Intravenous Lipid Emulsion: Discovery and Evolution of Novel Therapy
Intravenous lipid emulsion (ILE) is a topic of significant interest within the medical community, particularly in its use for treating local anesthetic systemic toxicity (LAST) and non-LA toxicity. This innovative therapy, explored by Dr. Richard PJ Sebuwufu, has shown promise in cases of cardiovascular collapse and resistance to standard resuscitation protocols. With a focus on mechanisms such as acting as a lipid sink and improving cardiomyocyte ATP levels, ILE offers potential benefits in improving outcomes and survival rates in experimental models. The content delves into the composition, mechanisms, and experimental studies related to ILE, shedding light on its role in addressing critical medical challenges.
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Presentation Transcript
A FAT LOT OF GOOD Intravenous Lipid Emulsion by Dr Richard PJ Sebuwufu SpR in EM - QEH Kings Lynn 24th April 2012
INTRAVENOUS LIPID EMULSION Why the interest? Discovery and evolution Mechanisms Use in Local Anaesthetic Systemic Toxicity (LAST) Non-LA Toxicity Controversies Risks 24th April 2012
INTRAVENOUS LIPID EMULSION Interest in ILE Most common 20% Intralipid 20% Soya bean oil 1.2% egg yolk phospholipids 2.25% glycerin Water Sodium hydroxide 24th April 2012
INTRAVENOUS LIPID EMULSION Interest in ILE Novel therapy for LAST Cardiovascular collapse Resistance to standard resuscitation 24th April 2012
INTRAVENOUS LIPID EMULSION Discovery and Evolution Cardiovascular collapse with bupivacaine Severe Carnitine deficiency 1997 Experimental studies Rats Dogs 24th April 2012
INTRAVENOUS LIPID EMULSION Mechanisms Lipid sink Cardiomyocyte ATP levels Intramyocyte Calcium levels 24th April 2012
INTRAVENOUS LIPID EMULSION Mechanisms Lipid sink Weinberg et al 1998 Lipid phase expansion Drug from tissues (Brain, Heart) -> aqueous plasma phase -> lipid phase Emulsified fat droplets Bind lipophilic drugs Demonstrated using radiolabelled Bupivacaine by Weinberg et al using an experimental rat model and isolated heart model 24th April 2012
INTRAVENOUS LIPID EMULSION Mechanisms Cardiomyocyte ATP levels Fatty acid transport and oxidation Decreased ATP production ILE increase ICFATTYACIDS -> improve cardiomyocyte ATP production Cardiac myocyte ATP production in aerobic conditions Impacts on toxicity and survival Experimental support Dog model improved contractility from improved FA oxidation in ILE arm 24th April 2012
INTRAVENOUS LIPID EMULSION Mechanisms Intramyocyte Calcium levels Positive inotropic effect Fatty acids also shown to increase Ca2+ levels in cardiac myocytes 24th April 2012
INTRAVENOUS LIPID EMULSION Uses Local Anaesthetic Systemic Toxicity Non-Local Anaesthetic Toxicity 24th April 2012
INTRAVENOUS LIPID EMULSION Uses Local Anaesthetic Systemic Toxicity Case reports from regional blocks Use with onset of neurological symptoms Animal studies 24th April 2012
INTRAVENOUS LIPID EMULSION Uses Non-Local Anaesthetic Toxicity Lipophilic drugs Psychotropic drugs (mixed results) Clomopramine Quetiapine and Sertraline Lamotrigine + Bupropion *** Haloperidol 24th April 2012
INTRAVENOUS LIPID EMULSION Uses Non-Local Anaesthetic Toxicity Ca2+ channel blockers (multiple animal trials) Verapamil Beta Blockers Propanolol inconclusive Others Pesticides Herbicides 24th April 2012
INTRAVENOUS LIPID EMULSION Controversy No animal studies comparing standard resuscitative therapies with ILE of non-LA toxicity (Need ALS treated controls) Neurologic or cardiovascular compromise in unknown drug overdoses (lipophilic, not lipophilic) Needed More studies Better understanding of mechanisms Determine limitations 24th April 2012
INTRAVENOUS LIPID EMULSION Contraindications Lipid metabolism disorders Egg allergy Caution with Anaemia Severe liver disease Coagulopathy Pulmonary disease 24th April 2012
INTRAVENOUS LIPID EMULSION Complications Allergic reaction Fluid overload Impaired liver function Hypercoagulability pancreatitis 24th April 2012
INTRAVENOUS LIPID EMULSION Risks Adrenaline with ILE in setting of LAST No documented adverse effects in clinical trials so far Small sample sizes, generalisations of rare/longtem events Need for controlled clinical trials (RCTs may not be possible in this field) Reporting www.lipidregistry.org www.lipidrescue.org Favorable and unfavorable 24th April 2012
INTRAVENOUS LIPID EMULSION Novel therapy Established use in LAST Mounting evidence for toxicity with Local anaesthetic Non-local anaesthetic 24th April 2012
