INTRALIPIDS AS RESCUE
2:30-3:30
Objectives
• Describe signs and symptoms of local
anesthetic (LA) toxicity.
• Identify treatment modalities including use of
lipids for patients with LA toxicity.
• Identify factors influencing LA toxicity.
Mechanism of action
• Loss of sensation by
– inhibiting excitation at nerve endings
– blocking conduction in peripheral nerves
• Progression of anesthesia related to affected
nerve fiber:
– diameter
– myelination
– conduction velocity
• Prevent the development of action potential in
nerve
Regional Anesthesia
• Involves the use of a local anesthetic
strategically placed along the neural access to
produce:
– Surgical anesthesia
– Postoperative analgesia
– Analgesia for acute & chronic pain
management
• Goal: Block conduction of nociceptive (pain)
impulses
LOCAL AGENTS
• Levels dependent on:
– Dose
– Rate of injection
– Specific gravity of fluid
– Position of patient
LOCAL AGENTS
• ESTERS
Hydrolyzed in
Plasma
– Unstable in
solution
– Poor Penetrance
– Fair to Poor
Stability
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EXAMPLES
Cocaine – (1884)
Procaine - (Novacain)
– 1984
Chloroprocaine (Nesacaine)
Tetracaine(Pontocaine) - 1931
LOCAL AGENTS
• AMIDES
Metabolized by Liver
– Stable Good Penetrance
• Lidocaine - (Xylocaine)
• Mepivacaine - (Carbocaine)
• Prilocaine - (Citanest)
• Bupivacaine - (Marcaine, Sensorcaine)
• Etidocaine
• Ropivacaine
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LOCAL AGENTS
• Epinepherine Added to Local
– Vasoconstriction
– Slows Vascular Absorption
– Prolongs Effect
Local Anesthesia Toxicity
• Agents used in excessive doses or administered
improperly.
• Repetitive (small) doses to achieve an adequate
level of anesthesia may lead to eventual
administration of toxic dose.
• Anesthesia injected into confined space
• Doses may inadvertently be
delivered as intravascular injection
rather than epidurally
Local Anesthesia Toxicity
• Administration of toxic doses of LA
– Increase disruptions of cellular metabolism
– Interfere with inotropic function pathways that
regulate NA+, K+ and Cl- ion flow
– Modulation of autonomic system and enzymatic
processes for ATP formation
Toxicity
• Early: agitation, lightheadedness, altered
mental state, visual changes, slurred speech,
hypertension and tachycardia
• Middle: CNS excitation, cardiac dysrhythmias,
contractile depression & conduction blockade.
Seizure ( 20-30 minutes)
• Severe: Hypotension, bradycardia, Ventricular
dysrhythmia and cardiovascular collapse
CNS Toxicity
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Sedation
CNS excitation at low drug concentration
Dizziness, ringing in the ear, Metallic taste
Paresthesia (circumoral tingling)
Anxiety
Fear of death
Uncontrolled muscle activity
Tonic –clonic seizures
CNS depression
Bupivacaine ( CNS & Cardiac toxicity simultaneously
Cardiovascular Toxicity
• Block of sodium, calcium and potassium
channels
• Difficult to resuscitate on patient with asystole
with Bupivacaine toxicity due to long term
• Bupivacaine is cardiotoxic, strong attraction to
myocardial sodium channel, slow dissociation
from the sodium channels due to its lipophilic
properties.
Management of Local Anesthesia Toxicity
• ACLS protocol
– Airway
– Vital Signs
– Resuscitative Medications
Chance Observation
• Noted that patient with carnitine deficiency exhibited
sensitivity to bupivacaine induced cardiac dysrhythnias,
therefore postulated that bupivacaine might interfere
with carnitine metabolism.
• Carnitine = essential component of biochemical
pathways that transport fatty acids into mitochondria
where they provide the majority of cardiac energy
needs.
• Interestingly enough, the opposite was discovered –
infusing lipids made them more resistant to
bupivacaine-induced asystole.
• Lipid infusion improves the success of resuscitation
from bupivacaine toxicity.
2006 Case
• 17 year old developed seizure activity and CV
collapse after intentional ingestion.
• Ingested: Bupropion (Antidepressant) and
Lamotrigine (Anticonvulsant)
• Unsuccessful resuscitation attempts for 70
minutes
• 100 ml IV bolus of 20% lipid emulsion given
• After 1 minute, an effective sustained pulse
was observed. Patient recovered with no
major neurologic deficit.
91 year old
History: COPD, HTN, CAD, Reflux
• Infraclavicular brachial plexus block for olecranon bursa
excision.
• Given 1% mepivicaine 30 ml
• 20 min after injection was then injected with 10 ml 1%
Prilocaine.
• 5 minutes after injection of prilocaine, (20 min after
patient received the Mepivicaine) patient developed
dizziness, nausea, agitation & then lost consciousness
• Given 1ml/kg bolus of 20% intralipid followed by
infusion and patient recovered within minutes and
surgery proceeded.
60 year old male with CAD, diabetes
and end-stage renal disease
• For Supraclavicular Brachial plexus block he received:
– 30 ml 1.5% mepivacaine with bicarbonate and epi
– 10 ml 0.5% bupivacaine
• Developed labored respiration followed by
obtundation 5 min after injection
• CPR without re-establishment of effective cardiac
rhythm
• Given 20% lipid (250 ml over 30 min)
patient recovered
Local Anesthetic Systemic Toxicity
(LAST) requiring treatment
• 20 out of 10,000 peripheral nerve blocks
• 4 out of 10,000 epidural blocks
• Initial symptoms of LA Overdose
– Mild hypertension
– Tachycardia
– Mild agitation
– Confusion
Cardiac Toxicity
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Hypotension
Atrioventricular conduction delay
Idioventricular rhythms
Respiratory depression
Cardiovascular collapse
Local Anesthetic Toxicity
• Can occur after ingestion
• IV administration
• Topical Administration
Checklist for Treatment of LAST
(ASRA & Pain Medicine)
• Get Help
• Initial focus
– Airway management
– Seizure suppression ( Benzodiazepines NOT Propofol)
– Alert nearest facility having Cardiopulmonary bypass
capability
• Manage cardiac dysrhymias
– BLS & ACLS
– Avoid Vasopressin, Calcium channel blockers, beta
blockers and local anesthetics
– Reduce epinepherine doses to <1mcg/kg
Checklist for Treatment of LAST
(ASRA & Pain Medicine)
• Lipid emulsion therapy (20%)
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Bolus 1.5 ml/kg IV over 1 minute
Continuous infusion 0.25 ml/kg/min
Repeat bolus once or twice for persistent CV collapse
Double the infusion rate to 0.5 ml/kg/min if BP low
Continue infusion for at least 10 min after attaining
circulatory stability
– Recommend upper limit: 10ml/kg/lipid emulsion over
30 min.
• Post LAST events at www.lipidrescue.org or
www.lipidregistry.org
Lipid Sink
• Expanded plasma lipid compartment that traps
lipophilic drugs
• Infused intravascular lipid mass binds the offending
toxin in sufficient quantity to pull drug from the target
tissue, thereby reversing the toxicity.
• Successful resuscitation suggest the efficacy of lipid
emulsion infusion for treating non-local anesthetic
overdoses across a wide spectrum of drugs: beta
blockers, calcium channel blockers, parasiticides,
herbicides and several varieties of psychotropic agents.
2 Proposed methods of
How Intralipids Work
• 1. Lipid infusion creates a lipid phase in the plasma to
which local anesthetics partition into.
• 2. Reversal of mitochondrial fatty acid transport
inhibition
– Believed LA inhibit carnitine acylcarnitine translocase
(CACT) – an enzyme used in mitochrondrial fatty acid
metabolism and transport
– Because fatty acids are involved in 80-90% of cardiac
adenosine 5-triphosphate (ATP) synthesis, inhibition of
CACT may contribute to cardiac toxicity.
– Lipid infusion may increase the intracellular fatty acid
content enough to overcome the inhibition of the CACT
enzyme by the anesthetic.
Death of woman at a Laser Treatment
Center
• Patient received cream containing 10%
Lidocaine and 10% Tetracaine.
• Patient applied cream over Large areas of skin
then wrapped her legs in cellophane which
increased the absorption of the drug.
• Found seizing in her car.
• Unable to resuscitate
Lipid Therapy Side Effect
• Allergic reaction, headache, somnolence,
dizziness, dyspnea, diaphoresis, N&V,
hyperthermia and hypercoagulability
• Thrombocytopenia, jaundice, overloading
syndrome, Increased liver function,
leucopenia, hepatomegaly, splenomegaly
• Pulmonary hypertension with long term
therapy
• Yeast infection
Conclusions
• Lipid infusion appears to reverse cardiotoxicity
rapidly and is easier than cardiopulmonary
bypass.
• Lipid emulsion is readily available at a much
lower cost.
• Lipid rescue therapy is to be reserved until
ACLS procedures have been unsuccessful in
cases of local anesthetic toxicity
Summary
• Nurses plan an important role towards a
successful outcome for patients with local
anesthesia toxicity
• Know your high risk patients
• Recognize signs and symptoms of toxicity
• Have adequate emergency equipment available
when resuscitation needs arise
• Know your facility policy for Local Anesthesia
Toxicity