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Miracle Cure? #1: Lipid Rescue® for Local Anesthetic Toxicity

Miracle Cure? #1: Lipid Rescue® for Local Anesthetic Toxicity. Joe Dietrick, CRNA, M.A . Truman Medical Center Kansas City, MO. Objectives. Review history of cardiovascular collapse with local anesthetics Discuss effect of local anesthetic toxicity on myocardial function

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Miracle Cure? #1: Lipid Rescue® for Local Anesthetic Toxicity

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  1. Miracle Cure? #1:Lipid Rescue® for Local Anesthetic Toxicity Joe Dietrick, CRNA, M.A. Truman Medical Center Kansas City, MO

  2. Objectives • Review history of cardiovascular collapse with local anesthetics • Discuss effect of local anesthetic toxicity on myocardial function • Discuss treatment options, focusing on infusion of Intralipids®

  3. History of the world… • Anesthesia for CS • Epidurals in 70 – 80’s 1 • Short-acting  Bupivacaine 0.5 – 0.75% • 1979: CV collapse with etidocaine/bupivacaine • Difficult (impossible) prolonged resuscitation • 1983: 59 cardiac (35 OB) cases • 39 Epidurals, 27 used Bupiv 0.75% • 31 deaths (24 mother &/or baby) • 83% of LA toxicity  neurologic injury / death • FDA: Bupiv 0.75% not recommended for OB

  4. History of the world… Part II • Early ’90s • Pencil point spinal needles   SAB for CS •  epidural injection of high concentration LA • Late ’90s • Ropivacaine approved for general use • Generally 30% improvement in safety margin • Max concentration for OB: 0.5% (150 mg)

  5. CV Toxicity2 • Act on Na+ channel inside cell • Reversible nerve conduction block • CNS: most susceptible to toxic effects • CV effects •  cardiac conduction   PR, QRS • Inhibition of K+ channel  QTc • Dextrorotary   K+ blk • Highly selective for vascular K-ATP channels • Bupiv dissociation 10x longer vs. Lido

  6. Stay out of trouble2 • Potency • Ropiv < Bupiv • CV toxicity: Ropiv < Bupiv • Animal studies appear to suggest dose to induce CV toxicity: Ropiv dose approx twice Bupiv dose

  7. What Weinberg says. • Incidentally found lipid emulsion reversed LA-induced cardiac arrest • 2003 report with dogs, Bupiv10 mg/kg3 • 10’ CPR • Lipid 20% 4 ml/kg vs NS • Survival • TX: 6/6 • Ctrl: 0/6

  8. Perceived MOA • 2 theories5 • Fat sink  reverse [gradient] for lipophilics • LA inhibits FA entry to mitochondria • Bupiv effect on myocardial acidosis4 • Bupiv or NS injected, then VF induced • Monitored 20’ or pHm = 7.0 • Bupiv Intralipid; both groups defibrillated • Bupiv group had less myocardial acidosis • “inhibition of cellular metabolism”

  9. Really? • www.lipidrescue.org • Lists studies & case reports • Published (17) • Submitted case reports (a bunch) • Recommends standard resuscitation, then • Intralipid® 20% • 1.5 ml/kg bolus, MR for persistent asystole • 0.25 ml/kg/min for 30-60’

  10. ACLS is da’ bomb – or it bombs • Ropivacaine & Levobupivacaine have had successful standard resuscitations • Anesthesiology: Mar 2007 • Mult letters regarding Rosenblatt case report • ROSC immed after lipid, but 20’ of conventional management could have contributed • c/o shocking asystole • c/o global term “LA toxicity” vs racemic Bupiv, and ? CNS efficacy • “Failure to ventilate & maintain cardiac perfusion?”

  11. Compared to standard resuscitation6 • Weinberg: Lipid vs. Epinephrine vs. saline6 • Rats, Bupiv 20 mg/kg  asystole • Lipid: 5 ml/kg + 0.5 ml/kg/min • Epi: 30 μg/kg • Doses repeated @ 2.5’ & 5’ • ROSC @ 10’ • Lipid 5/5 • Epi 4/5 • Ctrl 2/5

  12. Lipid EPI NS Compared to standard resuscitation6 • Weinberg: Lipid vs. Epinephrine vs. saline6 • Rats, Bupiv 20 mg/kg  asystole • Lipid: 5 ml/kg + 0.5 ml/kg/min • Epi: 30 μg/kg • Doses repeated @ 2.5’ & 5’ • ROSC @ 10’ • Lipid 5/5 • Epi 4/5 • Ctrl 2/5

  13. Lipids don’t help ACLS9 • Hicks (2009) swine model • Bupivacaine 10 mg/kg • CPR x 5’ • EPI 100 μg/kg + vasopressin 1.5 units/kg • EPI 15 every 3’ • If no ROSC @ 20’ • Intralipids 20% 4 ml/kg • Intralipids did not improve rates of ROSC

  14. ‘Cause you give too much EPI8 • Hiller’s (2009) rat model • Received bupivacaine 20 mg/kg, • CPR x 3’ • Saline control • Intralipid control: 30%, 5ml/kg (@ 2 & 5’) • Compared escalating doses of EPI • All with Intralipid treatment • μg/kg: 0, 1, 2.5, 10, 25 • ROSC among all animals in a group • Lipid + Epi (1 or 2.5 μg/kg)

  15. Hiller (2009)8

  16. You pigs… • Bushey et al (2011)12 • Swine with bupivacaine & hypoxic arrest • ACLS, 12 per group (lipids vs saline) • Intralipids 4 ml/kg + infusion @ 4.25’ mark • Outcome • ROSC: control = 4, lipid = 6 • pH @ 4.25’: 7.33 (both groups) • Success in animals other than pigs • Pigs closer to humans

  17. Risk?5 • Pulmonary vasoconstriction? • Editorial opinion by Picard & Meek: • Animal studies: benefit >> risk • Brull (2008): poss allergic rxn,  ICP • Imprudent to withhold in toxic events • Marwick (2009) reported recurrence • Bupiv brach plexus blk  asystole • 40’ after termination of lipid  VT • Recommend 1000 ml available

  18. Risk – push the limit10 • Intralipids 20% • 20, 40, 60, or 80 ml/kg • Rats euthanized & histologically examined • Estimated LD50 = 67 (±10.7) ml/kg • Lung & liver microscropic ∆ • NL: Myocardium, brain, pancreas, & kidney • Safe at doses used

  19. And all this means • If you use cardiotoxic doses (volume blocks) of any local anesthetic • Have a plan • Have Intralipid® emulsion available • Have administration instructions • Package these together • Consider in other lipid-soluble drug toxicities www.lipidrescue.org

  20. Courtesy: K. McCully, CRNA

  21. References • Herlocker, T. & Wedel, D. (2002). Local Anesthetic Toxicity—Does Product Labeling Reflect Actual Risk? Regional Anesthesia and Pain Medicine, 27 (6):562–567. • Leone, S. et al (2008). Pharmacology, toxicology, and clinical use of new long acting local anesthetics, ropivacaine and levobupivacaine. ACTA BIOMED 79: 92-105. • Weinberg G, et al (2003). Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med;28:198–202. • Weinberg G, et al (2004). The effect of bupivacaine on myocardial tissue hypoxia and acidosis during ventricular fibrillation. Anesth Analg. 98(3):790-5. • Picard, J. & Meek, T. (2006). Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob. Anaesthesia, 61:107–109. • Weinberg GL et al (2008). Resuscitation with lipid versus epinephrine in a rat model of bupivacaine overdose. Anesthesiology, 108(5):907-13. • Bania T, et al (2007). Hemodynamic effects of intravenous fat emulsion in an animal model of verapamil toxicity resuscitated with atropine, calcium and saline. Acad. Emerg. Med, 14:105-11. • Hiller, D et al (2009). Epinephrine Impairs Lipid Resuscitation from Bupivacaine Overdose. Anesthesiology, 111(3):498-505. • Hicks, S et al(2009). Lipid Emulsion Combined with Epinephrine and Vasopressin Does Not Improve Survival in a Swine Model of Bupivacaine-induced Cardiac Arrest. Anesthesiology, 111(1):138-146. • Hiller, D et al. (2010). Safety of high volume lipid emulsion infusion: a first approximation of LD%) in rats. Regional Anesthesia & Pain Medicine, 35(2):140-144. • Neal, J et al (2010). Local Anesthetic Systemic Toxicity 2010. Regional Anesthesia & Pain Medicine, 35(2):152-193. • Bushey, B et al (2011). Combined Lipid Emulsion and ACLS Resuscitation Following Bupivacaine- and Hypoxia-Induced Cardiovascular Collapse in Unanesthetized Swine. AANA Journal, 79(2): 129-138.

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