Intralipid
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  • 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