Side Effects of Marcaine (bupivacaine)

Marcaine (bupivacaine) is a local anesthetic similar to lidocaine and mepivacaine (amide type). 

Marcaine, like other local anesthetics, reduces the flow of sodium in and out of nerves. This decreases the initiation and transfer of nerve signals in the area in which the drug is applied. This blockage leads first to a loss of sensation of pain, then temperature, touch, deep pressure, and muscle control. The concentration of the drug will determine how quickly it starts working. 

Common side effects of Marcaine are related to higher doses, as well as unintentional injection into alternative sites. Absorption into the bloodstream may lead to side effects such as

• low blood pressure,
• slow heart rate,
• strong or irregular heartbeat, and
• cardiac arrest. 

Other side effects of Marcaine include

• nausea, vomiting,
• fecal and urinary incontinence,
• loss of sexual function,
• blurred vision,
• ringing in the ears, and
• loss of joint cartilage.

Serious but rare side effects of Marcaine include

• decreased function of the nervous system,
• activation of the nervous system (resulting in seizures),
• paraplegia,
• nerve disorder,
• total block of spinal nerves, and
• respiratory arrest. 

Drug interactions of Marcaine include beta-blockers, such as atenolol (Tenormin), as they may increase the concentration of Marcaine.

• Monitor therapy with peginterferon Alfa-2b as it may decrease the concentration of Marcaine and lead to diminished effects.
• Hyaluronidase may increase how quickly Marcaine starts to work as well as increase how much Marcaine is absorbed into the bloodstream.
• Monitor for toxic reactions such as low blood pressure, decreased heart rate, irregular heart rhythm, or cardiac arrest.
• Technetium Tc 99m tilmanocept should not be simultaneously injected with the Marcaine as it interferes with how well the technetium Tc 99m tilmanocept is able to spread and be used for diagnostic purposes. 

There are no adequate studies of Marcaine in pregnant women. Marcaine may be used for obstetrical anesthesia or analgesia if the benefits outweigh the risks. 

Marcaine is excreted in breast milk and should not be used by breastfeeding mothers.

Side effects are related to higher doses, as well as unintentional injection into alternative sites. Absorption into the blood stream may lead to the following sied effects:

• low blood pressure,
• slow heart rate,
• strong or irregular heartbeat,
• and cardiac arrest.

Other important side effects include:

• nausea,
• vomiting,
• fecal and urinary incontinence,
• loss of sexual function,
• blurred vision,
• ringing in the ears, and
• loss of joint cartilage.

Rare, but serious complications include decreased function of the nervous system, activation of the nervous system (resulting in seizures), paraplegia, nerve disorder, total block of spinal nerves, and respiratory arrest. Specific warnings exist about using the 0.75 % dose in obstetrical anesthesia as there have been reports of cardiac arrest.

• Reactions to Marcaine are characteristic of those associated with other amide-type local anesthetics. A major cause of adverse reactions to this group of drugs is excessive plasma levels, which may be due to overdosage, unintentional intravascular injection, or slow metabolic degradation.
• The most commonly encountered acute adverse experiences which demand immediate counter-measures are related to the central nervous system and the cardiovascular system.
• These adverse experiences are generally dose related and due to high plasma levels which may result from overdosage, rapid absorption from the injection site, diminished tolerance, or from unintentional intravascular injection of the local anesthetic solution. In addition to systemic dose-related toxicity, unintentional subarachnoid injection of drug during the intended performance of caudal or lumbar epidural block or nerve blocks near the vertebral column (especially in the head and neck region) may result in underventilation or apnea (“Total or High Spinal”).
• Also, hypotension due to loss of sympathetic tone and respiratory paralysis or underventilation due to cephalad extension of the motor level of anesthesia may occur. This may lead to secondary cardiac arrest if untreated.
• Patients over 65 years, particularly those with hypertension, may be at increased risk for experiencing the hypotensive effects of Marcaine.
• Factors influencing plasma protein binding, such as acidosis, systemic diseases which alter protein production, or competition of other drugs for protein binding sites, may diminish individual tolerance.

Central Nervous System Reactions

• These are characterized by excitation and/or depression.
• Restlessness, anxiety, dizziness, tinnitus, blurred vision, or tremors may occur, possibly proceeding to convulsions. However, excitement may be transient or absent, with depression being the first manifestation of an adverse reaction. This may quickly be followed by drowsiness merging into unconsciousness and respiratory arrest. Other central nervous system effects may be nausea, vomiting, chills, and constriction of the pupils.
• The incidence of convulsions associated with the use of local anesthetics varies with the procedure used and the total dose administered. In a survey of studies of epidural anesthesia, overt toxicity progressing to convulsions occurred in approximately 0.1% of local anesthetic administrations.

Cardiovascular System Reactions

• High doses or unintentional intravascular injection may lead to high plasma levels and
  • related depression of the myocardium,
  • decreased cardiac output,
  • heartblock,
  • hypotension,
  • bradycardia,
  • ventricular arrhythmias, including
    • ventricular tachycardia and ventricular fibrillation, and
    • cardiac arrest.

Allergic

• Allergic-type reactions are rare and may occur as a result of sensitivity to the local anesthetic or to other formulation ingredients, such as the antimicrobial preservative methylparaben contained in multiple-dose vials or sulfites in epinephrine-containing solutions.
• These reactions are characterized by signs such as
  • urticaria,
  •  pruritus,
  • erythema,
  • angioneurotic edema (including laryngeal edema),
  • tachycardia,
  • sneezing,
  • nausea,
  • vomiting,
  • dizziness,
  • syncope,
  •  excessive sweating,
  • elevated temperature, and possibly,
  • anaphylactoid-like symptomatology (including severe hypotension).
• Cross sensitivity among members of the amide-type local anesthetic group has been reported. The usefulness of screening for sensitivity has not been definitely established.

Neurologic

• The incidences of adverse neurologic 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. Many of these effects may be related to local anesthetic techniques, with or without a contribution from the drug.
• In the practice of caudal or lumbar epidural block, occasional unintentional penetration of the subarachnoid space by the catheter or needle may occur.
• Subsequent adverse effects may depend partially on the amount of drug administered intrathecally and the physiological and physical effects of a dural puncture.
• A high spinal is characterized by paralysis of the legs, loss of consciousness, respiratory paralysis, and bradycardia.
• Neurologic effects following epidural or caudal anesthesia may include
  • spinal block of varying magnitude (including high or total spinal block);
  • hypotension secondary to spinal block;
  • urinary retention;
  • fecal and urinary incontinence;
  • loss of perineal sensation and sexual function;
  • persistent anesthesia, paresthesia, weakness, paralysis of the lower extremities and loss of sphincter control all of which may have slow, incomplete, or no recovery;
  • headache;
  • backache;
  • septic meningitis;
  • meningismus;
  • slowing of labor;
  • increased incidence of forceps delivery; and
  • cranial nerve palsies due to traction on nerves from loss of cerebrospinal fluid.
• Neurologic effects following other procedures or routes of administration may include persistent anesthesia, paresthesia, weakness, paralysis, all of which may have slow, incomplete, or no recovery.

Clinically Significant Drug Interactions

• The administration of local anesthetic solutions containing epinephrine or norepinephrine to patients receiving monoamine oxidase inhibitors or tricyclic antidepressants may produce severe, prolonged 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 and of ergot-type oxytocic drugs may cause severe, persistent hypertension or cerebrovascular accidents.
• Phenothiazines and butyrophenones may reduce or reverse the pressor effect of epinephrine.