Recognition and Treatment of

Local Anesthetic Systemic Toxicity

(LAST)
Brooke Bauer, M.D & Jeremy Dority, MD
KSPAN 3/12/2016
Department of Anesthesiology
University of Kentucky College of Medicine
Lexington, KY

An Equal Opportunity University

 Disclosures
The authors have no financial disclosures to report

http://www.shutterstock.com/s/empty+pockets/search.html
 Objectives

https://sites.google.com/site/schoolstartinglater/visuals-and-statistics
 Objectives
Stay awake after lunch

Understand background information about Local

Anesthetic Systemic Toxicity (LAST) to become
more familiar with the pathology and causation

Recognize symptom presentation to raise

suspicion of a diagnosis of LAST
 Objectives
Become comfortable with LAST treatment:
Pharmacologic and supportive

Utilize information from this presentation and your

experience in an interactive question session

Experience a LAST scenario through simulation

Be Interactive!
 Case #1
38 y/o female s/p resection of mass at left
cerebellopontine angle
PMH: morbid obesity, anxiety, frequent PVCs
s/p failed cardiac ablation, HTN,
hypothyroidism
2mg versed, desflurane, succinylcholine,
250mcg fentanyl, remifentanil, low dose
lidocaine infusion throughout
IVF 3000mL, UOP 1500mL, EBL 25mL

Myers, Rebecca & Dority, Jeremy. Altered Mental Status Following Craniotomy. GCC Presentation. UK Department of Anesthesiology.
 Case #1
Patient agitated, moaning during PACU transport c/o head and
back pain
BP 174/93, HR 103
Given multiple 50 mcg fentanyl boluses without improvement in
agitation and groaning
Additionally received 2 mg hydromorphone, 4 mg morphine,
1mg lorazepam, 12.5mg meperidine
BP 155/100 (HR 110), SpO2 fell to 86% and she became
minimally responsive.
Nasal trumpet applied, started on nonrebreather; saturation
rose to low 90s.
TO BE CONTINUED

Myers, Rebecca & Dority, Jeremy. Altered Mental Status Following Craniotomy. GCC Presentation. UK Department of Anesthesiology.
 Which is diagnosis is highest on
your differential?
A. LAST
B. Hypercarbia
C. Narcotic overdose
D. Lack of pain control
 Which was the first local
anesthetic to be used medically?
A. Lidocaine
B. Prilocaine
C. Cocaine
D. Ropivacaine

- Neal JM, Bernards CM, Butterworth JF et al, ASRA Practice Advisory on Local Anesthetic Systemic Toxicity. Regional Anesthesia and Pain Medicine. 35; 2:151-61.
- https://en.wikipedia.org/wiki/Cocaine
 History of Local Anesthetics
Cocaine was introduced
into medical practice in
the 1880s & was the first
local anesthetic to be
used for medical
purposes
1891 Cocaine Poisoning
was published in Med
Surg Rep
- Neal JM, Bernards CM, Butterworth JF et al, ASRA Practice Advisory on Local Anesthetic Systemic Toxicity. Regional Anesthesia and Pain Medicine.
35; 2:151-61.
- Mattison JB. Cocaine Poisoning. Med Surg Rep. 1891;115:645-50.
- http://doctorspiller.com/Local_Anesthetics/local_anesthetics.htm
 Local Anesthetic Mechanism

https://www.netterimages.com/local-anesthetics-spinal-afferents-and-local-anesthetic-mechanisms-of-action-unlabeled-pharmacology-james-a-perkins-11123.html
 Types of Local Anesthetic
Esters: Amides
Only one i 2 is
Procaine, benzocaine, Lidocaine, bupivacaine,
chloroprocaine ropivacaine
Metabolized very Metabolized by a much
quickly by esterases in slower process in the
the plasma liver

- Boghdadly KE, Chin KJ. Local Anesthetic Systemic Toxicity: Continuing Professional Development. Can J Anesth 2016; 63:330-49.
- https://upload.wikimedia.org/wikipedia/commons/3/3b/Struktur-Lokalansthetika.png
 Local Anesthetic Systemic Toxicity
Rare life threatening
complication due to
intra-arterial injection
intravenous injection
systemic absorption
Affects Na Channels of
highly vascular organs
Central nervous system
Cardiovascular system
- Boghdadly KE, Chin KJ. Local Anesthetic Systemic Toxicity: Continuing Professional Development. Can J Anesth 2016; 63:330-49.
- http://www.lookfordiagnosis.com/mesh_info.php?term=Injections%2C+Intra-Arterial&lang=1
 Incidence
0.4 3.7 per 10,000 peripheral nerve
blocks1,2
0.7 1.8 per 10,000 epidurals3,4
>1823 nerve blocks and epidurals
performed by the acute pain service at UK in
2015; 2 presumed episodes of LAST

1. Liu SS, Ortolan S, Sandoval MV, et al. Cardiac arrest and seizures due to local anesthetic systemic toxicity after peripheral nerve blocks: should
we still fear the reaper? Reg Anesth Pain Med. 2016;41:5-21.
2. Heinonen JA, Litonius E, Pitkanen M, Rosenberg PH. Incidence of severe local anaesthetic toxicity and adoption of lipid rescue in Finnish
anaesthesia departments in 2011-2013. Acta Acaesthesiol Scand. 2015;59:1032-1037.
3. Auroy Y, Benhamou D, Bargues L, Ecoffey C, et al. Major complications of regional anesthesia in France: The SOS Regional Anesthesia Hotline
Service. Anesthesiology 2002; 97:1274-80.
4. Brown DL, Ransom DM, Hall JA, Leicht CH, Schroeder DR, Offord KP. Regional anesthesia and local anesthetic-induced systemic toxicity:
seizure frequency and accompanying cardiovascular changes. Anesth Analg 1995; 81:321-8.
- Gregorio GD, Neal JM, Rosenquist RW, Weinberg GL. Clinical Presentation of Local Anesthetic Systemic Toxicity: A Review of Published Cases,
1979 to 2009. Regional Anesthesia and Pain Medicine. 2010; 35:2 181-87.
 CNS Toxicity
Intracellular Na channels are blocked, inhibiting
depolarization and preventing neuronal transmission
1st Inhibitory pathways
2nd Excitatory pathways

- Boghdadly KE, Chin KJ. Local Anesthetic Systemic Toxicity: Continuing Professional Development. Can J Anesth 2016; 63:330-49.
- Neal JM, Bernards CM, Butterworth JF, et al. ASRA Practice Advisory on Local Anesthetic Systemic Toxicity. Regional Anesthesia and Pain Medicine. 35; 2:152-61.
- Di Gregorio G, Neal JM, Rosenquist RW, Weinberg GL. Clinical presentation of local anesthetic systemic toxicity: a review of published cases 1979 to 2009. Reg Anesth Pain Med
2010; 35: 181-7.
 Which is the most commonly
reported neurologic symptom
during LAST?
A. Dysarthria
B. Seizure
C. Drowsiness
D. Loss of Consciousness

- Gregorio GD, Neal JM, Rosenquist RW, Weinberg GL. Clinical Presentation of Local Anesthetic Systemic Toxicity: A Review of Published Cases, 1979
to 2009. Regional Anesthesia and Pain Medicine. 2010; 35:2 181-87.
 CNS Toxicity

- Gregorio GD, Neal JM, Rosenquist RW, Weinberg GL. Clinical Presentation of Local Anesthetic Systemic Toxicity: A Review of Published Cases, 1979
to 2009. Regional Anesthesia and Pain Medicine. 2010; 35:2 181-87.
 CVS Toxicity
Potassium and calcium channels are blocked,
causing myocardial depression
Conducting sodium channels are blocked,
prolonging depolarization, which leads to
arrhythmias
Avoid medications that slow this more!

- Boghdadly KE, Chin KJ. Local Anesthetic Systemic Toxicity: Continuing Professional Development. Can J Anesth 2016; 63:330-49.
- Neal JM, Bernards CM, Butterworth JF, et al. ASRA Practice Advisory on Local Anesthetic Systemic Toxicity. Regional Anesthesia and Pain Medicine. 35; 2:152-61.
 CVS Toxicity

- Gregorio GD, Neal JM, Rosenquist RW, Weinberg GL. Clinical Presentation of Local Anesthetic Systemic Toxicity: A Review of Published Cases,
1979 to 2009. Regional Anesthesia and Pain Medicine. 2010; 35:2 181-87.
 Onset of Symptoms/Signs

- Gregorio GD, Neal JM, Rosenquist RW, Weinberg GL. Clinical Presentation of Local Anesthetic Systemic Toxicity: A Review of Published Cases,
1979 to 2009. Regional Anesthesia and Pain Medicine. 2010; 35:2 181-87.
 Which factor(s) increase risk of
LAST?
A. Extremes of age metabolism/clearance
reduced
B. Cardiac dysfunction prolonged
circulation time
C. Pregnancy decreased protein binding
D. Location of nerve block
E. All of the above

- Meunier JF, Goujard E, Dubousset AM, Samii K, Mazoit JX. Pharmacokinetics of bupivacaine after continuous epidural infusion in infants with an without biliary atresia.
Anesthetiology 2001; 95: 87-95.
- Rosenberg PH, Veering BT, Urmey WF. Maximum recommended doses of local anesthetics: a multifactoral concept. Reg Anesth Pain Med 2004; 29: 564-75.
- Tsen LC, Tarshis J, Denson DD, Osanthanondh R, Datta S, Bader AM. Measurements of maternal protein binding of bupivacaine throughout pregnancy. Anesth Analg 199; 89: 965-
 Risk Factors
Location of nerve block/LA injection
1. IV
2. Tracheal
3. Intercostal
4. Caudal epidural
5. Paracervical
6. Epidural
7. Brachial plexus
8. Sciatic
9. Subcutaneous

Ranasinghe JS, Wahl KM, Harris EA, Lubarsky DA. Anesthesiology Board Review Third Edition. Pearls of Wisdom. 2002; p251.
 Recommended Maximum Dosage

- Boghdadly KE, Chin KJ. Local Anesthetic Systemic Toxicity: Continuing Professional Development. Can J Anesth 2016; 63:330-49.
 Continued Case #1
Lidocaine
Total: 800mg lidocaine 7.67mg/kg=
0.85mg/kg/hr
9ml 0.5% ropivacaine for occipital nerve block
Treatment
1.5mL/kg 20% lipid emulsion with immediate
resolution of symptoms
Agitation recurred at 25 minutes after rx
2nd bolus given and drip started at 0.25mL/kg/min with
complete resolution

Myers, Rebecca & Dority, Jeremy. Altered Mental Status Following Craniotomy. GCC Presentation. UK Department of Anesthesiology.
20
http://www.berktree.com/baxter-healthcare-intralipid-20-iv-fat-emulsion-solution-50-each-model-2b6023.html
 Lipid Infusion Side Effects

http://tywkiwdbi.blogspot.com/2010_11_01_archive.html
 Lipid Emulsion Mechanism
Theories
1. Lipid sink
2. Mass effect
3. Ion channels

Cave, Grant and Harvey, Martyn. Intravenous Lipid Emulsion as Antidote Beyond Local Anesthetic Toxicity: A Systematic Review. Academic Emergency Medicine. 2009; 16:9, 815-24.
- Di Gregorio G, Schwartz D, Ripper R, et al. Lipid emulsion is superior to vasopressin in a rodent model of resuscitation from toxin-induced cardiac arrest. Crit Care Med. 2009;37:993-99.
- http://www.scielo.br/scielo.php?pid=S0102-35862003000600014&script=sci_arttext&tlng=en
 Case #2
57yoM I&D left hand for chronic infection
PMHx: CAD, MI 2007 s/p PCI, EF 20%, HTN,
tachycardia, PVD s/p bilateral AKAs at groin,
DM, CVA, Seizure disorder
Uncomplicated supraclavicular block
performed in pre-op holding area (10mL
0.5% Ropivacaine + 10mL 2% Lidocaine)
VSS and denied any immediate symptoms
following block

Jerrod McCarty, Beril Abraham, Greg Rose, Shelly Ferrell. Local Anesthetic Toxicity After Supraclavicular Block. GCC. University of Kentucky Department of Anesthesia.
 Case #2
After 15 minutes found to be minimally
responsive; oriented and follows commands
with stimulation then quickly returns to
obtunded state
Labored & tachypneic respirations -
Supplemental O2 placed (poor SpO2
waveform 2/2 PVD)
Glucose 121
CXR Diaphragm in normal position

Jerrod McCarty, Beril Abraham, Greg Rose, Shelly Ferrell. Local Anesthetic Toxicity After Supraclavicular Block. GCC. University of Kentucky Department of Anesthesia.
 Case #2
Diagnosis : Hypercarbia vs LAST
Given 1.5mL/kg intralipid & started infusion
0.25mL/kg/min
Mental status improved after bolus and
returned to baseline after 1 hour
Adm overnight without further
complication & DCd next day

Jerrod McCarty, Beril Abraham, Greg Rose, Shelly Ferrell. Local Anesthetic Toxicity After Supraclavicular Block. GCC. University of Kentucky Department of Anesthesia.
 References
Auroy Y, Benhamou D, Bargues L, Ecoffey C, et al. Major complications of regional anesthesia in France: The SOS
Regional Anesthesia Hotline Service. Anesthesiology 2002; 97:1274-80.
Boghdadly KE, Chin KJ. Local Anesthetic Systemic Toxicity: Continuing Professional Development. Can J Anesth 2016;
63:330-49.
Brown DL, Ransom DM, Hall JA, Leicht CH, Schroeder DR, Offord KP. Regional anesthesia and local anesthetic-
induced systemic toxicity: seizure frequency and accompanying cardiovascular changes. Anesth Analg 1995;
81:321-8.
Cave, Grant and Harvey, Martyn. Intravenous Lipid Emulsion as Antidote Beyond Local Anesthetic Toxicity: A
Systematic Review. Academic Emergency Medicine. 2009; 16:9, 815-24.
Checklist for Treatment of Local Anesthetic Systemic Toxicity. American Society of Regional Anesthesia and Pain
Medicine.
Di Gregorio G, Schwartz D, Ripper R, et al. Lipid emulsion is superior to vasopressin in a rodent model of resuscitation
from toxin-induced cardiac arrest. Crit Care Med. 2009;37:993-99.
Gregorio GD, Neal JM, Rosenquist RW, Weinberg GL. Clinical Presentation of Local Anesthetic Systemic Toxicity:
A Review of Published Cases, 1979 to 2009. Regional Anesthesia and Pain Medicine. 2010; 35:2 181-87.
Heinonen JA, Litonius E, Pitkanen M, Rosenberg PH. Incidence of severe local anaesthetic toxicity and adoption of
lipid rescue in Finnish anaesthesia departments in 2011-2013. Acta Acaesthesiol Scand. 2015;59:1032-1037.
Liu SS, Ortolan S, Sandoval MV, et al. Cardiac arrest and seizures due to local anesthetic systemic toxicity after
peripheral nerve blocks: should we still fear the reaper? Reg Anesth Pain Med. 2016;41:5-21.
Mattison JB. Cocaine Poisoning. Med Surg Rep. 1891;115:645-50.
McCarty J, Abraham B, Rose G, Ferrell S. Local Anesthetic Toxicity After Supraclavicular Block. GCC. University of
Kentucky Department of Anesthesia.
Meunier JF, Goujard E, Dubousset AM, Samii K, Mazoit JX. Pharmacokinetics of bupivacaine after continuous
epidural infusion in infants with an without biliary atresia. Anesthetiology 2001; 95: 87-95.
Myers, Rebecca & Dority, Jeremy. Altered Mental Status Following Craniotomy. GCC Presentation. UK
Department of Anesthesiology.
Neal JM, Bernards CM, Butterworth JF, et al. ASRA Practice Advisory on Local Anesthetic Systemic Toxicity.
Regional Anesthesia and Pain Medicine. 35; 2:152-61.
Ranasinghe JS, Wahl KM, Harris EA, Lubarsky DA. Anesthesiology Board Review Third Edition. Pearls of Wisdom.
2002; p251.
Tsen LC, Tarshis J, Denson DD, Osanthanondh R, Datta S, Bader AM. Measurements of maternal protein binding
of bupivacaine throughout pregnancy. Anesth Analg 199; 89: 965-8.
 Visuals
http://www.scielo.br/scielo.php?pid=S0102-
35862003000600014&script=sci_arttext&tlng=en
http://tywkiwdbi.blogspot.com/2010_11_01_archive.html
http://www.berktree.com/baxter-healthcare-intralipid-20-iv-fat-emulsion-
solution-50-each-model-2b6023.html
http://www.lookfordiagnosis.com/mesh_info.php?term=Injections%2C+Intra-
Arterial&lang=1
https://upload.wikimedia.org/wikipedia/commons/3/3b/Struktur-
Lokalansthetika.png
https://www.netterimages.com/local-anesthetics-spinal-afferents-and-local-
anesthetic-mechanisms-of-action-unlabeled-pharmacology-james-a-perkins-
11123.html
http://doctorspiller.com/Local_Anesthetics/local_anesthetics.htm
https://en.wikipedia.org/wiki/Cocaine