Xylocaine Spinal (Lidocaine HCl – Glucose)

XYLOCAINE® SPINAL 5%

Astra

Lidocaine HCl – Glucose

Local Anesthetic for Spinal Anesthesia

Action And Clinical Pharmacology: Mechanism of Action: Lidocaine stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses, thereby effecting local anesthetic action. Local anesthetics of the amide type are thought to act within sodium channels of the nerve membrane.

Onset of Action: The onset of action is rapid. The duration of anesthesia provided with 1 to 2 mL Xylocaine Spinal 5% (50 to 100 mg lidocaine) is 1 to 1.5 hours.

Xylocaine Spinal 5% is hyperbaric and its initial spread in the subarachnoid space is considerably affected by gravity.

Hemodynamics: Lidocaine, like other local anesthetics, may also have effects on excitable membranes in the brain and myocardium. If excessive amounts of drug reach systemic circulation rapidly, symptoms and signs of toxicity will appear, emanating from the central nervous and cardiovascular systems.

CNS toxicity (see Overdose: Symptoms and Treatment) usually precedes the cardiovascular effects since it occurs at lower plasma concentrations. Direct effects of local anesthetics on the heart include slow conduction, negative inotropism and eventually cardiac arrest.

Indirect cardiovascular effects (hypotension, bradycardia) may occur after epidural or spinal administration depending on the extent of the concomitant sympathetic block.

Pharmacokinetics: Lidocaine is completely absorbed following parenteral administration. The rate of absorption depends on the dose, route of administration, and the vascularity of the injection site. The highest peak plasma levels are obtained following intercostal nerve block (approximately 1.5 g/mL/100 mg injected) while abdominal s.c. injections give the lowest (approximately 0.5 g/mL/100 mg injected). Epidural and major nerve blocks are intermediate.

Absorption of lidocaine from the subarachnoid space is relatively slow and this, together with the small dose required for spinal anesthesia, limits the maximum plasma concentration, which is approximately 0.5 g/mL for every 100 mg injected.

Lidocaine has a total plasma clearance of 0.95 L/min, a volume of distribution at steady-state of 91 L, an elimination half-life of 1.6 h and an estimated hepatic extraction ratio of 0.65. The clearance of lidocaine is almost entirely due to liver metabolism, and depends both on liver blood flow and the activity of metabolizing enzymes.

The plasma binding of lidocaine is dependent on drug concentration, and the fraction bound decreases with increasing concentration. At concentrations of 1 to 4 g of free base/mL, 60 to 80% of lidocaine is protein bound. Binding is also dependent on the plasma concentration of the alpha-1-acid glycoprotein.

Lidocaine readily crosses the placenta, and equilibrium in regard to free, unbound drug will be reached. Because the degree of plasma protein binding in the fetus is less than in the mother, the total plasma concentration will be greater in the mother, but the free concentrations will be the same.

Lidocaine 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. Only 2% of lidocaine is excreted unchanged. Most of it is metabolized first to monoethylglycinexylidide (MEGX) and then to glycinexylidide (GX) and 2,6-xylidine. Up to 70% appears in the urine as 4-hydroxy-2,6-xylidine.

The elimination half-life of lidocaine following i.v. bolus injection is typically 1.5 to 2 hours. The elimination half-life in neonates (3.2 hours) is approximately twice that of adults. The half-life may be prolonged two-fold or more in patients with liver dysfunction. Renal dysfunction does not affect lidocaine kinetics but may increase the accumulation of metabolites.

Acidosis increases the systemic toxicity of lidocaine while the use of CNS depressants may increase the levels of lidocaine required to produce overt CNS effects. Objective adverse manifestations become increasingly apparent with increasing venous plasma levels above 6.0 g free base/mL.

Indications And Clinical Uses: For the production of spinal (subarachnoid) anesthesia in surgical and obstetrical procedures when a regional block of 1 to 1.5 hours’ duration is required.

Contra-Indications: The following conditions are contraindicated in spinal anesthesia: known sensitivity to local anesthetics of the amide type; acute active disease of the CNS, such as meningitis, tumors, poliomyelitis, and cranial hemorrhage. The presence of active tuberculosis or metastatic lesions in the vertebral column is also contraindicated; cardiogenic or hypovolemic shock; pyrogenic infection of the skin at or adjacent to the site of puncture; septicemia; pernicious anemia with subacute combined degeneration of the spinal cord; coagulation disorders or ongoing anticoagulant treatment.

Manufacturers’ Warnings In Clinical States: Local anesthetics should only be employed 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 Effects 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.

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.

Some cases of neurologic complications (e.g., cauda equina) have been reported after the use of lidocaine 5% with 7.5% glucose when given undiluted, especially if the injection is very slow, e.g., with very fine needles or catheters (see Dosage). Until the cause of this complication has been elucidated, lidocaine 5% with 7.5% glucose is not recommended for continuous spinal anesthesia.

Spinal anesthesia can be unpredictable and very high blockades are sometimes encountered with paralysis of the intercostal muscles, and even the diaphragm, especially in pregnancy. On rare occasions it will be necessary to assist or control ventilation.

Precautions: The safety and effectiveness of Xylocaine Spinal 5% depend on proper dosage, correct technique, adequate precautions and readiness for emergencies. Standard textbooks should be consulted for specific techniques and precautions for spinal anesthetic procedures.

Resuscitative equipment, oxygen, and other resuscitative drugs should be available for immediate use (see Warnings and Overdose: Symptoms and Treatment). The lowest dosage that results in effective anesthesia should be used to avoid high plasma levels and serious adverse effects.

I.V. access, e.g., an i.v. infusion, should be in place before starting the spinal anesthesia.

Repeated doses of Xylocaine Spinal 5% are not recommended.

Xylocaine Spinal 5% should be used with caution in patients with poorly controlled epilepsy, neurological diseases such as multiple sclerosis and old hemiplegia due to stroke, impaired cardiac conduction, and other severe cardiac diseases.

Since amide-type local anesthetics are metabolized by the liver, lidocaine 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 a greater risk of developing toxic plasma concentrations.

Lidocaine 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 AV conduction produced by these drugs.

The following conditions may preclude the use of spinal anesthesia, depending upon the physician’s ability to deal with the complications which may occur (see Contraindications): Chronic backache and preoperative headache; hypotension and hypertension; arthritis or spinal deformity; technical problems (persistent paresthesias, persistent bloody tap); psychotic or uncooperative patients.

Regardless of the local anesthetic used, hypotension and bradycardia may occur. This risk can be reduced either by preloading the circulation with crystalloidal or colloidal solutions or by injecting a vasopressor, such as ephedrine 20 to 40 mg i.m. or treating promptly with, e.g., ephedrine 5 to 10 mg i.v. and repeating as necessary.

Hypotension is common in patients with hypovolemia due to hemorrhage or dehydration, and in those patients with aortocaval occlusion due to abdominal tumors or the pregnant uterus in late pregnancy. Hypotension is poorly tolerated by patients with coronary or cerebrovascular disease.

Chronic neurological disorders such as multiple sclerosis, old hemiplegia due to stroke, etc., are not thought to be adversely affected by spinal anesthesia but caution is advised.

Spinal anesthesia may be preferable to general anesthesia in some high-risk patients. Attempts should be made to optimize their general condition preoperatively when time allows.

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 CNS toxicity.

Many drugs used during the conduct of anesthesia are considered potential triggering agents for familial malignant hyperthermia. It has been shown that the use of amide local anesthetics in malignant hyperthermia is safe. However, there is no guarantee that neural blockade will prevent the development of malignant hyperthermia during surgery. It is also difficult to predict the need for supplemental general anesthesia. Therefore a standard protocol for the management of malignant hyperthermia should be available.

Lidocaine 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.

Local anesthetic procedures should not be used when there is inflammation and/or sepsis in the region of the proposed injection.

Drug Interactions: Lidocaine should be used with caution in patients receiving other local anesthetics or agents structurally related to local anesthetics, since the toxic effects are additive.

Information for the Patient: When appropriate, patients should be informed in advance that they may experience temporary loss of sensation and motor activity, usually in the lower half of the body, following proper administration of spinal anesthesia.

Pregnancy : It is reasonable to assume that a large number of pregnant women and women of childbearing age have been given lidocaine. No specific disturbances to the reproductive process have so far been reported, e.g., no increased incidence of malformations. However, care should be given during early pregnancy when maximum organogenesis takes place.

There are no adequate and well-controlled studies in pregnant women.

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. 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 CNS, 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.

Spinal anesthesia may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. However, spinal anesthesia has also been reported to prolong the second stage of labor by removing the parturient’s reflex urge to bear down or by interfering with motor function. The use of obstetrical anesthesia may increase the need for forceps assistance.

Lactation : Lidocaine is excreted in the breast milk, but in such small quantities that there is generally no risk of affecting the infant at therapeutic dose levels.

Adverse Reactions: In general, almost all adverse effects seen with spinal anesthesia are due to the nerve blockade itself and not the drug used. These effects include hypotension, bradycardia, and post-spinal headache. Other adverse effects in connection with spinal anesthesia are:

High or Total Spinal Blockade: A rare, though severe, adverse reaction following spinal anesthesia is high or total spinal blockade resulting in cardiovascular and respiratory depression. The cardiovascular depression is caused by extensive sympathetic blockade which may result in profound hypotension and bradycardia, or even cardiac arrest. Respiratory depression is caused by blockade of the innervation of the respiratory muscles, including the diaphragm.

Neurologic: Neurological damage is a rare, though recognized, consequence of spinal anesthesia. It may have one of several causes such as direct injury to the spinal cord or spinal nerves, anterior spinal artery syndrome, injection of an irritant substance, injection of a nonsterile solution or the development of a space-occupying lesion (hematoma or abscess) within the spinal canal. These may result in localized areas of paresthesia or anesthesia, motor weakness, loss of sphincter control and paraplegia. Occasionally these are permanent. Neurological complications of this type have been reported with all local anesthetics used for spinal anesthesia. Some cases of neurologic complications (e.g., cauda equina) have been reported after the use of lidocaine 5% with 7.5% glucose when given undiluted, especially if the injection is very slow, e.g., with very fine needles or catheters (see Dosage). Until the cause of this complication has been elucidated, lidocaine 5% with 7.5% glucose is not recommended for continuous spinal anesthesia.

Low Back Pain: Transient pain and sometimes tenderness developing in the low back and buttocks and radiating to the lateral thighs and calves, may be seen in patients after spinal anesthesia of Xylocaine Spinal 5%. A lithotomy position and/or early mobilization may contribute. The symptoms respond to analgesics (e.g., NSAIDs) and usually resolve spontaneously within 3 days.

Allergic: Allergic reactions are characterized by cutaneous lesions, urticaria, edema or, in the most severe instances, anaphylactic shock. Allergic reactions of the amide type are extremely rare and may occur as a result of sensitivity either to the local anesthetic agent or to other components in the formulation.

Additional adverse experiences 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 overdosage or rapid absorption.

Serious adverse experiences are generally systemic in nature. However, the dose required for spinal anesthesia is so small (20% or less than that required for epidural anesthesia) that acute systemic toxicity is extremely unlikely. Acute toxic effects on the central nervous and cardiovascular systems include the following:

CNS: CNS manifestations are excitatory and/or depressant and may be characterized by circumoral paresthesia, lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, hyperacusis, tinnitus, blurred 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 is usually an early sign of a high lidocaine plasma level and may occur as a consequence of rapid absorption.

Cardiovascular: Cardiovascular manifestations are usually depressant and are characterized by bradycardia, hypotension, and cardiovascular collapse, which may lead to cardiac arrest.

Symptoms And Treatment Of Overdose: Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics and originate mainly in the central nervous and the cardiovascular systems (see Adverse Effects, Warnings, and Precautions).

With accidental intravascular injections, the toxic effect will be obvious within 1 to 3 minutes, while with overdosage, peak plasma concentrations may not be reached for 20 to 30 minutes depending on the site of injection, with signs of toxicity thus being delayed. Toxic reactions mainly involve the central nervous and the cardiovascular systems.Symptoms: CNS toxicity is a graded response, with symptoms and signs of escalating severity. The first symptoms are circumoral paresthesia, numbness of the tongue, lightheadedness, hyperacusis and tinnitus. Visual disturbance and muscular tremors are more serious and precede the onset of generalized convulsions. Unconsciousness and grand mal convulsions may follow, which may last from a few seconds to several minutes. Hypoxia and hypercarbia occur rapidly following convulsions due to the increased muscular activity, together with the interference with normal respiration. In severe cases apnea may occur. Acidosis increases the toxic effects of local anesthetics.

Recovery is due to redistribution and metabolism of the local anesthetic drug. Recovery may be rapid unless large amounts of the drug have been administered.

Cardiovascular effects may be seen in cases with high systemic concentrations. Severe hypotension, bradycardia, arrhythmia and cardiovascular collapse may be the result in such cases.

Cardiovascular toxic effects are generally preceded by signs of toxicity in the CNS, unless the patient is receiving a general anesthetic or is heavily sedated with drugs such as a benzodiazepine or barbiturate.

Treatment: 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 administration. At the first sign of change, oxygen should be administered.

The first step in the management of convulsions 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 i.v.

An anticonvulsant should be given i.v. if the convulsions do not stop spontaneously in 15 to 20 seconds. Thiopental 100 to 150 mg i.v. will abort the convulsions rapidly. Alternatively, diazepam 5 to 10 mg i.v. may be used, although its action is slower.

Succinylcholine will stop the muscle convulsions rapidly, but will require tracheal intubation and controlled ventilation, and should only be used by those familiar with these procedures.

If cardiovascular depression is evident (hypotension, bradycardia), ephedrine 5 to 10 mg i.v. should be given and may be repeated, if necessary, after 2 to 3 minutes.

Should circulatory arrest occur, immediate cardiopulmonary resuscitation should be instituted. Optimal oxygenation and ventilation and circulatory support as well as treatment of acidosis are of vital importance, since hypoxia and acidosis will increase the systemic toxicity of local anesthetics. Epinephrine (0.1 to 0.2 mg as i.v. or intracardial injections) should be given as soon as possible and repeated, if necessary.

Dosage And Administration: Spinal injections should only be made after the subarachnoid space has been clearly identified by lumbar puncture. No drug should be injected until clear cerebrospinal fluid (CSF) is seen to escape from the spinal needle, or is detected by aspiration. It is recommended that Xylocaine Spinal 5% be diluted with an equal volume of cerebrospinal fluid before injection. Intrathecal distribution of anesthetic may be facilitated by using a spinal needle of sufficient gauge, e.g., 22 or 25 gauge.

Spinal anesthesia may be induced in the right or left lateral recumbent or the sitting position. Since Xylocaine Spinal 5% is a hyperbaric solution, the anesthetic will tend to move in the direction in which the table is tilted. After the desired level of anesthesia is obtained and the anesthetic has become fixed, usually in 5 to 10 minutes with Xylocaine Spinal 5%, the patient may be positioned according to the requirement of the surgeon or obstetrician.

Failure of spinal anesthesia has been reported in 1 to 5% of the patients. One reason for failure could be an intrathecal maldistribution of the local anesthetic, e.g., entrapment in the caudal end of the dural sac or within a “pocket” with restricted communication to the major cerebrospinal fluid space. In such cases a better spread, i.e. a sufficient block, may be achieved after temporary change(s) in the patient’s position. If a supplementary block is necessary, it should be performed at a different level and with a reduced volume of local anesthetic. Only one extra attempt should be made.

Injections should be made slowly. Consult standard textbooks for specific techniques for spinal anesthetic procedures.

Adults: Table I provides recommended dosages for normal healthy adults and serves only as a guide to the amount of anesthetic required for most routine procedures. In all cases, the smallest dose that will produce the desired result should be given.

If the technique is properly performed and the needle is properly placed in the subarachnoid space, it should not be necessary to administer more than 1 vial (2 mL or 100 mg lidocaine). Doses greater than 100 mg are not recommended.

Children: The dosage recommendations in healthy adolescents, 16 years of age and older, is the same as for normal, healthy adults. There is insufficient data in children below the age of 16 years to make dosage recommendations.

Sterilization, Storage and Technical Procedures: 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.

Xylocaine Spinal 5% may be autoclaved at 15 lbs pressure at 121°C for 15 minutes (USP Standard). Since the preparation contains glucose, caramelization may occur under prolonged heating and, in some instances, prolonged storage.

Therefore, this preparation should not be re-sterilized and should not remain in the sterilizer any longer than necessary.

The solution should not be used if it is discolored or if a precipitate is present.

Additions to spinal solutions are generally not recommended.

The vials should be stored at controlled room temperature (15 to 30°C).

Xylocaine Spinal 5% is preservative-free and is for single use. Discard unused portion.

Availability And Storage: Each mL contains: lidocaine HCl 50 mg and d-glucose 75 mg. Nonmedicinal ingredients: sodium hydroxide and/or hydrochloric acid to adjust to pH 5.0 to 7.0. Glass vials of 2 mL. Packages of 10.

XYLOCAINE® SPINAL 5% Astra Lidocaine HCl – Glucose Local Anesthetic for Spinal Anesthesia

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