Summarize the following text to main points and sub-points and make detailed explain for them:

se :
•
volume of LA administrated               greater number of ml/g injected                 resulting circulatory blood level 
•
“The smallest dose of a given drug that is clinically effective should be administered”
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Significantly high blood levels of the local anesthetic can be achieved in dental situations because of the 
greater vascularity of the intraoral injection site or inadvertent intravascular injection of the drug 
4. Route of Administration :
•
one factor involved in terminating pain control by a local anesthetic consists of its diffusion out of the nerve and its 
subsequent entry into the CVS and removal from the site of deposition
•
“ intravascular injection” : Extremely high drug levels can be obtained in a short time, leading to serious overdose reactions
•
Absorption of local anesthetics through oral mucous membranes is also potentially dangerous because of the rate at 
which some topically applied anesthetics enter the CVS : 
Lidocaine hydrochloride and tetracaine hydrochloride
Benzocaine
absorbed well after topical application to mucous 
membranes
not water soluble and therefor is  poorly
absorbed
5. Rate of injection :
•
Single most important factor
•
The rate at which a drug is injected is a very important factor in the causation or prevention of overdose reactions from 
intravascular administration 
•
Rapid IV < Slow IV 
Rapid intravenous administration (≤15 seconds) of 36
mg of lidocaine
Slow intravenous administration (≥60 seconds) of 36
mg of lidocaine
produces greatly elevated levels and virtually
ensures an overdose reaction
produces significantly lower levels in the
blood, with a lesser risk of a severe overdose reaction 
6. Vascularity of the injection site:
•
The greater the vascularity of the injection site, the more rapid the absorption of the drug from that area into the circulation
•
“Oral Cavity” :
one of the most highly vascular areas of the entire body
some areas within the oral cavity are less well perfused
the site for LA deposition in the Gow-Gates mandibular 
nerve block
Other areas are more well-perfused
those for the inferior alveolar or posterior superior alveolar nerve block
Less well perfused area
More well perfused areas
Gow-Gates
IANB
PSA nerve block 
7. Presence of Vasoconstrictors :
•
Produces a decrease in the perfusion of an area
•
Decreased rate of systemic absorption of the drug
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And therefor decreases the clinical toxicity of the local anesthetic
Causes of Overdose
1. Biotransformation of the drug is unusually slow.
2. The unbiotransformed drug is too slowly eliminated from the body through the kidneys.
3. Too large a total dose is administered.
4. Absorption from the injection site is unusually rapid.
5. Intravascular administration
Biotransformation and Elimination
Excessive Total Dose
Rapid Absorption Into the CVS
IV Injection
o
Esters undergo more rapid 
biotransformation in both blood and liver 
than the amides
o
Atypical pseudocholinesterase:
Patients are unable to biotransform ester 
agents at the
usual rate, and higher levels of ester 
anesthetics may develop in their blood
Relative contraindication (ester<amide)
o
Relative contraindications of amide LA:

In an ambulatory patient with a history 
of liver disease (ASA 2 or 3) (Minimum 
effective volumes of anesthetic should be
Used)
If ASA 4 or 5 , average , even low-average, 
doses may be capable of producing an 
overdose
o
Renal Dysfunction :
Can delay elimination of the active LA 
from the blood
may lead to a gradual increase in the level 
of active local anesthetic in the blood
The MRD of parenterally 
administered (injected) 
drugs is commonly 
calculated after 
consideration of a 
number of factors, 
including:
1) Age :
Individuals at either end 
of the age spectrum 
(younger 6 years and 
older than 65 years)
2) Physical status :
For medically 
compromised individuals 
(ASA classes 3, 4, and 5) 
the calculated MRD
should be decreased
3)Weight :
With a usual dose the 
blood level of the drug is 
lower in the heavier 
patient, and a larger 
milligram dose can be 
administered safely
o
Vasoconstrictors : increase the depth and 
the duration of anesthesia and reduce the 
systemic toxicity of most local anesthetics 
by delaying their absorption into the CVS
o
Topical anesthesia:

absorption of some topically applied LA 
into the circulation is rapid, exceeded in 
rate only by direct intravascular injection
amide topical anesthetics, when applied to 
wide areas of mucous membrane , increase 
the risk of serious reactions
Benzocaine :
•
an ester anesthetic, which is poorly, if at all, 
absorbed into the CVS
•
less likely to produce an overdose reaction 
than amides
•
cases of methemoglobinemia from 
excessive benzocaine administration have 
been reported

Risk of allergy (esters > amides) 
Limited area of application

spray topical anesthetic :  use of metered 
dosage forms is strongly recommended 
(Disposable nozzles)
Ointments or gels: used in small amounts 
on the tip of a cotton applicator stick 
o
Occurs more 
likely when a 
nerve block is 
administered
o
Both intravenous 
and intraarterial 
injections are 
capable of 
producing 
overdose
o
a rapidly 
administered 
intra-arterial 
injection may 
cause retrograde 
blood flow in 
the artery 
o
How to avoid it?
1)
knowledge of 
the anatomy of 
the site to be 
anesthetized
2)
proper 
technique of 
aspiration
Prevention of intravascular 
injection
Use an aspirating syringe
Use a needle larger than 27 gauge
•
resistance to the return of blood into the lumen of smaller-gauge needles is increased, leading to an increased likelihood of 
an unreliable aspiration test
25-gauge needle
27-gauge needle
30-gauge needle
For injection techniques with a greater 
likelihood
of positive aspiration  
can be used in lieu of a 25-gauge needle
as it provides relatively reliable 
aspiration
should be avoided when
injections are administered into more 
vascular areas of the oral cavity
Aspirate in at least two planes before injection
After the initial aspiration, rotate the syringe about 45 degrees (up or down) to reorient the needle bevel relative to the 
wall of the blood vessel, and reaspirate
Slowly inject the anesthetic (the most important factor in 
preventing ADRs from intravascular administration—even more 
important than aspiration)
•
Rapid intravascular injection of 1.8 mL of a 2% local anesthetic 
solution produces a blood level in excess of that necessary for 
overdose
•
Definition of Rapid injection : administration of the entire volume of 
a dental cartridge in 30 seconds or less
•
The same volume of anesthetic deposited intravascularly slowly (minimum of 60 seconds) produces slightly elevated blood 
levels that are still below the minimum for serious overdose (seizure)
•
the observed signs and symptoms will be less severe than those noted following more rapid injection
•
The ideal rate of local anesthetic administration is 1.0 mL/min (corresponds to deposition of a 1.8-mL cartridge in not less 
than 60 seconds)
Swiss-Cheese Model ?
Review of the too many cases that resulted in serious morbidity or death reveals a 
number of shared factors, none of which in themselves might pose a serious problem; 
however, when added together, they act to produce clinical signs and symptoms of local 
anesthetic overdose.
1. Treatment plan where all four quadrants are treated with local anesthetic at one visit.
2. Local anesthetic administered is a plain solution (no vasoconstrictor).
3. Full cartridges (1.8 mL) administered with each injection.
4. Local anesthetic administered to all four quadrants at one time.
5. Exceeding the maximum dose based on patient’s body weight.
So what are those factors?
Treatment Plan
Choice of LA
Volume of LA 
administrated
LA administrated to all 4 
quadrants at one time
Exceeding the maximum dose 
based on patient’s body weight
Case example : A  young 2 to 6 
years), lightweight (<30 kg 
[<66 lb]), and well-Behaved
requiring multiple procedures 
in four quadrants:
•
treat all four quadrants at 
one visit using local 
anesthesia alone?
Here an unexperienced 
general dentist might feel 
pressured into agreeing to this 
request from the child’s 
parents , thus increasing the 
risk for local anesthetic 
overdose.
•
Limiting treatment to one 
or two quadrants per 
visit?
A pediatric dentist would go 
for this more rational 
approach for the  patient’s 
needs and safety 
In Pediatrics :

Use of “plain” LA  either 3% 
mepivacaine (usually) or 4% 
prilocaine? 
(1) most pediatric appointments 
are of short duration
(2)  shorter duration of residual 
soft tissue anesthesia, minimizing 
the likelihood of soft tissue injury 
(only when treatment is minimal 
and limited to one quadrant)

Use of a vasoconstrictor ?
If treatment extends to two or
more quadrants at that same visit

Prevention of Postoperative 
soft tissue injury:
•
cotton roll in the buccal fold
•
Advising the parent to watch 
the child
•
The LA reversal agent 
phentolamine mesylat

Summary :