1) A 58-year-old man presented with a torn rotator cuff and received a brachial plexus block with bupivacaine and mepivacaine. He subsequently experienced two seizures and went into cardiac arrest. 2) Standard ACLS was unsuccessful for 20 minutes. Intravenous lipid emulsion (Intralipid) was then administered, which resulted in restoration of sinus rhythm within 15 seconds and detectable blood pressure. 3) Intralipid acts as a "lipid sink" to remove lipophilic drugs like bupivacaine from cardiac tissue and enhance their metabolism. It has been used successfully in numerous case reports of local anesthetic toxicity when standard ACLS fails

1. Intralipid
Fat, Stat.
Jeff Hall, DO EM2
Capt, USAF

2. Criticism
• Alaska Women
• “Born in Oregon, Holly
Madison calls Prince
of Wales Island,
Alaska home!”

3. Case
• 58 yo M OR holding room - R torn rotator cuff
• PMHx: CAD, HTN, Angina
• PSHx: CABG 43 yo
• Meds: nitro prn, isosorbide mononitrate,
lisinopril, atenolol, clopidogrel, and asa
• Allergies: NKDA
• Pre-op ECG: RBBB, LAHB, old anterior wall MI

4. Case
• 120/80, 98% RA, HR: 60, T: 98.9, RR: 16
• O2 - 3 l/min NC, PIV – 20 gauge L hand
• 2 mg midazolam and 50 μg fentanyl
• 50-mm, 22-gauge stim needle - brachial
plexus
• 20ml bupivacaine, 0.5%
• 20ml mepivacaine, 1.5%
• No blood aspirated, no p/p

5. Case
• 30 s later - incoherent, tonic–clonic seizure
• What now?
• Oxygen, 50 mg propofol, seizure stopped
• 90 s later, seized again, 100 mg propofol
• ECG: asystole, no pulse, no BP
• What now?

6. Case
• ACLS
• Intubate
• 20 min - 3 mg epinephrine, 2 mg atropine,
300 mg amiodarone, 40 U vasopressin
– Monophasic defib 200, 300, 360 x2
– Primary rhythms- pulseless v-tach and asystole

7. Case
• What now?
• Call for help – colleagues, poison center

8. Case
• 20 min - 100 ml of 20% Intralipid IV, 360 J D-fib
• Single sinus beat, 1 dose atropine/epinephrine
• Within 15 s, SR 90, detectable BP and pulse
• Intralipid infusion 0.5 ml/kg/min x2 h then d/c’d
• Remained in SR, extubated 2.5h
• Awake/responsive, RUE weakness c/w block
• Disposition?

9. Case
• Overnight obs
• No complitactions 2 weeks following
• Cath’d 2/2 incr. cardiac markers s/p arrest
• Total RCA occlusion and EF 32%
• Defibrillator placed and d/c’d home

10. Intralipid: Goals
• Brief History
• *Mechanism
• Complications
• LAST
• Other toxicities
• Evidence
• *Applications
• *Our ED
• *Dose

11. Brief History
• IV fat - soybean oil, egg yolk phospholipids,
glycerin, and water
• ’98 - bupivacaine OD in rat study with
soybean oil – poss tx for cardiac toxicity
• ‘03 – bupivacaine toxicity in dogs undergoing
internal cardiac massage – IL recovered
• ’06 - isolated rat heart – bupivacaine
removed faster from cardiac muscle – IL

12. Silver Bullet ?!

13. *Mechanism
• 2 main ideas:
– 1. Partitioning – “Lipid sink”
– 2. Enhanced metabolism
– Others:
• NA channels
• CA channels

14. Complications
• Lab errors
• Pancreatitis
• Fat embolization
• Allergic reactions
• Hepatotoxicity
• Dyspnea
• Local thrombophlebitis, sepsis

15. LAST
• Local anesthetic systemic toxicity
• ’06 case report – 1st published human use
• Case reports – witnessed, standard ACLS
failed, ROSC s/p lipid, underlying heart dz
– Most reports with bupivacaine toxicity

16. LAST

17. Lidocaine Toxicity
• Lightheadedness, dizzin
ess
• Headache
• Visual disturbance
• Perioral/tongue tingling
• Sedation
• Impaired
concentration
• Dysarthria
• Tinnitus
• Metallic taste
• Muscular twitching,
tremors

18. Lidocaine
• Intra-lipid rescue for CNS toxicity after
Lidocaine local for excision of breast mass
– 35 yo F - breast mass excised, 40cc of 1% lido w/o
– PACU – jerking motions UE/LE
– MS waning, tachycardic 110s
– Bolus 120cc 20% intralipid over 15min
– A+Ox3 end of bolus
– Infusion 0.25cc/kg/min over 1 hour
– No post-ictal/further comp, d/c’d 5 hours later

19. Lidocaine
• Intractable cardiac arrest due to lidocaine
toxicity successfully resuscitated with lipid
emulsion
– Prolonged lidocaine toxicity – pt ressusitated
with intralipid
– Consider intralipid in ACLS for lidocaine toxicity
as well as other lipid soluble drug intoxications

20. Other Toxicities
• TCAs, BBs, CCBs
• Common theme – lipophillicity
• Case reports – bias
– RCT not ethical

21. Evidence
• Cochrane – nada
• BestBets:
– TCA OD - no clear evidence about effectiveness
of Intralipid in TCA OD
– BB OD – same
– Reference Toxbase – Intralipid rec in TCA and BB
OD with cv collapse not responsive to stnd tx

22. Literature Review
• Lipid emulsions in the treatment of acute
poisoning: a systematic review of human and
animal studies. (Clinical Toxicology 2010)
– 23 animal trials, 50 human and 1 animal case rep
– Conclusion
• Weak evidence
• Suggest some benefits - bupivacaine, verapamil,
chlorpromazine, some TCAs and BBs
• Safety not established

23. Case Report
• 17 yo F sz and cv collapse s/p 7.95 g
bupropion & 4 g of lamotrigine (2008)
– ACLS x 70min unsuccessful
– 100-mL IV 20% lipid emulsion administered
– 1 min later – ROSC
– Pt suffered ALI but recovered with near-normal
neurologic function

24. *Applications
• Highly lipid soluble:
bupivacaine, ropivacaine, verapamil, propran
olol, TCAs
• Moderate lipid soluble:
bupropion, organophosphates
• Others: other CCBs, BBs, and LAs

25. *Applications
• ACLS
• Airway
• LA toxicity-> Intralipid
• TCA, BB, CCB -> stnd tx
• Failed tx -> Intralipid

26. *Our ED
• Not currently stocked
• Pharmacy – call, bedside in minutes
• Potential stock in future
• Shortage, use for dietary therapy

27. *Dose
• 20% Lipid Emulsion (70 kg patient)
• Bolus 1.5 mL/kg IV over 1 min (100 mL)
– Repeat 1-2x for persistent CV collapse
• Infusion 0.25 mL/kg/min (18 mL/min)
– Double if BP remains low
• Infuse at least 10 min once stable
• Upper limit: 10-12 mL/kg over first 30 min
• lipidrescue.org

28. Review
• Mechanism
• Current applications
• Where in our hospital
• Dose

29. Questions?

30. 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
• 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
• 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
• 4. 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
• 5. Spence AG: Lipid reversal of central nervous system symptoms of bupivacaine
toxicity. ANESTHESIOLOGY 2007; 107:516–7

31. References
• 6. Rothschild L, Bern S, Oswald S, Weinberg G: Intravenous lipid emulsion in clinical
toxicology. Scand J Trauma Resusc Emerg Med 2010; 18:51
• 7. Sirianni AJ, Osterhoudt KC, Calello DP, Muller AA, Waterhouse MR, Goodkin MB,
Weinberg GL, Henretig FM: Use of lipid emulsion in the resuscitation of a patient
with prolonged cardiovascular collapse after overdose of bupropion and
lamotrigine. Ann Emerg Med 2008; 51:412–5, 415.e1
• 8. Weinberg G, Lin B, Zheng S, Di Gregorio G, Hiller D, Ripper R, Edelman L, Kelly K,
Feinstein D: Partitioning effect in lipid resuscitation: Further evidence for the lipid
sink. Crit Care Med 2010; 38:2268–9
• 9. http://bestbets.org/bets/bet.php?id=1939
• 10. http://bestbets.org/bets/bet.php?id=1934
• 11. Lipid Emulsion Infusion: Resuscitation for Local Anesthetic and Other Drug
Overdose. Anesthesiology: July 2012 - Volume 117 - Issue 1 - p 180–187. doi:
10.1097/ALN.0b013e31825ad8de