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, coma
Cardiovascular: hypotension, arrhythmia, bradycardia, heart block, cardiac arrestToxicity 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.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 cartilage 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, 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
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. Society and culture
Legal status
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. 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 of bupivacaine, with a longer duration of action, producing less vasodilation.