TOXICOLOGY
Lipid Rescue:
a Novel Antidote?
Dr. Wilco Botha, BSc BVSc
Small Animal Internal Medicine Resident
Faculty of Veterinary Science, University of Pretoria.
Intravenous lipid emulsion has been utilised as the fat component of parenteral nutrition and as
a vehicle for drug delivery in drugs such as propofol for over half a century. More recently it has
gained acceptance in the treatment of lipid soluble (lipophilic) drug toxicities.
Intravenous lipid emulsion has been utilised as the fat component of parenteral nutrition and as a vehicle for drug delivery in drugs such as propofol for over half a century. More
recently it has gained acceptance in the treatment of lipid
soluble (lipophilic) drug toxicities.
The potential benefits of intravenous lipid emulsion therapy
(ILET) in altering toxicokinetics were discovered in the 1980’s
when researchers noted its effect on lipophilic drugs such as
cyclosporine in rabbits. Ever since, the value of ILET on various lipophilic drug toxicosis has been experimentally evaluated and eventually utilised in the emergency room.
In 2009 the first successful treatment of moxidectin induced
toxicosis in a puppy in clinical veterinary medicine was published. Presently, in human medicine, ILET is reserved for
life-threatening, severe toxicosis or for when conventional
antidotes or resuscitation therapies have failed. In veterinary
medicine the approach differs slightly in that ILET is often
instituted earlier in the management of toxicities. The successful use of ILET in clinical toxicology has been reported in numerous case reports and case series. In veterinary
medicine the successful treatment of macrocyclic lactone,
local anaesthetic, calcium channel blocker, beta-blocker,
central-acting muscle relaxant and insecticide toxicosis have
been described.
The exact mechanism of action of ILET is unknown but four
hypotheses have been proposed. The most widely accepted
hypothesis is thought to be that ILET acts by creating a new
intravenous lipid compartment (“lipid sink phenomenon”)
which functions to trap and hold the lipophilic toxicant,
leaving less active toxicant available to effector tissues causing clinical effects of toxicity. Additional possible hypotheses have been described with specific reference to local
anaesthetic systemic toxicosis for which it was initially most
commonly used for in human medicine. For more detail see
Cave et al. The latest studies, however, suggest that ILET
functions by acting as a vehicle for the toxicant, drawing the
toxin from highly perfused effector organs such as the brain,
liver and heart into the aqueous phase and now extended
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lipid phase,and transporting the toxin to tissues of
poorer perfusion. ILET has been reported to shorten
the excretion time and lower the LD 50 of lipophilic
drugs supporting the latest hypothesis.
ILET is generally considered a safe treatment for appropriate cases. The use of ILET should be reserved
for severe toxicoses with a high mortality rate where
there is no established antidote or where the established antidote or supportive therapy is cost prohibitive such as when mechanical ventilation is required.
Additionally, the toxicant should be known to be adequately lipid soluble. The lipid solubility or lipophilicity
of a drug is expressed as a partition coefficient value
designated as the Log P value. A toxicant with a Log P
value greater than one is considered lipophilic. However, the solubility of toxicants is also dependent on
factors such as the acid-base balance of the patient
due to pH ionisation effect, patient temperature and
haemodynamic stability of the patient. These factors
should be corrected prior to ILET. ILET is only suitable
for toxicants with short to moderate half-lives and not
suitable in long-lived toxicosis with for example rodenticides (anticoagulant and vitamin D compounds).
Lipid emulsions, as all parenteral nutrition components, are ideal growth mediums for microbes. If
ILET is considered in a patient the practice should be
equipped to allow for aseptic infusion practice, intensive monitoring during therapy and allow for precise
dose and rate administration using a drip pump.
The use of ILET is off-label and considered experimental which should be carefully explained to and
approved by the owner. The recommended dosage
guidelines in veterinary medicine were extrapolated
from that recommended in human medicine. In a review evaluating all the published literature and dosage
recommendations in human medicine Fernandez et
al. proposed a bolus administration of a 20% intravenous lipid emulsion (Intralipid® 20%, Fresenius Kabi
is most commonly used)at 1.5ml/kg over 1 minute