Episode 222: Local Anesthetic Systemic Toxicity (LAST)

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Show Notes I. Pathophysiology & Mechanisms

• Definition: Systemic toxicity secondary to local anesthetic (LA) via accidental intravascular injection or excessive systemic absorption.

• Threshold: Occurs when plasma concentration exceeds the safety threshold for cardiac and neural tissue.

• Agent Profile: Bupivacaine (High Risk)

  • Highly lipophilic with high protein binding.

  • “Fast-on, Slow-off” Kinetics: Strong Na+ channel binding with extremely slow dissociation during diastole.

  • Myocardial Depression: Direct inhibition of Ca2+ release from the sarcoplasmic reticulum, impairing contractility.

  • Low CC:CNS Ratio: The dose required for cardiac collapse is very close to the dose that triggers seizures (narrow safety margin).

• Contributing Factors:

  • Acidosis/Hypercapnia: Increases the fraction of free drug and promotes ion trapping in the brain/heart; shifts the LA-binding curve toward higher toxicity.

  • Hypoxemia: Exacerbates myocardial depression and lowers seizure threshold.

II. Risk Assessment & Prevention Patient-Specific Risk Factors

• Extremes of Age: Neonates (low α-1-acid glycoprotein) and elderly (reduced clearance).

• Body Composition: Low muscle mass/frailty (decreased volume of distribution).

• Organ Dysfunction:

  • Hepatic: Reduced metabolism of amide LAs.

  • Renal: Accumulation of metabolites; risk of metabolic acidosis lowering seizure threshold.

  • Cardiac: Reduced cardiac output slows hepatic delivery/clearance; heart failure patients are more sensitive to Na+ channel blockade.

• Pregnancy: Increased sensitivity to cardiotoxicity.

Procedural Risk Factors

• Vascularity of Site (Highest to Lowest Risk):

  1. Intercostal blocks (highest absorption rate).

  2. Caudal/Epidural.

  3. Interfascial plane blocks (e.g., TAP block).

  4. Psoas compartment/Sciatic.

  5. Brachial plexus.

• Technique: Large volume infiltration, lack of ultrasound, lack of incremental injection.

Prevention Mandates

• Weight-Based Dosing:

  • Lidocaine (Plain): Max 4.5 mg/kg.

  • Lidocaine (with Epi): Max 7 mg/kg.

  • Bupivacaine: Max 2.5–3 mg/kg.

• Incremental Injection: 3–5 mL aliquots with frequent aspiration.

• Intravascular Marker: Use Epinephrine (1:200,000) to detect accidental IV placement (HR increase >10 bpmor SBP increase >15 mmHg).

III. Clinical Presentation Neurologic Phase (Early to Late)

• Subjective: Metallic taste, tinnitus, circumoral numbness/tingling.

• Objective: Visual disturbances, agitation, confusion, tremors.

• Critical: Generalized tonic-clonic seizures, rapid progression to CNS depression, coma, and apnea.

• Note: Early phases are often masked in patients receiving midazolam or propofol.

Cardiovascular Phase

• Initial: Hypertension and tachycardia (if epi used) or transient stimulatory phase.

• Conduction Defects: PR prolongation, QRS widening (classic sign), bundle branch blocks.

• Dysrhythmias: Bradycardia (most common), VT/VF, PEA, asystole.

• Contractility: Profound, refractory hypotension and cardiogenic shock.

IV. Immediate Management Algorithm

Goal: Prevent hypoxia/acidosis and sequester the toxin.

1. Initial Actions

• Stop Injection: Immediately halt all LA administration.

• Call for Help: Specify “LAST Protocol” and “Intralipid Kit.”

• Airway Management:

  • 100% O2​.

  • Hyperventilate slightly if needed to counter respiratory acidosis.

  • Low threshold for intubation (hypoxia/acidosis rapidly worsen LAST).

2. Seizure Control

• First-line: Benzodiazepines (e.g., Midazolam).

• Avoid: Propofol if hemodynamically unstable (exacerbates cardiac depression).

• Neuromuscular Blockers: May be needed for ventilation, but remember they do not stop CNS seizure activity.

3. Lipid Emulsion Therapy 20%

• Indications: Start at first sign of serious toxicity (airway compromise, seizures, or CV instability).

• Bolus: 1.5 mL/kg IV over 1 minute.

• Infusion: 0.25 mL/kg/min immediately following bolus.

• If Instability Persists:

  • Repeat bolus (up to 2 times).

  • Increase infusion to 0.5 mL/kg/min.

• Upper Limit: ≈12 mL/kg total dose.

4. Modified ACLS

• Epinephrine: Use low doses (<1 mcg/kg) to avoid worsening arrhythmias and interfering with lipid rescue.

• Antiarrhythmics: Amiodarone is preferred.

• CONTRAINDICATED:

  • Lidocaine: (Class Ib antiarrhythmic—will worsen toxicity).

  • Vasopressin: Associated with poor outcomes in animal LAST models.

  • Calcium Channel Blockers / Beta Blockers: Exacerbate myocardial depression.

• Refractory Arrest: Early consultation for ECMO or Cardiopulmonary Bypass (CPB).

V. Differential Diagnosis for the Peri-Procedural Patient

• High Spinal: Ascending sensory/motor block, profound sympathectomy (hypotension/bradycardia).

• Anaphylaxis: Urticaria, wheezing (rare with amides, more common with esters).

• Air/Gas Embolism: Sudden dyspnea, “mill-wheel” murmur, acute right heart strain.

• Vasovagal Syncope: Bradycardia/hypotension, usually lacks the QRS widening or seizure activity.

VI. Post-Resuscitation & Complications

• Observation:

  • At least 2 hours after a CNS-only event.

  • At least 4–6 hours after a CV event.

• Lipid Complications:

  • Lab Interference: Lipemia interferes with hemoglobin, creatinine, and electrolyte measurements (draw labs before ILE if possible).

  • Pancreatitis: Rare, delayed complication of high-dose ILE.

  • Fat Embolism/Overload: Rare pulmonary complications.

VII. Clinical “Red Flags” for Toxicity

• Unexpected Agitation: In a patient who just received a block, don’t assume “anxiety.”

• Wide QRS: Any widening of the QRS complex post-injection is LAST until proven otherwise.

• Refractory Arrest: Standard ACLS failing in a patient who received LA. Lipid must be given.

Critical Note: LAST is a clinical diagnosis. Do not wait for serum lidocaine levels or laboratory confirmation to initiate Lipid Emulsion Therapy. Immediate correction of pH and PaCO2​ is as vital as the lipid itself.