title: The effects of intravenous lipid emulsion on hemodynamic recovery and myocardial cell mitochondrial function after bupivacaine toxicity in anesthetized pigs.
abstract: Local anesthetic toxicity is thought to be mediated partly by inhibition of cardiac mitochondrial function. Intravenous (i.v.) lipid emulsion may overcome this energy depletion, but doses larger than currently recommended may be needed for rescue effect. In this randomized study with anesthetized pigs, we compared the effect of a large dose, 4 mL/kg, of i.v. 20% Intralipid®( n = 7) with Ringer's acetate ( n = 6) on cardiovascular recovery after a cardiotoxic dose of bupivacaine. We also examined mitochondrial respiratory function in myocardial cell homogenates analyzed promptly after needle biopsies from the animals. Bupivacaine plasma concentrations were quantified from plasma samples. Arterial blood pressure recovered faster and systemic vascular resistance rose more rapidly after Intralipid than Ringer's acetate administration ( p < 0.0001), but Intralipid did not increase cardiac index or left ventricular ejection fraction. The lipid-based mitochondrial respiration was stimulated by approximately 30% after Intralipid ( p < 0.05) but unaffected by Ringer's acetate. The mean (standard deviation) area under the concentration-time curve (AUC) of total bupivacaine was greater after Intralipid (105.2 (13.6) mg·min/L) than after Ringer's acetate (88.1 (7.1) mg·min/L) ( p = 0.019). After Intralipid, the AUC of the lipid-un-entrapped bupivacaine portion (97.0 (14.5) mg·min/L) was 8% lower than that of total bupivacaine ( p < 0.0001). To conclude, 4 mL/kg of Intralipid expedited cardiovascular recovery from bupivacaine cardiotoxicity mainly by increasing systemic vascular resistance. The increased myocardial mitochondrial respiration and bupivacaine entrapment after Intralipid did not improve cardiac function.
authors.affiliation: 1 Department of Anesthesiology and Intensive Care Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: J A
authors.initials: JA
authors.lastname: Heinonen
authors.affiliation: 1 Department of Anesthesiology and Intensive Care Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: A A
authors.initials: AA
authors.lastname: Schramko
authors.affiliation: 1 Department of Anesthesiology and Intensive Care Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: M B
authors.initials: MB
authors.lastname: Skrifvars
authors.affiliation: 2 Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA.
authors.forename: E
authors.initials: E
authors.lastname: Litonius
authors.affiliation: 3 Department of Clinical Pharmacology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: J T
authors.initials: JT
authors.lastname: Backman
authors.affiliation: 4 Department of Pharmacology, University of Helsinki, Helsinki, Finland.
authors.forename: E
authors.initials: E
authors.lastname: Mervaala
authors.affiliation: 1 Department of Anesthesiology and Intensive Care Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
authors.forename: P H
authors.initials: PH
authors.lastname: Rosenberg
mesh_terms: D000779:Anesthetics, Local / Q000097:blood / Q000633:toxicity*; D000818:Animals; D002045:Bupivacaine / Q000097:blood / Q000633:toxicity*; D019069:Cell Respiration / Q000187:drug effects; D004655:Emulsions / Q000494:pharmacology; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010743:Phospholipids / Q000494:pharmacology*; D013024:Soybean Oil / Q000494:pharmacology*; D013552:Swine
chemical_list: D000779:Anesthetics, Local; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D010743:Phospholipids; C545823:soybean oil, phospholipid emulsion; D013024:Soybean Oil; D002045:Bupivacaine
keywords: Bupivacaine; lipid emulsion; local anesthetic toxicity; mitochondrial respiration