Lipid emulsion

Why this drug is interesting

Lipid emulsion is a nutritional product. Its licence is parenteral nutrition; its formulation was designed to deliver calories and essential fatty acids to people who cannot eat. Nothing about its development anticipated that it would end up on resuscitation trolleys as the only specific treatment for a cardiac arrest caused by a local anaesthetic.

That history matters, because it explains the shape of the evidence. There is no randomised trial of lipid emulsion in local anaesthetic systemic toxicity (LAST) and there will not be one. What exists is a coherent mechanism, consistent animal data, and a body of case reports in which patients who appeared to be dying stopped dying. In a condition this rare and this lethal, that has been judged sufficient — and reasonably so.

The regimen changed — check your wall

What actually changed

The current regimen

The whole pathway, not just the lipid

Lipid emulsion is one step in a sequence, and giving it without the rest is a recognised failure mode. The QRH sequence is:²

1. Stop injecting the local anaesthetic — and remember infusion pumps, which are the commonest thing left running.
2. Call for help and tell the immediate clinical team what the problem is.
3. Call for the cardiac arrest trolley and the lipid rescue pack.
4. Give 100% oxygen and ensure adequate ventilation. Maintain the airway and secure it with a tracheal tube if necessary. Avoid hypercarbia — consider mild hyperventilation.
5. Confirm or establish intravenous access.
6. If circulatory arrest: continuous CPR by standard protocols, plus lipid emulsion, plus a reduced adrenaline dose (≤1 µg/kg), avoiding vasopressin. Recovery may take more than an hour, and cardiopulmonary bypass should be considered if available. If no circulatory arrest: conventional treatment of hypotension and arrhythmia, and consider lipid emulsion.
7. Control seizures — a small incremental dose of benzodiazepine is the drug of choice. Thiopental or propofol may be used but are negatively inotropic. Consider neuromuscular blockade if seizures cannot be controlled.

After the event

• Arrange safe transfer to an appropriate clinical area
• Exclude pancreatitis — regular clinical review with daily amylase or lipase
• Report on your local critical incident system and to the relevant national system

Pharmacology and mechanism

How it is thought to work

Two mechanisms are proposed, and they are not mutually exclusive.

Lipid sink

The infused lipid creates an expanded intravascular lipid phase into which lipophilic drug partitions, lowering the free concentration available to the myocardium. This predicts that lipid works best for the most lipophilic agents — which fits the clinical pattern, bupivacaine being both the most lipophilic common local anaesthetic and the most cardiotoxic.

Metabolic and cardiotonic effects

Lipid provides fatty acid substrate to a myocardium in which local anaesthetic has inhibited mitochondrial fatty acid transport, and appears to have direct positive inotropic and vasoconstrictor effects independent of any sequestration.

The product

20% Intralipid is a soybean-oil-in-water emulsion stabilised with egg phospholipid, in glycerol. Note the egg content: it is a theoretical concern in egg allergy, and a wholly unpersuasive reason to withhold it in a cardiac arrest.

Beyond local anaesthetic toxicity

Lipid emulsion is frequently proposed as a rescue for poisoning by other lipophilic cardiotoxic drugs — calcium channel blockers, tricyclic antidepressants, beta-blockers, bupropion. The reasoning is mechanically appealing and the evidence is considerably weaker than for LAST.

There is also a practical hazard specific to poisoning: lipaemic serum interferes with laboratory assays, and can render subsequent blood results — including drug concentrations you may want — uninterpretable for a period. That is an acceptable price in an arrest and a poor trade in a stable patient.

Adverse effects

• Pancreatitis — the reason the QRH mandates daily amylase or lipase after the event
• Fat overload syndrome — hyperlipidaemia, fever, hepatosplenomegaly, coagulopathy, described with high cumulative doses; the 12 mL/kg ceiling caps the exposure
• Laboratory interference from lipaemic serum, potentially for hours
• Acute respiratory distress and impaired oxygenation, reported after large doses
• Extracorporeal circuit fouling — relevant if ECMO or bypass is being used simultaneously
• Allergic reaction to egg or soya components (rare, and not a reason to withhold in arrest)

In the context in which lipid emulsion is actually given — a patient who is arresting or peri-arrest from a local anaesthetic — none of these is a reason to hesitate. They are reasons for the 12 mL/kg ceiling and for the follow-up, not for the decision.

Critical appraisal

1. The evidence is case reports and animal models, and that is unlikely to change. LAST is rare, sudden and lethal; a placebo-controlled trial is neither feasible nor ethical. The honest position is that lipid emulsion is recommended on mechanistic and observational grounds, and that this is a legitimate warrant for a treatment of this kind — but it should not be mistaken for the kind of evidence that supports, say, tranexamic acid in trauma.
2. Publication bias is unusually likely here. The literature is built from case reports, and case reports of a dying patient who then survived are far more likely to be written and accepted than reports of a dying patient who received lipid and died anyway. The apparent success rate of lipid rescue is therefore certainly overstated by some unknown amount.
3. Incidence has fallen, which changes the calculus quietly. Ultrasound guidance, aspiration before injection, incremental dosing and reduced use of bupivacaine for large-volume blocks have all made severe LAST rarer. That is a good thing, but it also means most clinicians will never see a case, and skills that are never used decay — which shifts the burden from individual knowledge onto systems and checklists.
4. The systems problem dominates the pharmacological one. In reported cases the delay is almost never in deciding to give lipid; it is in finding it. A rescue pack with the current QRH card inside it, stored where local anaesthetic is used and known to the people who use it, is worth more than any amount of memorised dosing.

References

1. 1
   Association of Anaesthetists. Management of severe local anaesthetic toxicity — archived guideline page. anaesthetists.org. States that the 2010 laminate has been withdrawn and that the Quick Reference Handbook is now the reference version. Verified 23 Aug 2026.
2. 2
   Association of Anaesthetists. Quick Reference Handbook, 3-10 Local anaesthetic toxicity, version 2, June 2023. anaesthetists.org/qrh. Source of the regimen and sequence quoted above; CC BY-NC-SA 4.0. Verified 23 Aug 2026.
3. 3
   St-Onge M, Anseeuw K, Cantrell FL, et al. Experts consensus recommendations for the management of calcium channel blocker poisoning in adults. Crit Care Med 2017;45(3):e306–15. PubMed
4. 4
   Neal JM, Barrington MJ, Fettiplace MR, et al. The Third American Society of Regional Anesthesia and Pain Medicine practice advisory on local anesthetic systemic toxicity — executive summary. Reg Anesth Pain Med 2018;43(2):113–23. The current ASRA LAST checklist (2020, v1.1) gives a weight-banded alternative: over 70 kg, bolus ~100 mL over 2–3 min and infuse ~250 mL over 15–20 min; under 70 kg, bolus ~1.5 mL/kg and infuse ~0.25 mL/kg/min; same 12 mL/kg ceiling. asra.com
5. 5
   TOXBASE — local anaesthetics; intravenous lipid emulsion. National Poisons Information Service. toxbase.org (NHS login required; the authoritative UK source for non-LAST indications.)
6. 6
   Intralipid 20% emulsion for infusion — product information, Fresenius Kabi. Note that no lipid emulsion product carries a UK licence for local anaesthetic toxicity; this use is off-label.