1. Local Anesthesia Systemic Toxicity LA(S)T RECOGNITION and Treatment
Sallie Poepsel. PhD, MSN, CRNA, APRN
Director, AANA Region IV

2. Financial disclosure

3. Objectives STAY AWAKE after Lunch
Describe the background information associated with Local Anesthetic Systemic Toxicity (LAST) .

4. Objectives
Recognize the signs and symptoms raising your suspicion of a diagnosis of LAST.
Outline the LIPIDS Rescue Protocol
Use the information from this session, along with your experience in an interactive question session.

5. Historical Background
rodent model of bupivacaine toxicity
(Weinberg et al 1998)
Rosenblatt et al reported the first clinical application of lipid emulsion therapy in treating LAST (2006)
Anesthesiology Jul; 117(1): 180–187.
doi:   /ALN.0b013e31825ad8de
Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006;105:217–8. [PubMed]
infusion of soy-bean oil emulsion, total parenteral nutrition solution, could prevent (by pretreatment) or improve efficacy of resuscitation from cardiovascular collapse caused by severe bupivacaine overdose in the intact, anesthetized rat.
return of spontaneous circulation after a bupivacaine challenge occurred in all animals receiving lipid, but in none of the saline controls3.
A middle aged man developed cardiac arrest shortly after a peripheral nerve block combining mepivacaine and bupivacaine. The patient failed to respond to standard resuscitative efforts for approximately 20 minutes but achieved normal vital signs shortly after receiving a 100 mL bolus of lipid emulsion. He subsequently recovered completely with no neurological deficit or cardiovascular sequelae.

6. Ultrasound
Ultrasound speeds up safety and how well and effective your block is…

7. ULTRASOUND First line of defense is to be conservative!!!!
If the surgeon asks you what the dose is – go under!!—Minimum effective doses should be used
Aspirate prior to injection
Check of HEME
Who is helping you? Incremental dosing…… we need to do it correct

8. LAST (Bupivacaine Toxicity)
CARDIOTOXIC: enters sodium channels rapidly and leaves
them very slowly; diffusses during diastole
depresses conduction and inducing reentrant-type ventricular arrhythmias.
direct effects: Arrhythmias initially, (-) inotropy, (-) chronotropy
results in Systolic Dysfunction, especially involving right ventricle, which precedes the occurrence of arrhythmias
Isnt our goal is to block nerve Impulses? NOT in the CARDIAC Tissues!!

9. What are the Signs? CNS: excitation, agitation, confusion, twitching,
seizures
Depression, sedation, coma, apnea
Metallic taste, circumoral numbness, diplopia, tinnitus, dizzy
Cardiac: initial hyper dynamic, then hypo dynamic
Benzodiazepines and Barbiturates are useful in prevention and treatment of local anesthetic-induced seizures.)

10. LAST: Things to KNOW no symptoms. EKG changes including prolonged PR
interval, widened QRS.. CO &
peripheral vasodilation
asystole and
circulatory collapse
CV:
At less than 5 mcg/ml of lidocaine,
At 5-10 mcg/ml there are EKG changes including prolonged
At > 10 mcg/ml, asystole and circulatory collapse

11. LIPIDS RESCUE How it Works
LA interfere with fatty acid transport into the mitochondria of the cardiac cells inhibiting the heart from performing oxidative phosphorylation and this is what leads to cardiac dysrhythmias.
LIPIDS act as a SINK - Most (and current???)
thought pattern
The sink – the lipids provide a alternative binding site for the LA
Cheap and found by accident
when it is cheap what drug company will fund research?

12. LIPIDS SINK Mechanism of action: ……..Most agree it is a LIPID sink
lipids reverse local anesthetic cardio toxicity may be increasing cardiac clearance. This nonspecific, observed extraction of local anesthetics from aqueous plasma or cardiac tissue is the lipid sink
Mechanism of action: several suggested reasons-

13. Lipid Sink Theory LA love the lipids..
Bind them with...sink
Initial increase in plasma levels
Then Lipids rapidly decrease in serum
It partitions the local anesthetic away from receptors
the infused intravascular lipid mass binds the offending toxin in sufficient quantity to pull drug from the target tissue, thereby reversing the toxicity. Indirect evidence in support of this theory includes the fact that lipid can reverse both neurologic and cardiac toxicity, though the brain does not metabolize fatty acids as an energy source to an appreciable degree. Furthermore, as noted above, lipid infusion is reported to reverse toxicity caused by an array of drugs lacking a common mechanism, site of action, chemical structure or clinical effect (e.g., calcium channel blockers, beta blockers, typical and atypical antipsychotics, tricyclic and other 

14. Generally Accepted Approach
airway management as the first priority
then seizure suppression
basic life support
in order to assure optimal oxygenation and ventilation;
2) preferably with a benzodiazepine; then lipid emulsion infusion to reverse signs and symptoms of toxicity.
3) including chest compressions must be used when clinically indicated in order to assure tissue perfusion and circulation of resuscitation drugs including lipid.

15. Goal Current treatments:
to prevent complications; with proper injection techniques and careful dosing
ACLS, BYPASS, LIPID rescue
Goal
Current treatments:

17. LAST RESCUE PROTOCOL Immediately:
Give an initial IV bolus of 20% Lipid emulsion
(1.5 ml/kg over 1 minute)
Start IV infusion
Lipid emulsion
15 ml/kg/hr
After 5 minutes:
Give a max. of 2 repeat bolus(same dose) if:
Cardiovascular stability has not been restored;
Adequate circulation deteriorates
(leave 5 minutes between) boluses
AND continue Infusion until:
1) cardiovascular status is
stable.
2) adequate circulation
restored OR
3) max. lipid dose given.

18. 20% INTRALIPIDS 20% Soya bean oil 1.2% egg yolk phospholipids
2.25% glycerin
Water
Sodium hydroxide

19. Case Report
50 year old female with Grade III Rotator Cuff (incurred from a fall) scheduled for RTC
Softball athlete in H-School
PMH: HTN under control with Enalapril
Family Hx of HTN
PSH: S/P TAH w/BSO
Physical Assessment:
Systems Review: unremarkable except for R
shoulder pain
Height: cm. Weight: kg BMI - 30
MRI Results RTC; labrium tear
LABS: within normal limits

20. Sequence of Events
Scheduled for R Interscalene block prior to RTC repair
PACU: monitors –BP, EKG, Oximetry, 2L/NC
IV: started with G-18 IV cath. LR 1000 ml
Meds: Versed 1mg IV titrated prior
LOCAL Anesthetic: Lidocaine 1% for skin infiltration
Bupivacaine 0.25% NP 15 ml (max dose no>
400 mg)
Lidocaine 0.5% 15 ml
Nerve Stimulator: Set initially at > MA..
Puncture Site: Interscalene level of the Cricoid
Equipment & Supplies: B. Braun Medical insulated Stimuplex guide (percutaneous guidance technique)

21. Lidocaine injected @ 3-5 ml increment following aspiration
Bupivacaine injected incrementally similarly following lidocaine.
IS Block completed
within 10 minutes, noticed increased PVC, pt
restless & panicky,
started seizures, unresponsive, progressive
desaturation from 99% to low 60s

22. LIPIDS Rescue Airway established – intubated ambu’d 100%
Within 1-2 minutes LIPIDS Rescue Protocol
Dysrhythmia dissipated; stable VS; seizures resolved
Two repeat boluses of LIPIDS (100 ml);
Lipids infusion
Total LIPIDS: 1500ml
Transferred to nearby hospital for ICU observation
LIPIDS Rescue

23. Con’t Transferred to nearby hospital for ICU observation
Discharged after 4 days – off for a week
NOW: she’s back teaching

24. Summary Background Information associated with LAST Signs and symptoms
LIPIDS Rescue touted as the treatment for LAST
(since 2006)
Current Suggestion: have LIPIDS available in all facilities

25. References
1. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology. 1998;88:1071–5. [PubMed]
2. Weinberg GL, Ripper R, Murphy P, Edelman LB, Hoffman W, Strichartz G, Feinstein DL. Lipid infusion accelerates removal of bupivacaine and recovery from bupivacaine toxicity in the isolated rat heart. Reg Anesth Pain Med. 2006;31:296–303. [PubMed]
3. Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med. 2003;28:198–202. [PubMed]
4. Jamaty C, Bailey B, Larocque A, Notebaert E, Sanogo K, Chauny JM. Lipid emulsions in the treatment of acute poisoning: A systematic review of human and animal studies. Clin Toxicol (Phila) 2010;48:1–27.[PubMed]
5. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisenkraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006;105:217–8. [PubMed]
6. McCutchen T, Gerancher JC. Early Intralipid therapy may have prevented bupivacaine-associated cardiac arrest. Reg Anesth Pain Med. 2008;33:178–80. [PubMed]
7. Foxall G, McCahon R, Lamb J, Hardman JG, Bedforth NM. Levobupivacaine-induced seizures and cardiovascular collapse treated with Intralipid. Anaesthesia. 2007;62:516–8. [PubMed]
8. Spence AG. Lipid reversal of central nervous system symptoms of bupivacaine toxicity. Anesthesiology. 2007;107:516–7. [PubMed]
9. Shah S, Gopalakrishnan S, Apuya J, Martin T. Use of Intralipid in an infant with impending cardiovascular collapse due to local anesthetic toxicity. J Anesth. 2009;23:439–41. [PubMed]
10. Rothschild L, Bern S, Oswald S, Weinberg G. Intravenous lipid emulsion in clinical toxicology. Scand J Trauma Resusc Emerg Med. 2010;18:51. [PMC free article] [PubMed]

26. Excellent Resource
LIPID EMULSION INFUSION, RESUSCITATION FOR LA AND OTHER DRUG OVERDOSE
G.WEINBERG, ANESTHESIOLOGY JUL 2012
A description of background, safety, mechanism, controversies and recommendations. All are addressed above.
LIPIDRESCUE.ORG

27. Discussion