DURANEST (etidocaine hcl) INJECTIONS FOR INFILTRATION AND NERVE BLOCK SHOULD BE EMPLOYED ONLY BY CLINICIANS WHO ARE WELL VERSED IN DIAGNOSIS AND MANAGEMENT OF DOSE-RELATED TOXICITY AND OTHER ACUTE EMERGENCIES THAT MIGHT ARISE FROM THE BLOCK TO BE EMPLOYED AND THEN ONLY AFTER ENSURING THE IMMEDIATE AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS, CARDIOPULMONARY EQUIPMENT, AND THE PERSONNEL NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES (see also ADVERSE REACTIONS and PRECAUTIONS). DELAY IN PROPER MANAGEMENT OF DOSE-RELATED TOXICITY, UNDERVENTILATION FROM ANY CAUSE AND/OR ALTERED SENSITIVITY MAY LEAD TO THE DEVELOPMENT OF ACIDOSIS, CARDIAC ARREST, AND POSSIBLY DEATH.
Duranest (Etidocaine HCl) Injections are sterile aqueous solutions that contain a local anesthetic agent and are administered parenterally by injection. See INDICATIONS AND USAGE for specific uses. The specific quantitative composition of each available solution is shown in Table 1.
Duranest Injections contain Etidocaine HCl, which is chemically designated as butanamide, N-(2,6-dimethylphenyl)-2-(ethylpropylamine)-, monohydrochloride and Epinephrine which is (-)-3, 4-Dihydroxy-a-[(methylamino) methyl] benzyl alcohol. Chemical structure is as follows:
The PKa of etidocaine (7.74) is similar to that of lidocaine (7.86). However, etidocaine possesses a greater degree of lipid solubility and protein binding capacity than does lidocaine. Duranest (etidocaine hcl) Injections are sterile and, except for the 1.5% concentration, are available with or without epinephrine 1:200,000. Single dose containers of Duranest (etidocaine hcl) Injection without epinephrine may be reautoclaved it necessary.
See Table 1 for composition of available injections.
Table1. Composition of Available Injections
Duranest (etidocaine HCl) Concentration % (mg/mL)
Epinephrine Dilution (as the bitartrate) (mg/mL)
Sodium chloride (mg/mL)
Single Dose Vials/Dental Cartridge Sodium metabisulfite (mg/mL)
Citric acid (mg/mL)
1 :200,000 (0.005 mg/mL)
1 :200,000 (0.005 mg/mL)
NOTE: pH of all solutions adjusted with sodium hydroxide and/ or hydrochloric acid. Duranest (etidocaine hcl) dental cartridges are only available as 1.5% solution with epinephrine 1:200,000. Filled under nitrogen.
Duranest (Etidocaine HCl) Injections are indicated for infiltration anesthesia, peripheral nerve blocks (e.g., brachial plexus, intercostal, retrobulbar, ulnar, inferior alveolar), and central neural block (i.e., lumbar or caudal epidural blocks).
DOSAGE AND ADMINISTRATION
As with all local anesthetic agents, the dose of Duranest (Etidocaine HCl) Injection to be employed will depend upon the area to be anesthetized, the vascularity of the tissues, the number of neuronal segments to be blocked, the type of regional anesthetic technique, and the physical condition and tolerance of the individual patient.
The maximum dose to be employed as a single injection should be determined on the basis of the status of the patient and the type of regional anesthetic technique to be performed. Although single injections of 450 mg have been employed for regional anesthesia without adverse effects, at present it is strongly recommended that the maximal dose as a single injection should not exceed 400 mg (approximately 8.0 mg/kg or 3.6 mg/lb based on a 50 kg person) with epinephrine 1:200,000 and 300 mg (approximately 6 mg/kg or 2.7 mg/lb based on a 50 kg person) without epinephrine. Because etidocaine has been shown to disappear quite rapidly from blood, toxicity is influenced by rapidity of administration, and therefore, injection in vascular areas is highly recommended. Incremental doses of Duranest (etidocaine hcl) Injection may be repeated at 2 - 3 hour intervals.
Caudal and Lumbar Epidural Block
As a precaution against the adverse experiences sometimes observed following unintentional penetration of the subarachnoid space, a test dose of 2 - 5 mL should be administered at least 5 minutes prior to injecting the total volume required for a lumbar or caudal epidural block. The test dose should be repeated if the patient is moved in a manner that may have displaced the catheter. Epinephrine, if contained in the test dose (10 - 15 mg have been suggested), may serve as a warning of unintentional intravascular injection. If injected into a blood vessel, this amount of epinephrine is likely to produce a transient "epinephrine response" within 45 seconds, consisting of an increase in heart rate and systolic blood pressure, circumoral pallor, palpitations and nervousness in the unsedated patient. The sedated patient may exhibit only a pulse rate increase of 20 or more beats per minute for 15 or more seconds. Patients on beta-blockers may not manifest changes in heart rate, but blood pressure monitoring can detect an evanescent rise in systolic blood pressure. Adequate time should be allowed for onset of anesthesia after administration of each test dose. The rapid injection of a large volume of Duranest (etidocaine hcl) Injection through the catheter should be avoided, and when feasible, fractional doses should be administered.
In the event of the known injection of a large volume of local anesthetic solution into the subarachnoid space, after suitable resuscitation, and if the catheter is in place, consider attempting the recovery of drug by draining a moderate amount of cerebrospinal fluid (such as 10 mL) through the epidural catheter.
Use in Dentistry
When used for local anesthesia in dental procedures the dosage of Duranest (Etidocaine HCl) Injection depends on the physical status of the patient, the area of the oral cavity to be anesthetized, the vascularity of the oral tissues, and the technique of anesthesia. The least volume of solution that results in effective local anesthesia should be administered. For specific techniques and procedures of local anesthesia in the oral cavity, refer to standard textbooks.
Dosage requirements should be determined on an individual basis. In maxillary infiftration and/or inferior alveolar nerve block, initial dosages of 1.0 - 5.0 mL (½ - 2 ½ cartridges) of Duranest (etidocaine hcl) Injection 1.5% with epinephrine 1:200,000 are usually effective.
Aspiration is recommended since it reduces the possibility of intravascular injection, thereby keeping the incidence of side effects and anesthetic failures to a minimum.
The following dosage recommendations are intended as guides for the use of Duranest (etidocaine hcl) Injection in the average adult patient. As indicated previously, the dosage should be reduced for elderly or debilitated patients or patients with severe renal disease.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit. The Injection is not to be used if its color is pinkish or darker than slightly yellow or if it contains a precipitate.
Table 2. Dosage Recommendations
|Duranest (etidocaine hcl) HCl with |
|Conc. (%)||Vol. (mL)||Total Dose (mg)|
|Peripheral Nerve Block |
Central Neural Block
|Intra-abdominal or Pelvic Surgery |
Lower Limb Surgery
|Maxillary Infiltration |
and/or Inferior Alveolar Nerve Block
Dosage Form and Volume
|Duranest Injection Concentration|| Epinephrine Dilution. |
(as the bitartrate)
|Single DoseVials*||30 mL||1.0 %||None||4.0-5.0||0186-0820-01|
|1.0 %||1: 200,000||3.0-4.5||0186-0825-01|
|20 mL||1.5 %||1: 200,000||3.0-4.5||0186-0836-03|
|DentalCartridge**||1.8 mL||1.5 %||1: 200,000||3.0-4.5||0186-0840-14|
Solutions containing epinephrine should be protected from light.
* Store at controlled room temperature 15°- 30° C (59°- 86° F).
** Store at room temperature, approx. 25° C (77° F).
Adverse experiences following the administration of etidocaine are similar in nature to those observed with other amide local anesthetic agents. These adverse experiences are, in general, dose-related and may result from high plasma levels caused by excessive dosage, rapid absorption or unintended intravascular injection, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the party of the patient. Serious adverse experiences are generally systemic in nature. The following types are those most commonly reported:
Central Nervous System
CNS manifestations are excitatory and/or depressant and may be characterized by light-headedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensations of heat, cold or numbness, twitching, tremors, convulsions, unconsciousness, respiratory depression and arrest. The excitatory manifestations may be very brief or may not occur at all, in which case the first manifestation of toxicity may be drowsiness merging into unconsciousness and respiratory arrest.
Drowsiness following the administration of etidocaine is usually an early sign of a high blood level of the drug and may occur as a consequence of rapid absorption.
Cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest.
Allergic reactions are characterized by cutaneous lesions, urticaria, edema or anaphylactoid reactions. Allergic reactions may occur as a result of sensitivity either to local anesthetic agents or to the methylparaben used as a preservative in multiple dose vials. The detection of sensitivity by skin testing is of doubtful value.
The incidences of adverse reactions associated with the use of local anesthetics may be related to the total dose of local anesthetic administered and are also dependent upon the particular drug used, the route of administration and the physical status of the patient.
In the practice of caudal or lumbar epidural block, occasional unintentional penetration of the subarachnoid space by the catheter may occur. Subsequent adverse effects may depend partially on the amount of drug administered subdurally. These may include spinal block of varying magnitude (including total spinal block), hypotension secondary to spinal block, loss of bladder and bowel control, and loss of perineal sensation and sexual function. Persistent motor, sensory and/or autonomic (sphincter control) deficit of some lower spinal segments with recovery (several months) or incomplete recovery have been reported in rare instances when caudal or lumbar epidural block has been attempted. Backache and headache have also been noted following use of these anesthetic procedures.
There have been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbar administration.
There have been rare reports of TRISMUS in patients who have received Duranest (etidocaine HCl) for dental anesthesia. Onset of symptoms occurs within hours or days upon resolution of blockade. No correlation has been demonstrated with dosage, administration technique or dental procedure. In most patients, symptoms resolved within days to weeks, although some reports have suggested that symptoms were present for many months. Symptomatic treatment with analgesics, moist heat and physiotherapy was helpful in some cases.
The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors, tricyclic antidepressants or phenothiazines may produce severe, prolonged hypotension or hypertension. Concurrent use of these agents should generally be avoided. In situations when concurrent therapy is necessary, careful patient monitoring is essential.
Concurrent administration of vasopressor drugs (for the treatment of hypotension related to epidural blocks) and ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents.
To avoid intravascular injection, aspiration should be performed before the local anesthetic solution is injected. The needle must be repositioned until no return of blood can be elicited by aspiration. Note, however, that the absence of blood in the syringe does not guarantee that intravascular injection has been avoided.
Local anesthetic solutions containing antimicrobial preservatives (e.g., methylparaben) should not be used for epidural anesthesia because the safety of these agents has not been established with regard to intrathecal injection, either intentional or accidental.
Vasopressor agents administered for the treatment of hypotension related to caudal or other epidural blocks should not be used in the presence of ergot-type oxytocic drugs, since severe persistent hypertension and even rupture of cerebral blood vessels may occur.
Duranest (etidocaine hcl) with epinephrine solutions contain sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in non asthmatic people.
The safety and effectiveness of etidocaine depend on proper dosage, correct technique, adequate precautions, and readiness for emergencies. Standard textbooks should be consulted for specific techniques and precautions for various regional anesthetic procedures. Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use. (See WARNINGS and ADVERSE REACTIONS.) The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects. Syringe aspirations should also be performed before and during each supplemental injection when using indwelling catheter techniques. During the administration of epidural anesthesia, it is recommended that a test dose be administered initially and that the patient be monitored for central nervous system toxicity and cardiovascular toxicity, as well as for signs of unintended intrathecal administration, before proceeding. When clinical conditions permit, consideration should be given to employing local anesthetic solutions that contain epinephrine for the test dose because circulatory changes compatible with epinephrine may also serve as a warning sign of unintended intravascular injection. An intravascular injection is still possible even if aspirations for blood are negative. Repeated doses of etidocaine may cause significant increases in blood levels with each repeated dose because of slow accumulation of the drug or its metabolites. Tolerance to elevated blood levels varies with the status of the patient. Debilitated, elderly patients, acutely ill patients, and children should be given reduced doses commensurate with their age and physical condition.
Etidocaine should also be used with caution in patients with severe shock or heart block.
Lumbar and caudal epidural anesthesia should be used with extreme caution in persons with the following conditions: existing neurological disease, spinal deformities, septicemia, and severe hypertension.
Local anesthetic solutions containing a vasoconstrictor should be used cautiously and in carefully circumscribed quantities in areas of the body supplied by end arteries or having otherwise compromised blood supply. Patients with peripheral vascular disease and those with hypertensive vascular disease may exhibit exaggerated vasoconstrictor response. Ischemic injury or necrosis may result. Preparations containing a vasoconstrictor should be used with caution in patients during or following the administration of potent general anesthetic agents, since cardiac arrhythmias may occur under such conditions.
Careful and constant monitoring of cardiovascular and respiratory (adequacy of ventilation) vital signs and the patient's state of consciousness should be accomplished after each local anesthetic injection. It should be kept in mind at such times that restlessness, anxiety, tinnitus, dizziness, blurred vision, tremors, depression or drowsiness may be early warning signs of central nervous system toxicity.
Since amide-type local anesthetics are metabolized by the liver, Duranest (etidocaine hcl) Injections should be used with caution in patients with hepatic disease.
Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at greater risk of developing toxic plasma concentrations. Duranest (etidocaine hcl) Injection should also be used with caution in patients with impaired cardiovascular function since they may be less able to compensate for functional changes associated with the prolongation of A-V conduction produced by these drugs.
Many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. Since it is not known whether amide-type local anesthetics may trigger this reaction and since the need for supplemental general anesthesia cannot be predicted in advance, it is suggested that a standard protocol for the management of malignant hyperthermia should be available. Early unexplained signs of tachycardia, tachypnea, labile blood pressure and metabolic acidosis may precede temperature elevation. Successful outcome is dependent on early diagnosis, prompt discontinuance of the suspect triggering agent(s) and institution of treatment, including oxygen therapy, indicated supportive measures and dantrolene (consult dantrolene sodium intravenous package insert before using).
Etidocaine should be used with caution in persons with known drug sensitivities. Patients allergic to para-aminobenzoic acid derivatives (procaine, tetracaine, benzocaine, etc.) have not shown cross sensitivity to etidocaine.
Use in the Head and Neck Area
Small doses of local anesthetics injected into the head and neck area, including retrobulbar, dental and stellate ganglion blocks, may produce adverse reactions similar to systemic toxicity seen with unintentional intravascular injections of larger doses. The injection procedures require the utmost care. Confusion, convulsions, respiratory depression and/or respiratory arrest, and cardiovascular stimulation or depression have been reported. These reactions may be due to intra-arterial injection of the local anesthetic with retrograde wflow to the cerebral circulation. They may also be due to puncture of the dural sheath of the optic nerve during retrobulbar block with diffusion of any local anesthetic along the subdural space to the midbrain. Patients receiving these blocks should have their circulation and respiration monitored and be constantly observed. Resuscitative equipment and personnel for treating adverse reactions should be immediately available. Dosage recommendations should not be exceeded. (See DOSAGE AND ADMINISTRATION.)
Use in Ophthalmic Surgery
When local anesthetic injections are employed for retrobulbar block, lack of corneal sensation should not be relied upon to determine whether or not the patient is ready for surgery. This is because complete lack of corneal sensation usually precedes clinically acceptable external ocular muscle akinesia.
Use in Dentistry
Because of the long duration of anesthesia, when Duranest (etidocaine hcl) 1.5 % with epinephrine is used for dental injections, patients should be cautioned about the possibility of inadvertent trauma to tongue, lips and buccal mucosa and advised not to chew solid foods or test the anesthetized area by biting or probing.
Drug Laboratory Test Interactions
The intramuscular injection of etidocaine may result in an increase in creatine phosphokinase levels. Thus, the use of this enzyme determination, without isoenzyme separation, as a diagnostic test for the presence of acute myocardial infarction may be compromised by the intramuscular injection of etidocaine.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Studies of etidocaine in animals to evaluate the carcinogenic and mutagenic potential have not been conducted. Studies in rats at 1.7 times the maximum recommended human dose have revealed no impairment of fertility.
Use in Pregnancy
Teratogenic Effects. Pregnancy Category B. Reproduction studies have been performed in rats and rabbits at doses up to 1.7 times the human dose and have revealed no evidence of harm to the fetus caused by etidocaine. There are, however, no adequate and well-controlled studies in pregnant women. Animal reproduction studies are not always predictive of human response. General consideration should be given to this fact before administering etidocaine to women of childbearing potential, especially during early pregnancy when maximum organogenesis takes place.
Labor and Delivery
Local anesthetics rapidly cross the placenta and when used for epidural, paracervical, pudendal or caudal block anesthesia, can cause varying degrees of maternal, fetal and neonatal toxicity. (See CLINICAL PHARMACOLOGY - Pharmacokinetics.) The incidence and degree of toxicity depend upon the procedure performed, the type and amount of drug used, and the technique of drug administration. Adverse reactions in the parturient, fetus and neonate involve alterations of the central nervous system, peripheral vascular tone and cardiac function.
Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. Elevating the patient's legs and positioning her on her left side will help prevent decreases in blood pressure. The fetal heart rate also should be monitored continuously and electronic fetal monitoring is highly advisable.
Epidural anesthesia may alter the forces of parturffion through changes in uterine contractility or maternal expulsive efforts. Because Duranest (etidocaine hcl) Injection may produce profound motor block, it is not recommended for epidural anesthesia in normal delivery. Duranest (etidocaine hcl) Injection is, however, recommended for epidural anesthesia when caesarean section is to be performed.
The use of some local anesthetic drug products during labor and delivery may be followed by diminished muscle strength and tone for the first day or two of life. The long-term significance of these observations is unknown.
Fetal bradycardia may occur in 20 to 30 percent of patients receiving paracervical nerve block anesthesia with the amide-type local anesthetics and may be associated with fetal acidosis. Fetal heart rate should always be monitored during paracervical anesthesia. The physician should weigh the possible advantages against risks when considering paracervical block in prematurity, toxemia of pregnancy, and fetal distress. Careful adherence to recommended dosage is of the utmost importance in obstetrical paracervical block. Failure to achieve adequate analgesia with recommended doses should arouse suspicion of intravascular or fetal intracranial injection. Cases compatible with unintended fetal intracranial injection of local anesthetic solution have been reported following intended paracervical or pudendal block or both. Babies so affected present with unexplained neonatal depression at birth, which correlates with high local anesthetic serum levels, and often manifest seizures within six hours. Prompt use of supportive measures combined with forced urinary excretion of the local anesthetic has been used successfully to manage this complication. Case reports of maternal convulsions and cardiovascular collapse following use of some local anesthetics for paracervical block in early pregnancy (as anesthesia for elective abortion) suggest that systemic absorption under these circumstances may be rapid. There are inadequate data in support of safe and effective use of etidocaine for obstetrical or non-obstetrical paracervical block, therefore, such use is not recommended.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when etidocaine is administered to a nursing woman.
No information is currently available on appropriate pediatric doses.
Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic solution (see ADVERSE REACTIONS, WARNINGS, and PRECAUTIONS).
Management of Local Anesthetic Emergencies
The first consideration is prevention, best accomplished by careful and constant monitoring of cardiovascular and respiratory vital signs and the patient's state of consciousness after each local anesthetic injection. At the first sign of change, oxygen should be administered. The first step in the management of convulsions, as well as under ventilation or apnea due to unintentional subarachnoid injection of drug solution, consists of immediate attention to the maintenance of a patent airway and assisted or controlled ventilation with oxygen and a delivery system capable of permitting immediate positive airway pressure by mask. Immediately after the institution of these ventilatory measures, the adequacy of the circulation should be evaluated, keeping in mind that drugs used to treat convulsions sometimes depress the circulation when administered intravenously. Should convulsions persist despite adequate respiratory support, and if the status of the circulation permits, small increments of an ultra-short acting barbiturate (such as thiopental or thiamylal) or a benzodiazepine (such as diazepam) may be administered intravenously. The clinician should be familiar, prior to use of local anesthetics, with these anticonvulsant drugs. Supportive treatment of circulatory depression may require administration of intravenous fluids and, when appropriate, a Vasopressor as directed by the clinical situation (e.g., ephedrine).
If not treated immediately, both convulsions and cardiovascular depression can result in hypoxia, acidosis, bradycardia, arrhythmias and cardiac arrest. Under ventilation or apnea due to unintentional subarachnoid injection of local anesthetic solution may produce these same signs and also lead to cardiac arrest if ventilatory support is not instituted. If cardiac arrest should occur, standard cardiopulmonary resuscitative measures should be instituted.
Endotracheal intubation, employing drugs and techniques familiar to the clinician, may be indicated, after initial administration of oxygen by mask, if difficulty is encountered in the maintenance of a patent airway or if prolonged ventilatory support (assisted or controlled) is indicated.
Dialysis is of negligible value in the treatment of acute overdosage with etidocaine.
The intravenous LD 50 of etidocaine HCl in female mice is 7.6 (6.6-8.5) mg/kg and the subcutaneous LD50 is 112 (96-166) mg/kg.
Etidocaine is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type.
Mechanism of Action
Etidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action.
Onset and Duration of Action
In vivo animal studies have shown that etidocaine has a rapid onset (3-5 minutes) and a prolonged duration of action (5-10 hours). Based on comparative clinical studies of lidocaine and etidocaine, the anesthetic properties of etidocaine in man may be characterized as follows: Initial onset of sensory analgesia and motor blockade is rapid (usually 3-5 minutes) and similar to that produced by lidocaine. Duration of sensory analgesia is 1.5 to 2 times longer than that of lidocaine by the peridural route. The difference in analgesic duration between etidocaine and lidocaine may be even greater following peripheral nerve blockade than following central neural block. Duration of analgesia in excess of 9 hours is not infrequent when etidocaine is used for peripheral nerve blocks such as brachial plexus blockade. Etidocaine produces a profound degree of motor blockade and abdominal muscle relaxation when used for peridural analgesia.
Excessive blood levels may cause changes in cardiac output, total peripheral resistance, and mean arterial pressure. With central neural blockade these changes may be attributable to block of autonomic fibers, a direct depressant effect of the local anesthetic agent on various components of the cardiovascular system, and/or the beta-adrenergic receptor stimulating action of epinephrine when present. The net effect is normally a modest hypotension when the recommended dosages are not exceeded.
Pharmacokinetics and Metabolism
Information derived from diverse formulations, concentrations and usages reveals that etidocaine is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon such factors as the site of administration and the presence or absence of a vasoconstrictor agent. Except for intravenous administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration.
The plasma binding of etidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At 0.5-1.0 µg/mL, 95% is bound to plasma protein.
Etidocaine crosses the blood-brain and placental barriers, presumably by passive diffusion.
Etidocaine is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidney. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. To date, approximately 20 metabolites of etidocaine have been found in the urine. The percent of dose excreted as unchanged drug is less than 10%.
The mean elimination half-life of etidocaine following a bolus intravenous injection is about 2.5 hours. Because of the rapid rate at which etidocaine is metabolized, any condition that affects liver function may alter etidocaine kinetics. Renal dysfunction may not affect etidocaine kinetics but may increase the accumulation of metabolites.
Factors such as acidosis and the concomitant use of CNS stimulants and depressants affect the CNS levels of etidocaine required to produce overt systemic effects. In the rhesus monkey, arterial blood levels of 4.5 mg/mL have been shown to be threshold for convulsive activity.
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