Bupivacaine

Bupivacaine Uses, Dosage, Side Effects, Food Interaction and all others data.

Bupivacaine injectioin is a preparation of bupivacaine, a long acting local anaesthetic agent that belongs to amide group. It blocks the generation and the conduction of nerve impulses, by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential.

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.

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 minDuration of action (route and dose-dependent): 2-9 hrHalf life: neonates, 8.1 hr, adults: 2.7 hrTime to peak plasma concentration (for peripheral, epidural, or caudal block): 30-45 minProtein binding: about 95%Metabolism: hepaticExcretion: renal (6% unchanged)Bupivacaine is a widely used local anesthetic agent. Bupivacaine is often administered by spinal injection prior to total hip arthroplasty. It is also commonly injected into surgical wound sites to reduce pain for up to 20 hours after surgery. In comparison to other local anesthetics it has a long duration of action. It is also the most toxic to the heart when administered in large doses. This problem has led to the use of other long-acting local anaesthetics:ropivacaine and levobupivacaine. Levobupivacaine is a derivative, specifically an enantiomer, of bupivacaine. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both.

Bupivacaine is a widely used local anesthetic agent. Bupivacaine is often administered by spinal injection prior to total hip arthroplasty. It is also commonly injected into surgical wound sites to reduce pain for up to 20 hours after surgery. In comparison to other local anesthetics it has a long duration of action. It is also the most toxic to the heart when administered in large doses. This problem has led to the use of other long-acting local anaesthetics:ropivacaine and levobupivacaine. Levobupivacaine is a derivative, specifically an enantiomer, of bupivacaine. Systemic absorption of local anesthetics produces effects on the cardiovascular and central nervous systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance are minimal. However, toxic blood concentrations depress cardiac conduction and excitability, which may lead to atrioventricular block, ventricular arrhythmias and to cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilation occurs, leading to decreased cardiac output and arterial blood pressure. Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression or both.

Bupivacaine
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Bupivacaine
Availability	Prescription only
Generic	Bupivacaine
Bupivacaine Other Names	Bupivacaina, Bupivacaine, Bupivacainum, DL-Bupivacaine, Racemic bupivacaine
Related Drugs	fentanyl, lidocaine ophthalmic, ketorolac, Toradol, cocaine nasal, cefotaxime, tetracaine topical, piperacillin, ropivacaine, Marcaine
Weight	5mg/ml
Type	Injectable Solution, Intrathecal Solution, Intravenous Solution, Implantation, Injection
Formula	C₁₈H₂₈N₂O
Weight	Average: 288.4277 Monoisotopic: 288.220163528
Protein binding	Bupivacaine is ~95% protein bound.
Groups	Approved, Investigational
Therapeutic Class	Regional anesthesia
Manufacturer	Accord Healthcare Limited
Available Country	United Kingdom, Australia, United States, Indonesia
Last Updated:	September 19, 2023 at 7:00 am

Uses

Bupivacaine is used for the production of local or regional anaesthesia or analgesia for surgery, for oral surgery procedures, for diagnostic and therapeutic procedures, and for obstetrical procedures. The routes of administration and used Bupivacaine concentrations are:

Local infiltration: 0.25%
Peripheral nerve block: 0.25%, 0.5%
Sympathetic block: 0.25%
Lumbar epidural: 0.25%, 0.5% and 0.75% (non-obstetrical)
Caudal: 0.25%, 0.5%

Bupivacaine is also used to associated treatment for these conditions: Acute Gouty Arthritis, Adrenal cortical hypofunctions, Alopecia Areata (AA), Ankylosing Spondylitis (AS), Berylliosis, Bullous dermatitis herpetiformis, Congenital Adrenal Hyperplasia (CAH), Congenital Hypoplastic Anemia, Dermatomyositis, Discoid Lupus Erythematosus (DLE), Edema of the cerebrum, Epicondylitis, Hemolytic Anemia, Keloid Scars, Leukemias, Mycosis Fungoides (MF), Necrobiosis lipoidica diabeticorum, Ocular Inflammation, Ophthalmia, Sympathetic, Osteoarthritis (OA), Pain, Labor, Polymyositis, Postoperative pain, Psoriatic Arthritis, Psoriatic plaque, Pure Red Cell Aplasia, Regional Enteritis, Rheumatoid Arthritis, Secondary thrombocytopenia, Stevens-Johnson Syndrome, Synovitis, Systemic Lupus Erythematosus (SLE), Temporal Arteritis, Trichinosis, Tuberculous Meningitis, Ulcerative Colitis, Uveitis, Acute Bursitis, Acute Idiopathic Nephrotic Syndrome, Acute Lupus Erythematosus, Acute Multiple sclerosis, Acute Rheumatic heart disease, unspecified, Acute nonspecific tenosynovitis, Cancer-associated hypercalcemia, Cystic tumors of aponeurosis, Cystic tumors of tendon, Disseminated Pulmonary Tuberculosis, Exfoliative erythroderma, Inflammatory lesions of granuloma annulare, Inflammatory lesions of lichen planus, Inflammatory lesions of lichen simplex, Non-suppurative Thyroiditis, Permphigus, Severe Allergic Reactions, General Anesthesia, Regional nerve block therapy, Local anesthesia therapy

How Bupivacaine works

Local anesthetics such as bupivacaine block the generation and the conduction of nerve impulses, presumably by increasing the threshold for electrical excitation in the nerve, by slowing the propagation of the nerve impulse, and by reducing the rate of rise of the action potential. Bupivacaine prevents depolarization by bindng to the intracellular portion of sodium channels and blocking sodium ion influx into neurons. In general, the progression of anesthesia is related to the diameter, myelination and conduction velocity of affected nerve fibers. Clinically, the order of loss of nerve function is as follows: (1) pain, (2) temperature, (3) touch, (4) proprioception, and (5) skeletal muscle tone. The analgesic effects of Bupivicaine are thought to potentially be due to its binding to the prostaglandin E2 receptors, subtype EP1 (PGE2EP1), which inhibits the production of prostaglandins, thereby reducing fever, inflammation, and hyperalgesia.

Dosage

Bupivacaine dosage

Percutaneous infiltration anesthesia For prolonged action: 9 mg with adrenaline (1 in 200,000), may repeat 2-10 mins later if needed. Max: 90 mg per dental sitting.

Peripheral nerve block: 12.5 mg (as 0.25% solution) or 25 mg (as 0.5% solution). Max: 150 mg/dose.

Sympathetic nerve block: As 0.25% solution: 50-125 mg.

Retrobulbar block: As 0.75% solution: 15-30 mg.

Caudal block In surgery: 37.5-75 mg (as 0.25% solution) or 75-150 mg (as 0.5% solution). Lumbar epidural block In surgery: 25-50 mg (as 0.25% solution) and 50-100 mg (as 0.5% solution).

Side Effects

Central Nervous System and Neurological: Restlessness, excitement, nervousness, dizziness, tinnitus, blurred vision, miosis, nausea, vomiting, numbness of the tongue and perioral region, chills, tremors, muscle twitching, convulsions.

Cardiovascular System Reactions: Myocardial depression and peripheral vasodilatation resulting hypotension and bradycardia, ventricular arrhythmia, cardiac arrest.

Hypersensitivity: urticaria, pruritus, erythema, angioneurotic edema ,tachycardia, sneezing, nausea, vomiting, dizziness, syncope, excessive sweating, elevated temperature, and possibly, anaphylactoid reactions.

Toxicity

The mean seizure dosage of bupivacaine in rhesus monkeys was found to be 4.4 mg/kg with mean arterial plasma concentration of 4.5 mcg/mL. The intravenous and subcutaneous LD 50 in mice is 6 to 8 mg/kg and 38 to 54 mg/kg respectively. Recent clinical data from patients experiencing local anesthetic induced convulsions demonstrated rapid development of hypoxia, hypercarbia, and acidosis with bupivacaine within a minute of the onset of convulsions. These observations suggest that oxygen consumption and carbon dioxide production are greatly increased during local anesthetic convulsions and emphasize the importance of immediate and effective ventilation with oxygen which may avoid cardiac arrest.

Precaution

Readiness for emergencies.The lowest dosage that gives effective anaesthesia should be used in order to avoid high plasma levels and serious systemic side effects. Injection of repeated doses of Bupivacaine Hydrocholoride may cause significant increase in blood levels with each additional dose, due to accumulation of the drug or its metabolites or due to slow metabolic degradation. Tolerance varies with the status of the patient. Debilitated, elderly patients and acutely ill patients should be given reduced doses commensurate with age and physical condition. Caution is advised in administration of repeat doses of Bupivacaine Hydrocholoride to patients with severe liver disease.Local anaesthetic procedures should be used with caution when there is inflammation and/or sepsis in the region of the proposed injection.

Interaction

Bupivacaine should be used with caution in patients receiving other local anaesthetics or agents structurally related to amide‐type local anaesthetics, e.g. certain anti‐arrhythmics, such as lidocaine and mexiletine, since the systemic toxic effects are additive.Specific interaction studies with Bupivacaine and anti arrhythmic drugs class III (e.g. amiodarone) have not been performed, but caution should be advised.

Food Interaction

No interactions found.

Bupivacaine Drug Interaction

Unknown: aspirin, aspirin, epinephrine, epinephrine, diphenhydramine, duloxetine, duloxetine, hydromorphone, hydromorphone, pregabalin, pregabalin, acetaminophen, acetaminophen, acetaminophen, valproic acid, valproic acid, cyanocobalamin, cyanocobalamin, cholecalciferol, cholecalciferol

Bupivacaine Disease Interaction

Moderate: cardiovascular disease, liver disease, renal impairment

Elimination Route

Systemic absorption of local anesthetics is dose- and concentration-dependendent on the total drug administered. Other factors that affect the rate of systemic absorption include the route of administration, blood flow at the administration site, and the presence or absence of epinephrine in the anesthetic solution.

Bupivacaine formulated for instillation with meloxicam produced varied systemic measures following a single dose of varying strength. In patients undergoing bunionectomy, 60 mg of bupivacaine produced a C_max of 54 ± 33 ng/mL, a median T_max of 3 h, and an AUC_∞ of 1718 ± 1211 ng*h/mL. For a 300 mg dose used in herniorrhaphy, the corresponding values were 271 ± 147 ng/mL, 18 h, and 15,524 ± 8921 ng*h/mL. Lastly, a 400 mg dose used in total knee arthroplasty produced values of 695 ± 411 ng/mL, 21 h, and 38,173 ± 29,400 ng*h/mL.

Half Life

2.7 hours in adults and 8.1 hours in neonates.

Bupivacaine applied together with meloxicam for postsurgical analgesia had a median half-life of 15-17 hours, depending on dose and application site.

Elimination Route

Only 6% of bupivacaine is excreted unchanged in the urine.

Pregnancy & Breastfeeding use

There are no adequate and well‐controlled studies in pregnant women of the effect of bupivacaine hydrochloride on the developing fetus. Bupivacaine should not therefore be given in early pregnancy only if the potential benefit justifies the potential risk to the fetus. Bupivacaine enters the mother's milk, but in such small quantities that there is no risk of affecting the child at therapeutic dose levels.

Contraindication

Hypersensitivity to Bupivacaine, other amide type local anaesthetics or other components of these preparations; Intravenous regional anaesthesia; obstetrical paracervical block anaesthesia.

Special Warning

Paediatrics: For children a reduced dose based on body weight and surface area should be used. The dosage should be calculated for each patient individually and modified in accordance with the physician's experience and knowledge of the patient.

Geriatrics: A reduction in dosage may be necessary for elderly patients especially those with compromised cardiovascular and/or hepatic function. Where epidural administration is to be used, a small dose may provide sufficient anaesthesia.

Impaired hepatic function: Although bupivacaine is metabolised by the liver, dosage reduction is probably not warranted. However, caution should be exercised with repeated doses.

Impaired renal function: Impairment of renal function is unlikely to affect bupivacaine clearance in the short term (up to 24 hours). However, toxicity due to accumulation may develop with prolonged or repeated administration.