Description: Tetracaine is an ester-type local anesthetic with an
intermediate to long duration of action. Relative to other local anesthetics,
tetracaine in considered the most toxic. Tetracaine is available in various
injectable forms for spinal anesthesia, as well as preparations for topical
use. These preparations are typically used prior to examination of the
larynx, trachea, or esophagus, to abolish laryngeal and esophageal reflexes
and provide local analgesia. Topical nonprescription products are also
available for the temporary relief of pain associated with herpes labialis.
Tetracaine received FDA approval in 1965. Mechanism of Action: Tetracaine,
like all local anesthetics, causes a reversible blockade of nerve conduction
by decreasing nerve membrane permeability to sodium. This decreases the
rate of membrane depolarization thereby increasing the threshold for electrical
excitability. All nerve fibers are affected, albeit, in a predictable
sequence: autonomic, followed by sensory, and finally, motor. These effects
diminish in reverse order. Clinically, loss of nerve function is as follows:
pain, temperature, touch, proprioception, skeletal muscle tone. Direct
nerve membrane penetration is necessary for effective anesthesia which
is achieved by applying the anesthetic topically or injecting it subcutaneously,
intradermally or submucosally around the nerve trunks or ganglia supplying
the area to be anesthetized. Pharmacokinetics: Systemic absorption of
tetracaine depends on the dose, concentration, route of administration,
tissue vascularity and degree of vasodilatation. The use of vasoconstrictor
containing mixtures will counteract the vasodilation produced by tetracaine.
This will slow the rate of absorption, prolong the duration of action
and maintain hemostasis. Systemic absorption from topical preparations
is minimal, but application to broken or bruised skin greatly increases
absorption. When used for spinal anesthesia the onset of action can be
delayed, often requiring up to fifteen minutes for full effect, with a
duration of 1.5�3 hours. For topical and aerosol solutions, the onset
of action is 3�10 minutes and the duration of action is 30�60 minutes.
For ophthalmic preparations, the onset of action is about 15 seconds,
with a duration of 15 minutes. Tetracaine is hydrolyzed to para-aminobenzoic
acid by plasma pseudocholinesterases. It has the slowest rate of hydrolysis
of the ester type local anesthetics and its metabolites are primarily
renally excreted.
Indications...Dosage For regional anesthesia or local anesthesia via
spinal anesthesia: �to anesthetize lower abdomen: Spinal dosage (Pontocaine�
with Dextrose Injection): Adults: 3�4 ml (9�12 mg) of a 0.3% solution.
�to anesthetize perineum: Spinal dosage (Pontocaine� with Dextrose Injection):
Adults: 1�2 ml (3�6 mg) of a 0.3% solution. �to anesthetize upper abdomen:
Spinal dosage (Pontocaine� with Dextrose Injection): Adults: 5 ml (15
mg) of a 0.3% solution. Children: Dosage has not been established. �for
obstetric anesthesia, low spinal (saddle block) anesthesia: Spinal dosage
(Pontocaine� with Dextrose Injection): Adults: 1�2 ml (2�4 mg) of a 0.2%
solution. Doses exceeding 15 mg are rarely required. �for anesthesia of
the perineum: Intrathecal dosage: Adults: 0.5 ml (5 mg ) as a 1% solution,
diluted with an equal amount of CSF or 10% dextrose injection, depending
on the technique required. �for anesthesia of the perineum and lower extremities:
Intrathecal dosage (Pontocaine� with Dextrose Injection): Adults: 1 ml
(10 mg) as a 1% solution, diluted with an equal amount of CSF or 10% dextrose
injection, depending on the technique used. �for anesthesia up to costal
margin: Intrathecal dosage (Pontocaine� with Dextrose Injection): Adults:
1.5�2 ml (15�20 mg) as a 1% solution, dilute with an equal amount of CSF.
For topical anesthesia: Topical Dosage (1% Cream or 0.5% Ointment): Adults:
Apply to affected areas as needed. Do not apply more than 28 g within
any 24 hour period. Children: Apply to affected areas as needed. Do not
apply not more than 7 g in a 24 hour period. �for topical anesthesia of
nose and throat or to abolish laryngeal and esophageal reflexes prior
to diagnostic procedures: Topical dosage (Pontocaine� Topical Solution):
Adults: Direct application of a 0.25% or 0.5% topical solution or by oral
inhalation of a nebulized 0.5% solution. When anesthetizing the larynx,
trachea, or esophagus, the total dose not to exceed 20 mg, and the manufacturer
recommends adding 0.06 mL of a 0.1% epinephrine solution per each ml of
anesthetic used to decrease systemic absorption of the anesthetic. Children:
Dosage has not been established. For the temporary relief of mild pain,
burning and/or pruritus associated with herpes labialis (i.e., cold sores
or fever blisters): Topical dosage (Cepacol� Viractin� Cream, Viractin�
Cream, Viractin� Gel): Adults and children >= 2 years: Apply to the affected
area no more than 3�4 times daily. For ophthalmic anesthesia: Ophthalmic
dosage (Pontocaine� or AK-T-Caine� Ophthalmic Solution): Adults: 1�2 drops
of a 0.5% solution. Patients with renal impairment: Specific guidelines
for dosage adjustments in renal impairment are not available; it appears
that no dosage adjustments are needed.
Administration Spinal Administration �This route should only be used
by specially trained healthcare professionals. Specialized references
should be consulted for specific procedures and administration techniques.
�Resuscitative equipment and drugs used in the management of adverse reactions
should be immediately available while administering spinal anesthesia.
�Injections containing preservatives should not be used. Prior to using,
the outside of ampules should be sterilized, preferably by autoclaving.
�Do not use solution if it is discolored or a precipitate is present.
�Discard any partially used injections that do not contain preservatives.
�Store in a refrigerator between 2 and 8 degrees C (36 and 46 degrees
F); do not freeze. Do not use if the product contains crystals, is cloudy
or discolored. Ampules may be autoclaved once, throw away if unused. Do
not store autoclaved solutions. Spinal or intrathecal block: �Administer
via 22 or 25 gauge spinal needles. Monitor blood pressure during administration.
�After the desired level of anesthesia is obtained and the anesthetic
has become fixed, usually within 5�10 minutes, the patient may be positioned
appropriately. Ophthalmic Administration �Ophthalmic ointment or solution
is for ophthalmic use only. �Do not to touch the tip of the dropper or
tube to the eye, fingertips, or other surface. �Store at room temperature
between 15 and 30 degrees C (59 and 86 degrees F); do not freeze. Protect
from light. Discard after the expiration date. Do not use if solutions
are cloudy or contain crystals. Topical Administration �Skin: Apply as
a cream or ointment. �Larynx, trachea, esophagus: Apply directly as a
spray, solution, or gel to the larynx, trachea, or esophagus. If applied
using a cotton pledget, the pledget should not be held in place for extended
periods of time. The manufacturer recommends adding 0.06 mL of a 0.1%
epinephrine solution per each ml of anesthetic used to decrease systemic
absorption of the anesthetic
Contraindications Tetracaine is contraindicated in patients with ester
local anesthetic hypersensitivity, sulfite hypersensitivity, or para-aminobenzoic
acid, PABA hypersensitivity. Use with caution in patients with paraphenylenediamine
(a hair dye) hypersensitivity. Local anesthetics should only be administered
by a clinician trained in the diagnosis and management of drug-related
toxicity and other acute emergencies that might arise from the administration
of a regional anesthetic block. The immediate availability of oxygen,
cardiopulmonary resuscitative equipment and drugs and the appropriate
support personnel for the management of toxic reactions or emergencies
must be ensured. Any delay in appropriate management may lead to the development
of acidosis, cardiac arrest and possibly death. Local anesthetics should
be used with caution in patients with hypotension, hypovolemia or dehydration,
myasthenia gravis, shock, or cardiac disease. Patients with impaired cardiac
function, particularly AV block, may be less able to compensate for functional
changes associated with prolonged A-V conduction (i.e., PR or QT prolongation)
caused by local anesthetics. Intravenous administration or intraarterial
administration of tetracaine should be avoided. Unintended intravenous
or intraarterial administration may result in cardiac arrest and may require
prolonged resuscitation. To avoid intravascular administration of procaine
during local anesthetic procedures, aspiration should be performed before
the local anesthetic is injected and after repositioning of the needle.
Syringe aspiration should also be performed before and during each supplemental
injection in continuous catheter techniques. Clinicians should be aware
that the absence of blood return does not guarantee that intravascular
injection has been avoided. Spinal and nerve block injections of tetracaine
are contraindicated in patients with the following: infection or inflammation
at the injection site, bacteremia, platelet abnormalities, thrombocytopenia
< 100,000/mm3, increased bleeding time, uncontrolled coagulopathy, or
anticoagulant therapy. Patients with the following conditions should receive
spinal anesthesia with caution: pre-existing CNS disorders such as poliomyelitis,
pernicious anemia, paralysis from nerve injuries or syphilis; infants,
children < 16 years, or elderly patients; chronic backache; preoperative
headache; hypotension; hypertension; arthritis or spinal deformity; technical
problems (persistent paresthesias, persistent bloody tap); psychotic or
uncooperative patients. Consult standard textbooks for specific techniques
and precautions for spinal anesthetic procedures. Elderly patients, especially
those receiving treatment for hypertension, may be at increased risk for
the hypotensive effects of local anesthetics. Prolonged use of topical
anesthetics is not recommended. Systemic toxicity may occur when significant
quantities of topical tetracaine are used. Ester-type local anesthetics
should be used cautiously, if at all, in patients with low plasma levels
of pseudocholinesterase (e.g., pseudocholinesterase deficiency). Tetracaine
is classified in FDA pregnancy category C. Long term animal studies to
evaluate carcinogenic and mutagenic potential and effect on fertility
have not been performed. During labor and obstetric delivery, local anesthetics
can cause varying degrees of maternal, fetal, and neonatal toxicities.
The potential for toxicity is related to the procedure performed, the
type and amount of drug used, and the technique of administration. Appropriate
patient positioning during obstetric delivery may decrease maternal hypotension
that can result from regional anesthesia. Injection of the local anesthetic
should be performed with the patient in the left lateral decubitus position
to displace the gravid uterus, thereby minimizing aortocaval compression.
The use of obstetrical anesthesia may alter the duration of various phases
of labor and increase the need for forceps assistance. Electronic fetal
monitoring for signs of fetal distress is highly recommended. Use with
caution during labor, obstetric delivery, or in pregnancies complicated
by fetal prematurity, fetal postmaturity, eclampsia, fetal distress, or
maternal or fetal sepsis. Use with tetracaine with caution mothers who
are breast-feeding as it is not known whether tetracaine is excreted in
breast milk. Pediatric dose is not well established. The use of this drug
in children is not recommended. After ocular use of tetracaine, the eye
may be inadvertently damaged while anesthetic effects remain. Patients
should avoid touching, rubbing or wiping the eyes. Contact lenses should
not be inserted until the anesthetic effects of tetracaine have completely
worn off (about 20 minutes.)
Interactions Ester-type local anesthetics such as tetracaine are metabolized
to PABA. Para-aminobenzoic acid, PABA, in turn, antagonizes the effects
of sulfonamides. Thus, tetracaine should not be used in patients receiving
sulfonamides. Local anesthetics can antagonize the effects of cholinesterase
inhibitors by inhibiting neuronal transmission in skeletal muscle, especially
if large doses of local anesthetics are used. Dosage adjustment of the
cholinesterase inhibitor may be necessary to control the symptoms of myasthenia
gravis. Use of local anesthetics with ganglionic blockers (e.g., guanadrel,
guanethidine, and mecamylamine) can increase the risk of hypotension and
bradycardia, particularly if sympathetic blockade is produced during epidural
anesthesia. Patients receiving MAOIs (including linezolid) and local anesthetics
may have an increased risk of hypotension. It is advisable to discontinue
MAOIs 10 days before surgery requiring a subarachnoid block. High doses
of local anesthetics can prolong and enhance the effects of neuromuscular
blockers by an unknown mechanism. Concomitant use of low-dose local anesthetics
(0.125�0.25%) and epidural opiate agonists (e.g., alfentanil, fentanyl,
morphine, and sufentanil), may increase analgesia and decrease opiate
dosage requirements. The vagal effects and respiratory depression induced
by opiate agonists can be increased by local anesthetics. Patients receiving
antihypertensive agents may experience additive hypotensive effects during
epidural administration of local anesthestics due to loss of sympathetic
tone in some cases. Use of local anesthetics with rapid-onset vasodilators,
such as nitrates, can result in hypotension.
Adverse Reactions Tetracaine, like all local anesthetics can produce
significant CNS and cardiovascular toxicity, particularly when high serum
concentrations are achieved. Tetracaine induced CNS toxicity usually presents
with symptoms of a CNS stimulation such as anxiety, apprehension, restlessness,
nervousness, disorientation, confusion, dizziness, tinnitus, blurred vision,
tremor, and/or seizures. Subsequently, depressive symptoms may occur including
drowsiness, respiratory arrest, or coma. In some patients the symptoms
of CNS toxicity may be minor and transient. Nausea/vomiting has also been
reported. CNS side effects resulting from tetracaine administration such
as respiratory depression should be treated with general supportive physiologic
measures. Seizures may be treated with benzodiazepines, although this
should be done cautiously as benzodiazepines are also a CNS depressant.
Cardiac effects of local anesthetics are due to the interference of conduction
within the myocardium. Cardiac effects are seen at very high doses and
usually occur after the onset of CNS toxicity. Tetracaine induced adverse
cardiovascular effects include myocardial depression, AV block, PR prolongation,
QT prolongation, atrial fibrillation, sinus bradycardia, cardiac arrhythmias,
hypotension, cardiovascular collapse and/or cardiac arrest or respiratory
arrest. These effects typically occur with high plasma drug concentrations
but have occurred with smaller doses in rare instances. Cardiovascular
side effects resulting from tetracaine administration such as respiratory
depression should be treated with general supportive physiologic measures
such as oxygen therapy, assisted ventilation and IV fluids. Neurologic
effects seen following spinal anesthesia include paresthesias, weakness
and paralysis of lower extremities, hypotension, high or total spinal
block, urinary retention, urinary incontinence, fecal incontinence, headache,
back pain, septic meningitis, meingismus, arachnoiditis, shivering, cranial
nerve palsies due to traction on nerves from loss of cerebrospinal fluid,
and loss of perineal sensation and sexual function. Persistent motor,
sensory, and/or autonomic (sphincter control) deficit of lower spinal
segments with slow (several months) or incomplete recovery has been reported
rarely. Transient burning may occur at the injection site. Pre-existing
inflammation or infection increases the risk of developing serious skin
side-effects. Patients should be monitored for an injection site reaction.
Tetracaine is more likely than other topical anesthetics to cause contact
reactions including, skin rash (unspecified), mucous membrane irritation,
erythema, pruritus, urticaria, burning, stinging, edema or tenderness.
More serious skin effects are likely if the patient has preexisting infection
or inflammation at the area of application. The developement of angioedema
(e.g., anaphylactoid reactions) warrants immediate medical attention.
In general, tetracaine is considered the most toxic topical anesthetic.
Some preparations of tetracaine contain acetone sodium bisulfite which
may cause severe allergic reactions including anaphylaxis, bronchospasm
and status asthmaticus in susceptible individuals. The overall incidence
of such reactions is low. Tetracaine ophthalmic preparations, when used
over a prolonged period, may cause severe keratitis, delayed corneal healing
and permanent corneal opacification and scarring leading to visual impairment.
The drug may also produce acute ocular pain and ocular irritation (burning,
stinging, or erythema). During labor and obstetric delivery, local anesthetics
can cause varying degrees of maternal, fetal, and neonatal toxicities.
The potential for toxicity is related to the procedure performed, the
type and amount of drug used, and the technique of administration. Fetal
heart rate should be monitored continuously because fetal bradycardia
may occur in patients receiving tetracaine anesthesia and may be associated
with fetal acidosis. Maternal hypotension can result from regional anesthesia;
patient position can alleviate this problem. The injection should be performed
with the patient in the left lateral decubitus position to displace the
gravid uterus, thereby minimizing aortocaval compression. Spinal tetracaine
may cause decreased uterine contractility or maternal expulsion efforts
and alter the forces of parturition.
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