
54
4
4
4
4
4
4
21
21
21
21
21
21
83
83
83
83
83
83
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
LDEP2
VAS
SCORE
21
21
21
21
21
21
9
9
9
9
9
9
0
0
0
0
0
0
54
54
54
54
54
54
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
114
114
114
114
114
114
36
36
36
36
36
36
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
37
37
37
37
37
37
34
34
34
34
34
34
54
54
54
54
54
54
66
66
66
66
66
66
21
21
21
21
21
21
37
37
37
37
37
37
21
21
21
21
21
21
54
54
54
54
54
54
63
63
63
63
63
63
173
CDEP1
VAS
SCORE
37
37
37
37
37
37
80
80
80
80
80
80
37
37
37
37
37
37
37
37
37
37
37
37
21
21
21
21
21
21
54
54
54
54
54
54
41
41
41
41
41
41
CINS2
VAS
SCORE
83
83
83
83
83
83
3
3
3
3
3
3
37
37
37
37
37
37
54
54
54
54
54
54
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
CPLC2
VAS
SCORE
83
83
83
83
83
83
4
4
4
4
4
4
21
21
21
21
21
21
21
21
21
21
21
21
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
CDEP2
VAS
SCORE
37
37
37
37
37
37
22
22
22
22
22
22
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
SUB
#
43
43
43
43
43
43
44
44
44
44
44
44
45
45
45
45
45
45
46
46
46
46
46
46
47
47
47
47
47
47
48
48
48
48
48
48
49
49
49
49
49
49
LPLC2
VAS
SCORE
0
0
0
0
0
0
83
83
83
83
83
83
54
54
54
54
54
54
0
0
0
0
0
0
7
7
7
7
7
7
37
37
37
37
37
37
5
5
5
5
5
5
LDEP2
VAS
SCORE
0
0
0
0
0
0
21
21
21
21
21
21
54
54
54
54
54
54
21
21
21
21
21
21
4
4
4
4
4
4
54
54
54
54
54
54
5
5
5
5
5
5
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
21
21
21
21
21
21
54
54
54
54
54
54
54
54
54
54
54
54
37
37
37
37
37
37
21
21
21
21
21
21
21
21
21
21
21
21
54
54
54
54
54
54
0
0
0
0
0
0
37
37
37
37
37
37
54
54
54
54
54
54
54
54
54
54
54
54
113
113
113
113
113
113
21
21
21
21
21
21
63
63
63
63
63
63
174
CDEP1
VAS
SCORE
54
54
54
54
54
54
83
83
83
83
83
83
113
113
113
113
113
113
21
21
21
21
21
21
54
54
54
54
54
54
21
21
21
21
21
21
46
46
46
46
46
46
CINS2
VAS
SCORE
0
0
0
0
0
0
21
21
21
21
21
21
0
0
0
0
0
0
21
21
21
21
21
21
8
8
8
8
8
8
0
0
0
0
0
0
28
28
28
28
28
28
CPLC2
VAS
SCORE
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
54
54
54
54
54
54
21
21
21
21
21
21
0
0
0
0
0
0
37
37
37
37
37
37
CDEP2
VAS
SCORE
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
SUB
#
50
50
50
50
50
50
51
51
51
51
51
51
52
52
52
52
52
52
53
53
53
53
53
53
54
54
54
54
54
54
55
55
55
55
55
55
56
56
56
56
56
56
LPLC2
VAS
SCORE
117
117
117
117
117
117
54
54
54
54
54
54
0
0
0
0
0
0
41
41
41
41
41
41
59
59
59
59
59
59
21
21
21
21
21
21
21
21
21
21
21
21
LDEP2
VAS
SCORE
46
46
46
46
46
46
37
37
37
37
37
37
0
0
0
0
0
0
10
10
10
10
10
10
12
12
12
12
12
12
0
0
0
0
0
0
0
0
0
0
0
0
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
78
78
78
78
78
78
113
113
113
113
113
113
21
21
21
21
21
21
52
52
52
52
52
52
11
11
11
11
11
11
54
54
54
54
54
54
21
21
21
21
21
21
110
110
110
110
110
110
83
83
83
83
83
83
21
21
21
21
21
21
51
51
51
51
51
51
121
121
121
121
121
121
113
113
113
113
113
113
54
54
54
54
54
54
175
CDEP1
VAS
SCORE
41
41
41
41
41
41
37
37
37
37
37
37
0
0
0
0
0
0
58
58
58
58
58
58
97
97
97
97
97
97
83
83
83
83
83
83
21
21
21
21
21
21
CINS2
VAS
SCORE
4
4
4
4
4
4
54
54
54
54
54
54
0
0
0
0
0
0
0
0
0
0
0
0
11
11
11
11
11
11
37
37
37
37
37
37
0
0
0
0
0
0
CPLC2
VAS
SCORE
3
3
3
3
3
3
83
83
83
83
83
83
0
0
0
0
0
0
0
0
0
0
0
0
128
128
128
128
128
128
21
21
21
21
21
21
0
0
0
0
0
0
CDEP2
VAS
SCORE
33
33
33
33
33
33
37
37
37
37
37
37
0
0
0
0
0
0
18
18
18
18
18
18
95
95
95
95
95
95
0
0
0
0
0
0
0
0
0
0
0
0
SUB
#
57
57
57
57
57
57
58
58
58
58
58
58
59
59
59
59
59
59
60
60
60
60
60
60
61
61
61
61
61
61
62
62
62
62
62
62
63
63
63
63
63
63
LPLC2
VAS
SCORE
21
21
21
21
21
21
0
0
0
0
0
0
0
0
0
0
0
0
21
21
21
21
21
21
2
2
2
2
2
2
94
94
94
94
94
94
17
17
17
17
17
17
LDEP2
VAS
SCORE
3
3
3
3
3
3
0
0
0
0
0
0
0
0
0
0
0
0
6
6
6
6
6
6
2
2
2
2
2
2
48
48
48
48
48
48
18
18
18
18
18
18
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
2
2
2
2
2
2
21
21
21
21
21
21
46
46
46
46
46
46
3
3
3
3
3
3
69
69
69
69
69
69
57
57
57
57
57
57
64
64
64
64
64
64
3
3
3
3
3
3
37
37
37
37
37
37
46
46
46
46
46
46
4
4
4
4
4
4
90
90
90
90
90
90
100
100
100
100
100
100
61
61
61
61
61
61
176
CDEP1
VAS
SCORE
19
19
19
19
19
19
83
83
83
83
83
83
46
46
46
46
46
46
4
4
4
4
4
4
17
17
17
17
17
17
18
18
18
18
18
18
34
34
34
34
34
34
CINS2
VAS
SCORE
21
21
21
21
21
21
21
21
21
21
21
21
3
3
3
3
3
3
3
3
3
3
3
3
2
2
2
2
2
2
88
88
88
88
88
88
24
24
24
24
24
24
CPLC2
VAS
SCORE
21
21
21
21
21
21
0
0
0
0
0
0
2
2
2
2
2
2
11
11
11
11
11
11
5
5
5
5
5
5
11
11
11
11
11
11
23
23
23
23
23
23
CDEP2
VAS
SCORE
21
21
21
21
21
21
0
0
0
0
0
0
2
2
2
2
2
2
3
3
3
3
3
3
4
4
4
4
4
4
13
13
13
13
13
13
34
34
34
34
34
34
SUB
#
64
64
64
64
64
64
65
65
65
65
65
65
66
66
66
66
66
66
67
67
67
67
67
67
68
68
68
68
68
68
69
69
69
69
69
69
70
70
70
70
70
70
LPLC2
VAS
SCORE
0
0
0
0
0
0
17
17
17
17
17
17
37
37
37
37
37
37
37
37
37
37
37
37
21
21
21
21
21
21
19
19
19
19
19
19
21
21
21
21
21
21
LDEP2
VAS
SCORE
21
21
21
21
21
21
2
2
2
2
2
2
21
21
21
21
21
21
1
1
1
1
1
1
21
21
21
21
21
21
4
4
4
4
4
4
21
21
21
21
21
21
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
37
37
37
37
37
37
59
59
59
59
59
59
54
54
54
54
54
54
54
54
54
54
54
54
37
37
37
37
37
37
26
26
26
26
26
26
21
21
21
21
21
21
21
21
21
21
21
21
74
74
74
74
74
74
83
83
83
83
83
83
83
83
83
83
83
83
21
21
21
21
21
21
52
52
52
52
52
52
54
54
54
54
54
54
177
CDEP1
VAS
SCORE
37
37
37
37
37
37
66
66
66
66
66
66
83
83
83
83
83
83
37
37
37
37
37
37
21
21
21
21
21
21
64
64
64
64
64
64
37
37
37
37
37
37
CINS2
VAS
SCORE
0
0
0
0
0
0
3
3
3
3
3
3
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
27
27
27
27
27
27
0
0
0
0
0
0
CPLC2
VAS
SCORE
0
0
0
0
0
0
21
21
21
21
21
21
21
21
21
21
21
21
0
0
0
0
0
0
36
36
36
36
36
36
35
35
35
35
35
35
37
37
37
37
37
37
CDEP2
VAS
SCORE
21
21
21
21
21
21
18
18
18
18
18
18
0
0
0
0
0
0
1
1
1
1
1
1
21
21
21
21
21
21
32
32
32
32
32
32
21
21
21
21
21
21
SUB
#
71
71
71
71
71
71
72
72
72
72
72
72
73
73
73
73
73
73
74
74
74
74
74
74
75
75
75
75
75
75
76
76
76
76
76
76
77
77
77
77
77
77
LPLC2
VAS
SCORE
83
83
83
83
83
83
56
56
56
56
56
56
37
37
37
37
37
37
54
54
54
54
54
54
83
83
83
83
83
83
0
0
0
0
0
0
7
7
7
7
7
7
LDEP2
VAS
SCORE
54
54
54
54
54
54
49
49
49
49
49
49
0
0
0
0
0
0
37
37
37
37
37
37
0
0
0
0
0
0
0
0
0
0
0
0
3
3
3
3
3
3
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
83
83
83
83
83
83
60
60
60
60
60
60
21
21
21
21
21
21
54
54
54
54
54
54
54
54
54
54
54
54
14
14
14
14
14
14
42
42
42
42
42
42
83
83
83
83
83
83
37
37
37
37
37
37
37
37
37
37
37
37
54
54
54
54
54
54
0
0
0
0
0
0
21
21
21
21
21
21
74
74
74
74
74
74
178
CDEP1
VAS
SCORE
54
54
54
54
54
54
21
21
21
21
21
21
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
37
3
3
3
3
3
3
21
21
21
21
21
21
CINS2
VAS
SCORE
113
113
113
113
113
113
34
34
34
34
34
34
21
21
21
21
21
21
54
54
54
54
54
54
54
54
54
54
54
54
15
15
15
15
15
15
14
14
14
14
14
14
CPLC2
VAS
SCORE
83
83
83
83
83
83
26
26
26
26
26
26
0
0
0
0
0
0
37
37
37
37
37
37
0
0
0
0
0
0
1
1
1
1
1
1
2
2
2
2
2
2
CDEP2
VAS
SCORE
54
54
54
54
54
54
5
5
5
5
5
5
0
0
0
0
0
0
37
37
37
37
37
37
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
SUB
#
78
78
78
78
78
78
79
79
79
79
79
79
80
80
80
80
80
80
81
81
81
81
81
81
82
82
82
82
82
82
83
83
83
83
83
83
84
84
84
84
84
84
LPLC2
VAS
SCORE
24
24
24
24
24
24
37
37
37
37
37
37
25
25
25
25
25
25
37
37
37
37
37
37
114
114
114
114
114
114
0
0
0
0
0
0
37
37
37
37
37
37
LDEP2
VAS
SCORE
39
39
39
39
39
39
34
34
34
34
34
34
13
13
13
13
13
13
21
21
21
21
21
21
21
21
21
21
21
21
0
0
0
0
0
0
21
21
21
21
21
21
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
16
16
16
16
16
16
54
54
54
54
54
54
64
64
64
64
64
64
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
17
17
17
17
17
17
21
21
21
21
21
21
74
74
74
74
74
74
83
83
83
83
83
83
21
21
21
21
21
21
21
21
21
21
21
21
37
37
37
37
37
37
179
CDEP1
VAS
SCORE
18
18
18
18
18
18
54
54
54
54
54
54
40
40
40
40
40
40
37
37
37
37
37
37
0
0
0
0
0
0
83
83
83
83
83
83
21
21
21
21
21
21
CINS2
VAS
SCORE
19
19
19
19
19
19
49
49
49
49
49
49
28
28
28
28
28
28
21
21
21
21
21
21
21
21
21
21
21
21
0
0
0
0
0
0
0
0
0
0
0
0
CPLC2
VAS
SCORE
17
17
17
17
17
17
21
21
21
21
21
21
27
27
27
27
27
27
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
CDEP2
VAS
SCORE
23
23
23
23
23
23
21
21
21
21
21
21
7
7
7
7
7
7
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
SUB
#
85
85
85
85
85
85
86
86
86
86
86
86
87
87
87
87
87
87
88
88
88
88
88
88
89
89
89
89
89
89
90
90
90
90
90
90
91
91
91
91
91
91
LPLC2
VAS
SCORE
83
83
83
83
83
83
37
37
37
37
37
37
41
41
41
41
41
41
21
21
21
21
21
21
22
22
22
22
22
22
21
21
21
21
21
21
37
37
37
37
37
37
LDEP2
VAS
SCORE
37
37
37
37
37
37
37
37
37
37
37
37
58
58
58
58
58
58
37
37
37
37
37
37
0
0
0
0
0
0
21
21
21
21
21
21
21
21
21
21
21
21
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
83
83
83
83
83
83
37
37
37
37
37
37
80
80
80
80
80
80
37
37
37
37
37
37
21
21
21
21
21
21
143
143
143
143
143
143
37
37
37
37
37
37
54
54
54
54
54
54
83
83
83
83
83
83
54
54
54
54
54
54
83
83
83
83
83
83
37
37
37
37
37
37
143
143
143
143
143
143
83
83
83
83
83
83
180
CDEP1
VAS
SCORE
21
21
21
21
21
21
37
37
37
37
37
37
37
37
37
37
37
37
0
0
0
0
0
0
21
21
21
21
21
21
114
114
114
114
114
114
21
21
21
21
21
21
CINS2
VAS
SCORE
83
83
83
83
83
83
21
21
21
21
21
21
70
70
70
70
70
70
54
54
54
54
54
54
21
21
21
21
21
21
83
83
83
83
83
83
21
21
21
21
21
21
CPLC2
VAS
SCORE
37
37
37
37
37
37
54
54
54
54
54
54
47
47
47
47
47
47
37
37
37
37
37
37
21
21
21
21
21
21
54
54
54
54
54
54
37
37
37
37
37
37
CDEP2
VAS
SCORE
21
21
21
21
21
21
0
0
0
0
0
0
30
30
30
30
30
30
0
0
0
0
0
0
0
0
0
0
0
0
21
21
21
21
21
21
21
21
21
21
21
21
SUB
#
92
92
92
92
92
92
93
93
93
93
93
93
94
94
94
94
94
94
95
95
95
95
95
95
96
96
96
96
96
96
97
97
97
97
97
97
98
98
98
98
98
98
LPLC2
VAS
SCORE
21
21
21
21
21
21
21
21
21
21
21
21
45
45
45
45
45
45
0
0
0
0
0
0
37
37
37
37
37
37
54
54
54
54
54
54
21
21
21
21
21
21
LDEP2
VAS
SCORE
21
21
21
21
21
21
14
14
14
14
14
14
21
21
21
21
21
21
21
21
21
21
21
21
0
0
0
0
0
0
21
21
21
21
21
21
21
21
21
21
21
21
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
37
37
37
37
37
37
54
54
54
54
54
54
54
54
54
54
54
54
37
37
37
37
37
37
37
37
37
37
37
37
21
21
21
21
21
21
53
53
53
53
53
53
114
114
114
114
114
114
37
37
37
37
37
37
54
54
54
54
54
54
54
54
54
54
54
54
37
37
37
37
37
37
21
21
21
21
21
21
52
52
52
52
52
52
181
CDEP1
VAS
SCORE
83
83
83
83
83
83
21
21
21
21
21
21
37
37
37
37
37
37
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
83
83
83
83
83
83
CINS2
VAS
SCORE
0
0
0
0
0
0
54
54
54
54
54
54
0
0
0
0
0
0
37
37
37
37
37
37
21
21
21
21
21
21
21
21
21
21
21
21
23
23
23
23
23
23
CPLC2
VAS
SCORE
0
0
0
0
0
0
0
0
0
0
0
0
37
37
37
37
37
37
0
0
0
0
0
0
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
21
CDEP2
VAS
SCORE
0
0
0
0
0
0
0
0
0
0
0
0
21
21
21
21
21
21
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
2
2
2
2
2
2
SUB
#
99
99
99
99
99
99
100
100
100
100
100
100
LPLC2
VAS
SCORE
21
21
21
21
21
21
0
0
0
0
0
0
LDEP2
VAS
SCORE
0
0
0
0
0
0
0
0
0
0
0
0
CINS1
CPLC1
VAS
VAS
SCORE SCORE
C=COMBO
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
54
90
90
90
90
90
90
182
CDEP1
VAS
SCORE
83
83
83
83
83
83
21
21
21
21
21
21
CINS2
VAS
SCORE
37
37
37
37
37
37
64
64
64
64
64
64
CPLC2
VAS
SCORE
21
21
21
21
21
21
21
21
21
21
21
21
CDEP2
VAS
SCORE
21
21
21
21
21
21
2
2
2
2
2
2
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
1
1
9
29
0
0
0
0
0
0
1
2
.
.
0
0
.
.
.
.
1
3
.
25
0
0
.
1
.
1
1
4
.
21
0
0
.
1
.
0
1
5
.
25
0
0
.
1
.
0
1
6
.
.
0
0
.
.
.
.
2
1
.
9
0
0
.
0
.
1
2
2
53
13
0
0
0
0
0
1
2
3
45
13
0
1
1
0
1
0
2
4
.
13
0
0
.
0
.
1
2
5
.
9
0
0
.
0
.
1
2
6
.
.
0
0
.
.
.
.
3
1
5
29
0
0
0
1
1
1
3
2
5
41
0
0
0
1
1
0
.
0
0
.
.
.
.
3
3
.
4
.
.
0
0
.
.
.
.
3
5
.
.
0
0
.
.
.
.
3
6
.
.
0
0
.
.
.
.
3
1
5
5
1
1
0
0
0
0
4
2
5
5
1
1
0
0
0
0
4
3
25
5
0
1
1
0
0
0
4
4
5
5
1
1
0
0
0
0
4
5
17
5
0
1
0
0
1
0
4
6
.
.
0
0
.
.
.
.
4
1
9
.
0
0
0
.
1
.
5
2
9
9
1
1
0
0
1
0
5
3
.
.
.
.
.
.
.
.
5
4
17
9
1
1
0
0
0
0
5
5
9
5
1
1
0
0
0
0
5
.
9
0
0
.
0
.
1
6
5
1
5
5
1
1
0
0
0
0
6
2
5
9
1
1
0
0
0
0
6
3
5
9
1
1
0
0
0
0
6
4
5
9
1
1
0
0
0
0
6
5
5
9
1
1
0
0
1
0
6
6
.
.
0
0
.
.
.
.
6
1
21
5
0
0
0
0
1
0
7
2
.
.
0
0
.
.
.
.
7
3
.
.
0
0
.
.
.
.
7
4
.
.
0
0
.
.
.
.
7
5
.
.
0
0
.
.
.
.
7
7
6
.
.
0
0
.
.
.
.
183
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
8
1
9
21
1
0
0
1
0
0
8
2
9
29
1
0
0
1
0
0
8
3
9
29
1
0
0
1
0
0
8
4
9
25
1
0
0
1
0
0
8
5
.
.
0
0
.
.
.
.
8
6
.
.
0
0
.
.
.
.
9
1
9
13
1
0
.
0
.
1
9
2
9
5
1
1
.
.
.
.
9
3
.
.
0
0
0
0
0
0
9
4
9
5
1
1
.
.
.
.
9
5
.
.
0
0
0
0
0
0
9
6
.
.
0
0
0
0
0
0
10
1
53
.
0
0
0
.
0
.
10
2
53
.
0
0
1
.
0
.
10
3
17
.
1
0
0
.
0
.
.
10
4
17
.
0
0
0
.
1
5
.
.
0
0
.
.
.
.
10
6
.
.
0
0
.
.
.
.
10
1
9
5
1
1
0
0
0
0
11
2
.
25
0
0
.
1
.
0
11
3
9
5
1
1
0
0
0
0
11
4
9
5
1
1
0
0
0
0
11
5
13
9
1
1
0
0
0
0
11
6
13
13
1
0
0
0
0
1
11
1
9
5
0
1
0
0
1
0
12
2
5
5
0
1
0
0
1
0
12
3
9
5
1
1
0
0
0
0
12
4
9
9
1
1
0
0
0
0
12
5
.
.
0
0
.
.
.
.
12
6
.
.
0
0
.
.
.
.
12
0
0
1
9
29
1
0
0
1
13
2
13
.
1
0
0
.
0
.
13
3
25
.
0
0
1
.
0
.
13
4
21
.
0
0
1
.
0
.
13
5
13
49
1
0
0
1
0
0
13
6
33
.
0
0
1
.
1
.
13
1
.
13
0
0
.
0
.
1
14
2
21
13
0
0
0
0
0
1
14
3
5
5
1
1
0
0
0
0
14
4
.
.
.
.
.
.
.
.
14
5
.
.
0
0
.
.
.
.
14
14
6
.
5
0
0
.
0
.
0
184
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
15
1
5
5
1
1
0
0
0
0
15
2
9
13
0
0
0
0
1
1
15
3
13
17
0
0
0
0
1
0
15
4
13
13
1
1
0
0
0
0
15
5
.
.
0
0
.
.
.
.
15
6
.
.
0
0
.
.
.
.
16
1
13
5
1
1
0
0
0
0
16
2
17
13
1
1
0
0
0
0
16
3
21
9
0
1
1
0
0
0
16
4
21
17
0
1
1
0
0
0
16
5
29
13
0
1
1
0
1
0
16
6
.
.
0
0
.
.
.
.
17
1
13
21
1
0
0
1
0
0
17
2
13
.
1
0
0
.
0
.
17
3
13
.
1
0
0
.
0
.
.
17
4
25
.
0
0
1
.
0
5
.
.
0
0
.
.
.
.
17
6
.
.
0
0
.
.
.
.
17
1
.
5
0
0
.
0
.
1
18
2
.
49
0
0
.
1
.
0
18
3
.
.
0
0
.
.
.
.
18
4
.
5
0
0
.
0
.
1
18
5
.
.
0
0
.
.
.
.
18
6
.
.
0
0
.
.
.
.
18
1
9
33
1
0
0
0
0
1
19
2
.
.
0
0
.
.
.
.
19
3
.
.
0
0
.
.
.
.
19
4
.
37
0
0
.
1
.
0
19
5
.
53
0
0
.
1
.
0
19
6
.
.
0
0
.
.
.
.
19
0
0
1
9
5
1
1
0
0
20
2
5
5
1
1
0
0
0
0
20
3
5
5
1
1
0
0
0
0
20
4
9
5
1
1
0
0
0
0
20
5
9
13
0
1
0
0
1
0
20
6
.
.
0
0
.
.
.
.
20
1
33
.
0
0
0
.
0
.
21
2
.
.
0
0
.
.
.
.
21
3
9
13
1
1
0
0
0
0
21
4
.
.
.
.
.
.
.
.
21
5
21
13
1
1
1
0
0
0
21
21
6
5
5
1
1
0
0
0
0
185
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
22
1
5
21
1
0
0
1
0
0
22
2
5
.
1
0
0
.
0
.
22
3
21
29
0
0
1
1
1
1
22
4
.
.
0
0
.
.
.
.
22
5
.
.
0
0
.
.
.
.
22
6
.
.
0
0
.
.
.
.
23
1
17
5
1
1
0
0
0
0
23
2
17
13
0
0
0
0
1
0
23
3
29
21
0
0
1
1
0
1
23
4
17
13
0
0
0
0
1
1
23
5
.
.
0
0
.
.
.
.
23
6
.
.
0
0
.
.
.
.
24
1
.
.
0
0
.
.
.
.
24
2
37
.
0
0
1
.
1
.
24
3
.
.
0
0
.
.
.
.
0
24
4
13
21
0
1
0
0
1
5
13
13
1
1
0
0
0
0
24
6
.
.
0
0
.
.
.
.
24
1
9
5
1
1
0
0
0
0
25
2
13
5
1
1
0
0
0
0
25
3
17
5
1
1
0
0
0
0
25
4
17
5
1
0
0
0
0
1
25
5
.
.
0
0
.
.
.
.
25
6
17
21
0
0
0
1
1
1
25
1
.
13
0
0
.
0
.
1
26
2
.
9
0
1
.
0
.
0
26
3
.
9
0
1
.
0
.
0
26
4
.
9
0
1
.
0
.
0
26
5
.
9
0
1
.
0
.
0
26
6
.
9
0
1
.
0
.
0
26
1
0
1
9
45
0
0
0
1
27
2
53
.
0
0
1
.
0
.
27
3
37
.
0
0
1
.
0
.
27
4
13
21
1
1
0
1
0
0
27
5
21
21
1
1
1
1
0
0
27
6
.
.
0
0
.
.
.
.
27
1
5
9
1
1
0
0
0
0
28
2
5
9
1
1
0
0
0
0
28
3
5
9
1
1
0
0
0
0
28
4
5
9
0
1
0
0
1
0
28
5
29
9
0
0
1
0
1
1
28
28
6
.
.
0
0
.
.
.
.
186
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
29
1
5
9
0
1
0
0
1
0
29
2
.
.
0
0
.
.
.
.
29
3
5
13
1
1
0
0
0
0
29
4
5
13
1
0
0
0
0
1
29
5
13
13
1
1
0
0
0
0
29
6
.
5
0
0
.
0
.
1
30
1
.
5
0
1
.
0
.
0
30
2
5
9
1
1
0
0
0
0
30
3
.
.
.
.
.
.
.
.
30
4
13
21
1
1
0
1
0
0
30
5
.
.
0
0
.
.
.
.
30
6
.
.
0
0
.
.
.
.
31
1
.
.
0
0
.
.
.
.
31
2
.
.
0
0
.
.
.
.
31
3
.
.
0
0
.
.
.
.
0
31
4
17
33
0
0
0
1
1
5
.
.
0
0
.
.
.
.
31
6
.
.
0
0
.
.
.
.
31
1
5
21
1
0
0
1
0
1
32
2
13
.
0
0
0
.
1
.
32
3
5
.
1
0
0
.
0
.
32
4
9
.
1
0
0
.
0
.
32
5
25
.
0
0
1
.
1
.
32
6
.
.
0
0
.
.
.
.
32
1
21
5
0
1
1
0
1
0
33
2
.
9
0
1
.
0
.
0
33
3
.
5
0
1
.
0
.
0
33
4
.
9
0
1
.
0
.
0
33
5
.
9
0
1
.
0
.
0
33
6
.
.
0
0
.
.
.
.
33
.
0
1
.
5
0
1
.
0
34
2
.
5
0
1
.
0
.
0
34
3
21
5
0
1
1
0
1
0
34
4
.
33
0
0
.
1
.
0
34
5
.
.
0
0
.
.
.
.
34
6
.
.
0
0
.
.
.
.
34
1
.
.
0
0
.
.
.
.
35
2
.
.
0
0
.
.
.
.
35
3
.
.
0
0
.
.
.
.
35
4
.
.
0
0
.
.
.
.
35
5
.
.
0
0
.
.
.
.
35
35
6
.
.
0
0
.
.
.
.
187
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
36
1
13
45
1
0
0
1
0
0
36
2
.
.
0
0
.
.
.
.
36
3
21
.
0
0
0
.
1
.
36
4
17
53
1
0
0
1
0
0
36
5
33
.
0
0
1
.
1
.
36
6
53
.
0
0
1
.
0
.
37
1
.
29
0
0
.
1
.
0
37
2
.
53
0
0
.
1
.
0
37
3
.
29
0
0
.
1
.
0
37
4
.
21
0
1
.
1
.
0
37
5
.
17
0
0
.
0
.
1
37
6
.
.
0
0
.
.
.
.
38
1
45
.
0
0
1
.
1
.
38
2
.
.
0
0
.
.
.
.
38
3
.
.
0
0
.
.
.
.
.
38
4
.
.
0
0
.
.
.
5
.
.
0
0
.
.
.
.
38
6
.
.
0
0
.
.
.
.
38
1
5
21
1
1
0
1
0
0
39
2
37
.
0
0
1
.
0
.
39
3
17
.
0
0
0
.
1
.
39
4
13
49
0
0
0
1
1
0
39
5
.
.
0
0
.
.
.
.
39
6
.
.
0
0
.
.
.
.
39
1
.
.
.
.
.
.
.
.
40
2
33
13
0
1
1
0
0
0
40
3
37
13
0
1
1
0
0
0
40
4
37
17
0
1
1
0
0
0
40
5
41
21
0
1
1
1
0
0
40
6
.
.
0
0
.
.
.
.
40
0
1
1
25
9
0
0
1
0
41
2
13
9
1
1
0
0
0
0
41
3
13
13
0
0
0
0
1
1
41
4
9
9
1
0
0
0
0
1
41
5
.
.
0
0
.
.
.
.
41
6
.
.
0
0
.
.
.
.
41
1
5
9
1
1
0
0
0
0
42
2
9
13
0
1
0
0
1
0
42
3
5
9
1
1
0
0
0
0
42
4
5
9
1
1
0
0
0
0
42
5
13
9
0
0
0
0
1
1
42
42
6
.
29
0
.
.
188
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
43
1
5
9
0
0
0
0
0
0
43
2
5
17
0
0
0
0
1
0
43
3
.
21
0
0
.
1
.
0
43
4
29
21
0
0
1
1
0
1
43
5
.
21
0
0
.
1
.
0
43
6
.
21
0
0
.
1
.
1
44
1
5
5
1
1
0
0
0
0
44
2
9
5
1
1
0
0
0
0
44
3
9
5
1
1
0
0
0
0
44
4
13
9
1
1
0
0
0
0
44
5
21
9
1
1
1
0
0
0
44
6
29
5
0
1
1
0
0
0
45
1
25
.
0
0
1
.
0
.
45
2
.
.
0
0
.
.
.
.
45
3
29
.
0
0
1
.
0
.
.
45
4
.
.
0
0
.
.
.
5
.
.
0
0
.
.
.
.
45
6
.
.
0
0
.
.
.
.
45
1
5
13
1
0
0
0
0
1
46
2
5
9
1
0
0
0
0
1
46
3
.
.
0
0
.
.
.
.
46
4
9
5
1
0
0
0
0
1
46
5
.
.
0
0
.
.
.
.
46
6
.
.
0
0
.
.
.
.
46
1
13
5
1
1
0
0
0
0
47
2
17
9
1
1
0
0
0
0
47
3
13
9
1
1
0
0
0
0
47
4
13
9
0
1
0
0
1
0
47
5
.
.
0
0
.
.
.
.
47
6
.
.
0
0
.
.
.
.
47
0
0
1
13
13
0
1
0
0
48
2
.
13
0
1
.
0
.
0
48
3
.
17
0
0
.
0
.
0
48
4
.
17
0
1
.
0
.
0
48
5
.
.
0
0
.
.
.
.
48
6
.
.
0
0
.
.
.
.
48
1
17
5
1
1
0
0
0
0
49
2
9
5
1
1
0
0
0
0
49
3
9
5
1
1
0
0
0
0
49
4
9
9
1
1
0
0
0
0
49
5
13
9
1
1
0
0
0
0
49
49
6
21
9
1
1
1
0
0
0
189
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
50
1
5
5
1
1
0
0
0
0
50
2
5
9
1
1
0
0
0
0
50
3
5
5
1
1
0
0
0
0
50
4
5
9
1
1
0
0
0
0
50
5
5
17
1
1
0
0
0
0
50
6
13
17
1
1
0
0
0
0
51
1
5
13
0
1
0
0
1
0
51
2
5
5
0
0
0
0
0
1
51
3
.
.
0
0
.
.
.
.
51
4
49
5
0
0
1
0
0
1
51
5
.
.
0
0
.
.
.
.
51
6
.
.
0
0
.
.
.
.
52
1
5
13
1
1
0
0
0
0
52
2
9
17
1
1
0
0
0
0
52
3
9
17
1
1
0
0
0
0
0
52
4
9
53
1
0
0
1
0
5
33
.
0
0
1
.
0
.
52
6
.
.
0
0
.
.
.
.
52
1
5
5
1
1
0
0
0
0
53
2
5
9
1
1
0
0
0
0
53
3
5
9
1
1
0
0
0
0
53
4
5
5
1
1
0
0
0
0
53
5
5
9
1
1
0
0
0
0
53
6
5
9
1
1
0
0
0
0
53
1
5
5
1
0
0
0
0
1
54
2
5
29
1
0
0
1
0
0
54
3
.
.
.
.
.
.
.
.
54
4
5
13
1
1
0
0
0
0
54
5
.
.
0
0
.
.
.
.
54
6
.
.
0
0
.
.
.
.
54
0
0
1
13
5
1
1
0
0
55
2
13
.
0
0
0
.
1
.
55
3
13
9
1
1
0
0
0
0
55
4
.
.
.
.
.
.
.
.
55
5
13
21
1
0
0
1
0
1
55
6
21
25
1
0
1
1
0
1
55
1
9
5
1
1
0
0
0
0
56
2
17
5
1
1
0
0
0
0
56
3
5
9
0
1
0
0
1
0
56
4
5
9
1
1
0
0
0
0
56
5
53
.
0
0
1
.
0
.
56
56
6
.
.
0
0
.
.
.
.
190
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
57
1
5
9
1
1
0
0
0
0
57
2
37
.
0
0
1
.
0
.
57
3
41
13
0
0
1
0
0
1
57
4
17
13
0
1
0
0
1
0
57
5
33
.
0
0
1
.
1
.
57
6
.
.
0
0
.
.
.
.
58
1
17
13
1
0
0
0
0
0
58
2
49
33
0
0
1
1
0
1
58
3
33
25
0
0
1
1
1
0
58
4
25
21
0
0
1
1
0
1
58
5
.
.
0
0
.
.
.
.
58
6
.
.
0
0
.
.
.
.
59
1
5
5
1
1
0
0
0
0
59
2
5
17
1
1
0
0
0
0
59
3
5
17
1
1
0
0
0
0
0
59
4
5
17
1
1
0
0
0
5
5
13
1
1
0
0
0
0
59
6
.
.
0
0
.
.
.
.
59
1
9
5
1
0
0
0
0
1
60
2
.
41
0
0
.
1
.
0
60
3
21
9
1
0
1
0
0
1
60
4
17
9
1
1
0
0
0
0
60
5
13
9
1
0
0
0
0
1
60
6
9
49
0
0
0
1
1
0
60
1
5
13
1
1
0
0
0
0
61
2
9
17
1
0
0
0
0
1
61
3
13
17
1
0
0
0
0
1
61
4
13
17
1
1
0
0
0
0
61
5
.
.
0
0
.
.
.
.
61
6
.
.
0
0
.
.
.
.
61
1
0
1
9
5
0
1
0
0
62
2
5
5
1
1
0
0
0
0
62
3
5
13
0
1
0
0
1
0
62
4
5
9
1
1
0
0
0
0
62
5
5
9
1
1
0
0
0
0
62
6
5
13
1
0
0
0
0
1
62
1
37
5
0
1
1
0
1
0
63
2
.
9
0
1
.
0
.
0
63
3
.
9
0
0
.
0
.
1
63
4
.
13
0
1
.
0
.
0
63
5
.
.
0
0
.
.
.
.
63
63
6
.
.
0
0
.
.
.
.
191
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
64
1
9
5
0
1
0
0
1
0
64
2
5
9
0
1
0
0
1
0
64
3
.
41
0
0
.
1
.
0
64
4
13
9
0
1
0
0
1
0
64
5
13
17
0
1
0
0
1
0
64
6
.
13
0
0
.
0
.
1
65
1
25
.
0
0
1
.
0
.
65
2
5
5
1
1
0
0
0
0
65
3
13
5
0
0
0
0
1
1
65
4
13
9
1
0
0
0
0
1
65
5
17
9
1
1
0
0
0
0
65
6
13
49
1
0
0
1
0
0
66
1
5
5
1
1
0
0
0
0
66
2
9
5
1
1
0
0
0
0
66
3
17
5
1
1
0
0
0
0
0
66
4
13
5
1
1
0
0
0
5
17
9
1
1
0
0
0
0
66
6
17
13
0
1
0
0
1
0
66
1
13
17
1
1
0
0
0
0
67
2
17
17
0
1
0
0
1
0
67
3
21
17
1
1
1
0
0
0
67
4
21
17
1
1
1
0
0
0
67
5
.
.
0
0
.
.
.
.
67
6
37
41
0
0
1
1
0
0
67
1
5
5
1
1
0
0
0
0
68
2
.
5
0
1
.
0
.
0
68
3
.
5
0
0
.
0
.
1
68
4
5
5
0
0
0
0
1
1
68
5
.
.
0
0
.
.
.
.
68
6
.
.
0
0
.
.
.
.
68
0
0
1
5
5
1
1
0
0
69
2
9
13
1
1
0
0
0
0
69
3
5
13
1
1
0
0
0
0
69
4
9
17
1
1
0
0
0
0
69
5
.
17
0
0
.
0
.
0
69
6
.
.
0
0
.
.
.
.
69
1
13
.
0
0
1
.
1
.
70
2
.
21
0
0
.
1
.
1
70
3
.
45
0
0
.
1
.
0
70
4
.
9
0
0
.
0
.
1
70
5
.
13
0
1
.
0
.
0
70
70
6
.
.
0
0
.
.
.
.
192
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
71
1
5
17
1
0
0
0
0
1
71
2
13
5
1
0
0
0
0
1
71
3
5
5
1
1
0
0
0
0
71
4
13
17
1
1
0
0
0
0
71
5
53
.
0
0
1
.
0
.
71
6
.
.
0
0
.
.
.
.
72
1
9
17
1
1
0
0
0
0
72
2
17
25
0
0
0
1
1
0
72
3
45
29
0
0
1
1
0
0
72
4
9
9
0
0
0
0
1
1
72
5
41
33
0
0
1
1
0
0
72
6
.
41
0
0
.
1
.
0
73
1
5
9
1
0
0
0
0
0
73
2
9
5
1
1
0
0
0
0
73
3
17
33
0
0
0
1
1
0
1
73
4
13
9
0
0
0
0
1
5
.
.
0
0
.
.
.
.
73
6
.
.
0
0
.
.
.
.
73
1
9
5
1
1
0
0
0
0
74
2
13
9
1
1
0
0
0
0
74
3
21
9
1
1
1
0
0
0
74
4
13
9
1
1
0
0
0
0
74
5
13
9
1
1
0
0
0
0
74
6
25
17
0
1
1
0
0
0
74
1
5
13
1
0
0
0
0
1
75
2
29
.
0
0
1
.
1
.
75
3
5
5
1
0
0
0
0
1
75
4
5
5
1
0
0
0
0
1
75
5
5
5
0
0
0
0
1
1
75
6
5
17
1
0
0
0
0
1
75
0
1
1
41
9
0
0
1
0
76
2
9
.
0
0
0
.
1
.
76
3
.
.
0
0
.
.
.
.
76
4
21
.
1
0
1
.
0
.
76
5
.
.
0
0
.
.
.
.
76
6
.
.
0
0
.
.
.
.
76
1
13
.
1
0
0
.
0
.
77
2
37
.
0
0
1
.
1
.
77
3
17
.
1
0
0
.
0
.
77
4
21
.
1
0
1
.
0
.
77
5
17
53
1
0
0
1
0
0
77
77
6
37
.
0
0
1
.
0
.
193
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
78
1
5
5
1
1
0
0
0
0
78
2
9
5
1
1
0
0
0
0
78
3
9
5
1
1
0
0
0
0
78
4
13
13
1
1
0
0
0
0
78
5
17
29
0
0
0
1
1
1
78
6
.
37
0
0
.
1
.
1
79
1
5
5
1
1
0
0
0
0
79
2
9
9
1
1
0
0
0
0
79
3
9
9
1
1
0
0
0
0
79
4
9
9
1
1
0
0
0
0
79
5
21
9
1
1
1
0
0
0
79
6
25
9
0
1
1
0
0
0
80
1
5
5
0
1
0
0
1
0
80
2
5
5
1
0
0
0
0
1
80
3
5
5
0
1
0
0
1
0
0
80
4
5
5
1
1
0
0
0
5
53
13
0
1
1
0
0
0
80
6
13
45
0
0
0
1
1
0
80
1
13
9
0
1
0
0
0
0
81
2
.
13
0
0
.
0
.
0
81
3
.
.
0
0
.
.
.
.
81
4
17
9
0
1
0
0
1
0
81
5
.
.
0
0
.
.
.
.
81
6
.
.
0
0
.
.
.
.
81
1
5
13
1
1
0
0
0
0
82
2
21
21
0
1
1
1
1
0
82
3
5
17
0
1
0
0
1
0
82
4
29
17
0
1
1
0
0
0
82
5
9
17
1
0
0
0
0
0
82
6
37
.
0
0
1
.
1
.
82
0
0
1
21
5
1
1
1
0
83
2
29
29
0
0
1
1
1
1
83
3
13
13
1
1
0
0
0
0
83
4
17
17
1
0
0
0
0
1
83
5
49
.
0
0
1
.
0
.
83
6
.
.
0
0
.
.
.
.
83
1
5
25
1
0
0
1
0
1
84
2
5
21
0
0
0
0
0
0
84
3
5
9
0
0
0
0
0
0
84
4
5
9
0
0
0
0
0
0
84
5
5
.
0
0
0
.
0
.
84
84
6
.
.
0
0
.
.
.
.
194
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
85
1
9
5
1
1
0
0
0
0
85
2
9
9
1
1
0
0
0
0
85
3
.
.
.
.
.
.
.
.
85
4
13
9
1
0
0
0
0
0
85
5
.
.
0
0
.
.
.
.
85
6
.
.
0
0
.
.
.
.
86
1
9
13
0
1
0
0
0
0
86
2
25
13
0
1
1
0
0
0
86
3
.
29
0
1
.
0
.
0
86
4
25
17
0
1
1
0
0
0
86
5
.
.
0
0
.
.
.
.
86
6
21
17
1
1
1
0
0
0
87
1
5
5
1
0
0
0
0
1
87
2
.
.
0
0
.
.
.
.
87
3
.
9
0
1
.
0
.
0
0
87
4
.
49
0
0
.
1
.
5
.
45
0
0
.
1
.
0
87
6
.
.
0
0
.
.
.
.
87
1
5
.
0
0
0
.
1
.
88
2
5
5
0
0
0
0
1
1
88
3
5
5
0
0
0
0
1
1
88
4
5
5
0
0
0
0
1
1
88
5
.
.
0
0
.
.
.
.
88
6
.
.
0
0
.
.
.
.
88
1
25
5
0
0
1
0
0
1
89
2
33
.
0
0
1
.
0
.
89
3
29
25
0
0
1
1
0
1
89
4
39
49
0
0
1
1
0
0
89
5
.
.
0
0
.
.
.
.
89
6
.
.
0
0
.
.
.
.
89
0
0
1
5
9
1
1
0
0
90
2
.
.
0
0
.
.
.
.
90
3
13
9
1
0
0
0
0
1
90
4
13
9
1
1
0
0
0
0
90
5
13
9
1
0
0
0
0
1
90
6
13
9
0
0
0
0
1
1
90
1
25
13
0
0
1
0
0
1
91
2
.
.
0
0
.
.
.
.
91
3
29
17
0
0
1
0
1
1
91
4
.
.
0
0
.
.
.
.
91
5
.
.
0
0
.
.
.
.
91
91
6
.
.
0
0
.
.
.
.
195
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
92
1
5
5
1
1
0
0
0
0
92
2
5
9
1
1
0
0
0
0
92
3
41
13
0
1
1
0
0
0
92
4
13
13
0
1
0
0
1
0
92
5
21
13
1
1
1
0
0
0
92
6
17
.
0
0
0
.
1
.
93
1
45
5
0
0
1
0
0
1
93
2
17
9
1
1
0
0
0
0
93
3
13
5
1
1
0
0
0
0
93
4
17
5
1
1
0
0
0
0
93
5
17
5
1
1
0
0
0
0
93
6
.
.
0
0
.
.
.
.
94
1
.
17
0
0
.
0
.
1
94
2
.
17
0
1
.
0
.
0
94
3
.
53
0
0
.
1
.
0
0
94
4
.
25
0
0
.
1
.
5
.
.
0
0
.
.
.
.
94
6
.
.
0
0
.
.
.
.
94
1
.
.
0
0
.
.
.
.
95
2
.
.
0
0
.
.
.
.
95
3
25
21
0
0
1
1
1
1
95
4
25
21
0
1
1
1
1
0
95
5
.
.
0
0
.
.
.
.
95
6
.
.
0
0
.
.
.
.
95
1
5
17
0
0
0
0
1
1
96
2
5
.
0
0
0
.
1
.
96
3
.
.
.
.
.
.
.
.
96
4
5
9
1
1
0
0
0
0
96
5
.
.
0
0
.
.
.
.
96
6
.
.
0
0
.
.
.
.
96
0
1
1
5
5
1
0
0
0
97
2
13
.
1
0
0
.
0
.
97
3
13
29
1
0
0
1
0
1
97
4
13
45
1
0
0
1
0
0
97
5
5
5
1
1
0
0
0
0
97
6
45
.
0
0
1
.
0
.
97
1
5
5
0
1
0
0
1
0
98
2
.
33
0
0
.
1
.
0
98
3
.
.
.
.
.
.
.
.
98
4
17
17
0
1
0
0
1
0
98
5
.
.
0
0
.
.
.
.
98
98
6
.
.
0
0
.
.
.
.
196
SUB
TOOTH LONSET CONSET LSUC CSUC LSLOW CSLOW LNONCT CNONCT
#
1=2MOL
2
2 consecutive
any 0 after 2
time of the first
consecutive
80 readings
consecutive 80s,
2=1MOL
of two consecutive 80 readings
after
followed by
3=2PRE
80 readings
within
15 minutes
another 80
4=1PRE
*with the exception of success, data is only record
5=LATINC
6=CENTINC
99
1
5
9
1
1
0
0
0
0
99
2
5
25
0
0
0
1
1
1
99
3
5
13
0
0
0
0
1
1
99
4
.
41
0
0
.
1
.
1
99
5
.
.
0
0
.
.
.
.
99
6
.
.
0
0
.
.
.
.
100
1
5
9
1
1
0
0
0
0
100
2
5
5
1
1
0
0
0
0
100
3
9
5
1
1
0
0
0
0
100
4
9
5
1
1
0
0
0
0
100
5
9
5
1
1
0
0
0
0
100
6
.
.
0
0
.
.
.
.
197
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
1
1
1
1
1
1
2
2
2
2
2
2
3
3
3
3
3
3
4
4
4
4
4
4
5
5
5
5
5
5
6
6
6
6
6
6
7
7
7
7
7
7
1
.
.
.
.
.
.
0
0
.
.
.
1
1
.
.
.
.
0
0
0
0
0
.
1
0
.
0
0
.
0
0
0
0
0
.
1
.
.
.
.
.
1
.
1
1
1
.
0
0
0
0
1
.
0
1
.
.
.
.
0
0
0
0
0
.
.
0
.
0
0
1
0
0
0
0
0
.
1
.
.
.
.
.
4
.
.
.
.
.
.
4
12
.
.
.
52
33
.
.
.
.
52
52
32
52
40
.
44
48
.
40
48
.
52
52
52
52
52
.
28
.
.
.
.
.
8
.
20
8
12
.
48
44
44
44
40
.
28
4
.
.
.
.
52
52
52
52
52
.
.
48
..
48
52
36
52
48
48
48
48
.
4
.
.
.
.
.
198
0
0
0
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
1
1
0
1
1
0
0
0
1
0
0
0
0
0
1
1
0
0
0
0
1
1
0
0
0
0
1
1
0
1
0
0
1
1
.
0
0
0
1
1
1
1
1
0
1
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
0
1
0
0
1
1
.
0
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
0
1
1
0
1
1
.
0
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
1
0
1
1
0
1
1
.
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
1
1
.
1
1
0
1
1
1
1
1
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
1
.
1
1
0
1
1
1
1
1
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
1
0
0
0
0
1
1
1
1
0
0
0
1
.
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
8
8
8
8
8
8
9
9
9
9
9
9
10
10
10
10
10
10
11
11
11
11
11
11
12
12
12
12
12
12
13
13
13
13
13
13
14
14
14
14
14
14
0
0
0
0
.
.
.
.
0
.
0
0
0
0
0
0
.
.
0
.
0
0
0
0
1
1
0
0
.
.
0
0
0
0
0
0
.
1
0
.
.
.
0
0
0
0
.
.
1
.
0
.
0
0
.
.
.
.
.
.
0
1
0
0
0
0
0
0
0
0
.
.
1
.
.
.
0
.
0
0
0
.
.
1
48
48
48
48
.
.
48
48
.
48
.
.
4
4
40
40
.
.
48
.
48
48
44
44
44
44
48
48
.
.
48
44
32
36
44
24
.
20
52
.
.
.
36
28
28
32
.
.
32
52
.
52
.
.
.
.
.
.
.
.
52
8
52
52
48
44
52
52
52
48
.
.
8
.
.
.
8
.
44
44
52
..
.
4
199
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
1
1
0
1
0
0
0
0
0
0
0
0
1
0
1
1
0
0
1
1
1
1
0
0
1
0
0
0
0
0
0
0
1
.
0
0
1
1
1
1
0
0
1
1
0
1
0
0
1
0
0
0
0
0
1
0
1
1
1
1
1
1
1
1
1
0
1
1
0
0
1
0
0
0
1
.
0
0
1
1
1
1
0
0
1
1
0
1
0
0
0
0
1
1
0
0
1
0
1
1
1
1
1
1
1
1
0
0
1
1
0
0
1
0
0
0
1
.
0
0
1
1
1
1
0
0
1
1
0
1
0
0
0
0
1
1
0
0
1
0
1
1
1
1
0
1
1
1
0
0
1
1
0
1
1
0
0
1
1
.
0
0
1
1
1
1
0
0
1
1
0
1
0
0
0
0
1
1
0
0
1
0
1
1
1
1
1
0
1
1
0
0
1
1
1
1
1
0
0
1
1
.
0
0
1
1
1
1
0
0
1
1
0
1
0
0
0
0
1
0
0
0
1
0
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
0
0
1
1
.
0
0
1
1
1
1
0
0
1
1
0
1
0
0
1
0
1
1
0
0
1
0
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
0
1
1
.
0
0
0
0
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
15
15
15
15
15
15
16
16
16
16
16
16
17
17
17
17
17
17
18
18
18
18
18
18
19
19
19
19
19
19
20
20
20
20
20
20
21
21
21
21
21
21
0
1
1
0
.
.
0
0
0
0
0
.
0
0
0
0
.
.
.
.
.
.
.
.
0
.
.
.
.
.
0
0
0
0
0
.
1
.
0
.
0
0
0
1
1
0
.
.
0
0
0
0
0
.
1
.
.
.
.
.
1
1
.
0
.
.
0
.
.
0
0
.
0
0
0
0
0
.
.
.
0
.
0
0
52
44
40
44
.
.
44
40
36
36
28
.
44
44
44
32
.
.
.
.
.
.
.
.
48
.
.
.
.
.
48
52
52
48
48
.
4
.
48
.
36
52
52
40
36
44
.
.
52
44
48
40
44
.
16
.
.
.
.
.
48
4
.
52
.
.
24
.
.
20
4
.
52
52
52
52
44
.
.
.
44
..
44
52
200
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
.
0
1
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
0
1
.
0
1
1
1
1
1
0
0
1
1
0
0
0
0
1
1
1
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
0
0
1
.
0
1
1
0
1
1
1
0
1
1
1
1
0
0
1
1
1
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
0
1
.
0
1
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
0
0
0
0
0
1
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
0
1
.
1
1
1
1
0
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
0
1
0
0
0
0
1
1
0
0
0
0
1
1
1
1
0
0
0
0
1
.
1
1
1
1
0
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
.
1
1
1
1
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
22
22
22
22
22
22
23
23
23
23
23
23
24
24
24
24
24
24
25
25
25
25
25
25
26
26
26
26
26
26
27
27
27
27
27
27
28
28
28
28
28
28
0
0
0
.
.
.
0
0
0
0
.
.
.
0
.
0
0
.
0
0
0
0
.
0
.
.
.
.
.
.
1
0
0
0
0
.
0
0
0
0
0
.
0
.
1
.
.
.
0
1
0
1
.
.
.
.
.
0
0
.
0
0
0
0
.
1
0
0
0
0
0
0
1
.
.
0
0
.
0
0
0
0
1
.
52
52
36
.
.
.
40
40
28
40
.
.
.
20
.
44
44
.
48
44
40
40
.
40
.
.
.
.
.
.
44
4
20
44
36
.
52
52
52
52
28
.
36
.
24
.
.
.
52
40
36
40
.
.
.
.
.
36
44
.
52
52
52
52
.
28
44
48
48
48
48
48
4
.
.
36
36
.
48
48
48
48
44
.
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
201
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
0
1
1
0
0
0
0
0
0
0
0
0
0
1
0
0
1
0
0
1
1
1
1
0
0
1
1
0
0
0
0
1
1
1
1
0
0
0
0
0
1
1
0
1
1
1
1
0
1
0
0
0
0
0
0
0
0
0
1
0
0
1
1
1
1
0
0
1
1
1
0
0
0
1
1
0
1
0
0
0
1
0
1
1
0
1
1
1
1
0
1
0
0
0
0
0
0
0
0
0
1
1
0
1
1
1
0
1
0
1
1
1
0
0
0
1
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
1
1
0
1
1
1
1
0
0
1
1
1
0
0
0
1
1
1
1
0
0
0
1
1
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
1
0
1
1
1
1
1
0
1
1
0
0
0
0
1
1
1
1
0
0
0
0
0
1
1
0
1
1
1
1
0
1
0
0
0
0
0
0
1
0
0
1
1
0
1
1
1
1
1
0
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
29
29
29
29
29
29
30
30
30
30
30
30
31
31
31
31
31
31
32
32
32
32
32
32
33
33
33
33
33
33
34
34
34
34
34
34
35
35
35
35
35
35
0
.
0
0
0
.
.
0
.
0
.
.
.
.
.
0
.
.
0
0
0
0
0
.
1
.
.
.
.
.
.
.
1
.
.
.
.
.
.
.
.
.
0
.
0
0
0
1
0
0
.
0
.
.
.
.
.
0
.
.
1
.
.
.
.
.
0
0
0
0
0
.
0
0
0
0
.
.
.
.
.
.
.
.
52
.
52
52
44
.
.
52
.
44
.
.
.
.
.
40
.
.
52
44
52
48
32
.
16
.
.
.
.
.
.
.
32
.
.
.
.
.
.
.
.
.
48
.
44
44
44
24
52
48
.
36
.
.
.
.
.
24
.
.
28
.
.
.
.
.
52
48
52
48
48
.
52
52
52
24
.
.
.
.
.
.
.
.
1
0
1
1
1
0
0
1
.
1
0
0
0
0
.
0
0
0
1
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
202
1
1
1
1
0
1
0
1
.
0
0
0
1
1
.
0
0
0
1
0
1
1
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
1
0
1
1
1
0
0
1
.
1
0
0
0
0
.
0
0
0
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
1
0
1
1
1
0
0
1
.
1
0
0
1
1
.
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
1
1
0
0
1
.
1
0
0
0
0
.
1
0
0
1
1
1
1
0
0
1
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
1
0
1
1
1
1
0
1
.
1
0
0
0
0
.
0
0
0
1
1
1
1
1
0
1
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
1
0
1
1
1
0
0
1
.
1
0
0
1
1
.
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
0
1
0
0
0
0
0
0
0
0
0
1
0
1
1
1
0
0
1
.
1
0
0
0
0
.
0
1
0
1
1
1
1
0
0
1
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
36
36
36
36
36
36
37
37
37
37
37
37
38
38
38
38
38
38
39
39
39
39
39
39
40
40
40
40
40
40
41
41
41
41
41
41
42
42
42
42
42
42
0
.
0
0
0
0
.
.
.
.
.
.
0
.
.
.
.
.
0
0
0
0
.
.
.
0
0
0
0
.
0
0
0
0
.
.
0
0
0
0
0
.
0
.
.
0
.
.
0
0
0
0
1
.
.
.
.
.
.
.
0
.
.
1
.
.
.
0
0
0
0
.
1
0
0
0
.
.
0
0
0
0
0
44
.
36
40
24
8
.
.
.
.
.
.
12
.
.
.
.
.
52
20
40
44
.
.
.
24
20
20
16
.
32
44
44
48
.
.
52
48
52
52
44
.
12
.
.
4
.
.
28
4
28
36
28
.
.
.
.
.
.
.
36
.
.
4
.
.
.
44
44
40
36
.
32
48
44
48
.
.
48
44
48
48
48
4
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
1
0
.
0
0
0
0
0
0
0
0
0
0
0
1
0
1
1
0
0
203
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
0
0
0
1
.
0
0
0
0
0
0
0
0
1
0
0
1
1
1
1
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
1
0
0
.
0
0
0
0
0
0
1
1
1
0
0
1
1
1
1
1
0
1
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
1
0
0
.
0
0
0
0
0
0
1
1
1
0
0
1
1
1
1
1
0
1
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
.
0
0
0
0
0
0
1
1
1
0
0
1
1
1
1
1
0
1
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
0
0
0
.
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
1
0
0
.
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
0
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
.
1
0
0
0
0
1
1
1
1
0
0
1
1
1
1
0
0
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
43
43
43
43
43
43
44
44
44
44
44
44
45
45
45
45
45
45
46
46
46
46
46
46
47
47
47
47
47
47
48
48
48
48
48
48
49
49
49
49
49
49
1
1
.
1
.
.
0
0
0
0
0
0
0
.
0
.
.
.
0
0
.
0
.
.
0
0
0
0
.
.
1
.
.
.
.
.
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
.
.
.
.
.
.
0
0
.
0
.
.
0
0
0
0
.
.
0
0
1
0
.
.
0
0
0
0
0
0
32
24
.
4
.
.
52
48
48
44
36
28
32
.
28
.
.
.
52
52
.
48
.
.
44
40
44
44
.
.
16
.
.
.
.
.
40
48
48
48
44
36
36
8
8
32
12
20
52
52
52
48
48
52
.
.
.
.
.
.
44
48
.
52
.
.
52
48
48
48
.
.
44
44
20
40
.
.
52
52
52
48
48
48
1
1
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
204
1
1
0
1
0
0
1
1
1
0
0
0
0
0
0
0
0
0
1
1
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
1
0
1
0
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
0
1
0
0
1
0
1
1
0
0
1
0
0
0
0
0
0
1
1
1
1
0
1
0
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
0
1
0
0
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
1
1
0
1
0
0
0
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
0
1
0
0
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
1
1
1
1
1
1
0
0
0
1
1
1
1
1
0
1
0
0
0
0
0
1
1
0
1
0
0
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
1
1
1
1
1
0
1
0
0
1
1
1
1
1
1
1
0
1
0
0
0
1
1
0
1
0
0
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
1
1
1
1
0
1
1
0
0
1
1
1
1
1
1
1
0
1
0
0
0
1
1
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
1
1
1
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
50
50
50
50
50
50
51
51
51
51
51
51
52
52
52
52
52
52
53
53
53
53
53
53
54
54
54
54
54
54
55
55
55
55
55
55
56
56
56
56
56
56
0
0
0
0
0
0
0
1
.
0
.
.
0
0
0
0
1
.
0
0
0
0
0
0
0
0
.
0
.
.
0
1
0
.
0
0
0
0
0
0
0
.
0
0
0
0
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0
0
0
.
0
.
.
0
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.
0
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0
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.
0
.
.
0
.
0
.
1
1
0
0
0
0
.
.
52
52
52
52
52
44
52
8
.
8
.
.
52
48
48
48
4
.
52
52
52
52
52
52
52
52
.
52
.
.
44
24
44
.
44
36
48
40
52
52
4
.
52
48
52
48
40
40
44
52
.
52
.
.
44
40
40
4
.
.
52
48
48
52
48
48
52
4
.
44
.
.
52
.
48
.
28
16
52
52
48
48
.
.
1
1
1
1
1
0
1
1
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
1
1
1
.
1
0
0
0
0
0
.
0
0
0
0
1
1
0
0
205
1
1
1
1
1
0
1
1
0
0
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
.
1
0
0
0
0
0
.
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
0
0
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
.
1
0
0
1
1
1
.
1
0
1
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1
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
.
1
0
0
1
1
1
.
1
0
1
1
0
1
1
0
1
1
1
1
1
1
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
.
1
0
0
1
0
1
.
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
.
1
0
0
1
1
1
.
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
.
1
0
0
1
0
1
.
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
.
1
0
0
1
1
1
.
1
1
1
1
1
1
0
0
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
57
57
57
57
57
57
58
58
58
58
58
58
59
59
59
59
59
59
60
60
60
60
60
60
61
61
61
61
61
61
62
62
62
62
62
62
63
63
63
63
63
63
0
1
1
0
0
.
0
0
0
0
.
.
0
0
0
0
0
.
0
.
0
0
0
0
0
0
0
0
.
.
0
0
0
0
0
0
0
.
.
.
.
.
0
.
0
0
.
.
1
0
1
0
.
.
0
0
0
0
0
.
0
1
0
0
0
0
0
1
0
0
.
.
0
0
0
0
0
0
0
0
0
0
.
.
52
4
4
40
24
.
40
8
24
32
.
.
52
52
52
52
52
.
48
.
36
40
44
48
52
48
44
44
.
.
48
52
52
52
52
52
20
.
.
.
.
.
48
.
44
44
.
.
36
24
24
36
.
.
52
40
40
40
44
.
52
12
48
48
48
8
44
32
40
40
.
.
52
52
44
48
48
44
52
48
48
44
.
.
1
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
0
0
0
0
0
0
1
1
1
1
1
0
0
0
0
0
0
206
1
1
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
0
0
0
1
1
1
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
0
0
0
1
1
0
0
0
0
0
0
1
1
1
1
1
0
1
0
1
0
1
1
1
1
1
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
0
0
1
0
0
1
0
0
1
0
0
1
1
1
1
1
0
1
0
0
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
0
1
1
0
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
0
0
1
0
0
1
0
1
1
0
0
1
1
1
1
1
0
1
0
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
0
0
0
0
0
1
0
0
1
1
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
0
0
0
1
0
0
1
1
0
1
0
1
1
0
0
1
1
1
1
1
0
1
0
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
64
64
64
64
64
64
65
65
65
65
65
65
66
66
66
66
66
66
67
67
67
67
67
67
68
68
68
68
68
68
69
69
69
69
69
69
70
70
70
70
70
70
0
0
.
0
0
.
1
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
.
0
0
.
.
0
.
.
0
0
0
0
.
.
1
.
.
.
.
.
0
0
0
0
0
0
.
0
1
0
0
1
0
0
0
0
0
0
0
0
0
0
.
0
0
0
0
0
.
.
0
0
0
0
1
.
.
1
0
0
0
.
48
52
.
44
44
.
28
52
40
44
40
44
52
48
40
44
40
40
44
40
36
36
.
20
52
.
.
52
.
.
52
48
52
48
.
.
24
.
.
.
.
.
52
48
16
48
40
44
.
52
36
48
48
4
52
52
52
52
48
44
40
40
40
40
.
16
52
52
52
52
.
.
52
44
44
40
4
.
.
24
12
48
44
.
0
1
0
0
0
0
0
1
1
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
0
0
1
0
0
1
0
1
0
0
0
0
0
0
0
0
0
207
1
1
0
0
0
0
0
1
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
0
1
0
1
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
1
1
0
0
1
1
1
0
1
1
1
0
1
0
0
1
0
0
0
0
0
1
0
0
1
0
0
1
1
1
1
1
0
1
0
0
0
0
0
1
1
0
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
1
0
0
0
0
0
1
1
0
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
1
0
0
0
0
1
1
1
1
0
0
0
0
0
0
0
0
0
1
0
1
1
0
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
0
1
1
0
0
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
0
0
1
0
0
1
1
1
1
0
0
1
0
0
1
0
0
1
0
0
0
0
0
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
0
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
71
71
71
71
71
71
72
72
72
72
72
72
73
73
73
73
73
73
74
74
74
74
74
74
75
75
75
75
75
75
76
76
76
76
76
76
77
77
77
77
77
77
0
0
0
0
0
.
0
0
0
1
0
.
0
0
0
0
.
.
0
0
0
0
0
0
0
0
0
0
0
0
1
1
.
0
.
.
0
0
0
0
0
0
1
0
0
0
.
.
0
0
0
0
0
1
1
0
1
1
.
.
0
0
0
0
0
0
0
.
0
0
0
0
0
.
.
.
.
.
.
.
.
.
0
.
52
44
52
44
4
.
48
40
12
44
16
.
52
48
40
44
.
.
48
44
36
44
44
32
52
28
52
52
52
52
12
40
.
36
.
.
44
20
40
36
40
20
32
52
52
40
.
.
40
32
28
48
24
12
44
52
4
24
.
.
52
48
48
48
48
40
44
.
52
52
48
40
32
.
.
.
.
.
.
.
.
.
4
.
1
0
1
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
0
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
208
1
0
1
0
0
0
1
0
1
1
0
0
1
1
0
0
0
0
1
0
0
0
0
0
1
0
1
1
1
1
0
1
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
1
0
0
1
0
0
1
1
0
1
0
0
1
1
1
1
1
1
1
0
1
1
1
1
0
1
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
0
1
1
0
1
0
1
1
1
1
0
1
0
0
0
0
1
0
1
0
1
0
1
1
1
1
0
0
1
1
0
0
0
0
1
1
1
1
0
0
1
1
1
1
1
0
1
0
1
1
1
1
0
1
0
1
0
0
1
0
1
1
1
0
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
1
1
1
1
0
1
0
1
0
0
1
0
1
1
1
0
1
1
1
1
0
0
1
0
0
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
1
0
1
0
0
1
0
1
1
1
0
1
1
1
1
0
0
1
0
1
0
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
0
1
0
1
0
1
0
0
1
0
1
1
1
0
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
78
78
78
78
78
78
79
79
79
79
79
79
80
80
80
80
80
80
81
81
81
81
81
81
82
82
82
82
82
82
83
83
83
83
83
83
84
84
84
84
84
84
0
0
0
0
0
.
0
0
0
0
0
0
0
0
0
0
0
0
1
.
.
0
.
.
0
0
0
0
0
0
0
0
0
0
1
.
0
1
1
1
1
.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
.
0
.
.
0
0
0
0
1
.
0
1
0
0
.
.
1
1
1
1
.
.
52
48
48
44
40
.
52
48
48
48
36
32
52
52
52
52
8
44
12
.
.
40
.
.
52
36
52
28
48
20
36
28
44
40
4
.
52
48
44
32
4
.
52
52
52
44
28
20
52
48
48
48
48
48
52
52
52
52
44
8
48
8
.
48
.
.
44
36
40
40
32
.
52
24
44
40
.
.
16
12
20
20
.
.
1
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
1
0
0
1
0
0
0
1
0
1
0
0
0
0
0
0
0
0
0
1
1
1
1
1
0
209
1
1
1
0
1
0
1
1
1
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
1
0
1
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
0
0
0
1
0
1
0
1
1
0
0
0
0
0
1
0
1
0
1
0
0
0
1
0
0
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
0
1
1
0
0
1
0
0
1
0
1
0
1
0
0
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
1
0
1
1
1
1
0
0
1
0
0
1
0
0
1
1
1
0
1
1
1
0
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
0
1
0
0
1
0
0
1
1
1
0
1
0
1
0
1
1
1
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
0
1
0
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
0
0
1
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
0
0
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
85
85
85
85
85
85
86
86
86
86
86
86
87
87
87
87
87
87
88
88
88
88
88
88
89
89
89
89
89
89
90
90
90
90
90
90
91
91
91
91
91
91
0
0
.
0
.
.
1
1
.
0
.
0
0
.
.
.
.
.
1
1
0
0
.
.
0
0
0
0
.
.
0
.
0
0
0
0
1
.
1
.
.
.
0
0
.
1
.
.
0
0
0
0
.
0
0
.
0
0
1
.
.
0
0
0
.
.
1
.
0
1
.
.
0
.
0
0
0
0
0
.
0
.
.
.
48
48
.
44
.
.
44
12
.
32
.
36
52
.
.
.
.
.
24
44
52
52
.
.
32
24
28
18
.
.
52
.
44
44
44
44
28
.
24
.
.
.
52
48
.
44
.
.
44
44
28
40
.
40
52
.
48
8
8
.
.
52
52
52
.
.
32
.
32
4
.
.
48
.
48
48
48
48
44
.
40
.
.
.
0
0
.
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
210
1
1
.
0
0
0
1
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
1
.
1
0
0
1
0
0
0
0
0
1
0
0
0
0
0
0
1
1
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
0
0
1
0
0
0
1
1
.
1
0
0
1
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
1
0
0
0
0
0
1
1
.
1
0
0
1
0
0
0
0
1
1
0
0
0
0
0
0
1
1
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
0
0
0
0
0
0
1
1
.
1
0
0
1
1
0
1
0
1
1
0
0
0
0
0
0
0
0
1
0
0
1
0
0
0
0
0
1
0
1
1
1
1
1
0
0
0
0
0
1
1
.
1
0
0
1
1
0
1
0
1
1
0
0
0
0
0
1
1
1
1
0
0
1
0
1
0
0
0
1
0
1
1
1
1
1
0
1
0
0
0
1
1
.
1
0
0
1
1
0
1
1
1
1
0
0
0
0
0
0
1
1
1
0
0
1
1
1
0
0
0
1
0
1
1
1
0
1
0
1
1
0
0
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
92
92
92
92
92
92
93
93
93
93
93
93
94
94
94
94
94
94
95
95
95
95
95
95
96
96
96
96
96
96
97
97
97
97
97
97
98
98
98
98
98
98
0
0
0
0
0
1
1
0
0
0
0
.
.
.
.
.
.
.
.
.
0
0
.
.
1
1
.
0
.
.
0
0
0
0
0
0
1
.
.
1
.
.
0
0
0
0
0
.
0
0
0
0
0
.
1
0
0
0
.
.
.
.
0
0
.
.
0
.
.
0
.
.
0
.
0
1
0
.
0
1
.
0
.
.
52
52
16
44
36
12
8
40
44
40
40
.
.
.
.
.
.
.
.
.
32
32
.
.
36
32
.
52
.
.
52
44
44
44
52
12
44
.
.
36
.
.
52
48
44
44
44
.
52
48
52
52
52
.
32
40
4
32
.
.
.
.
36
36
.
.
40
.
.
48
.
.
52
.
28
4
52
.
52
12
.
40
.
.
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
.
1
0
0
1
0
1
0
1
0
1
0
.
0
0
0
211
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
.
1
0
0
1
0
0
0
1
0
1
0
.
0
0
0
1
1
1
1
1
0
1
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
.
1
0
0
1
1
1
1
1
1
1
0
.
0
0
0
1
1
0
1
0
1
0
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
.
1
0
0
1
1
1
1
1
0
1
0
.
1
0
0
1
1
0
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
.
1
0
0
1
1
1
1
1
0
1
0
.
1
0
0
1
1
0
1
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
0
1
1
0
0
1
0
.
1
0
0
1
1
1
1
1
0
1
1
.
1
0
0
1
1
1
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
0
1
1
0
0
1
0
.
1
0
0
1
1
1
1
1
0
1
0
.
0
0
0
1
1
0
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
.
1
0
0
1
1
1
1
1
0
1
1
.
1
0
0
SUB LSHORT CSHORT LDURAT CDURAT LT5 LT9 LT13 LT17 LT21 LT25 LT29 LT33
#
time of last
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
80 reading minus 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
last 80 reading
time of first
is before 60 min
80 reading
ded if onset occurs
99
99
99
99
99
99
100
100
100
100
100
100
0
0
0
.
.
.
0
0
0
0
0
.
0
1
1
1
.
.
0
0
0
0
0
.
52
52
52
.
.
.
52
52
48
48
48
.
52
20
28
4
.
.
48
52
52
52
52
.
1
1
1
0
0
0
1
1
0
0
0
0
212
1
1
1
0
0
0
1
1
1
1
1
0
1
1
1
0
0
0
1
1
1
1
1
0
1
1
1
0
0
0
1
1
1
1
1
0
1
1
1
0
0
0
1
1
1
1
1
0
1
1
1
0
0
1
1
1
1
1
1
1
1
1
0
0
0
0
1
1
1
1
1
0
1
0
1
0
0
0
1
1
1
1
1
0
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
1
1
1
1
1
1
2
2
2
2
2
2
3
3
3
3
3
3
4
4
4
4
4
4
5
5
5.
5
5
5
6
6
6
6
6
6
7
7
7
7
7
7
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
1
1
.
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
1
1
.
1
1
0
1
1
1
1
1
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
1
1
.
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
1
1
.
1
1
0
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
1
.
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
0
0
0
0
0
1
1
0
0
0
1
1
1
1
1
0
0
0
.
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
1
0
0
0
0
0
1
0
0
0
1
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
.
0
1
0
1
0
0
0
0
0
1
0
0
0
0
0
213
0
0
0
0
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
1
1
1
0
0
1
.
1
1
1
1
1
1
1
1
0
1
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
1
1
1
0
0
1
.
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
1
1
1
0
0
1
.
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
1
1
1
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
0
1
1
.
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
1
0
1
0
0
0
0
0
1
1
1
1
1
0
0
1
.
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
1
0
0
0
1
0
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
1
.
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
8
8
8
8
8
8
9
9
9
9
9
9
10
10
10
10
10
10
11
11
11
11
11
11
12
12
12
12
12
12
13
13
13
13
13
13
14
14
14
14 .
14
14
1
1
1
1
0
0
1
1
0
1
0
0
0
0
1
1
0
0
1
0
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
0
1
1
1
1
1
1
1
0
1
1
0
1
0
0
0
0
1
1
0
0
1
1
1
1
1
1
1
0
1
1
0
0
1
1
1
1
1
1
0
1
1
.
0
0
1
1
1
1
0
1
1
1
0
1
0
0
0
0
1
1
0
0
1
0
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
0
0
1
.
0
0
1
1
1
1
0
0
1
1
0
1
0
0
0
0
1
1
0
0
1
0
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
0
0
1
.
.
0
0
1
1
1
1
0
0
1
1
0
1
0
0
1
1
1
1
0
0
1
0
1
1
1
1
1
0
1
1
0
0
1
1
1
1
1
0
0
0
1
0
0
1
1
1
1
0
0
1
1
0
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
0
0
1
1
0
0
1
1
1
1
1
1
0
0
1
.
0
0
0
0
0
0
0
0
1
1
0
1
0
0
0
0
0
0
0
0
1
0
1
1
0
0
1
1
1
0
0
0
0
0
0
0
0
0
1
0
1
.
0
0
0
0
0
0
0
0
0
1
0
1
0
0
0
0
0
0
0
0
1
0
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
.
0
1
214
0
0
0
0
0
0
1
1
0
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
.
0
1
0
1
0
0
0
0
1
1
0
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
.
1
0
1
0
1
0
0
0
1
1
0
1
0
0
0
0
0
0
0
0
1
0
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
.
0
0
1
0
0
1
0
0
1
1
0
1
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
.
0
0
1
1
1
1
0
0
0
1
0
1
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
0
0
0
0
0
0
0
1
.
0
0
1
1
1
1
0
0
0
1
0
1
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
0
0
0
0
0
1
0
1
.
0
0
0
0
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
15
15
15
15
15
15
16
16
16
16
16
16
17
17
17
17
17
17
18
18
18
18
18
18
19
19
19
19
19
19
20
20
20
20
20
20
21
21
21
21 .
21
21
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
1
0
1
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
0
1
.
1
1
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
0
1
.
1
1
1
1
1
1
1
0
1
1
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
1
1
.
.
1
1
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
0
0
1
1
1
1
0
0
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
0
1
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
1
1
.
1
1
1
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
0
0
1
0
0
0
0
0
0
0
0
1
1
1
1
0
0
0
0
0
.
1
1
1
0
0
0
0
0
1
0
1
0
0
0
0
0
0
0
0
0
1
0
0
1
0
0
1
0
0
0
0
0
1
1
1
1
0
0
0
0
0
.
0
1
215
1
1
0
1
0
0
1
1
1
0
1
0
0
0
0
0
0
0
1
0
0
1
0
0
0
0
0
0
0
0
1
1
1
1
1
0
0
0
1
.
0
1
1
1
1
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
0
0
1
0
0
0
0
0
0
0
0
1
1
1
1
1
0
0
0
1
.
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
0
0
0
1
.
1
1
1
0
1
1
1
0
1
1
1
1
1
0
1
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
0
1
.
1
1
1
1
1
1
0
0
1
1
1
1
1
0
1
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
0
0
0
1
.
1
1
1
0
1
1
0
0
1
1
1
1
1
0
1
0
0
0
0
0
1
1
0
1
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
0
1
.
1
1
1
1
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
22
22
22
22
22
22
23
23
23
23
23
23
24
24
24
24
24
24
25
25
25
25
25
25
26
26
26
26
26
26
27
27
27
27
27
27
28
28
28
28
28
28
1
1
1
0
0
0
1
0
1
0
0
0
0
1
0
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
1
1
0
1
1
1
1
1
0
1
1
1
0
1
0
1
1
1
1
0
0
0
1
0
1
1
0
1
1
1
1
0
1
0
0
0
0
0
0
0
0
1
1
1
0
1
1
1
1
1
0
1
1
0
0
0
0
1
1
1
1
0
0
0
0
0
1
1
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
0
1
1
1
1
0
0
1
1
1
0
0
0
1
1
1
1
0
0
0
0
1
1
1
0
1
1
1
1
0
1
0
0
0
0
0
0
1
0
1
1
1
0
1
1
1
1
1
1
1
1
0
0
0
0
1
1
1
1
0
0
0
0
0
1
1
0
1
1
1
1
0
1
0
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
1
0
1
1
1
0
0
0
1
1
1
1
0
0
0
1
1
1
1
0
1
1
1
1
0
1
0
0
0
0
0
0
0
1
1
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
216
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
0
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
0
1
0
0
0
0
0
0
1
0
1
1
1
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
0
1
0
0
0
0
0
0
1
0
1
1
1
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
0
1
0
1
0
0
0
1
1
1
1
0
0
0
0
1
1
1
0
1
1
1
1
0
1
1
1
1
1
1
1
0
1
0
1
1
0
1
1
1
1
1
0
1
0
0
0
0
0
1
1
1
0
0
0
0
1
0
1
1
0
1
1
1
1
0
1
1
1
1
1
1
1
0
0
0
1
1
0
1
1
1
1
1
0
1
0
1
0
0
0
1
1
1
1
0
0
0
0
0
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
0
0
0
1
1
0
1
1
1
1
1
0
1
0
1
0
0
0
1
1
1
1
0
0
0
0
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
0
0
0
1
1
0
1
1
1
1
1
0
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
29
29
29
29
29
29
30
30
30
30
30
30
31
31
31
31
31
31
32
32
32
32
32
32
33
33
33
33
33
33
34
34
34
34
34
34
35
35
35
35
35
35
1
0
1
1
1
0
0
1
.
1
0
0
0
0
.
0
0
0
1
1
1
1
0
0
1
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
1
0
1
1
1
0
0
1
.
1
0
0
0
0
.
1
1
0
1
0
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
0
1
1
1
1
0
1
.
1
0
0
0
0
.
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
0
0
1
.
1
0
0
0
0
.
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
1
1
1
0
0
1
.
1
0
0
0
0
.
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
1
0
1
1
1
0
0
1
.
1
0
0
0
0
.
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
0
.
0
0
0
0
0
.
0
0
0
0
0
0
0
0
0
1
0
1
0
0
0
1
1
1
0
0
0
0
0
0
0
0
0
217
1
0
0
0
0
1
1
1
.
0
0
0
0
0
.
0
0
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
1
0
0
0
0
0
0
0
0
0
1
0
1
1
1
0
1
1
.
0
0
0
0
0
.
0
0
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
1
0
0
0
0
0
0
0
0
0
1
0
1
1
1
0
1
1
.
0
0
0
0
0
.
0
0
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
1
0
0
0
0
0
0
0
0
0
1
0
1
1
1
1
1
1
.
1
0
0
0
0
.
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
0
0
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
.
1
0
0
0
0
.
0
0
0
1
0
0
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
1
1
.
1
0
0
0
0
.
0
0
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
1
0
0
0
0
0
0
0
0
0
1
0
1
1
1
0
1
1
.
1
0
0
0
0
.
1
0
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
36
36
36
36
36
36
37
37
37
37
37
37
38
38
38
38
38
38
39
39
39
39
39
39
40
40
40
40
40
40
41
41
41
41
41
41
42
42
42
42
42
42
1
0
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
.
1
1
1
0
0
1
1
0
1
0
0
1
0
1
1
0
0
1
0
1
1
1
0
1
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
.
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
0
0
1
0
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
.
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
.
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
0
0
1
0
1
1
0
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
0
0
0
.
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
0
.
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
.
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
218
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
.
0
0
0
0
0
1
1
0
1
0
0
1
0
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
.
1
1
0
0
0
1
1
1
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
.
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
0
0
1
1
0
0
0
0
0
0
0
1
0
0
0
0
0
.
1
1
1
1
0
0
1
1
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
.
1
1
1
1
0
1
1
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
1
1
0
0
0
0
0
0
0
0
1
0
1
0
0
0
.
1
1
1
1
0
0
1
1
1
0
1
1
1
1
1
0
1
0
0
0
0
0
0
1
0
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
.
1
1
1
1
0
0
1
1
1
0
0
1
1
1
1
1
1
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
43
43
43
43
43
43
44
44
44
44
44
44
45
45
45
45
45
45
46
46
46
46
46
46
47
47
47
47
47
47
48
48
48
48
48
48
49
49
49
49
49
49
1
0
0
0
0
0
1
1
1
1
1
1
1
0
1
0
0
0
1
1
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
0
1
0
0
0
1
1
0
1
0
0
1
1
1
0
1
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
0
1
0
0
0
1
1
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
0
1
0
0
0
1
1
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
0
1
0
0
0
1
1
1
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
1
0
1
0
0
0
1
1
0
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
0
0
1
0
0
0
0
0
0
1
0
0
1
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
1
1
0
0
0
219
1
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
1
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
0
0
0
0
1
1
1
1
0
0
1
1
0
0
0
0
1
1
1
1
1
1
1
1
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
0
0
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
1
0
0
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
1
1
1
0
1
1
1
1
1
1
0
0
0
0
0
0
0
1
0
0
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
1
1
0
1
1
1
1
1
1
0
0
0
0
0
0
0
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
50
50
50
50
50
50
51
51
51
51
51
51
52
52
52
52
52
52
53
53
53
53
53
53
54
54
54
54
54
54
55
55
55
55
55
55
56
56
56
56
56
56
1
1
1
1
1
1
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
.
1
0
0
1
1
1
.
1
1
1
1
1
1
1
0
1
1
1
1
1
1
1
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
.
1
0
0
1
0
1
.
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
.
1
0
0
1
0
1
.
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
.
1
0
0
1
0
1
.
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
.
1
0
0
1
0
1
.
1
1
1
1
1
1
1
0
1
1
1
1
1
1
1
0
0
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
.
1
0
0
1
0
1
.
1
1
1
1
1
1
1
1
1
0
1
0
0
0
1
1
0
1
0
0
0
0
0
0
0
0
1
0
0
1
0
0
1
1
.
0
0
0
1
0
0
.
0
0
1
1
0
0
0
0
220
1
1
1
1
0
0
0
1
0
1
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
0
.
0
0
0
1
0
1
.
0
1
1
1
1
1
0
0
1
1
1
1
0
0
1
0
0
1
0
0
1
0
0
0
0
0
1
1
1
1
1
1
1
0
.
1
0
0
1
0
1
.
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
0
1
0
0
1
1
1
0
0
0
1
1
1
1
1
1
1
0
.
1
0
0
1
1
1
.
0
1
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
0
0
0
1
1
1
1
1
1
1
0
.
1
0
0
1
0
1
.
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
0
1
0
0
1
1
1
0
0
0
1
1
1
1
1
1
0
0
.
1
0
0
1
0
1
.
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
0
0
0
1
1
1
0
0
0
1
1
1
1
1
1
1
1
.
1
0
0
1
0
1
.
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
1
0
1
0
0
1
1
1
0
0
0
1
1
1
1
1
1
1
1
.
1
0
0
1
1
1
.
1
1
1
1
1
1
0
0
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
57
57
57
57
57
57
58
58
58
58
58
58
59
59
59
59
59
59
60
60
60
60
60
60
61
61
61
61
61
61
62
62
62
62
62
62
63
63
63
63
63
63
1
1
0
1
1
0
1
0
1
1
0
0
1
1
1
1
1
0
1
0
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
0
1
0
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
1
0
0
0
0
1
0
1
1
0
0
1
0
0
1
0
0
1
1
1
1
1
0
1
0
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
0
0
0
1
0
0
1
1
0
1
1
1
1
0
0
1
1
1
1
1
0
1
0
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
0
0
0
1
0
0
1
1
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
0
0
0
1
0
1
1
1
0
0
0
0
0
0
1
0
0
1
1
0
1
1
1
1
0
0
1
1
1
1
1
0
1
0
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
1
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
1
0
0
0
0
0
221
1
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
0
1
1
1
0
0
0
0
0
0
0
1
1
0
1
1
0
1
1
1
0
0
0
1
0
1
1
0
0
1
0
0
0
0
0
1
0
0
0
1
0
1
0
1
1
1
1
1
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
0
1
0
1
1
0
0
1
0
0
0
0
0
1
1
1
1
1
0
1
0
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
0
1
1
0
0
1
1
0
1
0
0
1
1
1
1
1
0
1
0
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
0
0
1
0
0
1
0
1
1
0
0
1
1
1
1
1
0
1
0
1
1
0
0
1
1
0
1
0
0
1
1
1
1
1
1
1
1
0
1
0
0
1
0
1
1
0
0
1
0
1
0
0
0
1
1
1
1
1
0
1
0
0
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
0
1
0
0
1
0
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
0
1
0
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
64
64
64
64
64
64
65
65
65
65
65
65
66
66
66
66
66
66
67
67
67
67
67
67
68
68
68
68
68
68
69
69
69
69
69
69
70
70
70
70
70
70
1
0
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
1
1
0
1
0
0
1
1
1
1
0
0
1
1
0
0
0
0
1
1
0
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
1
0
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
0
1
1
0
1
1
0
1
1
1
1
1
1
1
1
0
1
0
1
1
0
1
1
0
0
1
0
0
1
1
1
1
0
0
0
1
0
0
0
0
1
1
1
1
1
0
1
1
0
1
1
1
1
1
1
1
1
0
1
1
1
1
0
1
1
0
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
0
1
1
0
1
1
1
1
1
1
1
1
1
1
1
0
1
1
1
1
0
1
1
0
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
0
1
1
0
0
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
1
0
1
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
0
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
1
0
0
1
0
0
0
0
0
0
0
0
0
0
0
222
1
1
0
1
1
0
0
1
1
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
1
1
1
0
1
0
0
0
0
0
0
0
0
1
0
0
1
1
0
1
0
1
1
1
1
1
1
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
0
0
1
1
1
0
0
0
0
0
0
1
1
0
1
1
0
1
1
1
0
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
0
0
0
1
1
1
0
1
1
0
1
1
0
0
1
0
1
1
0
1
1
1
1
1
1
1
1
1
1
0
0
1
1
0
0
0
0
1
1
1
1
1
0
0
1
0
1
1
0
1
1
0
1
1
1
0
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
0
0
0
1
0
1
1
0
1
1
0
1
1
1
0
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
0
0
1
1
0
1
0
0
1
1
1
1
0
0
0
0
0
1
1
0
1
1
0
1
1
1
0
1
0
0
1
0
1
1
1
1
1
1
1
1
1
1
0
0
1
1
0
1
1
0
1
1
1
1
0
0
0
0
1
1
1
0
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
71
71
71
71
71
71
72
72
72
72
72
72
73
73
73
73
73
73
74
74
74
74
74
74
75
75
75
75
75
75
76
76
76
76
76
76
77
77
77
77
77
77
1
1
1
1
0
0
1
1
0
0
0
1
1
1
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
1
0
0
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
1
1
1
1
1
1
0
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
0
1
0
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
1
1
0
1
1
1
0
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
0
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
0
0
1
1
1
1
1
1
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
0
1
1
1
1
1
0
0
1
0
0
1
0
1
1
1
1
1
1
1
1
1
0
1
1
1
0
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
1
0
0
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
1
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
223
0
1
1
0
0
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
1
0
0
0
1
1
1
0
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
1
0
0
1
1
0
1
0
0
1
1
1
1
1
0
1
1
1
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
0
1
1
0
0
1
0
0
1
0
0
1
1
0
0
0
0
1
1
1
1
1
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
1
0
0
1
0
0
1
1
0
1
0
0
1
1
1
1
1
1
1
1
1
1
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
0
0
1
1
0
0
0
0
1
1
0
1
0
0
1
1
1
1
1
1
1
0
0
1
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
0
1
1
0
0
1
1
1
1
0
0
1
1
0
0
0
0
1
1
1
1
1
1
0
0
1
0
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
78
78
78
78
78
78
79
79
79
79
79
79
80
80
80
80
80
80
81
81
81
81
81
81
82
82
82
82
82
82
83
83
83
83
83
83
84
84
84
84
84
84
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
1
0
0
0
0
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
1
0
0
1
1
1
1
1
1
1
0
1
1
1
0
1
1
1
0
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
1
1
0
1
1
0
1
0
1
1
0
0
1
1
1
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
0
0
0
1
0
0
1
1
1
1
1
1
1
1
1
1
1
0
1
1
1
0
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
1
0
0
1
0
1
1
1
0
1
1
1
1
1
0
1
1
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
0
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
0
0
0
0
0
224
1
1
1
0
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
0
0
1
0
0
0
0
0
0
0
0
1
1
0
0
0
0
0
0
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
1
0
1
0
0
1
0
0
0
0
0
1
0
1
0
0
0
0
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
0
1
1
1
1
0
0
1
0
1
1
1
0
1
1
1
1
1
0
1
0
1
1
0
0
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
0
1
1
0
1
0
0
1
1
1
1
1
0
1
0
1
1
0
0
0
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
0
1
0
0
1
0
0
1
1
1
1
1
0
1
0
1
0
0
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
0
1
0
0
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
0
1
0
0
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
0
1
0
0
0
0
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
85
85
85
85
85
85
86
86
86
86
86
86
87
87
87
87
87
87
88
88
88
88
88
88
89
89
89
89
89
89
90
90
90
90
90
90
91
91
91
91
91
91
1
1
.
1
0
0
1
1
0
1
0
1
1
0
0
0
0
0
0
1
0
1
0
0
1
1
1
0
0
0
1
0
1
1
1
0
1
0
1
0
0
0
1
1
.
1
0
0
1
0
0
1
0
0
1
0
0
0
0
0
0
0
1
1
0
0
1
1
1
0
0
0
1
0
1
1
1
0
1
0
1
0
0
0
1
1
.
1
0
0
1
0
0
1
0
1
1
0
0
0
0
0
0
1
1
0
0
0
1
1
1
0
0
0
1
0
1
1
1
0
1
0
1
0
0
0
1
1
.
1
0
0
1
0
0
1
0
1
1
0
0
0
0
0
0
1
1
1
0
0
1
1
1
1
0
0
1
0
1
1
1
1
1
0
0
0
0
0
1
1
.
1
0
0
1
0
0
1
0
1
1
0
0
0
0
0
0
0
1
0
0
0
1
1
1
1
0
0
1
0
1
1
1
0
1
0
1
0
0
0
1
1
.
1
0
0
0
0
0
1
0
1
1
0
0
0
0
0
0
0
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
0
.
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
0
1
1
1
0
0
1
0
0
0
0
0
0
0
0
0
0
0
1
0
1
0
0
0
225
1
1
.
1
0
0
0
0
0
0
0
0
1
0
1
1
0
0
0
1
1
1
0
1
1
0
0
0
0
0
1
0
1
1
1
1
0
0
0
0
0
0
1
1
.
1
0
0
1
1
0
0
0
0
1
0
1
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
1
0
1
1
1
1
1
0
0
0
0
0
1
1
.
1
0
0
1
1
0
1
0
1
1
0
1
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
1
0
1
1
0
1
1
0
1
0
0
0
1
1
.
1
0
0
1
1
1
1
0
1
1
0
1
1
0
0
1
1
1
1
0
0
1
0
0
0
0
0
1
0
1
1
1
1
1
0
1
0
0
0
1
1
.
1
0
0
1
1
0
1
0
1
1
0
1
0
0
0
0
1
1
1
0
0
0
0
1
0
0
0
1
0
1
1
1
1
1
0
0
0
0
0
1
1
.
1
0
0
1
1
1
1
0
1
0
0
1
0
1
0
0
1
0
1
0
0
0
0
1
0
0
0
1
0
1
1
1
1
1
0
0
0
0
0
1
1
.
1
0
0
1
1
1
1
0
1
1
1
1
0
0
0
0
1
1
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
1
0
0
0
0
0
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
92
92
92
92
92
92
93
93
93
93
93
93
94
94
94
94
94
94
95
95
95
95
95
95
96
96
96
96
96
96
97
97
97
97
97
97
98
98
98
98
98
98
1
1
0
1
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
0
1
1
0
0
0
1
.
1
0
0
1
1
1
1
1
0
0
0
.
1
0
0
1
1
1
1
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
.
1
0
0
1
1
1
1
1
0
1
1
.
0
0
0
1
1
1
0
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
1
0
0
0
0
0
.
1
0
0
1
1
1
1
1
1
1
0
.
1
0
0
1
1
1
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
.
1
0
0
1
1
1
1
1
1
1
0
.
1
0
0
1
1
1
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
.
1
0
0
1
1
1
1
1
1
0
0
.
1
0
0
1
1
1
1
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
.
1
0
0
1
1
1
1
1
1
0
1
.
0
0
0
1
0
0
0
0
0
1
0
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
.
0
0
0
1
0
0
0
1
0
1
0
.
0
0
0
226
1
1
0
0
0
0
1
1
1
1
1
0
1
0
0
0
0
0
0
0
1
0
0
0
0
0
.
1
0
0
1
0
0
0
1
0
1
0
.
0
0
0
1
1
1
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
0
0
0
0
.
1
0
0
1
0
1
0
1
0
1
0
.
0
0
0
1
1
1
1
1
0
0
1
1
1
1
0
1
1
0
0
0
0
0
0
0
0
0
0
1
1
.
1
0
0
1
0
0
0
1
0
1
0
.
1
0
0
1
1
1
1
1
0
1
1
1
1
1
0
1
1
0
0
0
0
0
0
1
1
0
0
1
0
.
1
0
0
1
0
1
1
1
0
1
0
.
1
0
0
1
1
1
1
1
0
1
1
1
1
1
0
0
1
0
1
0
0
0
0
1
1
0
0
1
1
.
1
0
0
1
0
0
0
1
0
1
0
.
1
0
0
1
1
1
1
1
0
1
1
1
1
1
0
1
1
0
1
0
0
1
1
0
1
0
0
1
0
.
1
0
0
0
0
1
1
1
0
1
0
.
1
0
0
1
1
1
1
1
0
0
1
1
1
1
0
0
1
0
1
0
0
0
0
0
1
0
0
1
0
.
1
0
0
0
0
1
0
1
0
1
1
.
1
0
0
SUB LT37 LT41 LT45 LT49 LT53 LT57 CT5 CT9 CT13 CT17 CT21 CT25 CT29 CT33
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 0=NO
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/
99
99
99
99
99
99
100
100
100
100
100
100
1
1
1
1
0
0
1
1
1
1
1
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
0
0
0
1
1
1
1
1
0
1
1
1
1
0
1
1
1
1
1
1
0
1
1
1
0
0
0
1
1
1
1
1
0
1
1
1
0
0
0
1
1
1
1
1
0
0
0
1
1
0
0
0
1
1
1
1
1
227
1
1
0
0
0
0
1
1
1
1
1
0
1
0
1
0
0
0
1
1
1
1
1
0
1
0
1
0
0
0
1
1
1
1
1
1
1
0
1
0
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
0
0
0
1
1
1
1
1
0
1
0
0
0
0
0
1
1
1
1
1
0
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
1
1
1
1
1
1
2
2
2
2
2
2
3
3
3
3
3
3
4
4
4
4
4
4
5
5
5.
5
5
5
6
6
6
6
6
6
7
7
7
7
7
7
1
0
0
0
1
0
0
1
1
1
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
1
0
0
0
0
0
0
1
1
1
1
1
0
1
1
0
0
0
0
1
1
1
1
1
1
0
1
.
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
1
0
0
0
1
1
1
0
0
0
1
1
0
0
0
0
1
1
1
1
1
0
0
1
.
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
0
1
1
1
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
.
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
1
1
0
0
1
.
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
.
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
228
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
8
8
8
8
8
8
9
9
9
9
9
9
10
10
10
10
10
10
11
11
11
11
11
11
12
12
12
12
12
12
13
13
13
13
13
13
14
14
14
14 .
14
14
1
1
1
1
0
0
0
1
0
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
1
1
1
1
0
0
1
0
0
0
0
0
0
0
1
1
1
1
1
0
0
0
1
0
1
0
0
0
0
0
0
0
0
1
0
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
0
1
1
.
0
0
1
1
1
1
0
0
1
1
0
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
.
0
0
1
1
1
1
0
0
0
1
0
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
0
0
1
1
.
0
0
1
1
1
1
0
0
0
1
0
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
1
1
1
1
0
0
0
0
0
0
1
0
1
0
1
.
0
0
1
1
1
1
0
0
0
1
0
1
0
0
0
0
0
0
0
0
1
0
1
1
1
1
1
1
1
1
0
0
0
1
0
0
1
0
1
1
1
.
0
0
0
0
229
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
15
15
15
15
15
15
16
16
16
16
16
16
17
17
17
17
17
17
18
18
18
18
18
18
19
19
19
19
19
19
20
20
20
20
20
20
21
21
21
21 .
21
21
1
0
1
1
0
0
1
1
1
1
1
0
1
0
0
0
0
0
1
0
0
1
0
0
1
0
0
1
0
0
1
1
1
1
1
0
0
0
1
1
1
1
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
0
0
1
0
0
0
0
0
1
0
0
1
1
1
1
1
0
0
0
1
.
1
1
1
0
1
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
0
0
1
0
0
1
0
0
1
0
0
1
1
1
1
1
0
0
0
1
.
1
1
1
0
1
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
0
0
0
0
1
0
0
1
0
0
1
1
1
1
1
1
0
0
1
.
1
1
1
1
1
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
0
0
0
0
1
0
0
1
1
0
1
1
1
1
1
0
0
0
1
.
1
1
1
0
0
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
1
0
0
1
0
1
1
1
0
1
1
1
1
1
0
0
0
1
.
1
1
1
1
230
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
22
22
22
22
22
22
23
23
23
23
23
23
24
24
24
24
24
24
25
25
25
25
25
25
26
26
26
26
26
26
27
27
27
27
27
27
28
28
28
28
28
28
1
0
0
0
0
0
1
1
1
1
0
0
0
0
0
1
1
0
1
1
1
0
0
1
1
1
1
1
1
1
1
0
0
1
1
0
1
1
1
1
1
0
1
0
1
0
0
0
1
1
0
1
0
0
0
0
0
1
1
0
1
1
1
1
0
1
0
1
1
1
1
1
0
0
0
1
1
0
1
1
1
1
1
0
1
0
1
0
0
0
1
1
1
1
0
0
0
0
0
1
1
0
1
1
1
0
0
0
1
1
1
1
1
1
1
0
0
1
1
0
1
1
1
1
1
0
1
0
1
0
0
0
1
1
1
1
0
0
0
0
0
1
1
0
1
1
1
0
0
1
1
1
1
1
1
1
1
0
0
1
1
0
1
1
1
1
0
0
1
0
1
0
0
0
1
1
1
1
0
0
0
1
0
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
0
0
0
1
1
0
1
1
1
1
1
0
1
0
0
0
0
0
1
0
1
0
0
0
0
0
0
1
1
0
1
1
1
1
0
0
1
1
1
1
1
1
0
0
1
1
1
0
1
1
1
1
0
0
231
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
29
29
29
29
29
29
30
30
30
30
30
30
31
31
31
31
31
31
32
32
32
32
32
32
33
33
33
33
33
33
34
34
34
34
34
34
35
35
35
35
35
35
1
0
1
1
1
0
1
1
.
1
0
0
0
0
.
1
1
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
1
1
1
0
1
1
.
1
0
0
0
0
.
1
0
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
1
1
1
0
1
1
.
1
0
0
0
0
.
1
1
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
1
0
1
0
1
1
.
1
0
0
0
0
.
1
0
0
1
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
0
1
0
0
0
0
0
0
1
0
1
0
1
0
1
1
.
1
0
0
0
0
.
1
1
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
0
0
0
0
1
0
0
0
1
0
1
1
1
0
1
1
.
1
0
0
0
0
.
1
0
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
0
1
0
1
0
0
0
0
232
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
36
36
36
36
36
36
37
37
37
37
37
37
38
38
38
38
38
38
39
39
39
39
39
39
40
40
40
40
40
40
41
41
41
41
41
41
42
42
42
42
42
42
0
0
0
0
0
0
1
0
1
1
0
0
0
0
0
0
0
0
1
0
1
0
0
0
.
1
1
1
1
0
0
1
1
1
0
0
1
1
1
1
1
0
0
0
0
0
0
0
1
0
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
.
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
0
0
1
0
0
0
0
0
1
0
1
1
1
0
0
0
0
0
0
0
1
0
1
0
0
0
.
1
1
1
1
1
0
1
1
0
0
0
1
1
1
1
1
0
1
0
0
0
0
0
1
0
1
1
0
0
0
0
0
0
0
0
1
0
0
1
0
0
.
1
1
1
1
0
0
1
1
1
0
0
1
1
1
1
1
0
1
0
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
1
1
0
0
.
1
1
1
1
0
0
1
1
1
0
0
1
1
1
1
0
0
1
0
0
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
0
0
0
0
0
.
1
1
1
1
1
0
1
1
1
0
0
1
1
1
1
1
0
233
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
43
43
43
43
43
43
44
44
44
44
44
44
45
45
45
45
45
45
46
46
46
46
46
46
47
47
47
47
47
47
48
48
48
48
48
48
49
49
49
49
49
49
1
0
0
0
0
1
1
1
1
1
1
1
0
0
0
0
0
0
0
1
0
1
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
1
0
1
1
1
1
1
1
1
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
1
1
0
1
0
0
1
1
1
1
1
1
1
0
0
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
1
1
0
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
0
0
0
0
0
1
1
1
1
0
0
1
1
0
1
0
0
1
1
1
1
1
1
0
0
0
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
1
0
0
1
1
0
1
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
1
1
0
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
0
0
1
1
0
1
0
0
1
1
1
1
1
1
234
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
50
50
50
50
50
50
51
51
51
51
51
51
52
52
52
52
52
52
53
53
53
53
53
53
54
54
54
54
54
54
55
55
55
55
55
55
56
56
56
56
56
56
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
0
0
0
1
1
1
1
1
1
1
0
.
1
0
0
1
0
1
.
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
1
0
0
1
1
1
0
0
0
1
1
1
1
1
1
1
0
.
1
0
0
1
0
1
.
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
0
1
1
0
0
1
1
1
0
0
0
1
1
1
1
1
1
1
0
.
1
0
0
1
0
1
.
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
0
1
0
0
1
1
1
0
0
0
1
1
1
1
1
1
1
0
.
1
0
0
1
0
1
.
1
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
0
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
0
0
.
1
0
0
1
0
1
.
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
0
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
0
.
1
0
0
1
0
1
.
0
0
1
1
1
1
0
0
235
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
57
57
57
57
57
57
58
58
58
58
58
58
59
59
59
59
59
59
60
60
60
60
60
60
61
61
61
61
61
61
62
62
62
62
62
62
63
63
63
63
63
63
1
0
0
1
0
0
1
1
1
1
0
0
1
1
1
1
1
0
1
0
1
1
1
0
1
0
1
1
0
0
1
1
1
1
1
0
1
1
0
1
0
0
1
0
0
1
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
1
0
1
0
0
1
0
0
1
0
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
1
0
1
0
1
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
0
0
1
0
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
0
1
1
1
1
0
0
0
1
0
0
1
1
1
1
1
0
0
1
1
1
1
1
1
0
1
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
1
0
1
1
0
0
0
1
0
1
0
0
1
1
1
1
1
0
1
0
1
1
1
1
1
0
1
1
0
0
1
1
1
1
1
1
1
1
1
1
0
0
236
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
64
64
64
64
64
64
65
65
65
65
65
65
66
66
66
66
66
66
67
67
67
67
67
67
68
68
68
68
68
68
69
69
69
69
69
69
70
70
70
70
70
70
1
1
0
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
0
0
1
1
1
1
0
0
0
0
0
0
1
0
1
1
1
1
1
0
0
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
0
1
1
1
1
1
0
0
1
1
1
1
0
0
0
0
0
1
1
0
1
1
1
1
1
0
0
1
0
1
1
0
1
1
1
1
1
1
1
1
1
1
0
1
1
1
1
1
0
0
1
1
1
1
0
0
0
1
1
1
1
0
1
1
1
1
1
1
0
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
0
0
0
0
1
1
1
0
1
1
1
1
1
1
0
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
1
1
1
1
1
0
1
1
1
1
0
0
0
0
1
1
1
1
1
1
1
1
1
1
0
1
0
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
1
1
1
0
0
0
0
1
1
1
0
237
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
71
71
71
71
71
71
72
72
72
72
72
72
73
73
73
73
73
73
74
74
74
74
74
74
75
75
75
75
75
75
76
76
76
76
76
76
77
77
77
77
77
77
0
0
1
1
0
0
1
1
1
1
1
0
1
1
1
0
0
0
1
1
1
1
1
1
1
0
0
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
0
0
1
1
1
1
1
1
1
1
0
0
0
0
1
1
1
1
1
1
1
0
1
1
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
0
0
1
1
1
1
1
1
1
1
0
0
0
0
1
1
1
1
1
1
1
0
1
1
0
1
0
0
0
0
0
0
0
0
1
0
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
0
0
0
0
1
1
1
1
1
1
1
1
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
1
0
0
1
1
1
1
1
1
1
1
0
0
0
0
1
1
1
1
1
1
0
0
0
1
1
1
0
0
0
0
0
0
0
0
0
0
1
0
0
1
1
1
0
0
1
1
1
1
1
0
0
1
0
0
0
0
1
1
1
1
1
1
1
0
1
1
0
1
0
0
0
0
0
0
1
0
1
0
1
0
238
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
78
78
78
78
78
78
79
79
79
79
79
79
80
80
80
80
80
80
81
81
81
81
81
81
82
82
82
82
82
82
83
83
83
83
83
83
84
84
84
84
84
84
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
0
0
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
0
1
0
0
1
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
0
0
0
0
0
1
1
1
1
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
0
0
1
0
0
1
1
1
1
1
0
1
0
1
1
0
0
0
0
0
0
0
0
1
1
1
1
1
0
1
1
1
1
1
1
1
0
1
1
1
1
1
0
0
1
0
0
1
1
1
1
1
0
1
1
1
1
1
0
0
0
0
0
0
0
1
1
1
1
0
1
1
1
1
1
1
1
1
0
1
1
1
1
1
0
0
1
0
0
1
1
1
1
0
0
1
1
1
1
0
0
0
0
0
0
0
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
0
1
1
0
0
1
1
1
1
0
0
1
0
1
1
0
0
0
0
0
0
0
0
239
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
85
85
85
85
85
85
86
86
86
86
86
86
87
87
87
87
87
87
88
88
88
88
88
88
89
89
89
89
89
89
90
90
90
90
90
90
91
91
91
91
91
91
1
1
.
1
0
0
1
1
1
1
0
1
1
0
1
1
1
0
0
1
1
1
0
0
1
0
0
0
0
0
1
0
0
1
1
0
1
0
1
0
0
0
1
1
.
1
0
0
1
1
1
1
0
1
1
0
1
0
0
0
0
1
1
1
0
0
0
0
0
0
0
0
1
0
0
1
1
0
1
0
0
0
0
0
1
1
.
1
0
0
1
1
1
1
0
1
1
0
1
0
1
0
0
1
1
1
0
0
0
0
1
0
0
0
1
0
1
1
1
1
0
0
0
0
0
0
1
1
.
1
0
0
1
1
1
1
0
1
1
0
1
1
1
0
1
1
1
1
0
0
0
0
1
1
0
0
1
0
1
1
1
0
0
0
0
0
0
0
1
1
.
1
0
0
1
1
1
1
0
1
1
0
1
1
1
0
0
0
1
1
0
0
0
0
1
1
0
0
1
0
1
1
1
0
1
0
1
0
0
0
1
1
.
0
0
0
1
1
1
1
0
1
1
1
1
1
0
0
1
1
1
1
0
0
0
0
1
0
0
0
1
0
1
1
1
1
1
0
1
1
0
0
240
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
92
92
92
92
92
92
93
93
93
93
93
93
94
94
94
94
94
94
95
95
95
95
95
95
96
96
96
96
96
96
97
97
97
97
97
97
98
98
98
98
98
98
1
1
1
1
1
0
0
1
1
1
1
0
1
1
0
1
0
0
0
0
1
1
0
0
0
0
.
1
0
0
0
0
0
0
1
0
1
1
.
1
0
0
1
1
1
1
1
0
1
1
1
1
1
0
1
1
0
1
0
0
0
1
1
1
0
0
1
0
.
1
0
0
1
0
1
0
1
0
1
1
.
1
0
0
1
1
1
1
1
0
1
1
1
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1
0
0
1
0
1
0
0
0
0
0
1
0
0
1
0
.
1
0
0
1
0
0
1
1
0
1
1
.
1
0
0
1
1
1
1
1
0
1
1
1
1
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0
1
1
0
1
0
0
0
0
1
1
0
0
0
0
.
1
0
0
0
0
0
1
1
0
1
0
.
1
0
0
1
1
1
1
1
0
1
1
1
1
1
0
0
1
1
1
0
0
0
0
1
1
0
0
0
0
.
1
0
0
1
0
0
0
1
0
1
0
.
1
0
0
1
1
1
1
1
0
1
1
1
1
1
1
0
1
1
1
0
0
0
0
1
1
0
0
1
1
.
1
1
0
1
0
1
0
1
0
1
0
.
1
0
0
241
SUB CT37 CT41 CT45 CT49 CT53 CT57
#
0=NO 0=NO 0=NO 0=NO 0=NO 0=NO 80/80
1=80/ 1=80/ 1=80/ 1=80/ 1=80/ 1=80/80
99
99
99
99
99
99
100
100
100
100
100
100
1
0
1
0
0
0
1
1
1
1
1
0
1
1
1
1
0
0
1
1
1
1
1
0
1
1
0
1
0
1
1
1
1
1
1
0
1
0
0
0
0
0
1
1
1
1
1
0
1
0
0
0
0
0
1
1
1
1
1
0
1
0
0
0
0
0
1
1
1
1
1
0
242
REFERENCES
1.
Nusstein J, Reader A, Beck FM. Anesthetic efficacy of different volumes of
lidocaine with epinephrine for inferior alveolar nerve blocks. Gen Dent.
2002;50:372-5.
2.
Nusstein J, Reader A, Nist R, Beck M, Meyers WJ. Anesthetic efficacy of the
supplemental intraosseous injection of 2% lidocaine with 1:100,000 epinephrine
in irreversible pulpitis. J Endod 1998;24:487-91.
3.
Reisman D, Reader A, Nist R, Beck M, Weaver J. Anesthetic efficacy of the
supplemental intraosseous injection of 3% mepivacaine in irreversible pulpitis.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1997;84:676-82.
4.
Cohen HP, Cha BY, Spångberg LS. Endodontic anesthesia in mandibular
molars: a clinical study. J Endod. 1993;19:370-3.
5.
Kennedy S, Reader A, Nusstein J, Beck M, Weaver J. The significance of
needle deflection in success of the inferior alveolar nerve block in patients with
irreversible pulpitis. J Endod 2003;29:630-3.
6.
Claffey E, Reader A, Nusstein J, Beck M, Weaver J. Anesthetic efficacy of
articaine for inferior alveolar nerve blocks in patients with irreversible pulpitis.
J Endod 2004;30:568-71.
7.
Bigby J, Reader A, Nusstein J, Beck. Anesthetic efficacy of
lidocaine/meperidine for inferior alveolar nerve blocks in patients with
irreversible pulpitis. J Endod 2007;33:7-10.
8.
Lindemann M, Reader A, Nusstein J, Drum M, Beck M. Effect of sublingual
triazolam on the success of inferior alveolar nerve block in patients with
irreversible pulpitis. J Endod 2008;34:1167–70.
9.
Tortamano IP, Siviero M, Costa CG, Buscariolo IA, Armonia PL. A comparison
of the anesthetic efficacy of articaine and lidocaine in patients with irreversible
pulpitis. J Endod 2009;35:165-8.
10.
Matthews R, Drum M, Reader A, Nusstein J, Beck M. Articaine for
supplemental, buccal mandibular infiltration anesthesia in patients with
irreversible pulpitis when the inferior alveolar nerve block fails. J Endod
2009;35:343–6.
243
11.
Aggarwal V, Singla M, Kabi D. Comparative evaluation of effect of
preoperative oral medication of ibuprofen and ketorolac on anesthetic efficacy
of inferior alveolar nerve block with lidocaine in patients with irreversible
pulpitis: a prospective, double-blind, randomized clinical trial. J Endod
2010;36:375-8.
12.
Oleson M, Drum M, Reader A, Nusstein J, Beck M. Effect of preoperative
ibuprofen on the success of the inferior alveolar nerve block in patients with
irreversible pulpitis. J Endod 2010;36:379–82.
13.
Aggarwal V, Singla M, Rizvi A, Miglani S. Comparative evaluation of local
infiltration of articaine, articaine plus ketorolac, and dexamethasone on
anesthetic efficacy of inferior alveolar nerve block with lidocaine in patients
with irreversible pulpitis. J Endod 2011;37:445-9.
14.
Simpson M, Drum M, Nusstein J, Reader A, Beck M. Effect of combination of
preoperative ibuprofen/acetaminophen on the success of the inferior alveolar
nerve block in patients with symptomatic irreversible pulpitis. J Endod
2011;37:593-7.
15.
Reader A, Nusstein J, Drum M. Successful Local Anesthesia for Restorative
Dentistry and Endodontics, 1st ed., Quintessence Publishing Co. Hanover Park,
IL.,2011.
16.
McLean C, Reader A, Beck M, Meyers WJ. An evaluation of 4% prilocaine and
3% mepivacaine compared with 2% lidocaine (1:100,000 epinephrine) for
inferior alveolar nerve block. J Endod. 1993;19:146-50.
17.
Rood JP, Caruana PE, Danford M, Pateromichelakis S. Prilocaine- an
investigation into its use in the presence of inflammation and in combination
with lignocaine. J Dent. 1981;9:240-7.
18.
Strichartz GR. Current concepts of the mechanism of action of local anesthetics.
J Dent Res. 1981;60:1460-70.
19.
Covino BG. Physiology and pharmacology of local anesthetic agents. Anesth
Prog. 1981;28:98-104.
20.
Malamed SF. Handbook of Local Anesthesia, 5th ed., The C.V. Mosby
Company. St. Louis, MO., 2004.
21.
de Jong RH, Wagman IH. Physiological mechanisms of peripheral nerve block
by local anesthetics. Anesthesiology. 1963;24:684-727.
22.
Yagiela JA. Local Anesthetics. Anesth Prog. 1991;38:128-41.
23.
Shandler L. Mechanism of action of local anesthetics. J Am Dent Soc
Anesthesiol. 1965;12:62-6.
243
24.
Strichartz G. Molecular mechanisms of nerve block by local anesthetics.
Anesthesiology. 1976;45:421-41.
25.
Lee AG. Model of action of local anaesthetics. Nature. 1976;262:545-8.
26.
Becker DE, Reed KL. Essentials of local anesthetic pharmacology. Anesth
Prog. 2006;53:98-109.
27.
de Jong RH. Neural blockade by local anesthetics. JAMA. 1977;238:1383-5.
28.
Yagiela JA. Local anesthetics: a century of progress. Anesth Prog. 1985;32:4756.
29.
Ritchie JM. A pharmacological approach to the structure of sodium channels in
myelinated axons. Annu Rev Neurosci. 1979;2:341-62.
30.
Agnew WS, Levinson SR, Brabson JS, Raftery MA. Purification of the
tetrodotoxin-binding component associated with the voltage-sensitive sodium
channel from Electrophorus electricus electroplax membranes. Proc Natl Acad
Sci U S A. 1978;75:2606-10.
31.
Hartshorne RP, Catterall WA. Purification of the saxitoxin receptor of the
sodium channel from rat brain. Proc Natl Acad Sci U S A. 1981;78:4620-4
32.
Barchi RL. Biochemical studies of the excitable membrane sodium channel. Int
Rev Neurobiol. 1982;23:69-101.
33.
Snoeck M. Articaine: a review of its use for local and regional anesthesia. Local
Reg Anesth. 2012;5:23-33.
34.
Gaffen AS, Haas DA. Retrospective review of voluntary reports of nonsurgical
paresthesia in dentistry. J Can Dent Assoc. 2009;75:579.
35.
Garisto GA, Gaffen AS, Lawrence HP, Tenenbaum HC, Haas DA. Occurrence
of paresthesia after dental local anesthetic administration in the United States. J
Am Dent Assoc. 2010;141:836-44.
36.
Moore PA, Haas DA. Paresthesias in dentistry. Dent Clin N Am. 2010;54:71530.
37.
Hillerup S, Jensen R. Nerve injury caused by mandibular block analgesia. Int J
Oral Maxillofac Surg. 2006;35:437-43.
38.
Moore PA, Hersh EV. Local anesthetics: pharmacology and toxicity. Dent Clin
N Am. 2010;54:587-99.
39.
Pogrel MA, Thamby S. Permanent nerve involvement resulting from inferior
alveolar nerve blocks. J Am Dent Assoc. 2000;131:901-7.
244
40.
Ogle OE, Mahjoubi G. Local anesthesia: agents, techniques, and complications.
Dent Clin North Am. 2012;56:133-48.
41.
Cummings DR, Yamashita DR, McAndrews JP. Complications of local
anesthesia used in oral and maxillofacial surgery. Oral Maxillofacial Surg Clin
N Am. 2011;23:369-77.
42.
de Jong RH. Toxic effects of local anesthetics. JAMA. 1978;239;1166-8.
43.
Sisk AL. Vasoconstrictors in local anesthesia for dentistry. Anesth Prog.
1992;39:187-93.
44.
Tolas AG, Pflug AE, Halter JB. Arterial plasma epinephrine concentrations and
hemodynamic responses after dental injection of local anesthetic with
epinephrine. J Am Dent Assoc. 1982;104:41-3.
45.
Donaldson M, Goodchild JH. Pregnancy, breast-feeding and drugs used in
dentistry. J Am Dent Assoc. 2012;143:858-71.
46.
Jorgensen NB and Hayden J Jr. Local and General Anesthesia in Dentistry, 2nd
ed., Philadelphia, PA: Lea & Febiger, 1967.
47.
Nusstein JM, Beck M. Effectiveness of 20% benzocaine as a topical anesthetic
for intraoral injections. Anesth Prog. 2003;50:159-63.
48.
Kramp LF, Eleazer PD, Scheetz JP. Evaluation of prilocaine for the reduction of
pain associated with transmucosal anesthetic administration. Anesth Prog.
1999;46:52-5.
49.
Wahl MJ, Overton D, Howell J, Siegel E, Schmitt MM, Muldoon M. Pain on
injection of prilocaine plain vs. lidocaine with epinephrine: a prospective
double-blind study. J Am Dent Assoc. 2001;132:1396-1401.
50.
Childers M. The anesthetic effectiveness of a periodontal ligament injection
after an inferior alveolar nerve block. Master’s Thesis: The Ohio State
University; 1993.
51.
Dunbar D. The anesthetic effectiveness of a combination inferior alveolar nerve
block/intraosseous injection. Master’s Thesis: The Ohio State University; 1994.
52.
Reitz J. The anesthetic efficacy of a repeated intraosseous injection following an
initial inferior alveolar nerve block/intraosseous injection. Master’s Thesis: The
Ohio State University; 1995.
53.
Clark S. A comparison of the anesthetic efficacy of the inferior alveolar nerve
block, the mylohyoid nerve block, and a combination of the inferior alveolar
and mylohyoid nerve blocks in human mandibular teeth. Master’s Thesis: The
Ohio State University; 1990.
245
54.
Willett J. An evaluation of diphenhydramine alone and in combination with
lidocaine in producing anesthesia in mandibular teeth utilizing the inferior
alveolar nerve block. Master’s Thesis: The Ohio State University; 1994.
55.
Whitcomb M, Drum M, Reader A, Nusstein J, Beck M. A prospective,
randomized, double-blind study of the anesthetic efficacy of sodium bicarbonate
buffered 2% lidocaine with 1:100,000 epinephrine in inferior alveolar nerve
blocks. Anesth Prog. 2010;57:59-66.
56.
Simon F, Reader A, Drum M, Nusstein J, Beck M. A prospective, randomized
single-blind study of the anesthetic efficacy of the inferior alveolar nerve block
administered with a peripheral nerve stimulator. J Endod. 2010;36:429-33.
57.
Wolf R. The anesthetic efficacy of a combination of 2% lidocaine with
1:100,000 epinephrine and 0.5 molar mannitol in human inferior alveolar nerve
block. Master’s Thesis: The Ohio State University; 1998.
58.
Guglielmo A. Anesthetic efficacy and heart rate effects of the supplemental
intraosseous injection of 2% mepivacaine with 1:20,000 levonordefrin. Master’s
Thesis: The Ohio State University; 1996.
59.
Mikesell P. The anesthetic efficacy of 2% lidocaine with epinephrine and 4%
articaine with epinephrine in inferior alveolar nerve block. Master’s Thesis: The
Ohio State University; 2003.
60.
Goodman A. The anesthetic efficacy of lidocaine plus meperidine in inferior
alveolar nerve blocks. Master’s Thesis: The Ohio State University; 2004.
61.
Steinkruger G. The effects of needle bevel orientation on the anesthetic efficacy
of an inferior alveolar nerve block and the effects of a two-stage injection on
inferior alveolar nerve block injection pain. Master’s Thesis: The Ohio State
University; 2004.
62.
Elmore SJ. Prospective, randomized single-blind study to evaluate the reversal
of soft tissue and pulpal anesthesia using phentolamine mesylate (Oraverse™).
Master’s Thesis: The Ohio State University; 2011.
63.
Vreeland DL, Reader A, Beck M, Meyers W, Weaver J. An evaluation of
volumes and concentrations of lidocaine in human inferior alveolar nerve block.
J Endod. 1989;15:6-12.
64.
Hinkley S. An evaluation of three commonly used local anesthetics in a human
inferior alveolar nerve block. Master’s Thesis: The Ohio State University; 1985.
65.
McLean C. A comparison of 3% mepivacaine and 4% prilocaine to 2%
lidocaine with 1:100,000 epinephrine in a human inferior alveolar nerve block.
Master’s Thesis: The Ohio State University; 1986.
246
66.
Yonchak T. An evaluation of the anesthetic efficacy of unilateral and bilateral
inferior alveolar nerve block injections, and infiltration injections in human
mandibular anterior teeth. Master’s Thesis: The Ohio State University; 1989.
67.
Goldberg S, Reader A, Drum M, Nusstein J, Beck M. Comparison of the
anesthetic efficacy of the conventional inferior alveolar, Gow-Gates, and
Vazirani-Akinosi techniques. J Endod. 2008;34:1306-11.
68.
Nusstein J, Steinkruger G, Reader A, Beck M, Weaver J. The effects of a 2stage injection technique on inferior alveolar nerve block injection pain. Anesth
Prog. 2006;53:126-30.
69.
Nist RA, Reader A, Beck M, Meyers WJ. An evaluation of the incisive nerve
block and combination inferior alveolar and incisive nerve blocks in mandibular
anesthesia. J Endod. 1992;18:455-9.
70.
Kanaa MD, Meechan JG, Corbett IP, Whitworth JM. Speed of injection
influences efficacy of inferior alveolar nerve blocks: a double-blind randomized
controlled trial in volunteers. J Endod. 2006;32:919-23.
71.
Davies RJ. Buffering the pain of local anaesthetics: a systematic review.
Emergency Medicine. 2003;15:81-8.
72.
Kashyap VM, Desai R, Reddy PB, Menon S. Effect of alkalinisation of
lignocaine for intraoral nerve block on pain during injection, and speed of onset
of anaesthesia. Br J Oral Maxillofac Surg. 2011;49:72-5.
73.
Ridenour S, Reader A, Beck M, Weaver J. Anesthetic efficacy of a combination
of hyaluronidase and lidocaine with epinephrine in inferior alveolar nerve
blocks. Anesth Prog. 2001;48:9-15.
74.
Wahl MJ, Schmitt MM, Overton DA. Injection pain of prilocaine plain,
mepivacaine plain, articaine with epinephrine, and lidocaine with epinephrine.
Gen Dent. 2006;54:168-71.
75.
Sumer M, Misir F, Celebi N, Muğlali M. A comparison of injection pain with
articaine with adrenaline, prilocaine with phenylpressin and lidocaine with
adrenaline. Med Oral Patol Oral Cir Bucal. 2008;13:427-30.
76.
Kanaa MD, Whitworth JM, Corbett IP, Meechan JG. Articaine buccal
infiltration enhances the effectiveness of lidocaine inferior alveolar nerve block.
Int Endod J. 2009;42:238-46.
77.
Kreimer TJ. The anesthetic efficacy of an inferior alveolar nerve block using
2% lidocaine with epinephrine and mannitol in teeth with irreversible pulpitis.
Master’s Thesis: The Ohio State University; 2001.
247
78.
Hinkley SA, Reader A, Beck M, Meyers WJ. An evaluation of 4% prilocaine
with 1:200,000 epinephrine and 2% mepivacaine with 1:20,000 levonordefrin
compared with 2% lidocaine with 1:100,000 epinephrine for inferior alveolar
nerve block. Anesth Prog. 1991;38:84-9.
79.
Chaney MA, Kerby R, Reader A, Beck FM, Meyers WJ, Weaver J. An
evaluation of lidocaine hydrocarbonate compared with lidocaine hydrochloride
for inferior alveolar nerve block. Anesth Prog. 1991;38:212-6.
80.
Childers M, Reader A, Nist R, Beck M, Meyers WJ. Anesthetic efficacy of the
periodontal ligament injection after an inferior alveolar nerve block. J Endod.
1996;22:317-20.
81.
Dunbar D, Reader A, Nist R, Beck M, Meyers WJ. Anesthetic efficacy of the
intraosseous injection after an inferior alveolar nerve block. J Endod.
1996;22:481-6.
82.
Dagher FB, Yared GM, Machtou P. An evaluation of 2% lidocaine with
different concentrations of epinephrine for inferior alveolar nerve block. J
Endod. 1997;23:178-80.
83.
Yared GM, Dagher FB. Evaluation of lidocaine in human inferior alveolar nerve
block. J Endod. 1997;23:575-8.
84.
Reitz J, Reader A, Nist R, Beck M, Meyers WJ. Anesthetic efficacy of the
intraosseous injection of 0.9 mL of 2% lidocaine (1:100,000 epinephrine) to
augment an inferior alveolar nerve block. Oral Surg Oral Med Oral Pathol Oral
Radiol Endod. 1998;86:516-23.
85.
Clark S, Reader A, Beck M, Meyers WJ. Anesthetic efficacy of the mylohyoid
nerve block and combination inferior alveolar nerve block/mylohyoid nerve
block. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1999;87:557-63.
86.
Hannan L, Reader A, Nist R, Beck M, Meyers WJ. The use of ultrasound for
guiding needle placement for inferior alveolar nerve blocks. Oral Surg Oral
Med Oral Pathol Oral Radiol Endod. 1999;87:658-65.
87.
Yonchak T, Reader A, Beck M, Meyers WJ. Anesthetic efficacy of unilateral
and bilateral inferior alveolar nerve blocks to determine cross innervation in
anterior teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.
2001;92:132-5.
88.
Mikesell P, Nusstein J, Reader A, Beck M, Weaver J. A comparison of articaine
and lidocaine for inferior alveolar nerve blocks. J Endod. 2005;31:265-70.
89.
Fernandez C, Reader A, Beck M, Nusstein J. A prospective, randomized,
double-blind comparison of bupivacaine and lidocaine for inferior alveolar
nerve blocks. J Endod. 2005;31:499-503.
248
90.
Goodman A, Reader A, Nusstein J, Beck M, Weaver J. Anesthetic efficacy of
lidocaine/meperidine for inferior alveolar nerve blocks. Anesth Prog.
2006;53:131-9.
91.
Steinkruger G, Nusstein J, Reader A, Beck M, Weaver J. The significance of
needle bevel orientation in achieving a successful inferior alveolar nerve block.
J Am Dent Assoc. 2006;137:1685-91.
92.
Foster W, Drum M, Reader A, Beck M. Anesthetic efficacy of buccal and
lingual infiltrations of lidocaine following an inferior alveolar nerve block in
mandibular posterior teeth. Anesth Prog. 2007;54:163-9.
93.
Willett J, Reader A, Drum M, Nusstein J, Beck M. The anesthetic efficacy of
diphenhydramine and the combination diphenhydramine/lidocaine for the
inferior alveolar nerve block. J Endod. 2008;34:1446-50.
94.
Wali M, Drum M, Reader A, Nusstein J. Prospective, randomized single-blind
study of the anesthetic efficacy of 1.8 and 3.6 milliliters of 2% lidocaine with
1:50,000 epinephrine for inferior alveolar nerve block. J Endod. 2010;36:145962.
95.
Hutchison G, Halcomb T, Reader A, Drum M, Nusstein J, Beck M. A
prospective, randomized single-blind study of the anesthetic efficacy of
frequency-dependent conduction blockade of the inferior alveolar nerve. J
Endod. 2011;37:938-42.
96.
Wolf R, Reader A, Drum M, Nusstein J, Beck M. Anesthetic efficacy of
combinations of 0.5 M mannitol and lidocaine with epinephrine in inferior
alveolar nerve blocks: a prospective randomized, single-blind study. Anesth
Prog. 2011;58:157-65.
97.
Guglielmo A, Reader A, Nist R, Beck M, Weaver J. Anesthetic efficacy and
heart rate effects of the supplemental intraosseous injection of 2% mepivacaine
with 1:20,000 levonordefrin. Oral Surg Oral Med Oral Pathol Oral Radiol
Endod. 1999;87:284-93.
98.
Gallatin E, Stabile P, Reader A, Nist R, Beck M. Anesthetic efficacy and heart
rate effects of the intraosseous injection of 3% mepivacaine after an inferior
alveolar nerve block. Oral Surg Oral Med Oral Pathol Oral Radiol Endod.
2000;89:83-7.
99.
Stabile P, Reader A, Gallatin E, Beck M, Weaver J. Anesthetic efficacy and
heart rate effects of the intraosseous injection of 1.5% etidocaine (1:200,000
epinephrine) after an inferior alveolar nerve block. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod. 2000;89:407-11.
249
100.
Hargreaves KM, Keiser K. Local anesthetic failure in endodontics: mechanisms
and management. Endodontic Topics. 2002;1:26-39.
101.
von Arx T, Hänni A, Sendi P, Buser D, Bornstein MM. Radiographic study of
the mandibular retromolar canal: an anatomic structure with clinical importance.
J Endod. 2011;37:1630-5.
102.
Potočnik I, Bajrović F. Failure of inferior alveolar nerve block in endodontics.
Endod Dent Traumatol. 1999;15:247-51.
103.
Heft MW, Parker SR. An experimental basis for revising the graphic rating
scale for pain. Pain. 1984;19:153-61.
104.
Nordenram A, Danielsson K. Local anaesthesia in elderly patients. An
experimental study of oral infiltration anaesthesia. Swed Dent J. 1990;14:19-24.
105.
Yagiela JA, Dowd FJ, Neidle EA. Pharmacology and Therapeutics for
Dentistry, 5th ed., Elsevier Mosby. St. Louis, MO., 2004.
106.
Malmberg AB, Yaksh TL. Antinociceptive actions of spinal nonsteroidal antiinflammatory agents on the formalin test in the rat. J Pharmacol Exp Ther.
1992;263:136-46.
107.
Chapman V, Dickenson AH. The spinal and peripheral roles of bradykinin and
prostaglandins in nociceptive processing in the rat. Eur J Pharmacol.
1992;219:427-33.
108.
Cassidy JP, Phero JC, Grau WH. Epinephrine: systemic effects and varying
concentrations in local anesthesia. Anesth Prog. 1986;33:289-97.
109.
Boakes AJ, Laurence DR, Teoh PC, Barar FS, Benedikter LT, Prichard BN.
Interactions between sympathomimetic amines and antidepressant agents in
man. Br Med J. 1973;1:311-5.
110.
Haas DA, Pynn BR, Sands TD. Drug use for the pregnant or lactating patient.
Gen Dent. 2000;48:54-60.
111.
Gibbs CP, Hawkins JL. Anesthesia for the pregnant patient requiring
nonobstetrical surgery. ASA Refresher Courses in Anesthesiology.
1994;22:127-40.
112.
Unruh AM. Gender variations in clinical pain experience. Pain. 1996;65:123-67.
113.
Liddell A, Locker D. Gender and age differences in attitudes to dental pain and
dental control. Community Dent Oral Epidemiol. 1997;25:314-8.
250
114.
Keogh E, Hatton K, Ellery D. Avoidance versus focused attention and the
perception of pain: differential effects for men and women. Pain. 2000;85:22530.
115.
Fillingim RB, Edwards RR, Powell T. The relationship of sex and clinical pain
to experimental pain responses. Pain. 1999;83:419-25.
116.
Huskisson EC. Measurement of pain. Lancet. 1974;2:1127-31.
117.
Flanagan T, Wahl MJ, Schmitt MM, Wahl JA. Size doesn’t matter: needle
gauge and injection pain. Gen Dent. 2007;55:216-7.
118.
Brownbill JW, Walker PO, Bourcy BD, Keenan KM. Comparisons of inferior
dental nerve block injections in child patients using 30-gauge and 25-gauge
short needles. Anesth Prog. 1987;34:215-9.
119.
Fuller NP, Menke RA, Meyers WJ. Perception of pain to three different
intraoral penetrations of needles. J Am Dent Assoc. 1979;99:822-4.
120.
Nakanishi O, Haas D, Ishikawa T, Kameyama S, Nishi M. Efficacy of
mandibular topical anesthesia varies with site of administration. Anesth Prog.
1996;43:14-9.
121.
Martin MD, Ramsay DS, Whitney C, Fiset L, Weinstein P. Topical anesthesia:
differentiating the pharmacological and psychological contributions to efficacy.
Anesth Prog. 1994;41:40-7.
122.
Gill CJ, Orr DL II. A double-blind crossover comparison of topical anesthetics.
J Am Dent Assoc. 1979;98:213-4.
123.
Rosa AL, Sverzut CE, Xavier SP, Lavrador MAS. Clinical effectiveness of
lidocaine and benzocaine for topical anesthesia. Anesth Prog. 1999;46:97-9.
124.
Rosivack RG, Koenigsberg SR, Maxwell KC. An analysis of the effectiveness
of two topical anesthetics. Anesth Prog. 1990;37:290-2.
125.
Mikesell AB. An evaluation of the analgesic efficacy of 1.8 mL and 3.6 mL of
2% lidocaine with 1:100,000 epinephrine in human maxillary local anesthetic
infiltration. Master’s Thesis: The Ohio State University; 1986.
126.
Meechan JG, Howlett PC, Smith BD. Factors influencing the discomfort of
intraoral needle penetration. Anesth Prog. 2005;52:91-4.
127.
Nist RA. A comparison of the anesthetic effectiveness of the conventional
inferior alveolar nerve block, the incisive nerve block, and a combination of
251
both techniques in human mandibular teeth. Master’s Thesis: The Ohio State
University; 1989.
128.
Meit SS, Yasek V, Shannon CK, Hickman D, Williams D. Techniques for
reducing anesthetic injection pain: an interdisciplinary survey of knowledge and
application. J Am Dent Assoc. 2004;135:1243-50.
129.
Kudo M. Initial injection pressure for dental local anesthesia: effects on pain
and anxiety. Anesth Prog. 2005;52:95-101.
130.
Morris R, McKay W, Mushlin P. Comparison of pain associated with
intradermal and subcutaneous infiltration with various local anesthetic solutions.
Anesth Analg. 1987;66:1180-2.
131.
McKay W, Morris R, Mushlin P. Sodium bicarbonate attenuates pain on skin
infiltration with lidocaine, with or without epinephrine. Anesth Analg.
1987;66:572-4.
132.
Lundy T, Stanley HR. Correlation of pulpal histopathology and clinical
symptoms in human teeth subjected to experimental irritation. Oral Surg Oral
Med Oral Pathol. 1969;27:187-201.
133.
Certosimo AJ, Archer RD. A clinical evaluation of the electric pulp tester as an
indicator of local anesthesia. Oper Dent. 1996;21:25-30.
134.
Dreven LJ, Reader A, Beck FM, Meyers WJ, Weaver J. An evaluation of an
electric pulp tester as a measure of analgesia in human vital teeth. J Endod.
1987;13:233-8.
135.
Modaresi J, Mozaveni MA, Dianat O. Comparing the quality of anaesthesia in
normal and inflamed teeth by pulp testing. Aust Endod J. 2005;31:120-2.
136.
Rucci FS, Pippa P, Boccaccini A, Barbagli R. Effect of injection speed on
anaesthetic spread during axillary block using the orthogonal two-needle
technique. Eur J Anaesthesiol. 1995;12:505-11.
137.
Neuwelt EA, Dahlborg SA. Blood-brain barrier disruption in the treatment of
brain tumors. Clinical implications. In: Implications of the Blood-Brain Barrier
and Its Manipulation. Vol 2. NewYork, NY: Plenum; 1989:195-261.
138.
Berns JM, Sadove MS. Mandibular block injection: a method of study using an
injected radiopaque material. J Am Dent Assoc. 1962;65:735-45.
139.
Galbreath JC. Tracing the course of the mandibular block injection. Oral Surg
Oral Med Oral Pathol. 1970;30:571-82.
252
140.
DiFazio CA, Carron H, Grosslight KR, Moscicki J, Bolding WR, Johns RA.
Comparison of pH-adjusted lidocaine solutions for epidural anesthesia. Anesth
Analg. 1986;65:760-4.
141.
Zahl K, Jordan A, McGroarty J, Sorensen B, Gotta AW. Peribulbar anesthesiaeffect of bicarbonate on mixtures of lidocaine, bupivacaine, and hyaluronidase
with or without epinephrine. Opthamology. 1991;98:239-42.
142.
Benson HT, Toleikis JR, Dixit P, Goodman I, Hill JA. Onset, intensity of
blockade and somatosensory evoked potential changes of the lumbosacral
dermatomes after epidural anesthesia with alkalinized lidocaine. Anesth Analg.
1993;76:328-32.
143.
Guglielmo A, Drum M, Reader A, Nusstein J. Anesthetic efficacy of a
combination palatal and buccal infiltration of the maxillary first molar. J Endod.
2011;37:460-2.
144.
Pfeil L, Drum M, Reader A, Gilles J, Nusstein J. Anesthetic efficacy of 1.8
milliliters and 3.6 milliliters of 2% lidocaine with 1:100,000 epinephrine for
posterior superior alveolar nerve blocks. J Endod. 2010;36:598-601.
145.
Mikesell A, Drum M, Reader A, Beck M. Anesthetic efficacy of 1.8 mL and 3.6
mL of 2% lidocaine with 1:100,000 epinephrine for maxillary infiltrations. J
Endod. 2008;34:121-5.
253