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Bupivacaine toxicity Rx


Based on the symptomatology. Treat seizures withGABA agonists. Treat convulsions withparalytics and airway management.Vasopressorsmay be indicated, although in some animal models they have been shown to promote CNS toxicity (still, on that basis they should not be withheld in the setting of cardiovascular collapse). Total cardiovascular collapse may be treated withCPR plus 1.5-4 mL/kg bolus of 20% lipid solution followed by 0.25-0.5 mL/kg/min for 10-60 minutes.

Bupivacaine Toxicity

  • Seizures: GABA agonists
  • Convulsions: paralytics and airway management as needed
  • Hypotension: vasopressors
  • Cardiovascular collapse: 20% intralipid (4 mL/kg then 0.5 mL/kg/min in Barash, 1.5 mL/kg then 0.25 mL/kg/min according to Guy Weinberg [founder of LipidRescue])


Dose-dependent blockade of sodium channels. Of note,1) bupivacaine binds more strongly to resting/inactivated Na channels as compared to lidocaine, and 2) bupivacaine dissociates from Na channels during diastole more slowly than lidocaine.

Diagnosis of LA Systemic Toxicity

Most local anesthetics produce a similar array of signs and symptoms, although the ratio of neurotoxicity:cardiotoxicity may be substantially different (with bupivacaine being the most cardiotoxic).

CNS signs

Initial CNS excitation followed by a rapid CNS depression– lightheadedness, dizziness, visual and auditory disturbances (difficulty focusing and tinnitus), disorientation, drowsiness, followed by muscle twitching, convulsions, unconsciousness, respiratory depression and arrest.

Cardiovascular signs

Direct cardiac effects

Myocardial depression (tetracaine, etidocaine, bupivacaine), cardiac dysrhythmias (bupivacaine), and cardiotoxicity in pregnancy. Negative inotropic effects on cardiac muscle that lead to hypotension. Bupivacaine is especially cardiotoxic.

Peripheral effects

Vasoconstriction at low doses, vasodilatation at higher doses (hypotension)

Cardiovascular signs and symptoms

Chest pain, shortness of breath, palpitations, lightheadedness, diaphoresis, hypotension, syncope

Hematological Signs of LA Systemic Toxicity

Methemoglobinemia has been frequently reported in association with benzocaine use; however, lidocaine and prilocaine have also been implicated. O-toluidine, the liver metabolite of prilocaine, is a potent oxidizer of hemoglobin to methemoglobin. At low levels (1-3%), methemoglobinemia can be asymptomatic, but higher levels (10-40%) may be accompanied by cyanosis, cutaneous discoloration (gray), tachypnea, dyspnea, exercise intolerance, fatigue, dizziness and syncope, and weakness.

Other References

  1. LipidRescue, by Guy Weinberg, MD, Accessed 2/27/15 Link
  2. Keys to the Cart: April 16, 2018; a 5-minute video review of ABA Keywords Link