Intravenous Lipid Emulsion by Dr Richard PJ Sebuwufu SpR in EM QEH Kings Lynn 24 th April 2012 INTRAVENOUS LIPID EMULSION Why the interest Discovery and evolution Mechanisms Use in Local Anaesthetic Systemic Toxicity LAST ID: 930469
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Slide1
24th April 2012
A FAT LOT OF GOOD
Intravenous Lipid Emulsion
by
Dr Richard PJ Sebuwufu
SpR in EM - QEH Kings Lynn
Slide224th April 2012
INTRAVENOUS LIPID EMULSION
Why the interest?
Discovery and evolution
Mechanisms
Use in
Local Anaesthetic Systemic Toxicity (LAST)
Non-LA Toxicity
Controversies
Risks
Slide324
th
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
Slide424
th
April 2012
INTRAVENOUS LIPID EMULSION
Interest in ILE
Novel therapy for LAST
Cardiovascular collapse
Resistance to standard resuscitation
Slide524th April 2012
INTRAVENOUS LIPID EMULSION
Discovery and Evolution
Cardiovascular collapse with
bupivacaine
Severe
Carnitine
deficiency 1997
Experimental studies
Rats
Dogs
Slide624th April 2012
INTRAVENOUS LIPID EMULSION
Mechanisms
Lipid sink
Cardiomyocyte
ATP levels
Intramyocyte
Calcium levels
Slide724th 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
Slide824th April 2012
INTRAVENOUS LIPID EMULSION
Mechanisms
Cardiomyocyte
ATP levels
Fatty acid transport and oxidation
Decreased ATP production
ILE increase IC
FATTY
ACIDS
-> 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
Slide924th April 2012
INTRAVENOUS LIPID EMULSION
Mechanisms
Intramyocyte
Calcium levels
Positive
inotropic
effect
Fatty acids also shown to increase Ca
2+
levels in cardiac myocytes
Slide1024th April 2012
INTRAVENOUS LIPID EMULSION
Uses
Local
Anaesthetic
Systemic Toxicity
Non-Local
Anaesthetic
Toxicity
Slide1124th April 2012
INTRAVENOUS LIPID EMULSION
Uses
Local Anaesthetic Systemic Toxicity
Case reports from regional blocks
Use with onset of neurological symptoms
Animal studies
Slide1224th April 2012
INTRAVENOUS LIPID EMULSION
Uses
Non-Local Anaesthetic Toxicity
Lipophilic drugs
Psychotropic drugs (mixed results)
Clomopramine
Quetiapine and Sertraline
Lamotrigine + Bupropion ***
Haloperidol
Slide1324th April 2012
INTRAVENOUS LIPID EMULSION
Uses
Non-Local
Anaesthetic
Toxicity
Ca
2+
channel blockers (multiple animal trials)
Verapamil
Beta Blockers
Propanolol
– inconclusive
Others
Pesticides
Herbicides
Slide1424th 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
Slide1524
th
April 2012
INTRAVENOUS LIPID EMULSION
Contraindications
Lipid metabolism disorders
Egg allergy
Caution with
Anaemia
Severe liver disease
Coagulopathy
Pulmonary disease
Slide1624
th
April 2012
INTRAVENOUS LIPID EMULSION
Complications
Allergic reaction
Fluid overload
Impaired liver function
Hypercoagulability
pancreatitis
Slide1724
th
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
Slide1824th April 2012
INTRAVENOUS LIPID EMULSION
Novel therapy
Established use in LAST
Mounting evidence for toxicity with
Local
anaesthetic
Non-local
anaesthetic