Bupivacaine, marketed under the brand name Marcaine among others, is a medication used to decrease feeling in a specific area. In nerve blocks, it is injected around a nerve that supplies the area, or into the spinal canal's epidural space. It is available mixed with a small amount of

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...

to increase the duration of its action. It typically begins working within 15 minutes and lasts for 2 to 8 hours. Possible side effects include sleepiness, muscle twitching, ringing in the ears, changes in vision, low blood pressure, and an irregular heart rate. Concerns exist that injecting it into a joint can cause problems with the

cartilage Cartilage is a resilient and smooth type of connective tissue. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck ...

. Concentrated bupivacaine is not recommended for epidural freezing. Epidural freezing may also increase the length of labor. It is a

local anaesthetic A local anesthetic (LA) is a medication that causes absence of pain sensation. In the context of surgery, a local anesthetic creates an absence of pain in a specific location of the body without a loss of consciousness, as opposed to a general a ...

of the amide group. Bupivacaine was discovered in 1957. It is on the World Health Organization's List of Essential Medicines. Bupivacaine is available as a generic medication. An implantable formulation of bupivacaine (Xaracoll) was approved for medical use in the United States in August 2020.

Medical uses

Bupivacaine is

indicated In medicine, an indication is a valid reason to use a certain test, medication, procedure, or surgery. There can be multiple indications to use a procedure or medication. An indication can commonly be confused with the term diagnosis. A diagnosi ...

for local infiltration, peripheral nerve block, sympathetic nerve block, and epidural and caudal blocks. It is sometimes used in combination with

to prevent systemic absorption and extend the duration of action. The 0.75% (most concentrated) formulation is used in

retrobulbar block A retrobulbar block is a regional anesthetic nerve block in the retrobulbar space, the area located behind the globe of the eye. Injection of local anesthetic into this space constitutes the retrobulbar block. This injection provides akinesia of ...

. It is the most commonly used local anesthetic in epidural anesthesia during labor, as well as in postoperative pain management. Liposomal formulations of bupivacaine (brand name EXPAREL) have shown to be more effective in providing pain relief than plain solutions of bupivacaine. The fixed-dose combination of bupivacaine with Type I collagen (brand name Xaracoll) is indicated for acute postsurgical analgesia (pain relief) for up to 24 hours in adults following open inguinal hernia repair. Bupivacaine (Posimir) is indicated in adults for administration into the subacromial space under direct arthroscopic visualization to produce post-surgical analgesia for up to 72 hours following arthroscopic subacromial decompression.

Contraindications

Bupivacaine is contraindicated in patients with known hypersensitivity reactions to bupivacaine or amino-amide anesthetics. It is also contraindicated in obstetrical paracervical blocks and intravenous regional anaesthesia ( Bier block) because of potential risk of tourniquet failure and systemic absorption of the drug and subsequent

cardiac arrest Cardiac arrest is when the heart suddenly and unexpectedly stops beating. It is a medical emergency that, without immediate medical intervention, will result in sudden cardiac death within minutes. Cardiopulmonary resuscitation (CPR) and possi ...

. The 0.75% formulation is contraindicated in epidural anesthesia during labor because of the association with refractory cardiac arrest.

Adverse effects

Compared to other local anaesthetics, bupivacaine is markedly cardiotoxic. However, adverse drug reactions are rare when it is administered correctly. Most reactions are caused by accelerated absorption from the injection site, unintentional intravascular injection, or slow metabolic degradation. However,

allergic Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic der ...

reactions can rarely occur. Clinically significant adverse events result from systemic absorption of bupivacaine and primarily involve the central nervous and cardiovascular systems. Effects on the central nervous system typically occur at lower

blood plasma Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the int ...

concentrations. Initially, cortical inhibitory pathways are selectively inhibited, causing symptoms of neuronal excitation. At higher plasma concentrations, both inhibitory and excitatory pathways are inhibited, causing central nervous system depression and potentially coma. Higher plasma concentrations also lead to cardiovascular effects, though cardiovascular collapse may also occur with low concentrations. Adverse effects on the central nervous system may indicate impending cardiotoxicity and should be carefully monitored. * Central nervous system: circumoral numbness, facial tingling, vertigo, tinnitus, restlessness, anxiety, dizziness,

seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with lo ...

coma A coma is a deep state of prolonged unconsciousness in which a person cannot be awakened, fails to respond normally to painful stimuli, light, or sound, lacks a normal wake-sleep cycle and does not initiate voluntary actions. Coma patients exhi ...

* Cardiovascular:

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the di ...

arrhythmia Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adult ...

bradycardia Bradycardia (also sinus bradycardia) is a slow resting heart rate, commonly under 60 beats per minute (BPM) as determined by an electrocardiogram. It is considered to be a normal heart rate during sleep, in young and healthy or elderly adults, ...

, heart block,

Toxicity can also occur in the setting of subarachnoid injection during high spinal anesthesia. These effects include:

paresthesia Paresthesia is an abnormal sensation of the skin (tingling, pricking, chilling, burning, numbness) with no apparent physical cause. Paresthesia may be transient or chronic, and may have any of dozens of possible underlying causes. Paresthesias a ...

, paralysis,

apnea Apnea, BrE: apnoea, is the temporal cessation of breathing. During apnea, there is no movement of the muscles of inhalation, and the volume of the lungs initially remains unchanged. Depending on how blocked the airways are ( patency), there ma ...

, hypoventilation, fecal incontinence, and urinary incontinence. Additionally, bupivacaine can cause chondrolysis after continuous infusion into a joint space. Bupivacaine has caused several deaths when the epidural anaesthetic has been administered intravenously accidentally.

Treatment of overdose

Animal evidence indicates intralipid, a commonly available intravenous lipid emulsion, can be effective in treating severe cardiotoxicity secondary to local anaesthetic overdose, and human case reports of successful use in this way. Plans to publicize this treatment more widely have been published.

Pregnancy and lactation

Bupivacaine crosses the placenta and is a pregnancy category C drug. However, it is approved for use at term in obstetrical anesthesia. Bupivacaine is excreted in breast milk. Risks of stopping breast feeding versus stopping bupivacaine should be discussed with the patient.

Postarthroscopic glenohumeral chondrolysis

Bupivacaine is toxic to

and its intra-articular infusions may lead to postarthroscopic glenohumeral chondrolysis.

Pharmacology

Pharmacodynamics

Bupivacaine binds to the intracellular portion of voltage-gated sodium channels and blocks sodium influx into

nerve cells A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...

, which prevents depolarization. Without depolarization, no initiation or conduction of a pain signal can occur.

Pharmacokinetics

The rate of systemic absorption of bupivacaine and other local anesthetics is dependent upon the dose and concentration of drug administered, the route of administration, the vascularity of the administration site, and the presence or absence of epinephrine in the preparation. * Onset of action (route and dose-dependent): 1–17 min * Duration of action (route and dose-dependent): 2–9 hr * Half life: neonates, 8.1 hr, adults: 2.7 hr * Time to peak plasma concentration (for peripheral, epidural, or caudal block): 30–45 min * Protein binding: about 95% * Metabolism: hepatic * Excretion: renal (6% unchanged)

Chemical structure

lidocaine Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lid ...

, bupivacaine is an amino-amide anesthetic; the aromatic head and the hydrocarbon chain are linked by an

amide bond In organic chemistry, an amide, also known as an organic amide or a carboxamide, is a compound with the general formula , where R, R', and R″ represent organic groups or hydrogen atoms. The amide group is called a peptide bond when it i ...

rather than an ester as in earlier local anesthetics. As a result, the amino-amide anesthetics are more stable and less likely to cause allergic reactions. Unlike lidocaine, the terminal amino portion of bupivacaine (as well as mepivacaine, ropivacaine, and levobupivacaine) is contained within a piperidine ring; these agents are known as pipecholyl xylidines.

Society and culture

Legal status

On 17 September 2020, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regardin ...

(CHMP) of the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Eur ...

(EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Exparel, intended for the treatment of post-operative pain. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. The applicant for this medicinal product is Pacira Ireland Limited. Exparel liposomal was approved for medical use in the European Union in November 2020.

Economics

Bupivacaine is available as a generic medication.

Research

Levobupivacaine is the (''S'')-(–)-

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical anti ...

of bupivacaine, with a longer duration of action, producing less vasodilation. Durect Corporation is developing a biodegradable, controlled-release drug delivery system for after surgery. It has currently completed a phase-III clinical trial.

References

External links

* {{Portal bar, Medicine Local anesthetics Piperidines AstraZeneca brands World Health Organization essential medicines Acetanilides Wikipedia medicine articles ready to translate