We discuss this ominous complication of providing local anesthesia.

Hosts:

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.

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.

Vascularity of Site (Highest to Lowest Risk):

Intercostal blocks (highest absorption rate).

Caudal/Epidural.

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

Psoas compartment/Sciatic.

Brachial plexus.

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

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).

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.

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.

Goal: Prevent hypoxia/acidosis and sequester the toxin.

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).

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.

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.

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).

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.

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.

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.