2. L.Kater Reg ED Royal Darwin Hospital
Lipid Emulsion in Local Anesthetic Toxicity a small search for evidence and recommendations
L.Kater
Reg ED Royal Darwin Hospital

3. Content How to recognize Local anesthetic (severe) toxicity, LA(S)T
Some background on lipid emulsion
Recommendations and dosing
Based on a few sources in the following order:

4. Sources Emergency Medicine Critical Care Jul/Aug 2014 - EMCC
Royal Darwin Hospital Guideline - RDH
Association of Anesthetists in Great Britain and Ireland Safety Guideline - AAGBI
American Society of Region Anesthesia and pain medicine Practice advisory ASRA
American College of Medical Toxiclogy Position statement - ACMT
Further readings

5. LA(S)T
CNS: sudden alteration mental status / agitation / light-headedness / visual disturbances / LOC / +/- tonic clonic convulsions
Cardiovascular collapse: hypotension / sinus bradycardia / conduction blocks / asystole / ventricular tachyarrhythmia’s
Following injection of local anesthetic

6. 1. EMCC 2014
Lipid emulsion
Composed of medium- and long-chain triglycerides, free fatty acids and phospholipids.
Pioneering work by Weinberg and others demonstrated benefit in tx of LAST and cardiotoxicity from many other lipophilic agents.

7. EMCC 2014 Critical appraisal of the literature:
Case reports / retrospective chart reviews / animal studies / poison center surveys / literature reviews / editorials
Cochrane: no results
National Guideline Clearinghouse: no results
American College of Medical Toxicology (ACMT): interim position statement
American Society of Regional Anesthesia (ASRA) and Pain Medicine: advisory

8. EMCC 2014
Mechanisms (also from article ’Lipid Emulsion Infusion’, Weinberg July 2012):
Lipid sink theory = intravascular lipid mass binds offending toxin and pulls drug from the target tissue.
Metabolic theory: a large lipid load can offset the potent inhibition of fatty acid metabolism (lipids are heart’s preferred energy substrate) caused by LA
Membrane effects: free fatty acids reduce LA inhibition of sodium channel currents

9. EMCC 2014
Patient selection currently supported by the available evidence:
As early antidotal therapy for pts with clinical signs of LAT
Predominantly neurologic
Cardiovascular abn. in Bupivacaine
Use for other drug toxicity: judicious use should be considered if standard supportive measures and other antidotal therapies fail to restore HD stability

10. EMCC 2014
Adverse effects (rare / rarely reported), esp. with prolonged infusions and doses > 4mL/kg:
Pancreatitis
Hyperamylasemia
Pyrogenic reactions
Gross hematuria
DVT
Predisposition to syst.infection, esp. yeast inf.
Risk acute lung injury in animal studies
Potential to interfere with spectrophotometric analysis of several lab studies

11. EMCC 2014
Dosing:
Optimal dosing not defined. Based on lean body mass. Most centers advise
Initial bolus of 1.5 mL/kg followed by an
Infusion of 0.25 mL/kg/min = 15mL/kg/h
Bolus may be repeated twice. When declining HD stability: increase infusion to 0.5 mL/kg/min.
Not more than 10 ml/kg over the first 30 min.
Optimal duration unclear. ASRA recommends >10 min after achieving HD stability.

12. 2. RDH Almost same dosing as advised in EMCC: max of 12ml/kg.
Same as AAGBI Safety Guideline 2010

13. 3. AAGBI endorsed by the AU and NZ College of Anaesthetics (ANZCA)
Consider iv lipid emulsion when signs of severe LAT without circulatory arrest
Give iv lipid emulsion when circulatory arrest in severe LAT

14. AAGBI

15. 4.ASRA
There are no RCT’s evaluating serious human LAST, future RCT’s unlikely – ethical and logistic concerns.
Derived from human and animal experimental studies. Guidelines based on existing literature and expert opinion.
Modification of a Classification of recommendations and Levels of Evidence scheme, developed by American Heart Association.

16. ASRA

17. ASRA Classic description of LAST:
subjective symptoms of CNS excitement and agitation that progress to seizures and / or CNS depression
Cardiac toxicity may follow, occur simultaneously or even precede it.
Case reports: atypical presentation in 40%: delayed or only cardiovascular symptoms.

18. ASRA Lipid emulsion therapy IIa, B recommendation =
Conflicting evidence / divergence of opinion: weight of evidence / opinion is in favour of usefulness / efficacy
Data derived from nonrandomized or laboratory eg animal studies; supported by multiple case reports or case series
Same dosing but max of 10 ml/kg for 30 min.

19. ASRA
Discussed that timing is controversial: Infusing at earliest sign can result in unnecessary treatment because a fraction of patients will progress to severe toxicity. Waiting after ALS unsuccessful unreasonable because Tx can prevent cardiovascular collapse -> Treat on clinical severity and rate of progression to LAST.

20. 5. ACMT
Lipid resuscitation therapy with the intent of reducing the clinical manifestations of toxicity from excessive doses of certain medications: Very promising results in animal models and uncertainty of its beneficial effect in human poisonings (anecdotal data)  no standard of care requirements to use, or to choose not to use LRT. In serious instability LRT is viewed as a reasonable consideration.

21. ACMT
Recommended guideline if the decision is made to initiate LRT: same dosages as previous guidelines

22. 6. Further readings
LIPID EMULSION INFUSION, RESUSCITATION FOR LA AND OTHER DRUG OVERDOSE
G.WEINBERG, ANESTHESIOLOGY JUL 2012
A description of background, safety, mechanism, controversies and recommendations. All are addressed above.
LIPIDRESCUE.ORG

23. Discussion