From the Guidelines
Bupivacaine toxicity presents with a progression of symptoms affecting multiple body systems, including CNS and cardiovascular symptoms, and management involves immediate cessation of bupivacaine administration, securing the airway, and administering 20% lipid emulsion therapy. The symptoms of bupivacaine toxicity can be divided into two main categories: central nervous system (CNS) toxicity and cardiovascular toxicity. CNS toxicity, which occurs in 77% to 89% of patients with local anesthetic systemic toxicity (LAST), includes symptoms such as seizures, agitation, syncope, obtundation, and dizziness 1. Cardiovascular toxicity, which occurs in 32% to 55% of patients with LAST, can be life-threatening and includes symptoms such as hypotension, bradycardia, and cardiac arrhythmias, including asystole, ventricular fibrillation, and ventricular tachycardia 1.
Management of Bupivacaine Toxicity
Management of bupivacaine toxicity begins with immediate cessation of bupivacaine administration and calling for help. The next steps include:
- Securing the airway, providing supplemental oxygen, and establishing IV access.
- Treating seizures with benzodiazepines, such as midazolam 2-5 mg IV or diazepam 5-10 mg IV.
- For cardiovascular collapse, initiating CPR if needed and administering 20% lipid emulsion therapy, with a bolus of 1.5 mL/kg followed by an infusion of 0.25 mL/kg/min for 30-60 minutes 1.
- Avoiding the use of lidocaine for arrhythmias, as it may worsen toxicity.
- Using vasopressors like epinephrine (10-100 mcg IV boluses) as needed for hypotension.
Prevention of Bupivacaine Toxicity
Prevention of bupivacaine toxicity is crucial and involves:
- Proper dosing, with a maximum dose of 2-3 mg/kg, and lower doses in elderly or debilitated patients.
- Aspiration before injection to avoid intravascular administration.
- Incremental administration of the drug.
- Use of ultrasound guidance to ensure accurate placement of the drug.
Bupivacaine toxicity occurs because the drug blocks sodium channels in neural and cardiac tissue, with cardiac toxicity occurring at lower concentrations than other local anesthetics due to its high protein binding and lipophilicity 1. The use of 20% lipid emulsion therapy has been shown to be effective in treating bupivacaine toxicity, and its administration is supported by animal studies, case reports, and registry studies 1.
From the FDA Drug Label
OVERDOSAGE Acute emergencies from local anesthetics are generally related to high plasma levels encountered during therapeutic use of local anesthetics or to unintended subarachnoid injection of local anesthetic solution If not treated immediately, convulsions with simultaneous hypoxia, hypercarbia, and acidosis plus myocardial depression from the direct effects of the local anesthetic may result in cardiac arrhythmias, bradycardia, asystole, ventricular fibrillation, or cardiac arrest. Respiratory abnormalities, including apnea, may occur 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 symptoms of bupivacaine toxicity include:
- Convulsions
- Cardiac arrhythmias
- Bradycardia
- Asystole
- Ventricular fibrillation
- Cardiac arrest
- Respiratory abnormalities, including apnea
- Hypoxia
- Hypercarbia
- Acidosis The management of bupivacaine toxicity involves:
- Establishment and maintenance of a patent airway and effective assisted or controlled ventilation with 100% oxygen
- Use of drugs to control convulsions, such as succinylcholine, diazepam, or thiopental
- Supportive treatment of circulatory depression, including administration of intravenous fluids and vasopressors
- Endotracheal intubation if necessary 2
From the Research
Symptoms of Bupivacaine Toxicity
- Central nervous system toxicity, including seizures and generalized convulsions 3, 4
- Cardiovascular toxicity, including dysrhythmias, asystole, and cardiac arrest 5, 6, 4
- Hemodynamic instability and cardiovascular collapse 3, 7
- Initial stimulating effects, followed by depressive components at higher concentrations 4
Management of Bupivacaine Toxicity
- Resuscitation with epinephrine and/or lipid emulsion 6
- External cardiac compressions and ventilation with 100% oxygen 6
- Administration of Intralipid infusion for treatment of cardiovascular collapse 7
- Use of vasopressin in combination with Intralipid may not be as effective as epinephrine and Intralipid combination 6
- Lipid resuscitation has been recommended for the treatment of local anesthetic-induced cardiac arrest 6
Comparison of Local Anesthetics
- Bupivacaine has a higher systemic toxicity compared to levobupivacaine and ropivacaine 5
- Ropivacaine appears to be the safest long-acting local anesthetic, with less cardiotoxicity compared to bupivacaine 4
- The use of pure optical S-(-)-isomers of local anesthetics may help to reduce catastrophic events 4