Transcript 1. EMCC 2014

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:
Sources
1.
Emergency Medicine Critical Care Jul/Aug 2014 - EMCC
2. Royal Darwin Hospital Guideline - RDH
3. Association of Anesthetists in Great Britain and Ireland
Safety Guideline - AAGBI
4. American Society of Region Anesthesia and pain
medicine Practice advisory 2010 - ASRA
5. American College of Medical Toxiclogy Position
statement - ACMT
6. Further readings
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
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.
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
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
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
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
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.
2. RDH
 Almost same dosing as advised in EMCC: max of
12ml/kg.
 Same as AAGBI Safety Guideline 2010
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
AAGBI
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.
ASRA
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.
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.
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.
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.
ACMT
Recommended guideline if the decision is made to
initiate LRT:
same dosages as previous guidelines
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
Discussion