Physiology · Year 1 · from Physiology
Case 3: Local Anesthetic Toxicity - Sodium Channel Blockade
Clinical Image
Source: Clinical illustration of sodium channel blockade mechanism
Patient Presentation
A 35-year-old female undergoes an interscalene brachial plexus block for shoulder surgery. Approximately 2 minutes after injection of 25 mL of 0.5% bupivacaine, she develops perioral numbness, tinnitus, metallic taste, and becomes increasingly agitated. She then has a generalized tonic-clonic seizure followed by cardiac arrest with pulseless electrical activity (PEA).
Demographics
- Age: 35 years
- Sex: Female
- Procedure: Interscalene nerve block with bupivacaine
Chief Complaint
Post-procedural seizure and cardiac arrest
Physical Examination (Pre-arrest)
- Mental status: Initially alert, then agitated, then unresponsive
- Neurological: Perioral and tongue numbness, tinnitus
- Cardiovascular: Tachycardia progressing to bradycardia, then PEA arrest
- Musculoskeletal: Generalized tonic-clonic seizure activity
Workup
- Clinical diagnosis based on timing and symptom progression
- ECG: Widened QRS complex, prolonged PR interval preceding arrest
- Arterial blood gas: Metabolic and respiratory acidosis during arrest
Diagnosis
Local Anesthetic Systemic Toxicity (LAST) from inadvertent intravascular injection or rapid systemic absorption of bupivacaine
Treatment
- Stop injection immediately
- Call for help and initiate LAST protocol
- Airway management with 100% oxygen (hyperventilation to raise pH)
- Benzodiazepines for seizures (avoid propofol in cardiovascular compromise)
- Intravenous lipid emulsion (Intralipid 20%): 1.5 mL/kg bolus followed by 0.25 mL/kg/min infusion - this is the specific antidote
- ACLS protocol if cardiac arrest occurs (avoid vasopressin, avoid large epinephrine doses)
- Consider cardiopulmonary bypass or ECMO if refractory
- Prolonged resuscitation may be required (patients can recover after prolonged CPR)
Physiological Principles Demonstrated
- Mechanism of local anesthetics: Local anesthetics block voltage-gated sodium channels from the intracellular side. They bind preferentially to the inactivated state (use-dependent block), which is why rapidly firing neurons are more susceptible.
- Action potential blockade: By preventing sodium channel opening, local anesthetics block the depolarization phase of the action potential, preventing nerve impulse propagation.
- CNS toxicity: The CNS is exquisitely sensitive to sodium channel blockade. Initial excitatory symptoms (seizures) occur because inhibitory interneurons are blocked first, releasing excitatory circuits from suppression. Higher doses block all neurons, causing CNS depression.
- Cardiac toxicity: Bupivacaine has high affinity for cardiac sodium channels and dissociates slowly ("fast-in, slow-out"). This prolongs QRS duration, decreases contractility, and can cause refractory arrhythmias and cardiac arrest.
- Lipid emulsion mechanism: Lipid emulsion creates a "lipid sink" that sequesters lipophilic bupivacaine from tissue binding sites. It also provides metabolic substrate for the myocardium and may enhance drug redistribution.
- Differential nerve block: Smaller, unmyelinated C fibers (pain) are blocked before larger myelinated A fibers (motor, proprioception) because they have higher surface-to-volume ratios and firing frequencies. This is why analgesia precedes motor block.