Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

Tacon on Lipid Rescue Therapy


Published on

This BCC talk is by Cath Tacon, an Intensivist whose currently working in Alice Springs. In this talk, Cath tells you everything you need to know about lipid emulsion therapy. Incidentally Cath has just written an excellent review paper on bacterial meningitis in kids, which is free access and the link is on Intensive Care Network

Published in: Health & Medicine
  • Be the first to comment

Tacon on Lipid Rescue Therapy

  1. 1. Fat Chance … or Passing Fad?:Lipid Rescue Therapy Cath Tacon
  2. 2. Suicide Attempt1: 17 yo, 55kg ♀ PMHx: bipolar and ADHD Meds: mixed salts of amphetamine, bupropion, lamotrigine  Missing pills: 7.95g bupropion, 4g lamotrigine ED 6hrs after ingestion:  BP 123/77, HR 116bpm,  Sats 100% 15LNRBM, RR 14  GCS 6 (withdrawal)  CXR - NAD Sirianni et al, Ann Emerg Med. 2008 1
  3. 3. Initial ECG Sirianni et al, Ann Emerg Med. 2008
  4. 4. Initial ECG: Na channel blockade Sirianni et al, Ann Emerg Med. 2008
  5. 5. ED to ICU Supportive therapy x 3hrs (NPA, NRBM, IVF)  Some eye opening Transferred to ICU – 10 hours post ingestion  Tonic-clonic seizure then PEA  VT  VF  Initial 18 minutes:  ETT  Defibrillated x 11  1mg adrenaline x 6  300mg amiodarone  1g MgS04  No ROSC
  6. 6. NaHCO3 50mEq/L ROSC within 2 minutes  BP 84/55, HR 97bpm Sirianni et al, Ann Emerg Med. 2008
  7. 7. ROSC x 17 minutes …Further PEA Further interventions:  Transcutaneous pacing (unsuccessful)  1mg adrenaline x 12  50mEq NaHCO3 x 2  1g CaCl  Continuous infusion high-dose adrenaline + noradrenaline ABG at 10 minutes:  pH 7.252, pCO2 46.6mmHg, pO2 48.1mmHg, HCO3 20.1mEq/L
  8. 8.  No sustained ROSC 200mL bright red blood ETT 52 minutes into 2nd period of ACLS:  100mL bolus 20% lipid emulsion (Intralipid)  1 minute later: sustained palpable pulse
  9. 9. Sirianni et al, Ann Emerg Med. 2008
  10. 10. So … Were lipids the cure …?
  11. 11. How it Started 16 yo 60kg patient1 - 22mg s/c bupivacaine  (0.37mg/kg < 2mg/kg)   Ventricular dysrythmias and hypotension  Subsequently discovered to have severe systemic carnitine deficiency ? Hypothesis that bupivacaine inhibited a carnitine-dependent step in fatty-acid metabolism  Subsequently confirmed to inhibit mitochondrial carnitine exchange  inhibition of fatty acid oxidation 1 Weinberg et al. J Clin Anesth. 1997.
  12. 12. Intravenous Lipid Emulsion Animal studies:  Examined use of intravenous lipid emulsion (ILE) in bupivacaine cardiotoxicity  Pre-treatment with ILE protected from lethal effects of systemic bupivacaine  Further studies showed that ILE given during resuscitation (ie post-treatment with LA) improved outcomes from bupivacaine-induced asystole
  13. 13. Local Anaesthetic SystemicToxicity (LAST) in Humans Rosenblatt et al, 20061:  1st case report of ILE treating local anaesthetic systemic toxicity (LAST) 58 yo ♂ bupivacaine/mepivacaine brachial plexus block for arthroscopic rotator cuff repair  Seizures followed by VT/asystole  unsuccessful resuscitation x 20 minutes; planned for cardiopulmonary bypass  Trial of 100mL 20% intralipid  ROSC  Intralipid continued at 0.5mL/kg/min x 2hours then discontinued  Extubated without neurological sequelae 1 Rosenblatt et al. Anesthesiology 2006.
  14. 14.  1st guidelines for use of ILE in local- anaesthetic induced cardiac arrest published in 2007
  15. 15. Mechanism:‘Lipid Sink’ Phenomenon Lipid emulsion infusion  expanded lipid phase Lipophilic substances (eg LA) are drawn into ‘lipid sink’  concentration gradient develops between tissue and blood Drives toxic drug from tissue  aqueous plasma phase  lipid phase
  16. 16. ‘Lipid Sink’ – Evidence? Indirect:  Lipids can reverse both neurological and cardiac toxicity of LA  Has been reported to reverse toxicity in a range of drugs lacking a common mechanism, site of action, chemical structure or clinical effect  only common factor of high lipid solubility Animal studies:  Shown lower tissue phase of drugs post lipid emulsion solutions But …  Healthy volunteers given small dose of bupivacaine – no difference in free bupivacaine concentration post lipid infusion
  17. 17. Alternate Mechanisms:Metabolism Fatty acids = heart’s preferred energy substrate for oxidative phosphorylation under normal aerobic conditions: LA block fatty acid transport and oxidation  ↓ATP production Lipid emulsion therapy theoretically increases intracellular fatty acid concentration ILE may also directly increase intramyocyte Ca ++ levels  +ve inotropic effect
  18. 18. Are all Lipids Equal? Different ILE preparations have varying fatty acid composition Intralipid:  Soy-based, long-chain fatty acid emulsion  Used in most studies  Theoretical advantage in binding capacity Other preparations with medium chain fatty acids:  In at least 2 case reports  Yet to have head-to-head studies for clinical efficacy
  19. 19. Safety and Side Effects Theoretical risks:  Infections, thrombophlebitis with peripheral administration, fat emboli, allergic reactions, drug interactions… Reported adverse effects:  Interference with laboratory studies due to lipaemia  Several hours only  Hyperlipidaemia-induced pancreatitis  ARDS  Probably multi-factorial
  20. 20. Use in Other non-LAToxicological Emergencies 1st case report in 2008:  Bupropion and lamotrigine overdose Since then case reports of use in:  Ca++ channel blockers (verapamil, diltiazem, amlodipine)  B-blockers (propanolol, atenolol)  TCAs (imipramine, amitriptyline, doxepin, dothiepin)  Anti-psychotics (quetiapine, haloperidol, lamotrigine, olanzapine)  Anti-depressants (sertraline, venlafaxine)  Glyphosate herbicide  Ivermectin (in a Border Collie and miniature Shetland Pony)
  21. 21. Ca-channel Blockers Verapamil,nifedipine, diltiazem all lipophilic Experimental evidence:  Verapamil in rats: prolonged survival  Verapamil in dogs: prolonged survival  Nifedipine in rats: no benefit Clinical Experience:  Several peer reviewed case reports Maybe …
  22. 22. B-blockers Propanolol more lipophilic than metoprolol Experimental evidence:  Propanolol: no evidence of benefit (MAP or survival time)  Metoprolol: no evidence of benefit (MAP) Case Reports:  2 peer-reviewed case reports  Propanolol and propanolol + EtOH  Abstracts  Atenolol Jury still out
  23. 23. TCAs Lipophilic Experimental evidence:  Rabbits: faster haemodynamic recovery  Rats: no benefit Clinical evidence:  Several case-reports  Varying results, haemodynamic improvement in some, not all
  24. 24. Recommendations? Established role in local anaesthetic toxicity with cardiovascular collapse  20% lipid emulsion 1.5ml/kg over 1 minute  (100mL in 70kg)  Infusion at 15ml/kg/hr  (1L/hr in 70kg)  Maximum cumulative dose = 12mL/kg  (840ml in 70kg)  Cease when cardiovascularly stable or maximum dose given
  25. 25. Recommendations? Other lipophilic drug toxicities with haemodynamic instability despite standard therapy?  Consider Intravenous Lipid Emulsion  But maybe it’s just a fat chance …