Generic Name: bupivacaine

Brand Names: Marcaine Spinal, Sensorcaine-MPF, Bupivacaine Hydrochloride Monohydrate, Bupivacaine Hydrochloride, Spinal, Sensorcaine, Marcaine HCl, Sensorcaine-MPF Spinal

Uses

Local or Regional Anesthesia

Local or regional anesthesia or analgesia in surgical procedures (including oral surgery), diagnostic and therapeutic procedures, and obstetrical procedures.

Dosage and Administration

General

• Determine dosage based on type and extent of surgical procedure, area to be anesthetized, vascularity of tissues, number of neuronal segments to be blocked, depth and duration of anesthesia, degree of muscular relaxation, individual tolerance, and physical condition of the patient. Use smallest dose required to produce the desired effect.
• During major regional nerve blocks, administer IV fluids via an indwelling catheter to ensure a functioning IV pathway.

Administration

Injection

For solution and drug compatibility information, see Compatibility under Stability.

Administer by local infiltration, peripheral nerve block, retrobulbar block, sympathetic block, lumbar epidural block, caudal block, or subarachnoid (spinal) block. IV regional anesthesia (Bier block) not recommended due to risk of cardiac arrest and death.

Consult specialized references for specific techniques and procedures for administering local anesthetics.

Avoid rapid injection of large volumes; when feasible, administer in fractional (incremental) doses.

For caudal or epidural block, use single-dose ampuls or vials only. Do not use multiple-dose vials containing antimicrobial preservatives (e.g., methylparaben), since safety of intrathecal administration using these preparations not established.

For chemical disinfection of container surface, moisten cotton or gauze with isopropyl (rubbing) alcohol (91%) or ethyl alcohol (70%) and wipe ampul or vial stopper thoroughly just prior to use.

Dosage

Available as bupivacaine hydrochloride, as fixed combination containing bupivacaine hydrochloride and epinephrine bitartrate, and as bupivacaine hydrochloride in dextrose injection. Dosage expressed in terms of bupivacaine hydrochloride.

Pediatric Patients

Local or Regional Anesthesia

Local Infiltration, Peripheral/Sympathetic Nerve Block, Lumbar Epidural/Caudal Block

Children ≥12 years of age: Use lower dosages than those suggested for healthy adults (see Adults under Dosage and Administration).

Adults

Local or Regional Anesthesia

Local Infiltration

Administer bupivacaine hydrochloride 0.25% solution (with or without epinephrine) at dosages up to maximum dosage (see Prescribing Limits under Dosage and Administration).

Lumbar Epidural Block

Prior to lumbar epidural anesthesia, administer test dose to detect accidental intravascular injection. Test dose should contain 10–15 mcg epinephrine and 10–15 mg (2–3 mL) of 0.5% bupivacaine hydrochloride (or equivalent dose of a short-acting amide type local anesthetic such as 30–40 mg of lidocaine hydrochloride). Following injection of test dose, monitor for increase in heart rate.

0.75% solution is for single-dose use; not for intermittent epidural technique. Reserve for surgical procedures requiring a high degree of muscle relaxation and prolonged anesthetic effect.

0.75% solution is not for obstetrical anesthesia; in obstetrics, use 0.25 or 0.5% injections only. (See Risks Associated with Obstetrical Use of Bupivacaine Hydrochloride 0.75% Injection under Cautions.)

75–150 mg (10–20 mL) of bupivacaine hydrochloride 0.75% solution (with or without epinephrine) produces complete motor blockade. Administer in incremental doses of 3–5 mL. Allow sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection.

50–100 mg (10–20 mL) of bupivacaine hydrochloride 0.5% solution (with or without epinephrine) produces moderate to complete motor blockade. Administer in incremental doses of 3–5 mL. Allow sufficient time between doses to detect toxic manifestations of unintentional intravascular or intrathecal injection.

25–50 mg (10–20 mL) of bupivacaine hydrochloride 0.25% solution (with or without epeniphrine) produces partial motor blockade.

Caudal Block

75–150 mg (15–30 mL) of bupivacaine hydrochloride 0.5% solution (with or without epinephrine) produces moderate to complete motor blockade.

37.5–75 mg (15–30 mL) of bupivacaine hydrochloride 0.25% solution (with or without epinephrine) produces moderate motor blockade.

Peripheral Nerve Block

25 mg (5 mL) to maximum dosage (see Prescribing Limits under Dosage and Administration) of bupivacaine hydrochloride 0.25% solution (with or without epinephrine) produces moderate to complete motor blockade.

12.5 mg (5 mL) to maximum dosage (see Prescribing Limits under Dosage and Administration) of bupivacaine hydrochloride 0.5% solution (with or without epinephrine) produces moderate to complete motor blockade.

Retrobulbar Block

15–30 mg (2–4 mL) of bupivacaine hydrochloride 0.75% solution (with or without epinephrine) produces complete motor blockade.

Sympathetic Block

50–125 mg (20–50 mL) of bupivacaine hydrochloride 0.25% solution.

Anesthesia in Maxillary and Mandibular Area (for oral surgery)

9 mg (1.8 mL) up to 90 mg (18 mL) of bupivacaine hydrochloride 0.5% solution per dental sitting.

Subarachnoid (Spinal) Block for Vaginal Delivery

6 mg (0.8 mL) of bupivacaine hydrochloride 0.75% in dextrose 8.25% injection produces complete motor and sensory block.

Subarachnoid (Spinal) Block for Cesarean Section

7.5–10.5 mg (1–1.4 mL) of bupivacaine hydrochloride 0.75% in dextrose 8.25% injection produces complete motor and sensory block.

Subarachnoid (Spinal) Block for Lower Extremity and Perineal Procedures (e.g., TURP, vaginal hysterectomy)

7.5 mg (1 mL) of bupivacaine hydrochloride 0.75% in dextrose 8.25% injection produces complete motor and sensory block.

Subarachnoid (Spinal) Block for Lower Abdominal Procedures (e.g., abdominal hysterectomy, tubal ligation, appendectomy)

12 mg (1.6 mL) of bupivacaine hydrochloride 0.75% in dextrose 8.25% injection produces complete motor and sensory block.

Prescribing Limits

Adults

Local or Regional Anesthesia

Local Infiltration, Peripheral/Sympathetic Nerve Block, Lumbar Epidirual/Caudal Block

Most experience to date has involved single doses up to 175 mg (without epinephrine) or 225 mg (with epinephrine 1:200,000).

Maximum 400 mg in any 24-hour period.

Special Populations

Hepatic Impairment

Reduce dosage in patients with hepatic impairment.

Geriatric Patients

Reduce dosage in geriatric patients.

Other Populations

Reduce dosage in patients with cardiac disease, debilitated patients, and acutely ill patients. Also reduce dosage in patients with increased intra-abdominal pressure (including obstetrical patients) undergoing spinal anesthesia.

Cautions

Contraindications

• Bupivacaine hydrochloride used for obstetrical paracervical block (this technique has resulted in fetal bradycardia and death).
• Contraindications to spinal anesthesia: severe hemorrhage, severe hypotension or shock, arrhythmias (e.g., complete heart block) that severely restrict cardiac output, local infection at site of lumbar puncture, and septicemia.
• Known hypersensitivity to bupivacaine, other local anesthetics of the amide type, sodium metabisulfite, or any ingredients in the formulation.

Warnings/Precautions

Warnings

Risks Associated with Obstetrical Use of Bupivacaine Hydrochloride 0.75% Injection

Risk of seizures, cardiac arrest, difficult resuscitation, or death following obstetrical epidural block (possibly due to systemic toxicity secondary to unintentional intravascular injection).

Not recommended for obstetrical anesthesia. Reserve for surgical procedures requiring a high degree of muscle relaxation and prolonged anesthetic effect.

Experience of Supervising Clinician

Should be used only by clinicians who are sufficiently knowledgeable in the diagnosis and management of dose-related toxicity and other acute emergencies that might arise. Oxygen, resuscitative equipment, and drugs must be available for immediate use. Delay in proper management of dose-related toxicity may result in acidosis, cardiac arrest, and, possibly, death.

Accidental Intravascular Injection

Accidental intravascular injection may result in confusion, seizures, CNS excitement and/or depression, myocardial depression, coma, and/or respiratory arrest. (See CNS Effects and also Cardiovascular Effects, under Cautions.)

Aspirate prior to administration to guard against intravascular injection.

Injection During Uterine Contractions

Do not inject spinal anesthetics during uterine contractions, since spinal fluid current may carry drug further cephalad than desired.

Epinephrine Administration

Some bupivacaine hydrochloride preparations contain epinephrine, which may cause ischemic injury or necrosis. Consider usual precautions associated with epinephrine administration. (See Cardiovascular Effects under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions and Cross Hypersensitivity

Allergic reactions are rare.

Possible urticaria, pruritus, erythema, angioneurotic edema (including laryngeal edema), tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and anaphylactoid reactions (including severe hypotension).

Cross hypersensitivity between amide-type local anesthetics reported.

Sulfite Sensitivity

Some epinephrine-containing bupivacaine preparations contain sodium metabisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

General Precautions

CNS Effects

Toxic plasma concentrations of local anesthetics (resulting from systemic absorption) associated with adverse CNS effects (e.g., restlessness, anxiety, dizziness, tinnitus, blurred vision, tremors, drowsiness, seizures).

Carefully monitor level of consciousness after each local anesthetic injection.

Cardiovascular Effects

Toxic plasma concentrations of local anesthetics (resulting from systemic absorption) associated with adverse cardiovascular effects (e.g., decreased cardiac output, heart block, hypotension, bradycardia, ventricular arrhythmias, cardiac arrest). Carefully monitor cardiovascular and respiratory vital signs after each local anesthetic injection.

Use with caution in patients with impaired cardiovascular function, hypotension, or heart block.

Possible peripheral vasodilation and hypotension following spinal anesthesia; monitor BP carefully, particularly in early phases of anesthesia. Use spinal anesthesia with caution in patients with severe disturbances of cardiac rhythm, shock, or heart block.

Some bupivacaine hydrochloride preparations contain epinephrine; risk of exaggerated vasoconstrictor response in patients with hypertensive vascular disease. Use with caution and in carefully restricted quantities in areas of the body supplied by end arteries or having otherwise compromised blood supply (e.g., digits, nose, external ear, penis).

Familial Malignant Hyperthermia

Many drugs used during the conduct of anesthesia may trigger familial malignant hyperthermia; not known whether amide-type local anesthetics trigger this reaction. However, standard protocol for management should be available. Early unexplained signs of tachycardia, tachypnea, labile BP, and metabolic acidosis may precede temperature elevation. If familial malignant hyperthermia is confirmed, discontinue triggering agent and initiate appropriate therapy (e.g., oxygen, dantrolene) and other supportive measures.

Preexisting Conditions Precluding Use of Spinal Anesthesia

Conditions that may preclude the use of spinal anesthesia (depending upon the clinician's evaluation of the situation and ability to manage potential complications) include preexisting CNS disease (e.g., disease associated with pernicious anemia, poliomyelitis, syphilis, tumor); hematological disorders predisposing to coagulopathies; current anticoagulant therapy; chronic backache; preoperative headache; hypotension or hypertension; technical problems (persistent paresthesias, persistent bloody tap); arthritis or spinal deformity; extremes of age; and psychosis or other causes of poor patient cooperation.

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category C.

Labor and Delivery

Maternal hypotension reported. To prevent decreases in BP, elevate patient's legs and position patient on her left side. Monitor fetal heart rate continuously; electronic fetal monitoring highly advisable.

Epidural anesthesia may prolong second stage of labor (by removing parturient's reflex urge to bear down or by interfering with motor function); may increase need for forceps assistance.

Possible diminished muscle strength and tone on neonate's first or second day of life.

Lactation

Distributed into milk. Discontinue nursing or the drug.

Pediatric Use

Bupivacaine hydrochloride injection with or without epinephrine not recommended in children <12 years of age. IV infusion associated with high plasma concentrations and seizures; high plasma concentrations associated with adverse cardiovascular effects.

Bupivacaine hydrochloride in dextrose injection not recommended in children <18 years of age.

Geriatric Use

Increased risk of hypotension, particularly in patients with hypertension. Dosage adjustments recommended.

Possible increased risk of toxicity in geriatric patients with renal impairment; monitor renal function.

Hepatic Impairment

Possible increased risk of toxicity, particularly in patients with severe hepatic impairment. Use with caution. Dosage adjustments recommended.

Renal Impairment

Possible increased risk of toxicity.

Common Adverse Effects

Adverse CNS and cardiovascular effects, respiratory paralysis, underventilation. (See CNS Effects and also Cardiovascular Effects, under Cautions.)

Interactions

Consider usual drug interactions associated with epinephrine administration.

Specific Drugs

Pharmacokinetics

Absorption

Bioavailability

Systemic absorption dependent upon total dose and concentration administered, route of administration, vascularity of administration site, and presence or absence of epinephrine in formulation.

Peak blood concentrations achieved approximately 30–45 minutes following injection for caudal, epidural, or peripheral nerve block.

Onset

Onset within 2–10 minutes following local infiltration or nerve block (for dental anesthesia) with 0.5% solution.

Onset within 4–17 minutes following epidural, caudal, peripheral, or sympathetic block with 0.25 or 0.5% solution. More rapid onset following epidural block with 0.75% solution.

Following 12-mg injection for spinal block, sensory blockade occurs within 1 minute; motor blockade occurs within 15 minutes.

Duration

Longer duration of anesthesia compared with other commonly used local anesthetics.

Duration of up to 7 minutes following local infiltration or nerve block (for dental anesthesia) with 0.5% solution.

Duration of 3–7 minutes following epidural, caudal, peripheral, or sympathetic block with 0.25 or 0.5% solution. Slightly longer duration (6–9 hours) with 0.75% solution.

Following a 12-mg injection for spinal block, sensory blockade persists for 2 hours (with or without 0.2 mg epinephrine); motor blockade persists for 3.5 hours (without epinephrine) or 4.5 hours (with 0.2 mg epinephrine). Similar duration of sensory blockade but shorter duration of motor blockade compared with mg-equivalent dose of tetracaine.

Special Populations

Increased peak plasma concentrations in geriatric patients. Maximal spread of analgesia and maximal motor blockade achieved more rapidly than in younger patients.

Distribution

Extent

Local anesthetics are distributed to some extent to all body tissues, with high concentrations found in highly perfused organs (e.g., liver, lungs, heart, brain).

Lower degree of placental transmission than other parenteral local anesthetics. Distributed into milk.

Plasma Protein Binding

95%.

Elimination

Metabolism

Systemically absorbed bupivacaine is metabolized in the liver via conjugation with glucuronic acid.

Elimination Route

Excreted principally in urine as inactive metabolites and small amounts (5%) of unchanged drug.

Half-life

Approximately 2.7–3.5 hours (in adults) or 8.1 hours (in neonates).

Special Populations

Decreased total plasma clearance in geriatric patients.

Stability

Storage

Parenteral

Injection

15–30°C. If preparation contains epinephrine, protect from light.

Compatibility

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Solution Compatibility

Drug Compatibility

Do not mix with other local anesthetics (insufficient clinical data).

Actions

• Local anesthetics block the generation and conduction of nerve impulses by increasing the threshold for electrical excitation, slowing the propagation of the nerve impulse, and reducing the rate of rise of the action potential.
• Bupivacaine exhibits analgesic effects that persist after return of sensation; thus need for strong analgesics is reduced.
• Some preparations formulated with epinephrine to decrease bupivacaine's rate and extent of systemic absorption and to prolong its duration of action.
• Has long duration of action.

Advice to Patients

• Prior to administration, advise patients of the possibility of temporary loss of sensation and muscle function (e.g., in lower half of body following caudal, lumbar epidural, or subarachnoid block).
• Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., cardiovascular or liver disease).
• Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions August 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.