LIPID: Will the Traditional Antidote Replace

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Crystal Strickland
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1 LIPID: Will the Traditional Antidote Replace Evvah Karakılıç MD, PhD. Ankara Numune Education and Research Hospital Department of Emergency Medicine

3 Intravenous lipid emulsions Routinely used for nutritional support During the past decate it has been increasingly studied 1998, as Weinberg antidotes et to al. reverse reported acute, the Recent lifethreatening effective research use drug of has toxicity. a lipid focused emulsion on the efficacy infusion of in lipid resuscitation emulsion of in resuscitating bupivacaine patients (Local anesthetic) from overdoses of lipophilic, overdose non-la in rats agents.

4 Mechanism of Action Lipid Sink Phenomenon Lipophilic substances, such as local The anesthetics, 'lipid sink' are phenomenon drawn into the is the "lipid most sink" widely and a concentration accepted mechanism gradient of develops action for ILE. Lipid between emulsion tissue infusion and blood creates which an cause expanded lipid local phase, anesthetics and the to move resulting away equilibrium from the drives heart or toxic brain drug (areas from of tissue high to the aqueous plasma concentrations) phase then to the to the "lipid lipid sink". phase.

5 Opposite idea J. Jovic-stotic et al. published a case report Severe Propranol intoxication (4.21 mg/ml) (highly lipid-soluble beta-blocker) after ILE treatment they observed that similar elimination pattern of propranolol These findings did not fit with the lipid sink theory

6 Other mechanisms Lipid emulsion could theoretically increase intracellular fatty acid content and therefore overcome the reduced ATP production, which results from LA block of fatty acid transport and oxidation. It is possible that the resulting increased intracellular fatty acid content contributes to improved ATP synthesis in the cardiomyocyte.

7 Other mechanisms Lipid emulsion infusion might also directly increase intramyocyte calcium levels and lead to a direct positive inotropic effect. Fatty acids have also been shown to increase calcium levels in cardiac myocytes.

8 Which kind of drug poisoning Lipophilic drugs There is a definition: The log P value is also known as a measure of lipophilicity. Weinberg G L says in his paper, Un-ionised form of the solit (log P) Log P: an oil, most commonly octanol, and water partition coefficient ILE treatment can use for lipidsoluble drugs Especially log P greater than 2

9 Opposite idea

10 Another study Literature case Malation Drug Log P: Log 2.36 P Perhaps Bupivacain we need 3.41 highly lipidsoluble drugs Propranolol 3.48 Log p may be > 2,5 or 3 Verapamil 3.79 Quetiapine 2.5

11 We can use ILE treatment highly liposoluble drugs poisoning Local anesthetics Calcium channel blockers Beta blockers Psychotropic drugs Other non-la drugs.

12 Dose For asystolic patients, or those with pulseless 1. 20% lipid emulsion (e.g. Intralipid) should be administered as 1.5 electrical ml/kg bolus. activity, The bolus who should do not be administered respond to the over 2-3 minutes. bolus, the dose may be repeated. 2. The If bolus there should is an be initial followed response immediately to the by bolus an infusion of 20% followed lipid emulsion by the at re-emergence a rate of 0.25 ml/kg/min. of hemodynamic 3. Blood pressure, heart rate, and other available hemodynamic parameters, instability, should the be infusion recorded rate at least could every 15 be minutes during the infusion. increased or, in severe cases, the bolus could be repeated.

13 Pediatric use The patients in this pediatric series apparently tolerated the lipid emulsion well in the context of drug toxicity and resuscitative care.

14 Adverse reaction Hyperlipidemia nausea Flushing Dyspnea cyanosis dizziness headache Sleepiness vomiting Reactions noted with long-term therapy hepatomegaly sweating Premature and low birth-weight splenomegaly leukopenia thrombocytopenia İncreased with death liver secondary function test to values Fat fat overload accumulation syndrome in the lungs. Hepatic fat deposition. values Chest and back pain infants which has been associated increased liver function test hyper-thermia hypercoagulability

15 As a result There are few antidotes in clinical toxicology In some poisonings; morbidity and mortality rates are high and supportive care is often ineffective. Intralipid is an exciting development in clinical toxicology.

16 Thank you for your listening

Update in Poison Management. Update in Poison Management. Antidote Use. Fomepizole. Pediatric Ingestions 1. No financial disclosures

Update in Poison Management. Update in Poison Management. Antidote Use. Fomepizole. Pediatric Ingestions 1. No financial disclosures Update in Poison Management No financial disclosures Robert J. Hoffman, MD,MS FACMT, FACEP, FAAEM, FAAP Department of Emergency Medicine Albert Einstein College of Medicine New York, New York Update in