Bupivacaine (Marcaine) block nerve conduction and initiation by decreasing the permeability of neurons to sodium influx.

It is used in the following situations:

• • It can be used as local or regional anesthesia;
  • It is widely used in spinal anesthesia (0.75% in dextrose 8.25% injection);
  • It can also be used in diagnostic and therapeutic procedures;
  • It is used in obstetrical procedures (only 0.25% and 0.5% concentrations)

• 0.25%:

  • Local infiltration, peripheral nerve block, sympathetic block, caudal or epidural block

• 0.5%:

  • Peripheral nerve block, caudal and epidural block

• 0.75% (not for obstetrical anesthesia):

  • Retrobulbar block, epidural block.

Bupivaciane Dose in Adults

• Its dose changes with the procedure, depth of anesthesia, vascularity of tissues, duration of anesthesia, and condition of the patient.
• Solutions having preservatives should not be used for caudal or epidural block.

Use in the treatment of Local anesthesia:

• Infiltration:

  • 0.25% is infiltrated locally
  • The maximum dose is 175 mg.

• Aspiration is done prior to each injection; however, the absence of blood in the syringe does not guarantee that intravascular injection has been averted

• Caudal block (preservative-free):

  • 15 to 30 mL of 0.25% or 0.5% is used

• Epidural block (other than caudal block; preservative-free):

  • Give in 3 to 5 mL increments.

  • It gives sufficient time to detect any harmful manifestations of unintentional IV or intrathecal administration:

    • 10 to 20 mL of 0.25% or 0.5% is used

  • Surgical procedures which need a high degree of muscle relaxation and prolonged effects only:

    • 10 to 20 mL of 0.75% is used

• Peripheral nerve block:

  • 5 mL of 0.25% or 0.5% is used
  • The maximum dose is 400 mg/day

• Sympathetic nerve block:

  • 20 - 50 mL of 0.25% is used

• Retrobulbar anesthesia:

  • 2 - 4 mL of 0.75% is used

• Spinal anesthesia:

  • Solution free of preservatives of 0.75% bupivacaine in 8.25% dextrose:

  • Lower extremity and perineal procedures:

    • 1 mL is given

  • Lower abdominal procedures:

    • 1.6 mL is given

  • Normal vaginal delivery:

    • 0.8 mL is given (higher doses are required in some patients)

  • Cesarean delivery:

    • 1 to 1.4 mL is given

Combined spinal-epidural technique for labor analgesia (off-label dosing [spinal component]):

• 1.75 - 2.5 mg is added with fentanyl 15 mcg

Combined spinal-epidural technique for anesthesia for Cesarean delivery (off-label dosing [spinal component]):

• 9 -12 mg is used with fentanyl 15 mcg
• in addition to fentanyl, a longer-acting opioids can only be used  (ie, morphine 100 to 150 mcg) for postoperative analgesia.

Bupivaciane Dose in Children

• Bupivacaine dose changes with the procedure, depth of anesthesia, vascularity of tissues, duration of anesthesia, and condition of the patient.
• Formulations free of preservatives are used for administration into the CNS space (eg, epidural, caudal, spinal).
• Consider incremental administration with negative aspiration before giving the injection
• however, the absence of blood in the syringe does not guarantee that intravascular injection has been avoided.
• It should only be given under the supervision of a qualified physician experienced in the use of anesthetics.
• In pediatric patients, dosing should be based on lean body mass.

Bupivacaine use in the treatment of Central nerve block/anesthesia:

• Caudal block:

  • Infants and Children:

    • The usual concentration of 0.25% solution or less with or without epinephrine can be used:

      • Mostly reported dose range is  0.5 - 1.3 mL/kg
      • The maximal volume of drug is 20 mL
      • The maximum dose is 2 mg/kg plain solution, or 3 mg/kg with epinephrine.
      • In infants, routine use of concentrations less than 0.25% has been advised to reduce the risk of bupivacaine cardiotoxicity.

  • Adolescents:

    • Usual concentration 0.25 to 0.5% solution with or without epinephrine:
    • 15 to 30 mL is used

• Epidural block:

  • Reported dosing variable
  • among other factors, dose-dependent on necessary dermatome level and the corresponding volume of epidural space :

  • Infants:

    • The usual concentration is ≤0.25% with or without epinephrine:
    • 0.7 to 0.75 mL/kg is given
    • The maximum dose is 2.5 mg/kg
    • For infants (mainly young infants), if injections have to be repeated, a decreased dose might be necessary to avoid drug accumulation.
    • Some people also suggest if at least 45 minutes since 1st dose,
    • reduce dose to/of the initial or if at least 90 minutes since 1st dose, then reduce dose to half of the initial.
    • If additional doses have to be given then doses should be reduced to half of the previous dose.

  • Children:

    • Usual concentration is 0.25% solution:
    • Initially, 0.3 to 0.6 mL/kg is given (with the maximum volume of the drug: 20 mL) to a maximum dose of 2.5 mg/kg

  • Adolescents:

    • 0.25% or 0.5% solution:
    • 10 to 20 mL is given in 3 to 5 mL increments
    • if a high degree of muscle relaxation and prolonged effects are required, might consider 0.75% solution: 10 to 20 mL

• Epidural, continuous infusion: Limited data available in infants and children <12 years

  • • Loading dose: Usual concentration given : 0.25%:
      • 2 to 2.5 mg/kg is used

• Infusion:

  • Infants <4 months:

    • 0.2 mg/kg/hour is given

  • Infants ≥4 months:

    • 0.25 mg/kg/hour is given

  • Children and Adolescents:

    • 0.3 mg/kg/hour is given

Use in the treatment of Peripheral nerve block: Limited data available in infants and children:

• Infants ≥6 months and Children:

  • The usual concentration is 0.125% or 0.25% solution with or without epinephrine:
    • The volume of dose (mL/kg) and concentration of solution usually site-specific according to anatomy and variable among patients and procedure.
    • For infants aged less than 6 months, maximum doses are reduced by 30%.
    • Maximum dose plain solution is 2 mg/kg or 150 mg whichever is less
    • maximum dose with epinephrine is 3 mg/kg or 200 mg of bupivacaine whichever is less.

  • Commonly suggested doses:

    • Head and neck:

      • 0.05 mL/kg is given

    • Upper extremity:

      • Brachial plexus:

        • 0.2- 0.3 mL/kg is given

      • Digital nerve:

        • 0.05 mL/kg is given

    • Truncal blocks:

      • Transversus abdominis plane:

        • 0.2 -0.5 mL is given

      • Rectus sheath:

        • 0.1 mL/kg is given

      • Ilioinguinal:

        • 0.075 mL/kg is given

    • Lower extremity blocks:

      • Femoral nerve:

        • 0.2 - 0.3 mL/kg is given

      • Sciatic nerve:

        • 0.2 - 0.3 mL/kg is given

  • Adolescents:

    • 0.25% or 0.5% solution is given with or without epinephrine:
      • 5 mL is given
      • The maximum daily dose is 400 mg/day

Use in the treatment of Local anesthesia:

• Infants, Children, and Adolescents:
  • Usual concentration is  0.25% solution
  • Infiltrate area local
  • The maximum dose in infants and children is 2.5 mg/kg or 150 mg whichever is less
  • The maximum dose in adolescents is 175 mg

Bupivacaine (Marcaine) Pregnancy Risk Factor: C

• During animal reproduction studies, adverse events were observed.
• Bupivacaine crosses the placenta.
• Bupivacaine can be used in obstetrical pain relief or analgesia at any time.
  • For obstetrical Anesthesia, a dose of 0.75 percent is not recommended.

Use of buprevacaine (Marcaine), during breastfeeding

• Bupivacaine 0.755% solutions can also cause cardiac arrest in patients who have received epidural anesthesia. It is not recommended to use this concentration for this purpose.
• It is not recommended for use in obstetrical paracervical anesthesia.
• It is excreted from breast milk.
• Nursing infants are at risk for serious adverse reactions. It is important to decide whether to stop nursing and/or discontinue using the drug.

Bupivacaine (Marcaine) dose in kidney disease:

• There are no dosage adjustments given in the manufacturer’s labeling
• use with caution.

Bupivacaine (Marcaine) dose in Liver disease:

• There are no dosage adjustments given in the manufacturer’s labeling
• use with caution.

Frequency of side effects of Bupivaciane is not defined.

Reactions listed are based on reports for other agents in this same pharmacologic class and may not be specifically reported for bupivacaine.

• Cardiovascular:

  • Bradycardia
  • Cardiac insufficiency
  • Circulatory shock
  • Heart block
  • Hypotension
  • Ventricular arrhythmia

• Central nervous system:

  • Anxiety
  • Arachnoiditis
  • Central nervous system depression
  • Central nervous system stimulation
  • Chills
  • Cranial nerve palsy
  • Dizziness
  • Headache
  • Localized numbness (perineal)
  • Meningism
  • Paralysis
  • Paraplegia
  • Paresthesia
  • Persistent anesthesia
  • Restlessness
  • Seizure
  • Shivering

• Gastrointestinal:

  • Fecal incontinence
  • Loss of anal sphincter control
  • Nausea
  • Vomiting

• Genitourinary:

  • Prolonged labor
  • Sexual disorder (loss of function)
  • Urinary incontinence
  • Urinary retention

• Hematologic & oncologic:

  • Methemoglobinemia

• Hypersensitivity:

  • Hypersensitivity reaction

• Infection:

  • Septic meningitis

• Neuromuscular & skeletal:

  • Asthenia
  • Back pain
  • Lower extremity weakness
  • Tremor

• Ophthalmic:

  • Blurred vision
  • Miosis

• Otic:

  • Tinnitus

• Respiratory:

  • Apnea
  • Hypoventilation (usually associated with unintentional subarachnoid injection during high spinal anesthesia)
  • Respiratory paralysis

Contraindication to Bupivacaine (Marcaine) include:

• Hypersensitivity to bupivacaine Hydrochloride, amide type local anesthetics or any part thereof; obstetrical paracervicalblock anesthesia
• Anesthesia for obstetric paracervical block
• Patients with severe shock and heart block
• Inflammation and infection around the injection site.

Warnings and precaution:

• Cardiovascular effects

  • It can lead to arrhythmias, heart arrest, and even death.
  • Infusion-related intra-articular chondrolysis
  • Chondrolysis, primarily of the shoulder joint, has been seen in the following infusion. Some patients may need arthroplasty or shoulder replacement.

• Methemoglobinemia

  • It was seen using local anesthetics
    • Clinically significant methemoglobinemia must be treated immediately.
    • The onset can occur immediately or after a prolonged period of anesthetic treatment.
    • Patients with (G6PD), glucose-6-phosphate-dehydrogenase deficiency or congenital or irreversible methemoglobinemia, cardiac compromise, or exposure to oxidizing agent or their metabolites or infants under 6 months old are at risk. They should be closely monitored for signs of methemoglobinemia (eg, cyanosis and light-headedness, fatigue and rapid pulse, shortness or breath),

• Respiratory arrest

  • A rare case of sudden respiratory arrest has been reported with local anesthetics, particularly when administered close to the neck or head.

• Seizures

  • Systemic toxicities can cause convulsions, leading to cardiac arrest. This has been observed presumably after intravascular injections or near the neck or head.

• Cardiovascular disease

  • Patients with heart disease, including those with hypotension, or heart block, should be careful.

• Hepatic impairment

  • Patients with hepatic impairment should be cautious.

Bupivacaine: Drug Interaction

Monitor:

• Vital signs
• state of consciousness
• signs of CNS toxicity

How to administer Bupivacaine?

• Preservative-containing solutions are not recommended for use in epidural and caudal blocks.
• The Infusion Pump On-Q is used to administer local anesthetics such as bupivacaine (eg lidocaine or ropivacaine) slowly to surgical wounds and/or to the peripheral nerves to provide postoperative pain relief.
• Injecting directly into the shoulder can cause articular cartilage destruction (chondrolysis).
• Never place On-Q pumps directly in any joint.

Mechanism of action of Bupivacaine (Marcaine):

• It reduces the neuronal membrane's permeability for sodium ions, which blocks both conduction and initiation of nerve impulses.
• It causes depolarization inhibition and conduction blockade.

The beginning of action: Anesthesia (route- and dose-dependent).

• Epidural: Takes up to 17 minutes to spread T6 dermatome
• Infiltration Fast
• Dental injections: 2-10 minutes
• Spinal: In 1 Minute
• Maximum dermatome level reached in 15 minutes most of the time

Duration (route and dose-dependent):

• Epidural: 2 to 7.7 hours
• Infiltration: 2 to 8 hours
• Dental injection: Up to 7 hours
• Spinal: 1.5 to 2.5 hours

Distribution: V : Infants:

• 3.9 ± 2 L/kg
• Children: 2.7 ± 0.2 L/kg

Protein binding:

• 84% to 95%

Metabolism:

• Mainly Hepatic; forms metabolite (pipecoloxylidine [PPX])

Half-life elimination (age-dependent):

• Neonates: 8.1 hours
• Adults: 2.7 hours

Time to peak, plasma:

• Caudal, epidural, or peripheral nerve block:
• 30 to 45 minutes

Excretion:

• Via Urine (~6% unchanged)

Clearance:

• Infants: 7.1 ± 3.2 mL/kg/minute
• Children: 10 ± 0.7 mL/kg/minute

Pharmacodynamics and Pharmacokinetics: Additional Considerations Geriatric:  

• Elderly patients reached the maximal spread of analgesia and maximal motor blockade quickly than younger patients.
• Elderly patients also showed higher peak plasma concentrations following the administration of this product.
• The total plasma clearance was decreased in these patients.

Bupivacaine international brands:

• Bupivacaine Spinal
• Marcaine
• Marcaine Preservative Free
• Marcaine Spinal
• P-Care M
• ReadySharp Bupivacaine Sensorcaine
• Sensorcaine-MPF
• Sensorcaine-MPF Spinal
• Anawin
• Anekain
• Betolina
• Bucain
• Bucaine
• Bunascan Spinal
• Bupicaina
• Bupican
• Bupican Heavy
• Bupine
• Bupinest S.P.
• Bupinex
• Bupiright
• Bupivacain Jenapharm
• Bupivacain-RPR
• Bupivacain-RPR CO!2
• Bupivacaine Aguettant
• Bupivacaine B.
• Braun
• Buvacaina
• Buvacainas
• Buvanest Spinal
• Carbostesin
• Chlorhydrate de Bupivacaine Dakota
• Dolanaest
• Duracain
• Duracaine
• Indevus Spinal Heavy
• Inibsacain
• Kamacaine
• Longocain
• Macaine
• Marcain Spinal
• Marcaina
• Marcaine
• Marcaine Heavy
• Marcaine Plain
• Marcaine Spinal Heavy
• Markyrene
• Nerkein
• Omnicain
• Pinacain
• Pucaine
• Recain
• Regivell
• Sanspen
• Senpivac
• Sivicaine Heavy
• Spica Spinal
• Sunnypivacaine
• Ultracaine

Bupivacaine brands in Pakistan: