International Dental Journal

CONCISE REVIEW
doi: 10.1111/idj.12615

Local anaesthesia in dentistry: a review

Derek Decloux1 and Aviv Ouanounou2
1
Discipline of Dental Anaesthesia, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada; 2Department of Clinical Sciences
(Pharmacology & Preventive Dentistry), Faculty of Dentistry, University of Toronto, Toronto, ON, Canada.

Over the past century, there is perhaps no greater contribution to the practice of clinical dentistry than the development
and application of local anaesthesia. What were once considered painful procedures have now been made routine by the
deposition and action of local anaesthetics. This article will serve as a review of basic pharmacological principles of local
anaesthesia, subsequent sequelae that can arise from their use, considerations when using local anaesthetics, and recent
advances in the delivery of local anaesthetics.

Key words: Local anaesthetics, pharmacology, adverse reaction, drug interaction, mechanism of action

reduce discomfort associated with mucosal needle

INTRODUCTION
puncture.
An average dentist will administer over 1,500 car-
tridges of dental local anaesthetic a year1. As such,
Mechanism of action
anyone administering this drug should be intimately
familiar with what the drug does to the body, as well Local anaesthetics all act in the same manner – they
as what the body does to that drug. This article will bind to cellular sodium channels and inhibit the influx
serve as a review of the pharmacokinetics and phar- of sodium into the cell which prevents cell depolarisa-
macodynamics of local anaesthetics, possible conse- tion and subsequent transmission of the previously
quences and adverse events from their use, and propagating action potential2. This is beneficial in that
emerging technologies pertaining to the use of local the action potential of a painful stimulus, such as dril-
anaesthetics. ling into the dentin of a tooth, can be stopped from
reaching the higher processing centres of the brain
and otherwise painful procedures can be completed
PHARMACOLOGY
with relative patient comfort.
Chemical structure
Onset
Modern local anaesthetics are typically differentiated
based on their chemical structure, specifically the link- The onset of local anaesthesia is contingent on two
age (an amide versus an ester linkage) between common factors: the lipid solubility and the pKa of the local
elements of the compound. The majority of commonly anaesthetic. The more lipid-soluble a local anaesthetic
used dental local anaesthetics fall into the amide cate- is, the greater its potency3.
gory (lidocaine, mepivacaine, bupivacaine, prilocaine), For the local anaesthetic base to be stable in solu-
though there are some amide-type local anaesthetics tion, it is formulated as a hydrochloride salt3. At that
that also contain an additional ester linkage (articaine). time, the molecules exist in a water-soluble state and
While both types of local anaesthetics have the same thus are unable to penetrate the neuron3. Therefore
mechanism of action, they differ slightly in their meta- the time for onset of local anaesthesia is directly
bolism as described below. It is rare in dentistry that related to the proportion of molecules that convert to
ester-type anaesthetics are used for local anaesthesia the lipid-soluble structure when exposed to physio-
purposes, though these types of anaesthetics are used logic pH (7.4). This proportion is determined by the
more commonly for topicalisation prior to injection to ionisation constant (pKa) for the anaesthetic and is
© 2020 FDI World Dental Federation 1
Decloux and Ouanounou

calculated using the Henderson-Hasselbalch equa- Local anaesthetic cartridge additives

tion3. This implies that the higher the pKa for a local
In addition to the local anaesthetic, the distilled water
anaesthetic, the fewer molecules are available in their
in which it is dissolved, and potentially a vasocon-
lipid-soluble form and thus the further is the delay in
strictor, there is the possibility of an oxidant included
the onset of action2,3. This is why it is harder to
in the cartridge. Local anaesthetics are generally stable
anaesthetise a patient with an infection, as the envi-
and are resistant to degradation, but vasoconstrictors
ronment pH is much lower (around pH of 5.2) and
present in the cartridge are much more susceptible to
this favours the water-soluble state.
degradation from the presence of molecular oxygen,
For instance, bupivacaine is the most lipid-soluble
light, elevated temperature, heavy metals, and an
local anaesthetic so a lower percent of drug dissolved
increase in pH9. As such, antioxidants such as
in solution is required to cause nerve blockade com-
metabisulfite are added to the local anaesthetic car-
pared to a less lipid-soluble local anaesthetic like
tridge to reduce the rate of deterioration of the vaso-
mepivacaine. Thus, for a rapid onset of action, the
constrictor.
lower the pKa of a local anaesthetic, the more ionised
Previously, methylparaben (an anti-fungal) was
drug is present in normal tissue and the faster the
included in local anaesthetic cartridges as it was origi-
onset of blockade.
nally included in the formulation of multi-dose vials
of local anaesthetics used for medical purposes. When
Duration of action single-use cartridges were introduced in the dental set-
ting, methylparaben was included until it was appreci-
The duration of action of a local anaesthetic is contin-
ated that it was no longer necessary to ensure an
gent on two factors: the protein binding and redistri-
additional infection control measure, and it was then
bution of the local anaesthetic. Protein binding of the
phased out of dental cartridges in North America with
local anaesthetic is an inherent drug characteristic –
the last amount of methylparaben included in 198410.
the more protein-bound a drug is, the longer the dura-
It should be noted that there are still countries where
tion of action4. Duration of action on dental pulp and
formulations of local anaesthetic exist with the addi-
soft tissues is contingent almost completely on diffu-
tion of methylparaben11.
sion away from the site of action of the local anaes-
thetic. If an area is more vascular, the faster the drug
will be absorbed into systemic circulation and away ADVERSE EVENTS
from the target tissue.
Systemic toxicity
Metabolism and elimination While local anaesthetics have the ability to produce
anaesthesia of intended nerves and anatomic areas,
Amide-type local anaesthetics are biotransformed into
they are not exempt from Paracelsus’ law, ‘Only the
water-soluble metabolites in the liver by hepatic
dose makes the poison’. That is, they too can be toxic
microsomal enzymes and subsequently excreted by the
in higher doses. When systemic concentrations of cir-
kidney5. Articaine is primarily metabolised via its
culating local anaesthetic become high enough, there
ester linkage by plasma esterases in the blood6,7.
can be unintended and severe consequences which are
neuralgic and cardiac in nature. Inhibitory neurons in
Vasoconstrictors the nervous system are generally those first affected,
which when blocked will produce excitatory symp-
Knowing that the duration of action of a drug is deter-
toms such as visual and sensory disturbances, seizures,
mined by its protein binding and redistribution, car-
and muscle toxicity12. As plasma concentrations con-
tridges of local anaesthetic can be modified to have
tinue to rise, depressive clinical manifestations begin
additional components present in the cartridge in order
to appear such as decreased level of consciousness pos-
to increase the duration of action. Specifically, a vaso-
sibly leading to coma and respiratory arrest. Following
constrictor such as epinephrine or levonordefrin can be
increased plasma concentration leading to adverse
added so that when the solution is deposited at the site
neurological events, cardiac conditions can arise from
of action, the surrounding vascular beds will vasocon-
heightened concentration of the drug. Local anaesthet-
strict, the drug will be more slowly absorbed into the
ics will again act to block sodium channels, but this
circulating bloodstream, and the duration of action of
time in areas of the heart required for propagation of
the local anaesthetic will be increased8. Local anaes-
cardiac conduction. A variety of sequelae can manifest
thetics with vasoconstrictors should be used carefully
from tachyarrhythmias to bradyarrhythmias, up to the
for patients with pre-existing hypertension or cardiac
point that plasma levels of the drug will inhibit car-
irritability as their presence in the body may further
diac function altogether and cause an arrest13.
increase blood pressure or cause cardiac dysrhythmias.
2 © 2020 FDI World Dental Federation
 Local anaesthesia in dentistry

The best means of avoiding local anaesthetic sys- Table 2 Example calculation of amount of local
temic toxicity is awareness of the patient’s weight, the anaesthetic in a dental anaesthetic cartridge
maximum per kilogram (or absolute) dose of the local
Information Calculation and amount
anaesthetic being administered (see Table 1), and
careful calculation so as to avoid systemic concentra- A 2% solution has a 20 mg/mL 9 1.8 mL = 36 mg
concentration of 20 mg/mL
tions of the drug that could disrupt regular cell mem- The cartridge has 1.8 mL of
brane function. Included in the Table is a list of the solution
most commonly used local anaesthetics in dentistry as A 4% solution has a 40 mg/mL 9 1.8 mL = 72 mg
concentration of 20 mg/mL
well as their associated maximums that can be admin- The cartridge has 1.8 mL of
istered to patients on a per kilogram basis. In order to solution
determine the maximum dose for a patient, one must
simply multiply the patient’s weight by the per kilo-
gram maximum specific to the local anaesthetic being of local anaesthetic occurs, and the patient demon-
used by the dentist. strates an abnormal reaction of systemic toxicity
In order to determine how much local anaesthetic is despite no pre-existing medical condition14, or per-
in a cartridge (see the example in Table 2), the per- haps the patient had an unknown medical condition
cent solution of the local anaesthetic expressed in mg/ that predisposed them to local anaesthetic systemic
mL must be multiplied by the amount of solution in toxicity15. As such, astute clinicians should be ready
the cartridge. Of note, percentage of local anaesthetic to recognise and treat the symptoms of local anaesthe-
represents the number of grams per 100 mL, or mg sia systemic toxicity (tinnitus, metallic taste, circum-
per mL. For example, a 2% solution represents oral numbness, altered medical status, slurred speech,
20 mg/mL and a 4% solution represents 40 mg/mL. hypotension, bradycardia, seizures, ventricular
A typical dental local anaesthetic cartridge in North arrhythmias, and cardiac arrest). The management of
America contains approximately 1.8 mL, while many local anaesthetic systemic toxicity includes (but is not
countries use 2.2 mL cartridges. limited to):
Again, the amount of local anaesthetic being depos- • Activating emergency medical services when in an
ited should be less than the per kilogram maximum ambulatory location in order to be able to transport
specific to the local anaesthetic being used and less and monitor the patient in a tertiary care facility
than the absolute maximum associated with that local • Ensuring adequate oxygenation (may include
anaesthetic (Table 1). administering supplemental oxygen and/or manual
Despite the best efforts of clinicians, drug errors ventilation of the patient)
occur when the patient receives too large a dose of • Provided that intravenous access is established and
local anaesthetic, or an intravascular administration the provider has been trained to administer intra-
venous rescue medications:
a Administering of intravenous Intralipid 20%
Table 1 Recommended Canadian maximum doses of (1.5 mL/kg for a child or 100 mL bolus for an
local anaesthetics1,13 adult over 65 kg and a subsequent infusion of
0.25 mL/mh/min or more if hypotension persists)
Drug Maximum to treat the cardiac aspects of local anaesthetic
Articaine WITH vasoconstrictor 7 mg/kg (up to 500 mg) systemic toxicity
5 mg/kg in children b Treating seizures, if present (titration of intra-
Bupivacaine WITH vasoconstrictor 2 mg/kg (up to 200 mg) venous midazolam beginning with 100 mcg/kg
Lidocaine WITH vasoconstrictor 7 mg/kg (up to 500 mg)
Mepivacaine WITH vasoconstrictor 6.6 mg/kg (up to 400 mg) for a child or 5 mg for an adult)
Prilocaine WITH vasoconstrictor 8 mg/kg (up to 500 mg) c Treating bradycardia and/or hypotension with an
Mepivacaine WITHOUT 6.6 mg/kg (up to 400 mg) intravenous vasopressor
vasoconstrictor
Prilocaine WITHOUT vasoconstrictor 8 mg/kg (up to 500 mg) d Monitoring for ventricular fibrillation or ventric-
ular tachycardias and treating as appropriate
The maximum recommended dose may vary from country to coun-
try. The maximum dosage means ‘a single volume administered’; if
e Anticipating acidosis, hypercarbia, hyperkalemia,
additional cartridges are administered at a later time in the proce- and treating as necessary.
dure then the calculation is no longer valid as one must incorporate
redistribution and drug half-lives into current systemic dose. Many
schools and organisations teach the maximum dose of lidocaine 2% Allergy
with 1:100,000 epinephrine as 4.4 mg/kg but there is no consensus
on the issue61,62. There have been some investigators who advocate True documented allergy to amide-type local anaes-
for abandoning the idea of maximum recommended doses63 and thetics is exceedingly rare16. While some literature
instead taking patient and clinician factors into consideration such
as the patient’s age, the site of injection, the speed of injection, and reports an incidence of allergy from 0.1% to 1%17,
the existence of other comorbidities64. recent data suggest a possible increase in the incidence
© 2020 FDI World Dental Federation 3
Decloux and Ouanounou

of this allergy (specifically to lidocaine)18. When an cardiovascular collapse (significant hypotension or

allergy to local anaesthetic is suspected, there exist asystole) or respiratory compromise (hypoxia, dysp-
several complex means of investigating whether the nea, tachypnea, coughing/bucking, bronchospasm)20.
symptoms present are a true anaphylactic reaction. The management of anaphylaxis includes (but is not
The patient should be referred to an allergist or limited to):
immunologist in order to determine if indeed an • Activating emergency medical services when in an
allergy exists and, if so, to determine the allergenic ambulatory location in order to be able to transport
components of the local anaesthetic cartridge. It is and monitor the patient in a tertiary care facility
now understood that an allergist-administered intra- • Discontinuing or removing the anaphylaxis-inciting
dermal administration test, followed by subsequent agent
provocation challenges (if necessary), can demonstrate • Ensuring airway patency (considering intubation)
adequate predictive value in order to rule out possible and administering 100% oxygen
local anaesthetic allergy18. • Administering epinephrine (0.3 mg for> 30 kg body
While some patients may note allergy-like symp- weight; 0.15 mg for up to 30 kg, IM in lateral
toms from a dental injection, it is likely that these thigh as an initial dose of epinephrine).
symptoms appear from either a psychogenic reaction, These additional steps may be carried out provided
which can mimic allergy and even anaphylaxis, or it the medications are available and the provider has
could be that the patient does have an allergy to one been trained in their administration:
of the contents in the local anaesthesia cartridge other • Administering an H1 and H2 blocker (respectively:
than the local anaesthesia itself. Historically, local diphenhydramine 1 mg/kg IM to a maximum of
anaesthetic multi-dose vials were re-used between 50 mg and ranitidine 1 mg/kg IM to a maximum
patients and so an agent, such as methylparaben – a of 50 mg)
bacteriostatic, anti-fungal agent – was also present in • Administering a corticosteroid like hydrocortisone
these vials. It was not uncommon for patients to expe- (2 mg/kg IM to a maximum of 100 mg)
rience allergic reactions from these types of agents. • Provided that intravenous access is established and
Today’s commonly used dental local anaesthetics with the provider has been trained to administer intra-
vasoconstrictors contain the preservative sodium venous rescue medications:
metabisulfite, which some case reports note can cause a Administering a bolus push of intravenous fluid
allergic reactions. (20 mL/kg to a maximum of 1 L, or more if nec-
It should be noted that ester-type local anaesthetics, essary).
such as benzocaine which is used in many formula-
tions of topical anaesthetics, is one of the more aller-
Psychogenic reactions
genic agents found in a dental office after latex, non-
steroidal anti-inflammatory drugs, and penicillin-type Pre-syncope and syncope (vasovagal reactions) are
antibiotics. Dental practitioners should pay particular among the most common medical emergencies that
attention for the signs and symptoms of allergy or occur in dental offices. Patients’ anxieties about the
anaphylaxis after the application of any ester-type deposition of local anaesthesia, or any other dental
topical anaesthetics19. Benzocaine applied as a topical procedure for that matter, may manifest clinically
anaesthetic may cause aphthous ulcers in some with variations in heart rate and blood pressure, pal-
patients (a possible sign of sensitivity or even allergy); lor, nausea, vomiting, and dyspnea21. Care should
should this occur, topical lidocaine would be more always be taken to probe a patient’s level of anxiety
appropriate for future appointments. in the dental office so as to be able to implement
With the above in mind, while noting that allergy pharmacologic or non-pharmacologic techniques that
to a local anaesthetic or a component in the cartridge will make patients comfortable for the duration of
is exceedingly rare, such an event is not altogether care in the office setting.
impossible and, as such, the prudent practitioner
should therefore be prepared to recognise and treat
Lip/cheek/tongue biting
the signs and symptoms of an allergic reaction. A con-
scious patient experiencing an anaphylactic reaction Another common issue for patients after having
would generally have a constellation of symptoms received local anaesthesia for a dental procedure is
involving the dermatologic (rashes, hives, urticaria, the associated soft tissue anaesthesia that persists and
erythema, mottling), respiratory (wheezing, dyspnea subsequent trauma to those anaesthetised tissues from
from airway angioedema), and gastrointestinal sys- lack of sensory feedback22. Care must be taken to
tems (cramping, vomiting, diarrhoea). A patient who warn patients about this time of vulnerability to those
is in a state of sedation may have some of these clini- tissues at risk. Additionally, cotton rolls or gauze can
cal features masked and may instead present with be used as a shield to prevent patients from gnawing/
4 © 2020 FDI World Dental Federation
 Local anaesthesia in dentistry

chewing on these structures. If possible, the use of a because the gauge of needle was too small. In either
local anaesthetic without epinephrine will reduce the case, if the contents of the cartridge are deposited
amount of time that this soft tissue anaesthesia per- directly into the bloodstream, patients can experience
sists. Additionally, a practitioner may decide that the immediate symptoms from both the local anaesthetic
use of phentolamine mesylate would be appropriate, and vasoconstrictor24. While these symptoms are
to be administered in order to cause local vasodilation often related to the blood flow from vessels adjacent
in the area where a vasoconstrictor was previous to the block being performed, they may present as
administered, thus accelerating the rate of redistribu- palpitations, headaches, visual disturbances, and ver-
tion of the local anaesthetic, accelerating the offset of tigo. While patient reassurance that these symptoms
the drug, and subsequently accelerating the reversal of will resolve is first-line management of an intravascu-
collateral soft tissue numbness. This medication is fur- lar injection, the dental practitioner would be prudent
ther discussed later in the paper. to continue to monitor level of consciousness and vital
signs until the local anaesthetic has redistributed away
from the site of injection and the patient has returned
Trismus
to their baseline state. Anecdotally, just one cartridge
Trismus, a reduction in the range of mandibular of lidocaine can and in cases has produced seizures,
motion, can occur after a dental injection. It is often illustrating how the speed attending intravascular
caused by the needle passing through a muscle of injection may be the decisive factor in the severity of
mastication which in turn causes spasticity to the local anaesthetic systemic toxicity.
muscle23. It can also be caused by the accumulation
of a haematoma (see below) impeding excursive
Haematoma
movements that permit full opening. Analgesics and a
soft diet are mainstay therapies in the acute phase of As the needle is passing through connective tissue, it
trismus following a dental injection, with a gradual is not uncommon for the tip to puncture a vascular
return to function and physiotherapy if necessary. structure. Occasionally, blood will extravasate from
this broach of endothelium into the surrounding
extravascular area and accumulate locally. This can
Intravascular injections
be associated with facial swelling, soreness, and tris-
In order to administer local anaesthesia, a loaded syr- mus from the expansion of the potential space where
inge with an attached needle is inserted into the desired the bleeding from the insult occurred25. If a haema-
location of deposition. New needles have an associated toma is suspected, a dentist should immediately apply
bevel that are sharp in order to comfortably puncture pressure to the area in order to aid in haemostasis of
oral mucosa, but that same quality reducing initial dis- the punctured vessel and to attempt to reduce the
comfort of mucosal puncture and travel through con- amount of extravasation in the area. The patient
nective tissue can lead to puncture of surrounding should only be dismissed once the dentist is confident
vascular structures. When a dentist has reached their that the bleeding has ceased.
intended endpoint where local anaesthesia is to be
deposited, it is recommended that, at minimum, one
Ocular complications
aspiration manoeuvre is performed. This act (via either
pressing an aspiration ring or withdrawing from a car- There have been case reports published for over
tridge that has a harpoon inserted into the cartridge’s 50 years about various ocular complications arising
rubber stopper) introduces negative pressure into the from the administration of inferior alveolar blocks.
local anaesthetic cartridge and serves the purpose of There may be one or more symptoms including, but
aspirating whatever matter is at the tip of the needle. If not limited to, amaurosis, diplopia, total ophthalmo-
a needle tip is located inside a vascular structure, the plegia, mydriasis, ptosis, and blanching of the perior-
negative pressure into the cartridge should in theory bital skin26. The common belief of the cause of this
draw visible blood into the cartridge and alert the den- phenomenon is the variable anatomy of the maxillary
tist of the needle’s tip inside a blood vessel. artery in which there is a subsequent intravascular
Unfortunately, there are times when an aspiration injection which could carry the local anaesthetic in a
manoeuvre is carried out while the needle tip is indeed retrograde manner from the middle meningeal artery
in a blood vessel but there is a false negative aspira- through the foramen spinosum and back to the lacrimal
tion (that is, no blood is visualised in the cartridge). and optic arteries resulting in anaesthetisation of cra-
This false negative event could be due to either the nial nerves 3, 4 and 6. Generally supportive measures
bevel of the needle being positioned in such a way and tincture of time suffice to resolve this complication,
that the action of aspiration draws the wall of the but a differential diagnosis should be formed and refer-
vascular structure to the bevel instead of blood, or ral to the appropriate sub-specialist if necessary.
© 2020 FDI World Dental Federation 5
Decloux and Ouanounou

Table 3 Example calculations of maximum dose for local anaesthetic for various patients
Information Calculation and Maximum

20 kg patient (e.g. a 5-year-old) 20 kg 9 7 mg/kg maximum = 140 mg maximum

2% lidocaine with 1:100,000 epinephrine in a 1.8 mL cartridge 140 mg maximum/36 mg per cartridge = 3.8 cartridges of 2% lidocaine
with 1:100,000 epinephrine
20 kg patient (e.g. a 5-year-old) 20 kg 9 7 mg/kg maximum = 140 mg maximum
4% articaine with 1:100,000 epinephrine in a 1.8 mL cartridge 140 mg maximum/72 mg per cartridge = 1.9 cartridges of 4% articaine
with 1:100,000 epinephrine
60 kg patient (e.g. a 40-year-old) 60 kg 9 7 mg/kg maximum = 420 mg maximum
2% lidocaine with 1:100,000 epinephrine in a 1.8 mL cartridge 420 mg maximum/36 mg per cartridge = 11.6 cartridges of 2% lidocaine
with 1:100,000 epinephrine
100 kg patient 100 kg 9 7 mg/kg maximum = 700 mg maximum
2% lidocaine with 1:100,000 epinephrine in a 1.8 mL cartridge BUT reported maximum is 500 mg
500 mg maximum/36 mg per cartridge = 13.8 cartridges of 2% lidocaine
with 1:100,000 epinephrine

Non-surgical paraesthesia supplemental oxygen should be administered (despite

an ineffective oxygen-carrying capacity from the
There are extremely rare cases in the literature and
methaemoglobinemia) and emergency medical services
closed-claim analysis where patients who had com-
contacted. Definitive treatment for this emergency is
pleted nerve blocks subsequently experienced perma-
the intravenous administration of methylene blue.
nent paraesthesias of associated nerves when there
Table 3 provides example calculations for maxi-
was no surgical procedure involved27. Given the rarity
mum dose for local anasthesia for various patients.
of such events, the study of non-surgical paraesthesias
is very difficult and almost exclusively retrospective in
nature. With that being said, speculation exists that a Interactions
combination of trauma to the nerve from the needle
Unless the patient is on a concomitant local anaesthe-
and higher percentages of local anaesthetics like arti-
sia infusion for an ailment (a potential risk for local
caine and prilocaine are the most likely causes of such
anaesthetic systemic toxicity), there are no significant
paraesthesias from direct neurotoxicity to nerve
drug interactions with non-epinephrine-containing
trunks28. Additionally, the number of respective nerve
local anaesthetics. Drug interactions stemming from
fascicles and the ratio of nerve fascicles affected may
the contents of a local anaesthetic cartridge are almost
correlate to the severity of paraesthesia (e.g. higher
exclusively from the included vasoconstrictor. The
incidence of lingual nerve paraesthesia and a lower
most notable interactions are noted in Table 4 below.
number of nerve fascicles generally present for the lin-
As such, epinephrine should be use with great caution
gual nerve)29. However, this topic does remain con-
when concomitant use of one of the drugs is present,
troversial as there has been other literature published
and levonordefrin should be avoided altogether when
noting that this hypothesis may not be the case30–32.
the patient is taking a tricyclic antidepressant.
In any and all cases of deposition of local anaesthetic,
the dental practitioner must weigh the pros and cons
of choice of drug and route of administration prior to CONSIDERATIONS
the injection.
Anatomic considerations leading to local anaesthesia
failure
Methaemoglobinemia
While supraperiosteal injections are generally sufficient
Exposure to some local anaesthetics (namely the ester-
to achieve pulpal anaesthesia for maxillary dentition,
type local anaesthetics and principally prilocaine) can
these types of injections are significantly less successful
precipitate a change in the iron atom in the haemoglo-
for mandibular teeth due to the thickness of the bone
bin, specifically from a ferrous state to a ferric state
cortex. As such, deposition of local anaesthetic adja-
to create a molecule called methaemoglobin. This is
cent to the inferior alveolar nerve (IAN) must be car-
of concern as the ferric haemoglobin molecule has a
ried out via one of several approaches, all of which
much greater affinity for oxygen, so much so that the
have varying rates of success33,34, and none of which
oxygen will not dissociate from the haemoglobin and
are able to accomplish nerve blockage 100% of the
therefore not be available for tissue and organ use. If
time35. This can be attributed to various hard and soft
an exposure causes enough haemoglobin to become
tissue characteristics creating uncertainty about the
methaemoglobin, the patient may experience signs
position of the needle tip relative to the IAN, fascial
and symptoms of hypoxemia such as cyanosis and
linings acting as a potential barrier to the diffusion of
shortness of breath. If this condition is suspected,
6 © 2020 FDI World Dental Federation
 Local anaesthesia in dentistry

Table 4 Drugs known to cause interactions with vasoconstrictors and potential associated effects
Drug Effect

Beta blockers (drugs that end in -olol) Beta-blockers block beta-adrenergic receptors and can produce
Ex. metoprolol, propranolol, labetalol, bisoprolol, atenolol unrecognised and unopposed alpha-adrenergic receptor agonism
with corresponding hypertension when epinephrine is present.
Volatile anaesthetics (drugs that end in -ane) Volatile anaesthetics sensitise the myocardium to catecholamines
Ex. halothane, sevoflurane, isoflurane, desflurane – cardiac arrhythmias can be induced with the injection of
exogenous epinephrine.
Amphetamines (names vary) Amphetamines increase blood pressure and can cause cardiac
Ex. cocaine, methamphetamine arrhythmias by themselves with the potential for adverse event
synergism from epinephrine.
Tricyclic antidepressants (names vary) Tricyclic antidepressants increase the systemic circulation of
Ex. amitriptyline, imipramine, trimipramine, nortriptyline, catecholamines and can lead to systemic hypertension when
protriptyline, desipramine supplementary epinephrine is present.

local anaesthetic solution, and the sphenomandibular animal studies42. The first trimester of pregnancy
ligament possibly impeding diffusion of local anaes- poses the highest threat for teratogenicity and so only
thetic to the IAN (likely because the needle tip was too emergent dental work should be completed during this
medial to the mandibular foramen)36. Accessory inner- trimester. It is currently believed that the second tri-
vation from the mylohyoid nerve, the long buccal mester poses the lowest risk of foetal harm and local
nerve, the greater auricular nerve, and even a bifid anaesthesia use should in theory be safe43. While it is
IAN can also carry additional sensory fibres to possible to complete elective dental treatment during
mandibular dentition31. Given the above information, the third trimester of pregnancy, there is a higher risk
all injections should be performed with prior examina- of aortocaval compression and increased conduction
tion of the patients’ anatomical features to permit blockade. If local anaesthesia is to be administered in
minor alterations to technique as necessary in order to the third trimester, lower doses should be used.
maximise chances of success of a nerve blockade.
Elderly
Inflamed dental pulps
Current demographic data show that the North Amer-
As carious lesions increase in size and proximity to ican population is aging, and projections suggest that
pulpal tissue, various biologic markers are produced the percentage of older people will continue to
and subsequent inflammatory mediators are recruited increase44. In those of advanced age, the pharmacoki-
to the site37. This inflammation creates a localised netics and pharmacodynamics of many drugs are
area of inflammatory acidosis where the lowered pH altered44. No significant differences in the response of
value inhibits the action of local anaesthetics due to the elderly to local anaesthetics are expected. How-
the altered interaction with components of the lipo- ever, as aging is accompanied by decreased liver and
somes38. Additionally, various isoforms of tetrodo- kidney function, doses below the maximum are rec-
toxin-resistant sodium channels (i.e. sodium channels ommended44.
on which lidocaine has a reduced antinociceptive Also, geriatric patients commonly have cardiovascu-
effect)39 are recruited in the inflammatory state40. lar disease and, thus, the dose of epinephrine con-
This combination of factors can make reliable and tained in anaesthetics should be limited to a
profound anaesthesia very difficult to achieve, and maximum of 0.04 mg44. Even without a history of
practitioners should be prepared to administer adjunc- overt cardiovascular disease, it is prudent to minimise
tive techniques such as intra-osseous or periodontal the use of epinephrine in elderly patients simply
ligament injections in order to provide a comfortable because of the expected effect of aging on the heart.
experience for their patients41. Monitoring blood pressure and heart rate is advised
when considering multiple administrations of epi-
nephrine-containing local anaesthetic.
Pregnancy
At this time, only lidocaine and prilocaine have an
Children
FDA foetal risk classification indicating no risk of ter-
atogenic effects based on the results of human and Children are at higher risk for soft tissue injury due to
animal studies. Other commonly used local anaesthet- a relative lack of awareness after local anaesthetic
ics (bupivacaine, articaine, mepivacaine) have an FDA administration. Children are at a higher risk for local
foetal risk classification indicating that teratogenic anaesthetic systemic toxicity because they weigh sig-
risk cannot be eliminated on the basis of human and nificantly less than an adult patient so their absolute
© 2020 FDI World Dental Federation 7
Decloux and Ouanounou

threshold for local anaesthesia deposition is much associated with injections and increase the speed of
lower than that of adults45. Practitioners should also onset of nerve blockade. Current studies show that
be wary of patient and personal safety when deliver- the above claims above are increasingly likely to be
ing local anaesthetic to a pre-cooperative or anxious true and dental manufacturing companies are creating
child as needle-stick injury may be more likely given a devices that alkanise, that is increase the pH of, local
mobile target for local anaesthesia deposition. anaesthetic solutions prior to dental injection50. It
should be noted that a recent meta-analysis shows
that buffered local anaesthetics have 2.23 times
Patients on anticoagulants
greater likelihood of achieving profound anaesthesia
It is currently understood that patients within thera- in pulpally involved teeth51.
peutic international normalised ratio (INR) ranges can
receive local anaesthetic nerve blocks without cessa-
Inhaled local anaesthetics
tion of the anticoagulant beforehand. Even if a hae-
matoma does occur, local haemostatic measures are A combination of local anaesthetics (tetracaine) and
generally sufficient to produce haemostasis. nasal decongestants (oxymetazoline) is being used to
anaesthetise maxillary anterior teeth. This combina-
tion of drugs may demonstrate less successful pulpal
ADVANCES
anaesthesia and more adverse events compared to tra-
ditionally deposited local anaesthetics52.
Computer-controlled local anaesthetic delivery
There are now several electronic devices on the mar-
Liposomal bupivacaine
ket that aid in the delivery of local anaesthesia, specif-
ically with digital controls that can be manipulated to In an attempt to increase the duration of local anaes-
aid in aspiration and continuous delivery of local thetics, a formulation of bupivacaine has been pro-
anaesthetic solution46. Many microprocessor-aided duced where the local anaesthetic molecule is loaded
local anaesthesia devices will monitor the counterpres- in multivesicular liposomes. This slow-release formu-
sure exerted by the tissues into which the local anaes- lation of drug is able to delay the release of local
thetic is being injected and vary the rate of deposition anaesthetic and therefore extend the duration of pain
of injectate accordingly47. In addition to assuming a relief for the patient for up to 72 hours, compared to
less threatening appearance than a traditional syringe unaltered bupivacaine traditionally providing up to
and needle armamentarium, these computer-controlled 8 hours of analgesia. It has been demonstrated to be
devices will ensure both appropriate aspiration and suitable for local infiltration leading to increased dura-
duration of delivery of the local anaesthesia which tion of action and subsequent sparing of other anal-
may reduce injection pain. gesic medications (such as opioids)53. The safety
profile is currently being established and appears not
to differ from that of bupivacaine with no additional
Phentolamine mesylate
incidence of adverse events being noted. Some trials
Most local anaesthetic cartridges deposited worldwide have noted no difference in reducing the duration of
contain epinephrine, so for patients at higher risk of analgesia of necrotic teeth from that of traditional
traumatic injury to soft tissues or simply patients who bupivacaine54. That being said, additional trials with
wish to have their blockade reversed more quickly, significant power are needed before its use can be rec-
phentolamine mesylate is a vasodilator that when ommended.
deposited in a similar location to the original epi-
nephrine-containing local anaesthetic solution can
Local anaesthetic infusion pumps for localised
overwhelm the previous vasoconstriction and aid in
deposition at the surgical site
the redistribution (and the clinical offset) of the local
anaesthetic48. Recent studies suggest that it may have Following surgical procedures, clinicians must deter-
particular use in children in providing a more rapid mine the most appropriate means of controlling any
recovery of lip sensation which may decrease the inci- post-operative pain associated with the procedure.
dence of soft tissue trauma associated with local This can be accomplished by a variety of localised or
anaesthetic delivery in this age group49. systemic means (some of which have been noted pre-
viously), one of which is an emerging method of
patient-controlled localised deposition of local anaes-
Buffered local anaesthetics
thetic at the site of injury or surgery. There are many
It is believed that an increased pH of a solution being examples of a patient-controlled local anaesthetic
deposited could decrease the amount of discomfort infusion pump such as the ON-Q pain pump being
8 © 2020 FDI World Dental Federation
 Local anaesthesia in dentistry

used for general medical surgery55–57, but there is still 7. Cazaubon Y, Mauprivez C, Feliu C et al. Population pharma-
cokinetics of articaine with 1:200,000 epinephrine during third
much research to be carried out about these infiltrat- molar surgery and simulation of high-dose regimens. Eur J
ing catheters and their potential benefit in treating the Pharm Sci 2018 114: 38–45.
head and neck region58, and possible intraoral appli- 8. Wahl MJ, Brown RS. Dentistry’s wonder drugs: local anesthetics
cations. and vasoconstrictors. Gen Dent 2010 58: 114–123: quiz 124-5.
9. Hondrum SO, Ezell JH. The relationship between pH and con-
centrations of antioxidants and vasoconstrictors in local anes-
Ultrasound-guided IAN blocks thetic solutions. Anesth Prog 1996 43: 85–91.
10. Malamed SF. Allergy and toxic reactions to local anesthetics.
In order to negate mandibular anatomical differences Dent Today 2003 22: 114–116, 118-21.
in varied patient populations, the use of ultrasonogra- 11. Silva GH, Bottoli CB, Groppo FC et al. Methylparaben concen-
phy to visualise and direct the blockage of the IAN tration in commercial Brazilian local anesthetics solutions. J
may prove worthwhile. Previous studies have either Appl Oral Sci 2012 20: 448.
used Doppler ultrasound (i.e. indirect assessment) of 12. El-Boghdadly K, Pawa A, Chin KJ. Local anesthetic systemic
toxicity: current perspectives. Local Reg Anesth 2018 11:
the IAN position for local anaesthetic deposition59 or 35–44.
injected coloured dye on cadavers to assess proximity 13. Sekimoto K, Tobe M, Saito S. Local anesthetic toxicity: acute
of injectate deposition to the IAN60. There are cur- and chronic management. Acute Med Surg 2017 4: 152–160.
rently ongoing studies using B-mode ultrasound (i.e. 14. Alsukhni RA, Ghoubari MS, Farfouti MT et al. Status epilepti-
direct assessment) to directly visualise the IAN while cus following local anesthesia in a previously healthy adult.
using intraoral ultrasound to guide intraoral inferior BMC Res Notes 2016 9: 300.
alveolar blocks on patients with subsequent objective 15. Kauferstein S, Kiehne N, Peigneur S et al. Cardiac channelopa-
thy causing sudden death as revealed by molecular autopsy. Int
pulpal anaesthesia testing. J Legal Med 2013 127: 145–151.
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This paper provides a review of the pharmacology, 17. Fisher MM, Bowey CJ. Alleged allergy to local anaesthetics.
Anaesth Intensive Care 1997 25: 611–614.
techniques, and advances of local anaesthesia use in
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dentistry and should serve as a baseline for under- becoming more prevalent. Dermatol Surg 2014 40: 1367–1372.
standing that general dental practitioners possess for 19. Jenerowicz D, Pola nska A, Gli
nska O et al. Allergy to lidocaine
safe treatment of patients. Clinicians are encouraged injections: comparison of patient history with skin testing in
to continue to expand both their didactic knowledge five patients. Postepy Dermatol Alergol 2014 31: 134–138.
and practical clinical skills through advanced reading, 20. Mali S. Anaphylaxis during the perioperative period. Anesth
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22. Chi D, Kanellis M, Himadi E et al. Lip biting in a pediatric
Acknowledgement dental patient after dental local anesthesia: a case report. J
Pediatr Nurs 2008 23: 490–493.
None. 23. Stone J, Kaban LB. Trismus after injection of local anesthetic.
Oral Surg Oral Med Oral Pathol 1979 48: 29–32.
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Conflict of interest dence of intravascular needle entrance during inferior alveolar
nerve block injection. J Dent Res Dent Clin Dent Prospects
None. 2008 2: 38–41.
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