A FAT LOT OF GOOD Intravenous Lipid Emulsion

A FAT LOT OF GOOD Intravenous Lipid Emulsion by Dr Richard PJ Sebuwufu Sp. R in EM - QEH Kings Lynn 24 th April 2012

INTRAVENOUS LIPID EMULSION FWhy the interest? FDiscovery and evolution FMechanisms FUse in F Local Anaesthetic Systemic Toxicity (LAST) F Non-LA Toxicity FControversies FRisks 24 th April 2012

INTRAVENOUS LIPID EMULSION F Interest in ILE F Most common – 20% Intralipid F 20% Soya bean oil F 1. 2% egg yolk phospholipids F 2. 25% glycerin F Water F Sodium hydroxide 24 th April 2012

INTRAVENOUS LIPID EMULSION F Interest in ILE F Novel therapy for LAST F Cardiovascular collapse F Resistance to standard resuscitation 24 th April 2012

INTRAVENOUS LIPID EMULSION F Discovery and Evolution F Cardiovascular collapse with bupivacaine F Severe Carnitine deficiency 1997 F Experimental studies F Rats F Dogs 24 th April 2012

INTRAVENOUS LIPID EMULSION F Mechanisms F Lipid sink F Cardiomyocyte ATP levels F Intramyocyte Calcium levels 24 th April 2012

INTRAVENOUS LIPID EMULSION F Mechanisms F Lipid sink F Weinberg et al 1998 F Lipid phase expansion F Drug from tissues (Brain, Heart) -> aqueous plasma phase -> lipid phase F Emulsified fat droplets F Bind lipophilic drugs F Demonstrated using radiolabelled Bupivacaine by Weinberg et al using an experimental rat model and isolated heart model 24 th April 2012

INTRAVENOUS LIPID EMULSION F Mechanisms F Cardiomyocyte ATP levels F Fatty acid transport and oxidation F Decreased ATP production F ILE increase ICFATTY ACIDS -> improve cardiomyocyte ATP production F Cardiac myocyte ATP production in aerobic conditions F Impacts on toxicity and survival F Experimental support F Dog model – improved contractility from improved FA oxidation in ILE arm 24 th April 2012

INTRAVENOUS LIPID EMULSION F Mechanisms F Intramyocyte Calcium levels F Positive inotropic effect F Fatty acids also shown to increase Ca 2+ levels in cardiac myocytes 24 th April 2012

INTRAVENOUS LIPID EMULSION F Uses F Local Anaesthetic Systemic Toxicity F Non-Local Anaesthetic Toxicity 24 th April 2012

INTRAVENOUS LIPID EMULSION F Uses F Local Anaesthetic Systemic Toxicity F Case reports from regional blocks F Use with onset of neurological symptoms F Animal studies 24 th April 2012

INTRAVENOUS LIPID EMULSION F Uses F Non-Local Anaesthetic Toxicity F Lipophilic drugs F Psychotropic drugs (mixed results) F Clomopramine F Quetiapine and Sertraline F Lamotrigine + Bupropion *** F Haloperidol 24 th April 2012

INTRAVENOUS LIPID EMULSION F Uses F Non-Local Anaesthetic Toxicity F Ca 2+ channel blockers (multiple animal trials) F Verapamil F Beta Blockers F Propanolol – inconclusive F Others F Pesticides F Herbicides 24 th April 2012

INTRAVENOUS LIPID EMULSION F Controversy F No animal studies comparing standard resuscitative therapies with ILE of non-LA toxicity (Need ALS treated controls) F Neurologic or cardiovascular compromise in unknown drug overdoses (lipophilic, not lipophilic) F Needed F More studies F Better understanding of mechanisms F Determine limitations 24 th April 2012

INTRAVENOUS LIPID EMULSION FContraindications FLipid metabolism disorders FEgg allergy FCaution with FAnaemia FSevere liver disease FCoagulopathy FPulmonary disease 24 th April 2012

INTRAVENOUS LIPID EMULSION FComplications FAllergic reaction FFluid overload FImpaired liver function FHypercoagulability Fpancreatitis 24 th April 2012

INTRAVENOUS LIPID EMULSION F Risks F Adrenaline with ILE in setting of LAST F No documented adverse effects in clinical trials so far F Small sample sizes, generalisations of rare/longtem events F Need for controlled clinical trials (RCTs may not be possible in this field) F Reporting F www. lipidregistry. org F www. lipidrescue. org F Favorable and unfavorable 24 th April 2012

INTRAVENOUS LIPID EMULSION F Novel therapy F Established use in LAST F Mounting evidence for toxicity with F Local anaesthetic F Non-local anaesthetic 24 th April 2012