Effects of Lipid Emulsion on the Pharmacokinetic and Pharmacodynamic Properties of Metoprolol.

Summary

The aim of this study is to investigate whether intravenous lipid emulsion is effective in attenuating the clinical effects of a cardioactive drug, exemplified by the beta-blocking agent metoprolol. In addition, the investigators will clarify how intravenous lipid emulsion affects the pharmacokinetic parameters of metoprolol.

Timeline

Start

2016-09

Primary completion

2017-03-10

Completion

2017-03-10

Publications

• Background Hoffman RS, Howland MA, Lewin NA, Nelson L, Goldfrank LR, Flomenbaum N, editors. Goldfrank's toxicologic emergencies. Tenth edition. New York: McGraw-Hill Education; 2015. 1882 p.
• Background Picard J, Ward SC, Zumpe R, Meek T, Barlow J, Harrop-Griffiths W. Guidelines and the adoption of 'lipid rescue' therapy for local anaesthetic toxicity. Anaesthesia. 2009 Feb;64(2):122-5. doi: 10.1111/j.1365-2044.2008.05816.x.
• Background Tebbutt S, Harvey M, Nicholson T, Cave G. Intralipid prolongs survival in a rat model of verapamil toxicity. Acad Emerg Med. 2006 Feb;13(2):134-9. doi: 10.1197/j.aem.2005.08.016. Epub 2006 Jan 25.
• Background Di Gregorio G, Schwartz D, Ripper R, Kelly K, Feinstein DL, Minshall RD, Massad M, Ori C, Weinberg GL. Lipid emulsion is superior to vasopressin in a rodent model of resuscitation from toxin-induced cardiac arrest. Crit Care Med. 2009 Mar;37(3):993-9. doi: 10.1097/CCM.0b013e3181961a12.
• Background Weinberg G, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med. 2003 May-Jun;28(3):198-202. doi: 10.1053/rapm.2003.50041.
• Background Weinberg GL, Di Gregorio G, Ripper R, Kelly K, Massad M, Edelman L, Schwartz D, Shah N, Zheng S, Feinstein DL. Resuscitation with lipid versus epinephrine in a rat model of bupivacaine overdose. Anesthesiology. 2008 May;108(5):907-13. doi: 10.1097/ALN.0b013e31816d91d2.
• Background 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 Apr;88(4):1071-5. doi: 10.1097/00000542-199804000-00028.
• Background 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 Jul;105(1):217-8. doi: 10.1097/00000542-200607000-00033. No abstract available.
• Background Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid infusion. Anaesthesia. 2006 Aug;61(8):800-1. doi: 10.1111/j.1365-2044.2006.04740.x.
• Background Bet 2: intralipid/lipid emulsion in beta-blocker overdose. Emerg Med J. 2011 Nov;28(11):991-3. doi: 10.1136/emermed-2011-200722.
• Background Blaber MS, Khan JN, Brebner JA, McColm R. "Lipid rescue" for tricyclic antidepressant cardiotoxicity. J Emerg Med. 2012 Sep;43(3):465-7. doi: 10.1016/j.jemermed.2011.09.010. Epub 2012 Jan 12.
• Background Espinet AJ, Emmerton MT. The successful use of intralipid for treatment of local anesthetic-induced central nervous system toxicity: Some considerations for administration of intralipid in an emergency. Clin J Pain. 2009 Nov-Dec;25(9):808-9. doi: 10.1097/AJP.0b013e3181af739e.
• Background Finn SD, Uncles DR, Willers J, Sable N. Early treatment of a quetiapine and sertraline overdose with Intralipid. Anaesthesia. 2009 Feb;64(2):191-4. doi: 10.1111/j.1365-2044.2008.05744.x.
• Background Foxall G, McCahon R, Lamb J, Hardman JG, Bedforth NM. Levobupivacaine-induced seizures and cardiovascular collapse treated with Intralipid. Anaesthesia. 2007 May;62(5):516-8. doi: 10.1111/j.1365-2044.2007.05065.x.
• Background Ludot H, Tharin JY, Belouadah M, Mazoit JX, Malinovsky JM. Successful resuscitation after ropivacaine and lidocaine-induced ventricular arrhythmia following posterior lumbar plexus block in a child. Anesth Analg. 2008 May;106(5):1572-4, table of contents. doi: 10.1213/01.ane.0000286176.55971.f0.
• Background Marwick PC, Levin AI, Coetzee AR. Recurrence of cardiotoxicity after lipid rescue from bupivacaine-induced cardiac arrest. Anesth Analg. 2009 Apr;108(4):1344-6. doi: 10.1213/ane.0b013e3181979e17.
• Background Shah S, Gopalakrishnan S, Apuya J, Shah S, Martin T. Use of Intralipid in an infant with impending cardiovascular collapse due to local anesthetic toxicity. J Anesth. 2009;23(3):439-41. doi: 10.1007/s00540-009-0754-3. Epub 2009 Aug 14.
• Background Warren JA, Thoma RB, Georgescu A, Shah SJ. Intravenous lipid infusion in the successful resuscitation of local anesthetic-induced cardiovascular collapse after supraclavicular brachial plexus block. Anesth Analg. 2008 May;106(5):1578-80, table of contents. doi: 10.1213/01.ane.0000281434.80883.88.
• Background Weinberg GL. Lipid infusion therapy: translation to clinical practice. Anesth Analg. 2008 May;106(5):1340-2. doi: 10.1213/ane.0b013e31816a6c09. No abstract available.
• Background Fettiplace MR, Akpa BS, Ripper R, Zider B, Lang J, Rubinstein I, Weinberg G. Resuscitation with lipid emulsion: dose-dependent recovery from cardiac pharmacotoxicity requires a cardiotonic effect. Anesthesiology. 2014 Apr;120(4):915-25. doi: 10.1097/ALN.0000000000000142.
• Background Litonius E, Tarkkila P, Neuvonen PJ, Rosenberg PH. Effect of intravenous lipid emulsion on bupivacaine plasma concentration in humans. Anaesthesia. 2012 Jun;67(6):600-5. doi: 10.1111/j.1365-2044.2012.07056.x. Epub 2012 Feb 21.

Drugs

Indications