Local Anesthetic Systemic Toxicity

LAST·Also: lipid rescue, Intralipid, lipid emulsion, bupivacaine toxicity, local anaesthetic systemic toxicity·Updated 2026-10-19

Systemic absorption or inadvertent intravascular injection of local anesthetic producing CNS and cardiovascular toxicity. Treated with lipid emulsion and a modified ACLS algorithm.

Clinical vignette

Five minutes after an interscalene block with 20 mL of 0.5% bupivacaine, the patient reports that their mouth tastes like metal.

1. Mechanism

Sodium channel blockade in the CNS and myocardium; also potassium and calcium channels, and mitochondrial energy production (carnitine-acylcarnitine translocase inhibition) — which is why bupivacaine is so cardiotoxic.
Bupivacaine is "fast-in, slow-out" at the sodium channel. Those kinetics drive re-entrant arrhythmias and refractory VF. Ropivacaine and levobupivacaine have a better CV:CNS ratio.
CV toxicity requires a smaller multiple of the convulsive dose for bupivacaine than for lidocaine. With lidocaine a seizure usually comes first and gives warning; with bupivacaine it may not.

2. Presentation

Classic progression: perioral numbness, metallic taste, tinnitus → agitation → seizures → CNS depression → arrhythmia, hypotension, arrest.
The real world is messier. A meaningful share of cases are atypical: isolated cardiovascular signs, delayed onset beyond 10–15 minutes (especially with continuous catheters or truncal blocks such as TAP and ESP), or cardiovascular collapse with no prodrome at all.
Under general anesthesia the CNS signs are masked. The first clue may be unexplained hypotension, a widened QRS, bradycardia, or ventricular ectopy.

3. Risk factors and prevention

Patient factors. Extremes of age, low muscle mass (the frail elderly), cardiac disease (low EF, conduction abnormalities), hepatic dysfunction, pregnancy, and low α1-acid glycoprotein (neonates).

Block site — vascularity drives uptake:

intercostal > caudal > epidural > brachial plexus > sciatic/femoral

Fascial plane blocks deserve their own mention because of the large volumes involved.

Prevention.

Ultrasound guidance — reduces the risk, does not eliminate it.
Lowest effective dose.
Incremental injection, 3–5 mL at a time, with aspiration between.
Epinephrine test dose as an intravascular marker.
Dose by lean body weight.
Watch the cumulative dose: block + surgeon infiltration + liposomal bupivacaine.

4. Management

Stop the injection, call for help, get the LAST kit, and consider lipid early — do not wait for arrest.
Airway: 100% oxygen. Avoid hypoxia, hypercarbia, and acidosis — all three worsen toxicity.
Seizures: benzodiazepine first. Small doses of propofol are acceptable if that is what is in your hand, but avoid it in hemodynamic instability.

Lipid emulsion 20%

Patient	Bolus	Infusion
Over 70 kg	100 mL over 2–3 minutes	200–250 mL over 15–20 minutes
70 kg or under	1.5 mL/kg over 2–3 minutes (lean body weight)	0.25 mL/kg/min (lean body weight)

If the patient remains unstable: repeat the bolus once or twice, and/or double the infusion rate.
Recommended upper dosing limit is approximately 12 mL/kg.
Propofol is not a substitute. It is formulated in 10% lipid emulsion, and the volume required to deliver an equivalent lipid dose is not survivable.

Modified ACLS

Epinephrine in reduced boluses, 1 mcg/kg or less.
Avoid vasopressin, calcium channel blockers, beta blockers, and further local anesthetic — no lidocaine or procainamide for the arrhythmias.
Amiodarone is the antiarrhythmic of choice.
Call for cardiopulmonary bypass or ECMO early if there is no response. Resuscitation may need to continue for more than an hour.

Monitoring afterward

At least 2 hours after a seizure.
At least 4–6 hours after cardiovascular instability.

Maximum Local Anesthetic Dose Calculator — cumulative dose across mixed local anesthetics.
Q-Bank: Critical Events — practice questions on LAST, MH, anaphylaxis, and VAE.

References

Neal JM, Neal EJ, Weinberg GL. American Society of Regional Anesthesia and Pain Medicine Local Anesthetic Systemic Toxicity Checklist: 2020 version. Reg Anesth Pain Med. 2021;46(1):81–82.
ASRA Practice Advisory on Local Anesthetic Systemic Toxicity.
Local Anesthetic Toxicity. StatPearls Publishing, NCBI Bookshelf.