Journal Reading

Local and Regional Anesthesia

Pembimbing :
Dr.Robert Sirait, SpAn
Disusun Oleh :
I Gede Bungas Arisudana
1061050067

KEPANITERAAN ANESTESI
FAKULTAS KEDOKTERAN UNIVERSITAS KRISTEN
INDONESIA
PERIODE 27 JULI 29 AGUSTUS 2015
JAKARTA

Local and Regional Anesthesia

Author: Robyn Gmyrek, MD; Chief Editor: Dirk M Elston, MD

Overview
Local anesthetics provide a reversible regional loss of sensation. Local anesthetics reduce pain,
thereby facilitating surgical procedures. Delivery techniques broaden the clinical applicability of
local anesthetics. These techniques include topical anesthesia, infiltrative anesthesia, ring blocks,
and peripheral nerve blocks (see the Technique section below for links to detailed, illustrated
articles demonstrating these techniques).
Local anesthetics are safer than general or systemic anesthetics; therefore, they are used
whenever possible. In addition, they are relatively easy to administer and readily available. Local
anesthetics have been undergoing development for centuries, and, as this article illustrates,
research continues to provide surgeons with pharmacologic variety and to provide patients with
anesthetic agents that have superior safety and efficacy profiles.
Background
Although the medical world cannot cure every disease, the control of pain to ensure patient
comfort should be a goal. In 1860, cocaine, the oldest anesthetic, was extracted from the leaves
of theErythroxylon coca bush. In 1884, Sigmund Freud and Karl Koller were the first to use it as
an anesthetic agent during ophthalmologic procedures.
Procaine, a synthetic alternative to cocaine, was not developed until 1904. Procaine is an ester of
para-aminobenzoic acid (PABA). As procaine is metabolized, PABA, a known allergen, is
released as a metabolic product. The potential for severe allergic reactions limits the use of
procaine and other ester-type anesthetic agents. Tetracaine, another ester-type anesthetic, was
introduced in 1930. Tetracaine is more potent than procaine, and it causes similar allergic
reactions.
In 1943, an alternative class of anesthetics was discovered when Lofgren developed lidocaine.
This agent is an amide derivative of diethylaminoacetic acid, not PABA; therefore, it has the
benefit of a low allergic potential. Since then, multiple amide-type anesthetics have been
introduced into clinical use. Slight chemical alterations to the compounds have imparted
beneficial characteristics, including increased duration and potency, to each. These compounds
offer the surgeon more choices, and anesthetics can be appropriately matched to different
procedures.
Pathophysiology
Reviewing the physiology of nerve conduction is important before any discussion of local
anesthetics. Nerves transmit sensation as a result of the propagation of electrical impulses; this
propagation is accomplished by alternating the ion gradient across the nerve cell wall, or
axolemma.
In the normal resting state, the nerve has a negative membrane potential of -70 mV. This resting
potential is determined by the concentration gradients of 2 major ions, Na+ and K+, and the
relative membrane permeability to these ions (also known as leak currents). The concentration

gradients are maintained by the sodium/potassium ATP pump (in an energy-dependent process)
that transports sodium ions out of the cell and potassium ions into the cell. This active transport
creates a concentration gradient that favors the extracellular diffusion of potassium ions. In
addition, because the nerve membrane is permeable to potassium ions and impermeable to
sodium ions, 95% of the ionic leak in excitable cells is caused by K+ ions in the form of an
outward flux, accounting for the negative resting potential. The recently identified 2-pore domain
potassium (K2P) channels are believed to be responsible for leak K+ currents.
When a nerve is stimulated, depolarization of the nerve occurs, and impulse propagation
progresses. Initially, sodium ions gradually enter the cell through the nerve cell membrane. The
entry of sodium ions causes the transmembrane electric potential to increase from the resting
potential. Once the potential reaches a threshold level of approximately -55 mV, a rapid influx of
sodium ions ensues. Sodium channels in the membrane become activated, and sodium ion
permeability increases; the nerve membrane is depolarized to a level of +35 mV or more.
Once membrane depolarization is complete, the membrane becomes impermeable to sodium ions
again, and the conductance of potassium ions into the cell increases. The process restores the
excess of intracellular potassium and extracellular sodium and reinstates the negative resting
membrane potential. Alterations in the nerve cell membrane potential are termed the action
potential. Leak currents are present through all the phases of the action potential, including
setting of the resting membrane potential and repolarization.
Mechanism of action
Local anesthetics inhibit depolarization of the nerve membrane by interfering with both Na+ and
K+ currents. The action potential is not propagated because the threshold level is never attained.
Although the exact mechanism by which local anesthetics retard the influx of sodium ions into
the cell is unknown, 2 theories have been proposed. The membrane expansion theory postulates
that the local anesthetic is absorbed into the cell membrane, expanding the membrane and
leading to narrowing of the sodium channels. This hypothesis has largely given way to the
specific receptor theory. This theory proposes that the local anesthetic diffuses across the cell
membrane and binds to a specific receptor at the opening of the voltage-gated sodium channel.
The local anesthetic affinity to the voltage-gated Na+ channel increases markedly with the
excitation rate of the neuron. This binding leads to alterations in the structure or function of the
channel and inhibits sodium ion movement. Blockade of leak K+ currents by local anesthetics is
now also believed to contribute to conduction block by reducing the ability of the channels to set
the membrane potential.
On the basis of their diameter, nerve fibers are categorized into 3 types. Type A fibers are the
largest and are responsible for conducting pressure and motor sensations. Type B fibers are
myelinated and moderate in size. Type C fibers, which transmit pain and temperature sensations,
are small and unmyelinated. As a result, anesthetics block type C fibers more easily than they do
type A fibers. Therefore, patients who have blocked pain sensation still feel pressure and have
mobility because of the unblocked type A fibers.
All local anesthetics have a similar chemical structure, which consists of 3 components: an
aromatic portion, an intermediate chain, and an amine group (see molecular diagram below). The
aromatic portion, usually composed of a benzene ring, is lipophilic, whereas the amine portion of

the anesthetic is responsible for its hydrophilic properties. The degree of lipid solubility of each
anesthetic is an important property because its lipid solubility enables its diffusion through the
highly lipophilic nerve membrane. The extent of an anesthetic's lipophilicity is directly related to
its potency.

Molecular diagram.
Local anesthetics are weak bases that require the addition of hydrochloride salt to be water
soluble and therefore injectable. Salt equilibrates between an ionized form and a non ionized
form in aqueous solution. Equilibration is crucial because, although the ionized form is
injectable, the nonionized base has the lipophilic properties responsible for its diffusion into the
nerve cell membrane. The duration of action of an anesthetic or the period during which it
remains effective is determined by its protein-binding activity, because the anesthetic receptors
along the nerve cell membrane are proteins.
The intermediate chain, which connects the aromatic and amine portions, is composed of either
an ester or an amide linkage (see molecular diagram above). This intermediate chain can be used
in classifying local anesthetics.
Indications
Anesthesia is indicated to reduce pain before surgical procedures.
Contraindications
Patient allergies may preclude the use of a particular anesthetic agent (see Complications section
below).
Anesthesia
Local anesthetics are classified into 2 groups: the ester group and the amide group. The
classification is based on the chemical structure of the intermediate chain. This structural
difference affects the pathway by which local anesthetics are metabolized and the allergic
potential.

Ester anesthetics are listed in the Table below. They are metabolized by hydrolysis, which
depends on the plasma enzyme pseudocholinesterase. Some patients have a rare genetic defect in
the structure of this enzyme and may be unable to metabolize ester-type anesthetics; this inability
increases the possibility of their having toxic reactions and elevated levels of anesthetics in the
blood. In addition, 1 of the metabolic products generated by hydrolysis is PABA, which inhibits
the action of sulfonamides and is a known allergen. In patients with a known allergy to an ester
anesthetic, the use of all other ester-type anesthetic agents should be avoided.
Amide-type local anesthetics (see Table below) are metabolized by microsomal enzymes located
in the liver. The specific microsomal enzyme responsible for the elimination of lidocaine is
cytochrome P-450 3A4. Therefore, amide-type anesthetics should be used with care in patients
with severe liver disease and patients taking medications that interfere with the metabolism of
the anesthetic, and the patients should be carefully monitored for signs of toxicity.
Cytochrome P-4503A4 is present in the small bowel and the liver. Commonly used medications
known to inhibit cytochrome P-4503A4 are listed below (adapted from Klein and Kassarjdian).
[1]
Specific potent inhibitors of cytochrome P-4503A4 that have been associated with clinically
relevant interactions include itraconazole, ketoconazole (azole antifungals), erythromycin,
clarithromycin, cyclosporin (macrolides), amprenavir, indinavir, nelfinavir, ritonavir (HIV
protease inhibitors), diltiazem, mibefradil (calcium channel blockers), and nefazodone.
Grapefruit juice is also a potent inhibitor of P-4503A4 but appears to affect only the enteric
enzyme, which does not play a role in the metabolism of local anesthetics.
If the enzyme is inhibited because of the concurrent use of medications, it is unavailable to
metabolize the anesthetic and potentially toxic levels of the anesthetic can occur. In addition,
beta-blockers may decrease blood flow to the liver; therefore, they may also decrease the
metabolism of amide-type anesthetics and may cause serum levels of the anesthetic to increase.
Table. Common Local Anesthetics* (Open Table in a new window)
Duration
Without
Epinephrine,

Duration With
Epinephrine,

Maximum Dose
Without
Epinephrine,

Maximum Dose
With
Epinephrine,

mg/kg

mg/kg

Anesthetic
min

min

Esters
Cocaine

45

2.8

Procaine

15-30

30-90

7.1

8.5

Chloroprocain
e

30-60

11.4

14.2

Tetracaine

120-240

240-480

1.4

Lidocaine

30-120

60-400

4.5

Mepivacaine

30-120

30-120

4.5

Bupivacaine

120-240

240-480

2.5

3.2

Etidocaine

200

240-360

4.2

5.7

Prilocaine

30-120

60-400

5.7

8.5

Amides

*Adapted from Dinehart.[2]

Technique
Specific local anesthetic techniques are described in detail in the following eMedicine topics:

Anesthesia, Regional, Digital Block

Anesthesia, Topical
Local Anesthetic Agents, Infiltrative Administration
Nerve Block, Deep Peroneal
Nerve Block, Dorsal Penile
Nerve Block, Dorsal Penile, Neonatal
Nerve Block, Inferior Alveolar
Nerve Block, Infraorbital
Nerve Block, Oral
Nerve Block, Median
Nerve Block, Mental
Nerve Block, Posterior Tibial
Nerve Block, Radial
Nerve Block, Saphenous
Nerve Block, Superficial Peroneal
Nerve Block, Supraorbital
Nerve Block, Sural

Complications
Local effects
Local effects are usually a result of the injection technique. These effects include pain,
ecchymosis, hematoma formation, infection, and nerve laceration. Pain is always felt when a
local anesthetic is injected; however, associated discomfort can be minimized by using good
technique. Several factors, including needle puncture of the skin, tissue irritation resulting from

the anesthetic, and distention of tissues caused by infiltration, are responsible for the discomfort
associated with the use of local anesthetics.
Pediatric patients and patients who are extremely anxious may benefit from pretreatment of the
injection area with a topical anesthetic.[3] Pretreatment eliminates the initial pain that occurs when
the needle perforates the skin. Small-diameter needles also decrease the pain associated with
injection. Fortunately, for most dermatologic procedures, a 30-gauge needle can be used to
infiltrate tissue.
Tissue irritation caused by local anesthetics is related to the acidity of the infiltrated solution;
therefore, increasing the pH of the mixture can decrease associated discomfort. The addition of
epinephrine to an anesthetic solution decreases the pH of the solution, making it more acidic (pH
3.5-4.5) and leading to a more painful injection. The solution can be neutralized by the addition
of sodium bicarbonate 8.4% to minimize discomfort. For example, sodium bicarbonate 8.4% can
be added to lidocaine with epinephrine in a 1:10 ratio to achieve a solution pH similar to that of
tissue fluid (pH 7.3-7.4).
Discomfort associated with distension of the tissues during the injection of local anesthetics is
caused by the rate of injection and the volume of fluid injected. To limit the pain, the anesthetic
should be slowly administered to allow the stretch receptors time to accommodate the new
volume of fluid.[4] In addition, the volume of solution injected should be the smallest volume
needed to achieve a loss of sensation at the surgical site.
Studies have shown that patients receiving subcutaneous or intradermal injection of local
anesthetics that were warmed to body temperature, as opposed to room temperature, experienced
less pain during injection. If possible, warming of local anesthetics should be done prior to
administration.[5]
The formation of ecchymosis or a local hematoma is a result of the perforation of cutaneous
blood vessels. These complications are encountered more commonly in areas of high vascularity,
including the mucous membranes, head, and genitalia. Ecchymosis and hematoma are even more
pronounced when the patient has a bleeding diathesis or when the patient has been taking aspirin
or other anticoagulants. If ecchymosis occurs, the patient should simply be reassured. If
hematoma formation occurs, the patient should be evaluated. The hematoma may require
drainage with an 18-gauge needle, followed by the application of a pressure dressing.
Infection is an additional local complication of anesthetic use that usually occurs when proper
sterile technique is not used. Cleansing the skin surface with alcohol is adequate in otherwise
clean or noninfected areas. If signs of infection are noted, treatment includes appropriate culture
studies and antimicrobial therapy. If abscess formation occurs, drainage may also be required.
Nerve laceration, although rare, may occur during the infiltration of a local anesthetic. This
complication more commonly occurs during the placement of regional blocks than the placement
of other blocks. Clinical indications of nerve laceration include paresthesias, shooting or sharp
stinging sensations, and excessive pain during needle insertion. Paresthesias of the infraorbital
nerve are characterized by sharp or shooting sensations involving the upper lip, nasal ala, and
upper teeth.

If the needle is suspected to have entered or lacerated a nerve, it should be withdrawn slowly and
deliberately by 1-2 mm, until the paresthesias are no longer present. The needle should never be
advanced further, moved laterally, or inserted into the foramen, because these maneuvers further
increase the risk of nerve laceration. Although dysesthesias may remain for an extended duration,
in most patients, the nerve regenerates and sensation normalizes over time.
Tendon injury is an inherent aspect of transthecal digital anesthesia since the needle is pushed
through the tendon. This may cause persistent discomfort lasting 1-2 days post surgery. Tendon
sheath infection and late occurrence of trigger finger have also been reported.
Cutaneous adverse effects that have been reported with the most commonly used topical
anesthetic EMLA include itching, burning, pain, pallor, erythema, edema, and purpura. Irritant
dermatitis, allergic contact dermatitis, and contact urticaria have also been reported, but these are
very unusual.[6]
Amethocaine may induce an urticarial reaction at the site of application, and the risk of such a
reaction seems to be significantly higher when amethocaine is used over the antecubital fossa
and in younger children.

Systemic effects
Systemic effects usually occur when blood concentrations of local anesthetic increase to toxic
levels.[7] Effects are most often encountered after the unintentional intravenous injection or
administration of an excessive dose of an anesthetic. Adding a vasoconstrictor (eg, epinephrine)
can reduce the systemic absorption of an anesthetic. When using topical anesthetics, strict
adherence to the maximal dose or area recommended is advised; additionally, great caution must
be exercised when using topical anesthetics on mucosal surfaces because of the much greater
absorption.
Importantly, remember that (1) the metabolism of ester anesthetics is decreased in patients with
deficient pseudocholinesterase activity and (2) the metabolism of amide anesthetics in patients
who are taking medications that inhibit the cytochrome P-450 system is decreased. In addition,
the potency of an anesthetic is directly correlated with the potential for toxicity. Allergic
reactions, although systemic, are not related to serum levels of the anesthetic, but rather, they are
considered idiosyncratic and can occur at any dose.
Maximal safe doses of lidocaine for local anesthesia have been determined. For adults, a
maximum of 4.5 mg of lidocaine per kilogram of body weight can be administered, whereas as
much as 7 mg/kg can be used if the lidocaine solution has 1:100,000 epinephrine added as a
vasoconstrictor. For children, lower maximal doses are recommended; only 1.5-2.5 mg/kg of
plain lidocaine and 3-4 mg/kg of lidocaine with epinephrine should be used.
Systemic toxicity resulting from excessive blood levels of anesthetics is clinically manifested as
adverse reactions in the CNS and cardiovascular system. The CNS is affected in a predictable
and dose-dependent fashion. As serum levels of lidocaine increase, effects on the CNS become
more severe.

Any physician who uses local anesthetics must be aware of the signs and symptoms of systemic
toxicity. At serum lidocaine levels in the range of 1-5 mcg/mL, patients may complain of
tinnitus, lightheadedness, circumoral numbness, diplopia, or a metallic taste in the mouth. In
addition, they may complain of nausea and/or vomiting, or they may become more talkative. As
serum levels increase to 5-8 mcg/mL, nystagmus, slurred speech, localized muscle twitching, or
fine tremors may be noticed. Patients also have been noted to have hallucinations at these levels.
If blood lidocaine levels reach 8-12 mcg/mL, focal seizure activity occurs; this can progress to
generalized tonic-clonic seizures. Respiratory depression occurs at extremely high blood levels
(20-25 mcg/mL) and can progress to coma.
If signs of CNS toxicity are noted, steps must be taken to reduce hypoxia and acidosis, because
these states increase the toxicity of local anesthetics. The patient's airway should be maintained,
and supplemental oxygen provided. If blood levels of carbon dioxide increase, protein binding of
lidocaine decreases and results in higher levels of free lidocaine in the blood. Increased
respiration and respiratory alkalosis increase the seizure threshold and decrease the uptake of the
local anesthetic into the CNS. If convulsions occur, the patient's airway should be maintained,
and supplemental oxygen administered. If seizure activity is sustained, 5-10 mg of diazepam
should be administered slowly (1-2 mg/min) until the seizures cease.
Compared with the CNS, the cardiovascular system is less susceptible to the effects of local
anesthetics. Most adverse effects of the cardiovascular system that occur with the administration
of local anesthetics are a result of the addition of epinephrine rather than direct effects of the
anesthetic. However, high blood levels of local anesthetics directly reduce cardiac contractility.
In addition to the direct vasodilatory effects of most local anesthetics, the decrease in cardiac
function can cause hypotension. Atrioventricular blocks, bradycardia, and ventricular
arrhythmias also are reported; these are more common in patients with known conduction
disturbances and requiring antiarrhythmic medications.
The treatment of conduction disturbances should be appropriately tailored to the type of reaction.
The treatment of hypotension requires the physician to initiate advanced cardiac life support
protocols, that is, he or she should ensure that the patient has a patent airway, provide
supplemental oxygen, and elevate the patient's legs. If necessary, intravenous fluid should be
administered, and the use of vasopressor agents such as ephedrine should be considered.
Ephedrine can be intravenously administered in 5-mL incremental doses to a total of 15-30 mg,
until a blood pressure response is noted.
Lidocaine and the FDA-approved topical anesthetics EMLA and LMX are pregnancy category B
medications.
Allergic reactions
Allergic reactions to local anesthetics are extremely rare, especially with amide local anesthetics,
and account for less than 1% of the reactions caused by local anesthetics. Reactions can be type 1
(ie, anaphylactic) or type 4 (ie, delayed-type hypersensitivity) reactions. These reactions are not
dose related, but, rather, they are idiosyncratic. Skin prick and intradermal test results are
negative in the vast majority of patients, but some authors recommend testing with the most
commonly used amide local anesthetic (lidocaine).

Type 1 reactions are usually caused by ester-type anesthetics. The ester group of local anesthetics
have a much greater allergenic potential than that of the amide group. Pseudocholinesterases,
which produce the highly allergenic metabolic product PABA, break down ester-type anesthetics.
Cross-reactivity exists among ester anesthetics; therefore, the use of all anesthetics in this
structural group should be avoided in a patient with an established sensitivity to one ester-type
anesthetic.
No cross-reactivity appears to exist between ester and amide anesthetics; however, crossreactivity in anaphylactic reactions has not been investigated thoroughly. In addition, reactions to
preservatives, specifically methylparaben and sodium metabisulfate (found in multiple-dose vials
of amide anesthetics), may cause adverse reactions in a patient who is allergic to an ester-type
anesthetic. Preservative-free single-dose vials of lidocaine are available for use if an amide
anesthetic is to be used in a patient with a true hypersensitivity reaction to ester-type anesthetics.
Clinical signs of type I reactions include pruritus, urticaria, facial swelling, wheezing, dyspnea,
cyanosis, laryngeal edema, nausea, vomiting, and abdominal cramping. Epinephrine with a
concentration of 1:1000 should be subcutaneously administered at a dose of 0.3-0.5 mL. This
dose can be repeated every 20-30 minutes to a maximum of 3 doses. If anaphylaxis ensues, a 5mL dose of epinephrine 1:10,000 should be administered intravenously.
Type IV (ie, delayed-type hypersensitivity) reactions account for 80% of allergic reactions to
local anesthetics. They are more common with the use of topical anesthetics and may occur with
anesthetics of the amide and ester subtypes. Clinical manifestations are similar to those of
allergic contact dermatitis and include erythema, plaques, and pruritus. Patients with a history of
type IV reactions are not at an increased risk of type I reactions due to amide-type anesthetics.
Contact dermatitis caused by topical anesthetics should be treated with topical steroid
preparations.
Alternative agents for use as anesthetics in patients with a known allergy to both ester- and
amide-type local anesthetics include isotonic sodium chloride solution and injectable
antihistamines. An intradermal injection of 0.9% sodium chloride solution can provide temporary
anesthesia suitable for shave or punch biopsy. Physical pressure on the nerve endings resulting
from the volume injected is postulated to be responsible for the anesthetic effect.
Nonbacteriostatic sodium chloride solution should be used if the patient has an allergy to the
methylparaben preservative in the local anesthetic. A bacteriostatic solution, which contains
benzyl alcohol, has known anesthetic properties and can be used for limited procedures such as
punch biopsy.
Injectable antihistamines, such as diphenhydramine, have been administered to patients who are
allergic to local anesthetics. The mechanism of anesthetic action is unknown. Injectable
diphenhydramine is effective, but it has a short duration of activity, it is sedating, and its
injection is painful. In addition, tissue necrosis is reported after the local injection of 5%
diphenhydramine. If used for injection, diphenhydramine should be diluted to 1% by mixing 1
vial of 50-mg diphenhydramine with 4 mL of a bacteriostatic sodium chloride solution.
Reactions to local anesthetic additives
Epinephrine

With the exception of cocaine, local anesthetics directly cause relaxation of the vascular smooth
muscle, which leads to vasodilation. This effect increases bleeding at the surgical site.
Vasoconstrictors, such as epinephrine, are often added to anesthetic solutions to counteract this
effect. The vasoconstrictor effect of epinephrine is maximal at 7-15 minutes, and this effect is
clinically evident as blanching of the skin. This blanching also is useful in determining the area
that is anesthetized.
Vasoconstriction not only decreases bleeding but also slows the rate of systemic absorption of the
anesthetic, which allows the body more time to metabolize the anesthetic and prolongs
anesthesia. Therefore, larger volumes of anesthetic can be injected when epinephrine is added to
a solution. A premixed solution of lidocaine with epinephrine in a concentration of 1:100,000 (1
mg/100 mL) is available. Concentrations greater than this are associated with a higher rate of
adverse effects, including an increased risk of tissue necrosis as a result of prolonged ischemia.
Systemic effects of epinephrine can occur with a dose as little as 2 mL of an anesthetic solution
containing epinephrine in a concentration of 1:100,000. The most common clinical manifestation
is transient tachycardia. At higher doses and with an inadvertent intravascular injection,
palpitations, diaphoresis, angina, tremors, nervousness, and hypertension can occur. The
maximum dose of epinephrine is 1 mg or 100 mL of a 1:100,000 solution. In patients with a
history of heart disease, especially unstable angina and arrhythmias, the maximum dose should
be decreased to 0.2 mg or 20 mL of a 1:100,000 solution (recommendation of the NY Heart
Association).
Epinephrine is contraindicated in patients with pheochromocytoma, hyperthyroidism, severe
hypertension, or severe peripheral vascular occlusive disease. Relative contraindications include
pregnancy and psychological instability; epinephrine can induce an acute psychotic episode in
predisposed patients.
The FDA designates epinephrine as a pregnancy category B medication (ie, usually safe but
benefits must outweigh the risks). No known adverse effects on the fetus are reported; however,
during the first trimester, vasoconstriction may cause fetoplacental ischemia and affect
organogenesis. In the last trimester, epinephrine can induce premature labor if placental ischemia
occurs. If possible, surgery should be performed without epinephrine, or it should be postponed
until after delivery.
Epinephrine must be used with caution in patients taking propranolol because life-threatening
reactions have been reported; these include hypertension, myocardial infarction, and stroke.
Epinephrine stimulates alpha-receptors to cause vasoconstriction and increase vascular
resistance. Beta-receptors balance this effect by causing vasodilation (beta2-receptors) and an
increased heart rate (beta1-receptors). Like other nonselective beta-blockers, propranolol
antagonizes both beta1-receptors and beta2-receptors. Therefore, in the presence of propranolol,
the effects of epinephrine on alpha-receptors are unbalanced, and the result is pure alpha
stimulation, which leads to severe hypertension and reflex bradycardia.
Although propranolol is the only nonselective beta-blocker reported to have this effect, probably
all nonselective beta-blockers have the potential to cause severe hypertension and reflex
bradycardia in the presence of epinephrine. A significant risk does not appear to be associated
with the use of epinephrine and cardioselective beta-blockers. Although the use of epinephrine in
patients who are taking nonselective beta-blockers is not contraindicated, it should be avoided if

possible. Apparently, the effect may be dose related, and caution should be exercised because
individual variability is reported.
In addition to nonselective beta-blockers, monoamine oxidase inhibitors, tricyclic
antidepressants, butyrophenones, and phenothiazines can cause hypotension or hypertension in
patients who are taking epinephrine.
Pain resulting from the infiltration of a local anesthetic can be reduced by using a solution with a
pH close to physiologic range (ie, pH 7.3-7.4). The pH of plain lidocaine is 6.3-6.4. When
epinephrine is added to lidocaine, the pH decreases to 3.5-4.5. The pH of the solution must be
acidic to prevent the degradation of epinephrine.
Sodium bicarbonate
To reduce the pain of an injection of lidocaine and epinephrine, 1 mL of sodium bicarbonate
8.4% is added to 10 mL of the anesthetic solution to neutralize the solution. Buffered solutions
should be discarded after 1 week because the effectiveness of epinephrine decreases by almost
25% during this time.
Hyaluronidase
Hyaluronidase is a bovine-derived enzyme that hydrolyzes hyaluronic acid in the connective
tissue and facilitates the diffusion of the anesthetic. Although it can increase the spread of
anesthesia, hyaluronidase also decreases the duration of action of the anesthetics because it
increases absorption. As expected, this increased absorption leads to the potential for a greater
incidence of toxic reactions that correspond to elevated blood levels. To decrease distortion of
the surgical site, the addition of hyaluronidase is useful for nerve blocks and procedures around
the orbit.
Hyaluronidase is marketed in ampules. One ampule is equivalent to 150 United States
Pharmacopeia (USP) units per milliliter. The usual dilution is 150 U in 30 mL of anesthetic. A
patient can have an allergy to hyaluronidase. Hyaluronidase is a foreign protein, and its use is
contraindicated in patients with a known allergy to bee stings. In addition, hyaluronidase
contains the preservative thimerosal, which is a known allergen. To evaluate the potential for an
allergic reaction before infiltration, a test dose should be injected intradermally. If urticaria is
observed at the site of the test injection, the use of hyaluronidase is contraindicated.
Future of Anesthetics
Tumescent anesthesia
In 1987, Jeffery Klein, a dermatologist, first created the technique of tumescent anesthesia in
liposuction procedures.[1] Tumescent anesthesia is based on the use of dilute solutions of
lidocaine (0.05-0.1%) in large volumes to provide superior anesthesia. Epinephrine (1:1,000,000)
is added for hemostasis, and the solution is buffered with sodium bicarbonate to decrease
injection discomfort. Concentrations as high as 55 mg/kg have been used safely with the
tumescent technique.
The use of such high total doses of anesthetic without systemic toxicity is understood. The
absorption kinetics of lidocaine change when high-volume, low-concentration solutions are used.

Decreased concentrations of lidocaine also result in slower plasma absorption with decreased
peak plasma levels. The development of this anesthetic delivery system has revolutionized the
surgical technique of liposuction

Anestesi lokal dan regional

Penulis: Robyn Gmyrek, MD; Kepala Editor: Dirk M Elston, MD

Pendahuluan
Anestesi lokal memberikan rasa hilangnya suatu sensasi yang reversible. Anestesi lokal
mengurangi rasa nyeri, karena itu, anestesi lokal sering dipakai sebaai suatu prosedur pada
pembedahan. Teknik pemberian pada anestesi lokal bermacam macam sehingga pemakaian
anestesi lokal dapat dipakai secara luas. Teknik ini mencakup anestesi topical, anestesi
infiltrative, blok ring, dan blok perifer.
Anestesi lokal lebih aman daripada anestesi umum sehingga dapat digunakan kapan pun bila
dibutuhkan. Sebagai tambahan, anestesi lokal juga mudah untuk diberikan dan persediaannya
juga cukup mudah didapat. Anestesi lokal telah dikembangkan selama bertahun tahun, dan
penelitian tentang anestesi lokal ini berlanjut secara terus menerus untuk memberi para ahli
bedah variasi pengobatan dan memberikan agen anestesi yang lebih aman dan efektif kepada
pasien

Latar Belakang
Walaupun dunia medis tak bisa menyembuhkan semua penyakit, kontrol terhadap nyeri
dan kenyamanan pasien adalah prioritas utama. Pada tahun 1860, kokain, yang merupakan
anestesi tertua, di ekstrak pada daun yang bernama erthroxylon coca. Pada tahun 1884,
Sigmund Freud dan Karl Koller lah yang pertama kali menggunakannya sebagai agen
anestesi pada operasi oftalmologi
Prokain, suatu sintesis dari kokain mulai dikembangkan tahun 1904. Prokain adalah
golongan ester yang merupakan turunan asam para-aminobenzoat(PABA). Setelah prokain
di metabolisme, terdapat pelepasan alergen sebagai produk dari metabolisme. Pelepasan
allergen ini menyebabkan reaksi alergi berat sehingga terdapat pembatasan pada
pemakaian prokain dan agen anestesi golongan ester lainnya. Tetrakain, gologan ester
lainnya mulai dikenalkan pada tahun 1930. Tetrakain lebih poten dari pada prokain tapi
tetap menyebabkan reaksi alergi yang sama
Pada tahun 1943, Lofgern menemukan golongan anestesi lain yang bernama lidokain.
Lidokain adalah golongan amide turunan dari asam diethylaminoacetic, bukan PABA,

karena itu agen anestesi ini jarang menyebabkan alergi. Sejak saat itu, beberapa agen
anestesi golongan amide mulai diperkenalkan dan dipakai secara klinis. Modifikasi dari
bahan bahan kimia yang ada pada agen anestesi ini menghasilkan suatu keuntungan
yang lebih, seperti peningkatan potensi dan durasi dari kerja anestesi. Perubahan ini
memberikan ahli bedah lebih banyak pilihan, dan ahli anestesi pun dapat menyesuaikan
agen anestesi sesuai dengan prosedur yang akan dilakukan

Patofisiologi
Sebelum mendiskusikan anestesi lokal, ada baiknya kita mereview tentang fisiologi
konduksi saraf. Saraf mentransmisikan sensasi yang dihasilkan dari peningkatan jumlah
impuls listrik. Peningkatan ini dicapai dengan merubah gradien ion yang ada di sepanjang
dinding pembuluh saraf
Pada keadaan istirahat normal, saraf mempunyai potensial membran yang negatif, yaitu
sebanyak -70mV. Potensial istirahat ini ditentukan oleh konsentrasi gradien 2 ion besar,
yaitu Na dan K, dan permeabilitas dari membran terhadap ion ion tersebut. Konsentrasi
gradien di jaga oleh pompa sodium/potassium yang mentransport ion sodium keluar sel
dan memasukan potassium kedalam sel. Oleh sebab itu, karena membran saraf bersifat
permeable terhadap ion potassium dan tidak permeable terhadap ion sodium, 95% dari
kebocoran ion pada sel yang tereksitasi disebabkan oleh fluktuasi luar yang dibentuk oleh
ion K dan menyebabkan potensial membran menjadi negatif. Pada penelitian terakhir
ditemukan kebocoran ion K yang terjadi oleh karena adanya 2-pore domain potassium
Ketika saraf terstimulasi, terjadi depolarisasi pada saraf, dan terbentuk proses peningkatan
impuls. Awalnya, ion sodium masuk kedalam sel melalui membrane sel saraf. Masuknya
ion sodium menyebabkan potensial istirahat meningkat menjadi potensial istrik
transmembran. Ketika suatu potensial sudah mencapai suatu titik tertentu kira kira
-55mV, terjadi influx cepat pada ion sodium. Saluran sodium pada membran teraktivasi,
dan permeabilitas sodium pun meningkat menyebabkan membrane saraf ter depolarisasi
menjadi diatas +35mV
Setelah depolarisasi selesai, membran menjadi tak permeable terhadap sodium dan
konduksi dari ion potasium ke dalam sel meningkat. Proses ini mengembalikan potasium
intraseluler yang berlebihan dan sodium ekstraseluler dan mengembalikan potensial
membran yang negatif. Perubahan dari potensial membran sel saraf dinamakan potensial
aksi.

Mekanisme Kerja
Anestesi lokal menghambat depolarisasi membrane saraf dengan mengganggu aliran Na

dan K sehingga potensial aksi tak akan terjadi karena titik tertentu yang dibutuhkan tak
akan tercapai.
Walaupun mekanisme pasti dari lokal anestesi belum diketahui, terdapat 2 teori yang
menggambarkannya. Teori ekspansi membran menyatakan anestesi lokal diabsorbsi ke
dalam membran sel, memperluas membran dan mengakibatkan penyempitan saluran
sodium. Hipotesis ini akhirnya tersingkirkan oleh teori reseptor. Teori reseptor ini
menyebutkan bahwa anestesi lokal berdifusi ke seluruh membran sel dan terikat oleh
reseptor reseptor tertentu saat pembukaan gerbang saluran sodium. Afinitas anestesi
lokal terhadap gerbang saluran natrium meningatkan rasio eksitasi neuron. Pengikatan ini
mengakibatkan perubahan struktur atau fungsi dari saluran dan menghambat pergerakan
ion sodium. Pemblokan aliran ion K oleh anestesi lokal dianggap dapat menyeabkan blok
konduksi dengan mengurangi kemampuan dari saluran untuk mengeset potensial
membran.
Dilihat dari diameternya, serabut saraf dikategorikan menjadi 3 tipe. Serabut tipe A
merupakan serabut terbesar dan bertanggung jawab dalam konduksi dan sensasi motorik.
Serabut tipe B berukuran sedang dan termyelinisasi. Serabut tipe C, berukuran kecil dan
tak termyelinisasi bekerja mengahantarkan rasa sakit dan sensasi suhu. Karena ukurannya
yang kecil, serabut saraf tipe C lebih mudah di blok disbanding serabut saraf tipe A.
karena itu, pasien yang sensasi nyerinya di blok masih dapat merasakan tekanan dan
mobilitas karena tidak terbloknya serabut saraf tipe A.
Semua anestesi lokal mempunyai struktur kimia yang sama, yaitu terdiri dari 3 komponen:
Bagian aromatik, rantai intermediasi, dan grup amine. Bagian aromatik terbentuk dari
benzenering yang bersifat lipofilik, sedangkan grup amine membuat anestesi lokal
menjadi hidrofilik. Derajat kelarutan lipid pada tiap agen anestesi merupakan hal yang
penting karena semakin larut agen anestesi maka difusi menuju membran saraf yang
bersifat lipofilik akan semakin baik. Batas dari lipofillisitas agen anestesi berbanding lurus
dengan potensi kerjanya.

Diagram Molekul.
Anestesi lokal membutuhkan garam hidroklorida agar dapat larut dalam air untuk
diinjeksikan. Garam menyeimbangkan antara bentuk ion dan non ion pada suatu larutan.
Penyeimbangan sangat diperlukan karena walaupun bentuk yang terionisasi sudah dapat
diinjeksi, bentuk yang tak terionisasi pun mempunyai peran dalam difusi menuju
membran sel saraf. Durasi kerja dari obat anestesi dipengaruhi oleh protein yang mengikat
agen anestesi tersebut, ini dikarenakan reseptor anestesi pada membran sel saraf adalah
protein

Indikasi
Anestesia ini digunakan untuk mengurangi nyeri sebelum proses operasi dimulai

Kontraindikasi
Pasien menderita alergi oleh agen anestesi tertentu

Anestesia
Anestesi lokal diklasifikasikan menjadi 2 bagian: Golongan Ester dan golongan amide.
Klasifikasi ini berdasarkan struktur kimia dari rantai intermediasi. Perbedaan struktur
mempengaruhi jalur metabolisme dan potensi alergi
Golongan ester dimetabolisme dengan hidrolisis, yang dipengaruhi oleh enzim
pseudokolinesterase di plasma. Pasien yang mempunyai kelainan genetik pada struktur
enzim ini mengakibatkan pasien tak dapat memetabolisme anestesi golongan ester;
ketidak mampuan untuk metabolisme ini memungkinkan pasien mendapat peningkatan

level serum anestesi pada darah dan menyebabkan reaksi toksik dalam tubuh. Sebagai
tambahan, salah satu produk metabolisme yang muncul adalah PABA, yang dapat
menghambat kerja sulfonamide dan merupakan alergen yang terkenal luas. Pada pasien
dengan alergi anestesi golongan ester, penggunaan agen anestesi ini harus dihindari
Golongan amide di metabolisme oleh enzim mikrosomal yang terletak pada hepar. Enzim
yang bertugas untuk mengeliminasi lidokain adalah cytochrome P-4503A4. Karena itu,
anestesi tipe amide harus hati hati diberikan pada pasien dengan gangguan hati berat dan
pasien yang meminum obat yang dapat mengganggu metabolisme anestesi, pasien juga
harus dimonitor tanda tanda dari keracunan
Cytochrome P-4503A4 berada di hepar dan usus kecil. Obat obat yang menghambat
cytochromeP-4503A4 tedapat pada tabel di bawah. Inhibitor spesifik dari cytochrome P4503A4 yang telah teruji secara klinis yaitu itrakonazol, ketokonazol, eritromisin,
klaritomisin, siklosporin, amprenavir, indinavir, nelfinavir, ritonavir, diltiazem, mibefradil,
dan nefazodon. Jus anggur juga merupakan inhibitor dari P-4503A4
Bila enzim ini terhambat karena pengaruh medikasi obat, enzim ini tak akan bisa
memetabolisme agen anestesi dan berpotensi menaikan dosis menjadi dosis toksik.
Sebagai tambahan, beta bloker dapat menurunkan aliran darah ke hepar; sehingga beta
bloker juga dapat menurunkan metabolisme dari golongan amide dan membuat level
serum agen anestesi dalam darah meningkat

Duration
Epinephrine,

Anesthetic

Without

Duration
Epinephrine,

With

Maximum
Epinephrine,

Dose

Without

Maximum
Epinephrine,

min

min

mg/kg

mg/kg

Cocaine

45

2.8

Procaine

15-30

30-90

7.1

8.5

Chloroprocain
e

30-60

11.4

14.2

Tetracaine

120-240

240-480

1.4

Lidocaine

30-120

60-400

4.5

Mepivacaine

30-120

30-120

4.5

Bupivacaine

120-240

240-480

2.5

3.2

Etidocaine

200

240-360

4.2

5.7

Prilocaine

30-120

60-400

5.7

8.5

Esters

Amides

*Adapted from Dinehart.

[2]

Dose

With

Komplikasi
Efek lokal
efek samping lokal biasanya terjadi akibat teknik penyuntikan. Efek samping yang muncul
adalah nyeri, ekimosis, hematom, infeksi dan nyeri saraf. Nyeri akan selalu muncul pada
saat anestesi lokal di injeksi; akan tetapi, nyeri tersebut dapat dikurangi dengan
menggunakan teknik tertentu. Faktor faktor seperti jarum, iritasi yang disebabkan oleh
anestesi, dan distensi jaringan yang disebabkan infeksi merupakan hal yang membuat
ketidaknyamanan pasien saat penggunaan anestesi lokal
Pasien anak dan pasien yang gelisah atau takut dapat diberi penanganan awal terlebih
dahulu dengan anestesi topikal. Penanganan awal ini menghilangkan nyeri yang terjadi
saat penyuntikan. Penyuntikan dengan jarum yang diameternya lebih kecil juga membantu
mengurangi nyeri.
Iritasi jaringan yang disebabkan oleh anestesi lokal terkait dengan tingkat keasaman
larutan yang akan disuntikan: karena itu, meningkatkan pH larutan akan mengurangi nyeri
atau ketidaknyamanan pasien. Penambahan epinefrin pada larutan anestesi mengurangi pH
larutan dan membuat larutan tersebut lebih asam dan mengakibatkan nyeri yang lebih
hebat saat penyuntikan. pH larutan dapat dinetralisir dengan pemberian sodium bikarbonat
8,4% untuk meminimalisir nyeri. Sebagai contoh, bikarbonat 8,4% dapat ditambahkan ke
lidokain dengan epinefrin dalam rasio 1:10 untuk mencapai pH yang sama dengan pH
jaringan (pH 7,3 7,4)
Nyeri yang dikarenakan distensi jaringan disebabkan oleh rasio penyuntikan dan volume
larutan yang diinjeksi. Untuk mengurangi rasa sakit, anestesi harus diberikan secara
perlahan guna menambah waktu pada reseptor untuk menampung volume cairan yang
baru. Karena itu lah volume larutan yang di injeksi harus menggunakan volume yang
terkecil.
Penelitian menunjukan pasien yang mendapat injeksi subkutan atau intradermal dengan
suhu larutan sama dengan suhu tubuh manusia membuat nyeri saat injeksi berkurang. Jika
memungkinkan, menghangatkan semua larutan anestesi lokal harus dilakukan sebelum
penyuntikan
Pembentukan ekimosis atau lokal hematoma adalah akibat dari perforasi pembuluh darah.
Komplikasi ini sering ditemukan pada area yang mepunyai vaskularisasi tinggi, termasuk
membran mukus, kepala, dan genitalia. Ekimosis dan hematoma akan lebih sering muncul
saat pasien mempunyai kelainan perdarahan atau meminum obat aspirin atau antikoagulan
lainnya. Jika terjadi ekimosis, berikan edukasi pada pasien. Bila hematoma muncul,
evaluasi pasien.

Infeksi adalah komplikasi lokal yang terjadi karena teknik sterilisasi yang tidak baik.
Membersihkan bagian kulit dengan alkohol wajib dilakukan. Bila tanda tanda infeksi
muncul, penatalaksanaan menggunakan antibiotik yang sesuai dengan kultur. Jika terjadi
abses, drainase mungkin diperlukan
Laserasi saraf dapat terjadi karena infiltrasi dari anestesi lokal. Komplikasi ini umumnya
terdapat saat melakukan blok regional. Gejala gejala yang muncul yaitu parestesia, rasa
tertusuk dan nyeri yang berlebih saat penyuntikan jarum. Parestesia nervus infraorbital
dikarakteristikan dengan sensasi nyeri pada bibir bagian atas, hidung, dan gigi bagian atas
Bila jarum sudah dicurigai memasuki atau menusuk bagian saraf, jarum tersebut harus
segera ditarik perlahan 1-2 mm sampai gejala parestesia menghilang. Jarum tak boleh
dimasukan lebih dalam lagi karena meningkatkan resiko laserasi saraf.
Cedera tendon adalah aspek turunan digital anestesi karena jarum diinjeksi menuju
tendon. Keadaan ini dapat menyebabkan gangguan 1 2 hari setelah pembedahan.
Efek samping kulit dilaporkan diakibatkan oleh penggunaan anestesi topikal dengan gejala
gejala gatal, rasa terbakar, nyeri, eritema, pucat, edema, purpura. Dermatitis kontak
iritan, dermatitis kontak alergika jug adapt terjadi tapi jarang.
Amethocaine dapat menyebabkan reaksi urtikaria pada tempat penyuntikan.

Sistemik
Efek sistemik umumnya terjadi ketika konsentrasi anestesi lokal dalam derah mencapai
level toksik. Pemebrian dosis dalam jumlah besar dapat memicu efek toksin ini.
Penambahan vasokonstriktor dapat mengurangi absorpsi sistemik dari obat anestesi.
Ketika menggunakan anestesi topikal, dianjurkan menggunakan tak lebih dari dosis
maksimal, dan harus lebih diperhatikan karena absorbsi pada jaringan mukosa pada kulit
lebih banyak.
Ingatlah bahwa (1) metabolisme golongan ester berkurang pada pasien dengan defisiensi
pseudocholinesterase dan (2) metabolisme golongan amide pada pasien yang memakai
obat penghambat cytochrome P-450 berkurang, sehingga potensi anestesi meningkat dan
berpotensi menjadi toksin. Reaksi alergi tidak terkait dengan level serum obat anestesi tapi
justru dapat terjadi pada dosis manapun
Dosis maksimal yang aman pada lidokain untuk lokal anestesi telah ditetapkan. Untu
dewasa dosis maksimum adalah 4,5 mg/kgBB. Dapat diberikan juga 7mg/kgBB bila
lidokain dilarutkan dengan perbandingan 1:100.000 epinefrin sebagai vasokonstriktor.
Dosis anak anak yang direkomendasikan 1,5 2,5 mg/kgBB dan 3-4 mg/kgBB
ditambah dengan epinefrin

Toksisitas sistemik yang diakibatkan oleh kenaikan level serum anestesi pada darah
merupakan manifestasi klinis dari efek samping sistem saraf pusat dan kardiovaskular.
System saraf pusat dipengarhi oleh dosis. Semakin tinggi level serum lidokain, semakin
berat efek pada sistem saraf pusat
Dokter yang menggunakan anestesi lokal harus berhati hati dengan tanda dan gejala dari
toksisitas sistemik. Pada level serum dalam darah berkisar 1-5 mcg/ml, pasien akan
mengeluh tinnitus, rasa melayang, diplopia. Ditambah lagi, pasien dapat mengeluh mual,
muntah. Bila level serum dalam darah berkisar 5-8 mcg/ml, pasien akan mengeluh
nystagmus, tremor, kaku otot. Pasien juga dapat menderita halusinasi. Pada level serum 812 mcg/ml, kejang fokal dapat terjadi; selanjutnya dapat mengakibatkan kejang tonik
klonik. Depresi pernafasan umumnya terjadi pada level serum 20-25 mcg/ml dan akan
berlanjut ke koma.
Bila tanda keracunan sistem saraf pusat terjadi, maka langkah langkah yang harus
dilakukan adalah mengurangi hipoksia dan asidosis karena keadaan ini dapat meningkatan
toksisitas anestesi lokal pertahankan jalan nafas pasien dan berikan oksigen yang cukup.
Bila karbondioksida dalam darah meningkat, protein pengikat lidokain pun akan menurun
menyebabkan peningkatan level lidokain bebas dalam darah. Meningkatnya respirasi dan
alkalosis respiratorik meningkatkan kemungkinan kejang dan menurunkan pengeluaran
anestesi lokal pada susunan saraf pusat. Jika konvulsi terjadi, pertahankan jalan nafas dan
oksigenisasi, bila kejang terus berlanjut berikan diazepam 5-10 mg
Dibandingkan dengan susunan saraf pusat, sistem kardiovaskular tidak rentan terhadap
efek lokal anestesi. Banyak efek samping dari sistem kardiovaskular yang terjadi adalah
dari hasil penambahan epinefrin dan bukan karena efek obat anestesi itu sendiri. Walaupun
begitu, tingginya level serum darah dari anestesi lokal menyebabkan penurunan fungsi
jantung lalu menyebabkan hipotensi, blok atrioventricular, bradikardi, dan ventricular
aritmia.
Penatalaksanaan gangguan konduksi harus disesuaikan dengan tipe reaksinya.
Penatalaksanaan bradikardia membutuhkan dokter untuk melakukan bantuan hidup dasar
dengan memastikan jalan nafas terjaga dan oksigenasi yang cukup. Ephedrine dapat
diberikan secara intravena sebanyak 5ml dosis bertahap hingga 15-30mg

Reaksi alergi
Reaksi alergi pada anestesi lokal jarang terjadi, terutama pada golongan amide. Reaksi
alergi dapat terjadi tipe 1 atau tipe 4. Reaksi ini tak bergantung pada dosis dan bias
muncul pada dosis berapapun.

Reaksi tipe 1 umumnya disebabkan tipe ester. Golongan ester mempunyai potensi alergi
yang lebih besar dibanding golongan amide. Ini disebabkan oleh pseudocholinesterase
menghasilkan produk metabolism berupa para amino benzoic acid yang merupakan
alergen kuat.
Tidak ada reaksi silang yang muncul antara golongan ester dan amide; tetapi, reaksi silang
pada reaksi anafilaktik belum diteliti secara jauh. Sebagai tambahan, reaksi methylparaben
dan sodium metabisulfate dapat menyebabkan efek samping pada pasien yang alergi
golongan ester.
Tanda tanda klinis reaksi tipe 1 adalah pruritus, urtikaria, pembengakakan pada wajah,
mengi, dispone, sianosis. Epinefrin dengan konsentrasi 1:1000 diberikan secara subkutan
dengan dosis 0,3 0,5 ml. dosis ini dapat diulang 20 30 menit dengan maksimum 3
dosis
Reaksi tipe 4 bertanggung jawab atas 80% dari reaksi alergi pada anestesi lokal.
Manifestasi klinis sama dengan gejala gejala dermatitis kontak alergika meliputi
eritema, plak, dan pruritus. Pasien dengan riwayat reaksi tipe 4 tidak mempunyai
peningkatan resiko reaksi tipe 1 karena golongan amide. Dermatitis kontak karena anestesi
topikal dapat diatasi dengan pemberian steroid topikal
Agen alternative yang dapat digunakan pada pasien alergi dengan golongan ester dan
amide adalah larutan isotonis sodium klorida dan antihistamin injeksi. Injeksi intradermal
larutan sodium klorida 0,9% dapat memberikan anesthesia sementara yang cocok pada
saat ingin melakukan biopsi.
Antihistamin injeksi seperti difenhidramin telah diberikan oleh pasien dengan alergi
anestesi lokal. Injeksi ini efektif, tetapi durasinya pendek, sedative, dan nyeri pada saat
penyuntikan. Untuk pemakaian injeksi, difenhidramin harus dilarutkan dengan campuran
50 mg difenhidramin ditmabah 4ml larutan sodium klorida

Efek penambahan obat lain pada anestesi lokal

EPINEFRIN
Dengan kokain sebagai pengecualian, anestesi lokal langsung menyebabkan relaksasi dari
vaskularisasi otot polos, yang akan mengakibatkan vasodilatasi. Efek ini akan
meningatkan perdarahan saat pembedahan. Vasokonstriksi seperti epinefrin umumnya
ditambahkan untuk melawan kerja anestesi ini. Efek vasokonstriktor pada epinefrin
berkisar maksimal 7 15 menit.
Vasokonstriksi tidak hanya mengurangi perdarahan tapi juga memperlambat absorbsi
sistemik dari anestesi, yang akan membuat tubuh mempunyai banyak waktu untuk
metabolisme obat anestesi dan memperlama kerja agen anestesi. Karena itu, volume
anestesi yang digunakan dapat lebih besar ketika ditambah dengan epinefrin. Pemakaian

epinefrin dengan konsentrasi lebih dari 1:100,000 dapat menyebabkan efek samping yaitu
terjadinya nekrosis karena iskemia yang berkepanjangan
Efek sistemik dari epinefrin dapat muncul dengan dosis 2mL dan dicampur dengan larutan
anestesi denga konsentrasi 1:100,000. Manifestasi klinis yang umum terjadi adalah
takikardia. Pada dosis yang lebih tinggi terdapat palpitasi, angina, tremor, diaporesis.
Dosis maksimum dari epinefrin adalah 1mg atau 100ml dengan larutan 1:100,000. Pasien
dengan riwayat jantung dosis maksimum dikurangi menjadi 0,2 mg atau 20mL dalam
larutan 1:100,000
Kontraindikasi epinefrin adalah pasien dengan pheochromocytoma, hipertiroid, hipertensi
berat, kehamilan.
FDA mengkategorikan epinefrin sebagai obat kategori B. Belum ada penelitian efek pada
fetus, tetapi pada trimester pertama, vasokonstriksi menyebabkan iskemik fetoplacental
dan mempengaruhi organogenesis. Pada trimester akhir, epinefrin dapat menyebabkan
lahir premature bila terdapat iskemia plasental.
Epinefrin harus digunakan dengan hati hati pada pasien yang meminum propranolol
karena terdapat reaksi yang membahayakan seperti miokard infark, stroke, dan hipertensi.
Epinefrin menstimulasi reseptor alfa untuk memicu vasokonstriksi dan meningkatkan
resistensi vaskular. Reseptor beta menyeimbangkan efek ini dengan membuat vasodilatasi
dan meningkatkan denyut nadi. Propanolol merupakan antagonis dari reseptor beta 1 dan
beta 2. Dengan demikian, pemberian propranolol menyebabkan efek epinefrin menjadi
tidak seimbang sehingga menyebabkan hipertensi berat dan bradikardia.

Sodium bikarbonat
Untuk mengurangi nyeri injeksi dari lidokain dan epinefrin, 1ml sodium bikarbonat 8.4%
ditambahkan pada 10 ml larutan anestesi untu menetralisir pH larutan

Hyaluronidase
Hyaluronidase adalah enzim turunan bovine yang menghidrolisis asam hyaluronad di
jaringan ikat dan memfasilitasi difusi pada agen anestesi. Walaupun hyaluronidase dapat
meningkatkan penyebaran anestesia, enzim ini dapat menurunkan durasi dari obat anestesi
karena dapat meningkatkan absorbs agen anestesi

Tumescent anesthesia
Pada tahun 1987, Jeffery Klein, seorang dermatologis menciptakan teknik tumescent
anesthesia pada prosedur penyedotan lemak. Tumescent anesthesia didasari penggunaan
larutan lidokain yang diencerkan (0,05 0,1%) dalam volume yang besar unurk
memberikan efek anestesi yang lebih besar. Epinefrin ditambahkan untuk hemostasis, dan

larutan diberi sodium bikarbonat untuk mengurangi nyeri saat penyuntikan. Konsentrasi
yang diberikan ialah 55mg/kgBB