Bupivacaine

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Bupivacaine
Bupivacaine skeletal.svg
Bupivacaine-from-xtal-3D-bs-17.png
Clinical data
Pronunciation /bjuːˈpɪvəkeɪn/
Trade names Marcaine, Sensorcaine, Posimir, others
AHFS/Drugs.com Monograph
License data
Pregnancy
category
Routes of
administration 		Parenteral, topical, implant
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability n/a
Protein binding 95%
Metabolism Liver
Onset of action Within 15 min [5]
Elimination half-life 3.1 hours (adults) [5]
8.1 hours (neonates) [5]
Duration of action 2 to 8 hr [6]
Excretion Kidney, 4–10%
Identifiers
  • (RS)-1-Butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.048.993 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C18H28N2O
Molar mass 288.435 g·mol−1
3D model (JSmol)
Melting point 107 to 108 °C (225 to 226 °F)
  • O=C(C1N(CCCC1)CCCC)NC2=C(C)C=CC=C2C
  • InChI=1S/C18H28N2O/c1-4-5-12-20-13-7-6-11-16(20)18(21)19-17-14(2)9-8-10-15(17)3/h8-10,16H,4-7,11-13H2,1-3H3,(H,19,21) Yes check.svgY
  • Key:LEBVLXFERQHONN-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Bupivacaine, marketed under the brand name Marcaine among others, is a medication used to decrease sensation in a specific small area. [5] In nerve blocks, it is injected around a nerve that supplies the area, or into the spinal canal's epidural space. [5] It is available mixed with a small amount of epinephrine to increase the duration of its action. [5] It typically begins working within 15 minutes and lasts for 2 to 8 hours. [5] [6]

Contents

Possible side effects include sleepiness, muscle twitching, ringing in the ears, changes in vision, low blood pressure, and an irregular heart rate. [5] Concerns exist that injecting it into a joint can cause problems with the cartilage. [5] Concentrated bupivacaine is not recommended for epidural freezing. [5] Epidural freezing may also increase the length of labor. [5] It is a local anaesthetic of the amide group. [5]

Bupivacaine was discovered in 1957. [7] It is on the World Health Organization's List of Essential Medicines. [8] Bupivacaine is available as a generic medication. [5] [9] An implantable formulation of bupivacaine (Xaracoll) was approved for medical use in the United States in August 2020. [10] [11] [12]

Medical uses

Bupivacaine is indicated for local infiltration, peripheral nerve block, sympathetic nerve block, and epidural and caudal blocks. It is sometimes used in combination with epinephrine to prevent systemic absorption and extend the duration of action. The 0.75% (most concentrated) formulation is used in retrobulbar block. [13] It is the most commonly used local anesthetic in epidural anesthesia during labor, as well as in postoperative pain management. [14] Liposomal formulations of bupivacaine (brand name EXPAREL) have not shown clinical benefit compared to plain bupivacaine when used in traditional perineural injections, [15] although some industry-funded studies have suggested benefits when used in local infiltration. [16] [17]

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. [11] [12]

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. [11] [18]

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. The 0.75% formulation is contraindicated in epidural anesthesia during labor because of the association with refractory cardiac arrest. [19]

Adverse effects

Compared to other local anaesthetics, bupivacaine is markedly cardiotoxic. [20] 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 reactions can rarely occur. [19]

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 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. [21] Adverse effects on the central nervous system may indicate impending cardiotoxicity and should be carefully monitored. [19]

Toxicity can also occur in the setting of subarachnoid injection during high spinal anesthesia. These effects include: paresthesia, paralysis, apnea, hypoventilation, fecal incontinence, and urinary incontinence. Additionally, bupivacaine can cause chondrolysis after continuous infusion into a joint space. [19]

Bupivacaine has caused several deaths when the epidural anaesthetic has been administered intravenously accidentally. [22]

Treatment of overdose

Animal evidence [23] [24] 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. [25] [26] Plans to publicize this treatment more widely have been published. [27]

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. [19]

Postarthroscopic glenohumeral chondrolysis

Bupivacaine is toxic to cartilage and its intra-articular infusions may lead to postarthroscopic glenohumeral chondrolysis. [28]

Pharmacology

Pharmacodynamics

Bupivacaine binds to the intracellular portion of voltage-gated sodium channels and blocks sodium influx into nerve cells, 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. [29]

Chemical structure

Like lidocaine, bupivacaine is an amino-amide anesthetic; the aromatic head and the hydrocarbon chain are linked by an amide bond 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. [14]

Society and culture

On 17 September 2020, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (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. [30] The applicant for this medicinal product is Pacira Ireland Limited. [30] Exparel liposomal was approved for medical use in the European Union in November 2020. [31]

Economics

Bupivacaine is available as a generic medication. [5] [9]

Research

Levobupivacaine is the (S)-(–)-enantiomer 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. As of 2010, it has completed a phase-III clinical trial. [32]

See also

Related Research Articles

<span class="mw-page-title-main">Anesthesia</span> State of medically-controlled temporary loss of sensation or awareness

Anesthesia or anaesthesia is a state of controlled, temporary loss of sensation or awareness that is induced for medical or veterinary purposes. It may include some or all of analgesia, paralysis, amnesia, and unconsciousness. An individual under the effects of anesthetic drugs is referred to as being anesthetized.

<span class="mw-page-title-main">Local anesthetic</span> Medications to reversibly block pain

A local anesthetic (LA) is a medication that causes absence of all sensation in a specific body part without loss of consciousness, providing local anesthesia, as opposed to a general anesthetic, which eliminates all sensation in the entire body and causes unconsciousness. Local anesthetics are most commonly used to eliminate pain during or after surgery. When it is used on specific nerve pathways, paralysis also can be induced.

<span class="mw-page-title-main">Lidocaine</span> Local anesthetic

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, lidocaine typically begins working within several minutes and lasts for half an hour to three hours. Lidocaine mixtures may also be applied directly to the skin or mucous membranes to numb the area. It is often used mixed with a small amount of adrenaline (epinephrine) to prolong its local effects and to decrease bleeding.

<span class="mw-page-title-main">Spinal anaesthesia</span> Form of neuraxial regional anaesthesia

Spinal anaesthesia, also called spinal block, subarachnoid block, intradural block and intrathecal block, is a form of neuraxial regional anaesthesia involving the injection of a local anaesthetic or opiod into the subarachnoid space, generally through a fine needle, usually 9 cm (3.5 in) long. It is a safe and effective form of anesthesia usually performed by anesthesiologists that can be used as an alternative to general anesthesia commonly in surgeries involving the lower extremities and surgeries below the umbilicus. The local anesthetic with or without an opioid injected into the cerebrospinal fluid provides locoregional anaesthesia: true analgesia, motor, sensory and autonomic (sympathetic) blockade. Administering analgesics in the cerebrospinal fluid without a local anaesthetic produces locoregional analgesia: markedly reduced pain sensation, some autonomic blockade, but no sensory or motor block. Locoregional analgesia, due to mainly the absence of motor and sympathetic block may be preferred over locoregional anaesthesia in some postoperative care settings. The tip of the spinal needle has a point or small bevel. Recently, pencil point needles have been made available.

<span class="mw-page-title-main">Anesthetic</span> Drug that causes anesthesia

An anesthetic or anaesthetic is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.

<span class="mw-page-title-main">Epidural administration</span> Medication injected into the epidural space of the spine

Epidural administration is a method of medication administration in which a medicine is injected into the epidural space around the spinal cord. The epidural route is used by physicians and nurse anesthetists to administer local anesthetic agents, analgesics, diagnostic medicines such as radiocontrast agents, and other medicines such as glucocorticoids. Epidural administration involves the placement of a catheter into the epidural space, which may remain in place for the duration of the treatment. The technique of intentional epidural administration of medication was first described in 1921 by Spanish military surgeon Fidel Pagés.

<span class="mw-page-title-main">Remifentanil</span> Synthetic opioid analgesic

Remifentanil, marketed under the brand name Ultiva is a potent, short-acting synthetic opioid analgesic drug. It is given to patients during surgery to relieve pain and as an adjunct to an anaesthetic. Remifentanil is used for sedation as well as combined with other medications for use in general anesthesia. The use of remifentanil has made possible the use of high-dose opioid and low-dose hypnotic anesthesia, due to synergism between remifentanil and various hypnotic drugs and volatile anesthetics.

<span class="mw-page-title-main">Ropivacaine</span> Local anaesthetic drug

Ropivacaine (rINN) is a local anaesthetic drug belonging to the amino amide group. The name ropivacaine refers to both the racemate and the marketed S-enantiomer. Ropivacaine hydrochloride is commonly marketed by AstraZeneca under the brand name Naropin.

<span class="mw-page-title-main">Nerve block</span> Deliberate inhibition of nerve impulses

Nerve block or regional nerve blockade is any deliberate interruption of signals traveling along a nerve, often for the purpose of pain relief. Local anesthetic nerve block is a short-term block, usually lasting hours or days, involving the injection of an anesthetic, a corticosteroid, and other agents onto or near a nerve. Neurolytic block, the deliberate temporary degeneration of nerve fibers through the application of chemicals, heat, or freezing, produces a block that may persist for weeks, months, or indefinitely. Neurectomy, the cutting through or removal of a nerve or a section of a nerve, usually produces a permanent block. Because neurectomy of a sensory nerve is often followed, months later, by the emergence of new, more intense pain, sensory nerve neurectomy is rarely performed.

<span class="mw-page-title-main">Articaine</span> Chemical compound

Articaine is a dental amide-type local anesthetic. It is the most widely used local anesthetic in a number of European countries and is available in many countries. It is the only local anaesthetic to contain a thiophene ring, meaning it can be described as 'thiophenic'; this conveys lipid solubility.

<span class="mw-page-title-main">Chloroprocaine</span> Local anaesthetic drug

Chloroprocaine is a local anesthetic given by injection during surgical procedures and labor and delivery. Chloroprocaine vasodilates; this is in contrast to cocaine which vasoconstricts. Chloroprocaine is an ester anesthetic.

<span class="mw-page-title-main">Levobupivacaine</span> Chemical compound

Levobupivacaine (rINN) is a local anaesthetic drug indicated for minor and major surgical anaesthesia and pain management. It is a long-acting amide-type local anaesthetic that blocks nerve impulses by inhibiting sodium ion influx into the nerve cells. Levobupivacaine is the S-enantiomer of racemic bupivacaine and therefore similar in pharmacological effects. The drug typically starts taking effect within 15 minutes and can last up to 16 hours depending on factors such as site of administration and dosage.

A retrobulbar block is a regional anesthetic nerve block in the retrobulbar space, which is 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 the extraocular muscles by blocking cranial nerves II, III, and VI, thereby preventing movement of the globe. Cranial nerve IV lies outside the muscle cone, and therefore is not affected by the local anesthesia. As a result, intorsion of the eye is still possible. It also provides sensory anesthesia of the conjunctiva, cornea and uvea by blocking the ciliary nerves. This block is most commonly employed for cataract surgery, but also provides anesthesia for other intraocular surgeries.

Dental anesthesia is the application of anesthesia to dentistry. It includes local anesthetics, sedation, and general anesthesia.

<span class="mw-page-title-main">Brachial plexus block</span>

Brachial plexus block is a regional anesthesia technique that is sometimes employed as an alternative or as an adjunct to general anesthesia for surgery of the upper extremity. This technique involves the injection of local anesthetic agents in close proximity to the brachial plexus, temporarily blocking the sensation and ability to move the upper extremity. The subject can remain awake during the ensuing surgical procedure, or they can be sedated or even fully anesthetized if necessary.

<span class="mw-page-title-main">Neosaxitoxin</span> Chemical compound

Neosaxitoxin (NSTX) is included, as other saxitoxin-analogs, in a broad group of natural neurotoxic alkaloids, commonly known as the paralytic shellfish toxins (PSTs). The parent compound of PSTs, saxitoxin (STX), is a tricyclic perhydropurine alkaloid, which can be substituted at various positions, leading to more than 30 naturally occurring STX analogues. All of them are related imidazoline guanidinium derivatives.

Fascia iliaca blocks is a local anesthetic nerve block, a type of regional anesthesia technique, used to provide analgesia or anaesthesia to the hip and thigh. FICB can performed by using ultrasound or with a loss of resistance technique, the latter sometimes referred to as the "two-pop-method". FICB works by affecting the femoral, obturator and the lateral cutaneous nerves with a local anesthetic.

Obstetric anesthesia or obstetric anesthesiology, also known as ob-gyn anesthesia or ob-gyn anesthesiology, is a sub-specialty of anesthesiology that provides peripartum pain relief (analgesia) for labor and anesthesia for cesarean deliveries ('C-sections').

<span class="mw-page-title-main">Caudal anaesthesia</span> Form of neuraxial regional anaesthesia

Caudal anaesthesia is a form of neuraxial regional anaesthesia conducted by accessing the epidural space via the sacral hiatus. It is typically used in paediatrics to provide peri- and post-operative analgesia for surgeries below the umbilicus. In adults, it can be used in the context of anorectal surgery or for chronic low back pain management.

References

  1. ↑ "Bupivacaine Use During Pregnancy". Drugs.com. 13 April 2020. Retrieved 21 September 2020.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 October 2023.
  3. ↑ "Marcaine- bupivacaine hydrochloride injection, solution Marcaine with epinephrine- bupivacaine hydrochloride and epinephrine bitartrate injection, solution". DailyMed. Retrieved 13 February 2021.
  4. ↑ "Sensorcaine MPF- bupivacaine hydrochloride injection, solution". DailyMed. Retrieved 13 February 2021.
  5. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 "Bupivacaine Hydrochloride". The American Society of Health-System Pharmacists. Archived from the original on 30 June 2015. Retrieved 1 August 2015.
  6. 1 2 Whimster DS (1997). Cambridge textbook of accident and emergency medicine. Cambridge: Cambridge University Press. p. 194. ISBN   9780521433792. Archived from the original on 5 October 2015.
  7. ↑ Egan TD (2013). Pharmacology and physiology for anesthesia : foundations and clinical application. Philadelphia, PA: Elsevier/Saunders. p. 291. ISBN   9781437716795. Archived from the original on 12 May 2016.
  8. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  9. 1 2 Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 22. ISBN   9781284057560.
  10. ↑ "Xaracoll: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 2 September 2020.
  11. 1 2 3 "FDA approval letter" (PDF). U.S. Food and Drug Administration (FDA). 28 August 2020. Retrieved 2 September 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  12. 1 2 "FDA Approves Xaracoll (bupivacaine HCl) Implant, a Non-opioid, Drug-device Treatment Option for Acute Postsurgical Pain Relief for up to 24 Hours Following Open Inguinal Hernia Repair in Adults" (Press release). Innocoll Pharmaceuticals. 31 August 2020. Retrieved 2 September 2020– via PR Newswire.
  13. ↑ Lexicomp. "Bupivacaine (Lexi-Drugs)". Archived from the original on 10 April 2014. Retrieved 20 April 2014.
  14. 1 2 3 Miller RD (2 November 2006). Basics of Anesthesia. Churchill Livingstone.
  15. ↑ Hussain N, Brull R, Sheehy B (February 2021). "Perineural Liposomal Bupivacaine Is Not Superior to Nonliposomal Bupivacaine for Peripheral Nerve Block Analgesia: A Systematic Review and Meta-analysis". Anesthesiology. 134 (2): 147–164. doi: 10.1097/ALN.0000000000003651 . PMID   33372953.
  16. ↑ Ma TT, Wang YH, Jiang YF, Peng CB, Yan C, Liu ZG, Xu WX (June 2017). "Liposomal bupivacaine versus traditional bupivacaine for pain control after total hip arthroplasty: A meta-analysis". Medicine. 96 (25): e7190. doi: 10.1097/MD.0000000000007190 . PMC   5484209 . PMID   28640101.
  17. ↑ Mont MA, Beaver WB, Dysart SH, Barrington JW, Del Gaizo DJ (January 2018). "Local Infiltration Analgesia With Liposomal Bupivacaine Improves Pain Scores and Reduces Opioid Use After Total Knee Arthroplasty: Results of a Randomized Controlled Trial". The Journal of Arthroplasty. 33 (1): 90–96. doi: 10.1016/j.arth.2017.07.024 . PMID   28802777.
  18. ↑ "Durect Corporation Announces U.S. FDA Approval of Posimir For Post-Surgical Pain Reduction for up to 72 Hours Following Arthroscopic Subacromial Decompression" (Press release). Durect Corporation. 2 February 2021. Retrieved 13 February 2021– via PR Newswire.
  19. 1 2 3 4 5 6 7 "Bupivacaine (Lexi-Drugs)". Archived from the original on 10 April 2014. Retrieved 20 April 2014.
  20. ↑ de La Coussaye JE, Eledjam JJ, Brugada J, Sassine A (1993). "[Cardiotoxicity of local anesthetics]". Cahiers d'Anesthésiologie. 41 (6): 589–598. PMID   8287299.
  21. ↑ Australian Medicines Handbook. Adelaide. 2006. ISBN   978-0-9757919-2-9.
  22. ↑ "Filipino nurse dies in UK due to wrong use of anaesthetic". ABS-CBN Interactive. 28 January 2014. Archived from the original on 9 July 2007.
  23. ↑ Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ (April 1998). "Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats". Anesthesiology. 88 (4): 1071–1075. doi: 10.1097/00000542-199804000-00028 . PMID   9579517. S2CID   1661916.
  24. ↑ Weinberg G, Ripper R, Feinstein DL, Hoffman W (2003). "Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity". Regional Anesthesia and Pain Medicine. 28 (3): 198–202. doi:10.1053/rapm.2003.50041. PMID   12772136. S2CID   6247454.
  25. ↑ Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB (July 2006). "Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest". Anesthesiology. 105 (1): 217–218. doi: 10.1097/00000542-200607000-00033 . PMID   16810015. S2CID   40214528.
  26. ↑ Litz RJ, Popp M, Stehr SN, Koch T (August 2006). "Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion". Anaesthesia. 61 (8): 800–801. doi:10.1111/j.1365-2044.2006.04740.x. PMID   16867094. S2CID   43125067.
  27. ↑ Picard J, Meek T (February 2006). "Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob". Anaesthesia. 61 (2): 107–109. doi:10.1111/j.1365-2044.2005.04494.x. PMID   16430560. S2CID   29843241.
  28. ↑ Gulihar A, Robati S, Twaij H, Salih A, Taylor GJ (December 2015). "Articular cartilage and local anaesthetic: A systematic review of the current literature". Journal of Orthopaedics. 12 (Suppl 2): S200–S210. doi:10.1016/j.jor.2015.10.005. PMC   4796530 . PMID   27047224.
  29. ↑ "bupivacaine hydrochloride (Bupivacaine Hydrochloride) injection, solution". FDA. Archived from the original on 21 April 2014. Retrieved 20 April 2014.
  30. 1 2 "Exparel: Pending EC decision". European Medicines Agency (EMA). 17 September 2020. Archived from the original on 23 September 2020. Retrieved 21 September 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  31. ↑ "Exparel liposomal EPAR". European Medicines Agency (EMA). 15 September 2020. Retrieved 11 December 2020.
  32. ↑ "Bupivacaine Effectiveness and Safety in SABER Trial (BESST)". ClinicalTrials.gov. 20 January 2010. Archived from the original on 27 December 2011. Retrieved 1 March 2012.
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