TETRACAINA EN VADEMECUM

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.

 

Tetracaine AK-T-Caine�, Cepacol� Viractin�, Pontocaine� (1 of 2), Pontocaine� (2 of 2), Opticaine�