• 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
Regional Anesthesia
• Involves the use of a local anesthetic
strategically placed along the neural access to
– Surgical anesthesia
– Postoperative analgesia
– Analgesia for acute & chronic pain
• Goal: Block conduction of nociceptive (pain)
• Levels dependent on:
– Dose
– Rate of injection
– Specific gravity of fluid
– Position of patient
Hydrolyzed in
– Unstable in
– Poor Penetrance
– Fair to Poor
Cocaine – (1884)
Procaine - (Novacain)
– 1984
Chloroprocaine (Nesacaine)
Tetracaine(Pontocaine) - 1931
Metabolized by Liver
– Stable Good Penetrance
• Lidocaine - (Xylocaine)
• Mepivacaine - (Carbocaine)
• Prilocaine - (Citanest)
• Bupivacaine - (Marcaine, Sensorcaine)
• Etidocaine
• Ropivacaine
• Epinepherine Added to Local
– Vasoconstriction
– Slows Vascular Absorption
– Prolongs Effect
Local Anesthesia Toxicity
• Agents used in excessive doses or administered
• 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
• 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
CNS excitation at low drug concentration
Dizziness, ringing in the ear, Metallic taste
Paresthesia (circumoral tingling)
Fear of death
Uncontrolled muscle activity
Tonic –clonic seizures
CNS depression
Bupivacaine ( CNS & Cardiac toxicity simultaneously
Cardiovascular Toxicity
• Block of sodium, calcium and potassium
• 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
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
• 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
• 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
• Given 1% mepivicaine 30 ml
• 20 min after injection was then injected with 10 ml 1%
• 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
• 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
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
• Manage cardiac dysrhymias
– 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%)
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 or
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
– 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
• 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
• Yeast infection
• Lipid infusion appears to reverse cardiotoxicity
rapidly and is easier than cardiopulmonary
• 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
• 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

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