Lidocaine Information
Lidocaine (Lidocaine)
Lidocaine (Lidocaine) Description
Lidocaine (Lidocaine) Hydrochloride Injection, USP is a local anesthetic which is a sterile, nonpyrogenic solution intended for parenteral injection. See for specific uses.
Lidocaine (Lidocaine) hydrochloride is chemically designated as 2-(Diethylamino)-2’, 6’-acetoxylidide monohydrochloride and has the following structural formula:
Each mL contains: Lidocaine (Lidocaine) hydrochloride 10 or 20 mg; methylparaben 0.1%; sodium chloride (7 mg and 6 mg of sodium chloride for 1% and 2% respectively) to render it isotonic; Water for Injection q.s. Hydrochloric acid and/or sodium hydroxide may have been added for pH adjustment (5.0 to 7.0).
Lidocaine (Lidocaine) Clinical Pharmacology
Information derived from diverse formulations, concentrations and usages reveals that Lidocaine (Lidocaine) HCl is completely absorbed following parenteral administration, its rate of absorption depending, for example, upon various factors such as the site of administration and the presence or absence of a vasoconstrictor agent. Except for intravascular administration, the highest blood levels are obtained following intercostal nerve block and the lowest after subcutaneous administration.
The plasma binding of Lidocaine (Lidocaine) HCl is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 mcg of free base/mL, 60 to 80% of Lidocaine (Lidocaine) HCl is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.
Lidocaine (Lidocaine) HCl crosses the blood-brain and placental barriers, presumably by passive diffusion.
Lidocaine (Lidocaine) HCl is metabolized rapidly by the liver, and metabolites and unchanged drug are excreted by the kidneys. Biotransformation includes oxidative N-dealkylation, ring hydroxylation, cleavage of the amide linkage, and conjugation. N-dealkylation, a major pathway of biotransformation, yields the metabolites monoethylglycinexylidide and glycinexylidide. The pharmacological/toxicological actions of these metabolites are similar to, but less potent than, those of Lidocaine (Lidocaine) HCl. Approximately 90% of Lidocaine (Lidocaine) HCl administered is excreted in the form of various metabolites, and less than 10% is excreted unchanged. The primary metabolite in urine is a conjugate of 4-hydroxy-2,6-dimethylaniline.
The elimination half-life of Lidocaine (Lidocaine) HCl following an intravenous bolus injection is typically 1.5 to 2 hours. Because of the rapid rate at which Lidocaine (Lidocaine) HCl is metabolized, any condition that affects liver function may alter Lidocaine (Lidocaine) kinetics. The half-life may be prolonged two-fold or more in patients with liver dysfunction. Renal dysfunction does not affect Lidocaine (Lidocaine) HCl kinetics but may increase the accumulation of metabolites.
Factors such as acidosis and the use of CNS stimulants and depressants affect the CNS levels of Lidocaine (Lidocaine) HCl required to produce overt systemic effects. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6 mcg free base/mL. In the rhesus monkey arterial blood levels of 18 to 21 mcg/mL have been shown to be threshold for convulsive activity.
Lidocaine (Lidocaine) Indications And Usage
Lidocaine (Lidocaine) Hydrochloride Injection, USP is indicated for the production of local anesthesia, by infiltration techniques, such as percutaneous injection, and by peripheral nerve block techniques, such as brachial plexus and inter-costal, when the accepted procedures for these techniques as described in standard textbooks are observed.
Lidocaine (Lidocaine) Contraindications
Lidocaine (Lidocaine) HCl is contraindicated in patients with a known history of hypersensitivity to local anesthetics of the amide type.
Lidocaine (Lidocaine) Warnings
Lidocaine (Lidocaine) HYDROCHLORIDE INJECTION 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 AVAILABILITY OF OXYGEN, OTHER RESUSCITATIVE DRUGS, CARDIOPULMONARY EQUIPMENT AND THE PERSONNEL NEEDED FOR PROPER MANAGEMENT OF TOXIC REACTIONS AND RELATED EMERGENCIES (see also and ). 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.
Intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures is an unapproved use, and there have been post-marketing reports of chondrolysis in patients receiving such infusions. The majority of reported cases of chondrolysis have involved the shoulder joint; cases of gleno-humeral chondrolysis have been described in pediatric and adult patients following intra-articular infusions of local anesthetics with and without epinephrine for periods of 48 to 72 hours. There is insufficient information to determine whether shorter infusion periods are not associated with these findings. The time of onset of symptoms, such as joint pain, stiffness and loss of motion can be variable, but may begin as early as the 2nd month after surgery. Currently, there is no effective treatment for chondrolysis; patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures and some required arthroplasty or shoulder replacement.
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 or spinal anesthesia because the safety of these agents has not been established with regard to intrathecal injection, either intentional or accidental.
Lidocaine (Lidocaine) Precautions
The safety and effectiveness of Lidocaine (Lidocaine) HCl 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 and ). 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. An intravascular injection is still possible even if aspirations for blood are negative. Repeated doses of Lidocaine (Lidocaine) HCl 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. Lidocaine (Lidocaine) HCl should also be used with caution in patients with severe shock or heart block.
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, Lidocaine (Lidocaine) HCl should be used with caution in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetic normally, are at greater risk of developing toxic plasma concentrations. Lidocaine (Lidocaine) HCl 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).
Lidocaine (Lidocaine) HCl 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 Lidocaine (Lidocaine) HCl.
Reproduction studies have been performed in rats at doses up to 6.6 times the human dose and have revealed no evidence of harm to the fetus caused by Lidocaine (Lidocaine) HCl. 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 Lidocaine (Lidocaine) HCl to women of childbearing potential, especially during early pregnancy when maximum organogenesis takes place.
Local anesthetics rapidly cross the placenta and when used for epidural, paracervical, pudenal, or caudal block anesthesia, can cause varying degrees of maternal, fetal and neonatal toxicity (see ). The potential for toxicity depends 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.
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.
Paracervical or pudendal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. In one study paracervical block anesthesia was associated with a decrease in the mean duration of first stage labor and facilitation of cervical dilation. The use of obstetrical anesthesia may increase the need for forceps assistance.
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% 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 a 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. The recommended maximum dose of each drug should not be exceeded. Injection should be made slowly and with frequent aspiration. Allow a 5-minute interval between sides.
Lidocaine (Lidocaine) Adverse Reactions
Adverse experiences following the administration of Lidocaine (Lidocaine) HCl 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 inadvertent intravascular injection, or may result from a hypersensitivity, idiosyncrasy or diminished tolerance on the part of the patient. Serious adverse experiences are generally systemic in nature.
The following types are those most commonly reported:
CNS manifestations are excitatory and/or depressant and may be characterized by lightheadedness, 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 Lidocaine (Lidocaine) HCl is usually an early sign of a high blood level of the drug and may occur as a consequence of rapid absorption.
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 a prospective review of 10,440 patients who received Lidocaine (Lidocaine) HCl for spinal anesthesia, the incidences of adverse reactions were reported to be about 3% each for positional headaches, hypotension and backache; 2% for shivering; and less than 1% each for peripheral nerve symptoms, nausea, respiratory inadequacy and double vision. Many of these observations may be related to local anesthetic techniques, with or without a contribution from the local anesthetic.
There have been reported cases of permanent injury to extraocular muscles requiring surgical repair following retrobulbar administration.
Lidocaine (Lidocaine) Overdosage
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 , and ).
Lidocaine (Lidocaine) Dosage And Administration
There have been adverse event reports of chondrolysis in patients receiving intra-articular infusions of local anesthetics following arthroscopic and other surgical procedures. Lidocaine (Lidocaine) is not approved for this use (see and ).
These recommended doses serve only as a guide to the amount of anesthetic required for most routine procedures. The actual volumes and concentrations to be used depend on a number of factors such as type and extent of surgical procedure, depth of anesthesia and degree of muscular relaxation required, duration of anesthesia required and the physical condition of the patient. In all cases the lowest concentration and smallest dose that will produce the desired result should be given. Dosages should be reduced for children and for elderly and debilitated patients and patients with cardiac and/or liver disease.
The onset of anesthesia, the duration of anesthesia and the degree of muscular relaxation are proportional to the volume and concentration (i.e. total dose) of local anesthetic used. Thus, an increase in volume and concentration of Lidocaine (Lidocaine) hydrochloride injection will decrease the onset of anesthesia, prolong the duration of anesthesia, provide a greater degree of muscular relaxation and increase the segmental spread of anesthesia. However, increasing the volume and concentration of Lidocaine (Lidocaine) hydrochloride injection may result in a more profound fall in blood pressure when used in epidural anesthesia. Although the incidence of side effects with Lidocaine (Lidocaine) is quite low, caution should be exercised when employing large volumes and concentrations, since the incidence of side effects is directly proportional to the total dose of local anesthetic agent injected.
Lidocaine (Lidocaine) Maximum Recommended Dosages
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For normal healthy adults, the individual maximum recommended dose of Lidocaine (Lidocaine) hydrochloride without epinephrine should not exceed 4.5 mg/kg (2 mg/lb) of body weight and in general it is recommended that the maximum total dose does not exceed 300 mg.
The maximum recommended dose per 90 minute period of Lidocaine (Lidocaine) hydrochloride for paracervical block in obstetrical and non-obstetrical patients is 200 mg total. One half of the total dose is usually administered to each side. Inject slowly, five minutes between sides (see also discussion of paracervical block in ).
THE ABOVE SUGGESTED CONCENTRATIONS AND VOLUMES SERVE ONLY AS A GUIDE. OTHER VOLUMES AND CONCENTRATIONS MAY BE USED PROVIDED THE TOTAL MAXIMUM RECOMMENDED DOSE IS NOT EXCEEDED.
It is difficult to recommend a maximum dose of any drug for children, since this varies as a function of age and weight. For children over three years of age who have a normal lean body mass and normal body development, the maximum dose is determined by the child’s age and weight. For example, in a child of five years weighing 50 lbs., the dose of Lidocaine (Lidocaine) hydrochloride should not exceed 75 to 100 mg (1.5 to 2 mg/lb).
In order to guard against systemic toxicity, the lowest effective concentration and lowest effective dose should be used at all times. In some cases it will be necessary to dilute available concentrations with 0.9% Sodium Chloride Injection in order to obtain the required final concentration.
Disinfecting agents containing heavy metals, which cause release of respective ions (mercury, zinc, copper, etc.) should not be used for skin or mucous membrane disinfection as they have been related to incidents of swelling and edema. When chemical disinfection of multi-dose vials is desired, either isopropyl alcohol (91%) or ethyl alcohol (70%) is recommended. Many commercially available brands of rubbing alcohol, as well as solutions of ethyl alcohol not of USP grade, contain denaturants which are injurious to rubber and therefore are not to be used.
Parenteral drug products should be visually inspected 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.
Lidocaine (Lidocaine) How Supplied
Lidocaine (Lidocaine) Hydrochloride Injection is preserved with 0.1% methylparaben and is available in the following concentrations:
All products available in packages of 25.
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
Protect from light.
Lidocaine (Lidocaine)
Lidocaine (Lidocaine)
