Propofol As Intralipid Therapy??

20% intravenous fat emulsion (IFE) may be useful to resuscitate severe cardiotoxicty due to fat-soluble drugs; the so-called lipid rescue. Propofol is a fat soluble anesthetic agent that is formulated and delivered in 3% IFE. If 20% IFE is not immediately available, can I use propofol as a substitute for 20% IFE?

What is Intravenous Lipid Emulsion?

• Also called ILE, Lipid resuscitation therapy (LRT), LipidRescue, or Intralipid
• Composed of  medium- and long-chain triglycerides, free fatty acids, and phospholipids
• Is a component of TPN

How does it work?

• Think of lipid rescue as dialysis for lipophilic drugs. IFE acts as a lipid sink, sequestering fat soluble drugs away from critical organ tissue
• Has shown promise in rat and dog models for treating lipid-soluble cardiotoxins 
• First successful clinical case report in 2006 - patient arrested immediately after interscalene block with bupivacaine and mepivacaine - after 20 min of ACLS, gave 100mL of Intralipid and had pulse/BP within a few minutes
• Theory of the “lipid sink”: draws medications into the lipid sink and away from target organs, but multiple theories exist 

What can it treat?

• ACMT says that there is no “standard of care” for this treatment yet
• Considered if patient is hemodynamically unstable from a substance with high lipid solubility and patient is unresponsive to standard therapies
• Local anesthetics have a more clear indication
• Other possible substances described in case reports: calcium-channel blockers, beta blockers, TCAs, antipsychotics, bupropion, chloroquine, glyphosate, and cocaine

How do you give it?

• 20% lipid emulsion (e.g. Intralipid) given as 1.5 ml/kg bolus over 2-3 minutes. 
• Follow immediately with infusion of Intralipid at a rate of 0.25 ml/kg/min
• May repeat bolus if patient remains in asystole or PEA 
• May increase infusion or even re-bolus if after an initial response, patient becomes unstable again
• Therapy should be stopped after 1 hour, or less, if the patient’s clinical status permits

Are there any adverse reactions?

• ILE has been associated with pancreatitis, fever, hematuria, and DVT
• Just like TPN - also associated systemic infections, especially fungemia 
• Animal studies show risk of acute lung injury

What lab tests are altered?

• AST
• Hgb
• Met-Hgb
• Electrolytes
• Coags
• ABG
• ASA? unknown

Why do people think Propofol will work?

• Propofol is in a medium/large chain triglyceride lipid emulsion, so it is also a fat emulsion, just like ILE
• However there have been some misquoted studied that lead people to believe that Propofol has proven efficacy as an antidote 
• One article that studied pressors (epinephrine and vasopressin for bupivacaine induced cardiac arrest in pigs) misquoted a study by Dr. Weinberg (MD behind “Lipid Rescue”) and stated that propofol treats bupivacaine toxicity
• Dr. Weinberg refuted this misquote in an editorial: “We have never recommended use of propofol for treating bupivacaine overdose, and strongly suspect that its use in cardiac arrest will impede resuscitation”​

Have any studies been performed?

• Ohmura 1999: In pigs: propofol vs sevoflurane 
• Higher doses of bupivacaine in propofol group to induce dysrhythmias, seizures, or 50% reduction of heart rate
• Zimmer 2007: Case report:  patient received BOTH propofol and intralipid
• Mauch 2011: In piglets: propofol with sevoflurane vs sevoflurane alone.  No change in toxic dose of bupivacaine between the groups
• Yilmaz 2014: Rat study with different preparations of propofol, propofol in intralipid, propofol in medialipid, or saline.  

                       * End points of: time to first dysrhythmia, times to 25% and 50% reduction in HR or BP, and time to asystole

                      * Propofol in intralipid group had longer time to each adverse outcome than the other groups

• Güngör 2015: Case report - 76 y.o. female had interscalene block with bupivacaine. Patient became unresponsive and seized, thus was intubated with thiopental and atracurium. Propofol infusion was started. 
• Bupivacaine levels were drawn just after intubation (1.6) and at the conclusion of the surgical case (undetectable at 135 min). Toxic level is 2-4. In the study discussion the authors believe that the Bupivacaine should have still been detectable and attribute this decrease to the propofol. 

What did I take away from this?

• Propofol has only been studied in animals or case reports
• Many of these are giving intralipid with propofol
• NEVER been used/studied in anything other than local anesthetic toxicity
• In severe toxicities that involve hemodynamic collapse (indication for lipid emulsion therapy), giving a medication that causes hypotension doesn’t seem to make sense

References:

• Antidotes For Overdose: Timely And Effective Counteraction, EM critical care, July 2014
• American College of Medical Toxicology (ACMT) National Office -  Interim guidance for the use of lipid resuscitation therapy
• Rosenblatt MA, Abel M, Fischer GW, et al. Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006;105(1):217-218.
• Mauch J, Kutter AP, Martin Jurado O, Spielmann N, Frotzler A, Bettschart-Wolfensberger R, Weiss M. [Bupivacaine toxicity and propofol anesthesia : animal study on intravascular bupivacaine injection]. Anaesthesist.  2011 Sep;60(9):814-8. doi: 10.1007/s00101-011-1898-8. Epub 2011 Jul 3. German. PubMed PMID: 21725675.
• Zimmer C, Piepenbrink K, Riest G, Peters J. [Cardiotoxic and neurotoxic effects after accidental intravascular bupivacaine administration. Therapy with lidocaine propofol and lipid emulsion]. Anaesthesist. 2007 May;56(5):449-53. German. PubMed PMID: 17277955.
• Weinberg G, Hertz P, Newman J. Lipid, not propofol, treats bupivacaine overdose. Anesth Analg. 2004 Dec;99(6):1875-6; author reply 1876. PubMed PMID: 15562099.
• A Comparison of Epinephrine and Vasopressin in a Porcine Model of Cardiac Arrest After Rapid Intravenous Injection of Bupivacaine, Mayr, Viktoria
• Güngör İ, Akbaş B, Kaya K, Çelebi H, Tamer U. Sudden developing convulsion during interscalene block: Does propofol anesthesia diminish plasma bupivacaine level? Agri. 2015 Jan;27(1):54-7. doi: 10.5505/agri.2015.82160. PubMed PMID: 25867875.
• Ohmura S, Ohta T, Yamamoto K, Kobayashi T. A comparison of the effects of propofol and sevoflurane on the systemic toxicity of intravenous bupivacaine in rats. Anesth Analg. 1999 Jan;88(1):155-9. PubMed PMID: 9895084
• Yilmaz M, Celebi H, Akcali D, Gurel N. Pre-treatment of bupivacaine-induced cardiovascular depression using different lipid formulations of propofol. Acta Anaesthesiol Scand. 2014 Mar;58(3):298-302. doi: 10.1111/aas.12263. Epub 2014 Jan 20. PubMed PMID: 24438483