Advertisement

Intravenous lipid emulsion prolongs survival in rats intoxicated with digoxin

Published:March 17, 2016DOI:https://doi.org/10.1016/j.ajem.2016.03.038

      Abstract

      Background

      Intravenous lipid emulsion eliminates the toxicity-related symptoms of several drugs. We hypothesized that intravenous lipid emulsion prolongs the survival time in digoxin-intoxicated rats.

      Methods

      Electrocardiograms of 14 anesthesized Wistar rats were monitored. All of the rats received digoxin infusion at a rate of 12 mL/h (0.25 mg/mL). Five minutes after the start of digoxin infusion, animals were treated either with 12.4 mL/kg intravenous lipid emulsion (group L) or saline (group C). The primary outcome variable was time elapsed until asystole development. Cumulative dose of digoxin required to induce asystole was also recorded.

      Results

      Mean time until asystole development in groups C and L were 21.28 ± 8.61 and 32.00 ± 5.41 minutes, respectively (P< .05). The mean lethal doses of digoxin in the groups C and L were 3.97 ± 1.54 and 6.09 ± 0.96 mg/kg, respectively (P< .05).

      Conclusion

      Intravenous lipid emulsion prolonged the time until asystole development and increased cumulative lethal dose in rats intoxicated with digoxin.
      To read this article in full you will need to make a payment
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The American Journal of Emergency Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Neal J.M.
        • Mulroy M.F.
        • Weinberg G.L.
        American Society of Regional Anesthesia and Pain Medicine. American Society of Regional Anesthesia and Pain Medicine checklist for managing local anesthetic systemic toxicity: 2012 version.
        Reg Anesth Pain Med. 2012; 37: 16-18
        • Weinberg G.L.
        • Ripper R.
        • Murphy P.
        • Edelman L.B.
        • Hoffman W.
        • Strichartz G.
        • et al.
        Lipid infusion accelerates removal of bupivacaine and recovery from bupivacaine toxicity in the isolated rat heart.
        Reg Anesth Pain Med. 2006; 31: 296-303
        • Sirianni A.J.
        • Osterhoudt K.C.
        • Calello D.P.
        • Muller A.A.
        • Waterhouse M.R.
        • Goodkin M.B.
        • et al.
        Use of lipid emulsion in the resuscitation of a patient with prolonged cardiovascular collapse after overdose of bupropion and lamotrigine.
        Ann Emerg Med. 2008; 51: 412-415
        • Bartos M.
        • Knudsen K.
        Use of intravenous lipid emulsion in the resuscitation of a patient with cardiovascular collapse after a severe overdose of quetiapine.
        Clin Toxicol (Phila). 2013; 51: 501-504
        • Huge V.
        • Baschnegger H.
        • Moehnle P.
        • Peraud A.
        • Briegel J.
        Amitriptyline-induced cardiac arrest: treatment with fat emulsion.
        Anaesthesist. 2011; 60: 541-545
        • Yurtlu B.S.
        • Hanci V.
        • Gür A.
        • Turan I.O.
        Intravenous lipid infusion restores consciousness associated with olanzapine overdose.
        Anesth Analg. 2012; 114: 914-915
        • Hillyard S.G.
        • Barrera-Groba C.
        • Tighe R.
        Intralipid reverses coma associated with zopiclone and venlafaxine overdose.
        Eur J Anaesthesiol. 2010; 27: 582-583
        • Tebbutt S.
        • Harvey M.
        • Nicholson T.
        • Cave G.
        Intralipid prolongs survival in a rat model of verapamil toxicity.
        Acad Emerg Med. 2006; 13: 134-139
        • Bania T.
        Hemodynamic effect of intralipid in amitriptyline toxicity.
        Acad Emerg Med. 2006; 13: S177
        • Yoav G.
        • Odelia G.
        • Shaltiel C.
        • Goor Y.
        • Goor O.
        • Cabili S.
        A lipid emulsion reduces mortality from clomipramine overdose in rats.
        Vet Hum Toxicol. 2002; 44: 30
        • Ozcan M.S.
        • Weinberg G.
        Intravenous lipid emulsion for the treatment of drug toxicity.
        J Intensive Care Med. 2014; 29: 59-70
        • Cave G.
        • Harvey M.
        Intravenous lipid emulsion as antidote: a summary of published human experience.
        Emerg Med Australas. 2011; 23: 123-141
      1. Florence Alexander T. Attwood David Physiochemical properties of pharmacy. 5th ed. Pharmaceutical Press, Cornwall, UK2011: 168
        • Kirilmaz B.
        • Saygi S.
        • Gungor H.
        • Onsel Turk U.
        • Alioğlu E.
        • Akyuz S.
        • et al.
        Digoxin intoxication: an old enemy in modern era.
        J Geriatr Cardiol. 2012; 9: 237-242
        • Ozbilgin S.
        • Ozbilgin M.
        • Kucukoztas B.
        • Kamaci G.
        • Unek T.
        • Yurtlu B.S.
        • et al.
        Gunerli A. Evaluation of the effectiveness of sugammadex for verapamil intoxication.
        Basic Clin Pharmacol Toxicol. 2013; 113: 280-285
        • Oubaassine R.
        • Bilbault P.
        • Roegel J.C.
        • Alexandre E.
        • Sigrist S.
        • Lavaux T.
        • et al.
        Cardio protective effect of glucose-insulin infusion on acute digoxin toxicity in rat.
        Toxicology. 2006; 224: 238-243
        • Ahmadi A.
        • Shirazi H.
        • Pourbagher N.
        • Akbarzadeh A.
        • Omidfar K.
        An electrochemical immunosensor for digoxin using core-shell gold coated magnetic nanoparticles as labels.
        Mol Biol Rep. 2014; 41: 1659-1668
        • Herrmann I.K.
        • Schlegel A.
        • Graf R.
        • Schumacher C.M.
        • Senn N.
        • Hasler M.
        • et al.
        Nanomagnet-based removal of lead and digoxin from living rats.
        Nanoscale. 2013; 5: 8718-8723
        • Eyer F.
        • Steimer W.
        • Nitzsche T.
        • Jung N.
        • Neuberger H.
        • Müller C.
        • et al.
        Intravenous application of an anticalin dramatically lowers plasma digoxin levels and reduces its toxic effects in rats.
        Toxicol Appl Pharmacol. 2012; 263: 352-359
        • Krieglstein J.
        • Meffert A.
        • Niemeyer D.H.
        Influence of emulsified fat on chlorpromazine availability in rabbit blood.
        Experientia. 1974; 30: 924-926
        • Weinberg G.L.
        • VadeBoncouer T.
        • Ramaraju G.A.
        • Garcia-Amaro M.F.
        • Cwik M.J.
        Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats.
        Anesthesiology. 1998; 88: 1071-1075
        • Rosenblatt M.A.
        • Abel M.
        • Fischer G.W.
        • Itzkovich C.J.
        • Eisenkraft J.B.
        Successful use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest.
        Anesthesiology. 2006; 105: 217-218
        • Smith H.M.
        • Jacob A.K.
        • Segura L.G.
        • Dilger J.A.
        • Torsher L.C.
        Simulation education in anesthesia training: a case report of successful resuscitation of bupivacaine-induced cardiac arrest linked to recent simulation training.
        Anesth Analg. 2008; 106: 1581-1584
        • Bania T.
        • Chu J.
        • Perez E.
        • Su M.
        Hemodynamic effects of intravenous fat emulsion in an animal model of severe verapamil toxicity resuscitated with atropine, calcium, and saline.
        Acad Emerg Med. 2007; 14: 105-111
        • Bania T.
        • Chu J.
        The hemodynamic effect of intralipid on propranolol toxicity.
        Acad Emerg Med. 2006; 13: S109
        • Cave G.
        • Harvey M.
        • Castle C.
        The role of fat emulsion therapy in a rodent model of propranolol toxicity: a preliminary study.
        J Med Toxicol. 2006; 2: 4-7
        • Harvey M.
        Intralipid infusion ameliorates propranolol-induced hypotension in rabbits.
        J Med Toxicol. 2008; 4: 71-76
        • Browne A.
        • Harvey M.
        Intravenous lipid emulsion does not augment blood pressure recovery in a rabbit model of metoprolol toxicity.
        J Med Toxicol. 2010; 6: 373-378
        • Harvey M.
        • Cave G.
        Intralipid outperforms sodium bicarbonate in a rabbit model of clomipramine toxicity.
        Ann Emerg Med. 2007; 49: 178-185
        • Harvey M.
        • Cave G.
        • Ong B.
        Intravenous lipid emulsion-augmented plasma exchange in a rabbit model of clomipramine toxicity; survival, but no sink.
        Clin Toxicol (Phila). 2014; 52: 13-19
        • Harvey M.
        • Cave G.
        Lipid rescue: does the sink hold water? And other controversies.
        Br J Anaesth. 2014; 112: 622-625
        • de Queiroz Siqueira M.
        • Chassard D.
        • Musard H.
        • Heilporn A.
        • Cejka J.C.
        • Leveneur O.
        • et al.
        Rhondali O. Resuscitation with lipid, epinephrine, or both in levobupivacaine-induced cardiac toxicity in newborn piglets.
        Br J Anaesth. 2014; 112: 729-734
        • Mauch J.
        • Martin Jurado O.
        • Spielmann N.
        • Bettschart-Wolfensberger R.
        • Weiss M.
        Comparison of epinephrine vs lipid rescue to treat severe local anesthetic toxicity-an experimental study in piglets.
        Paediatr Anaesth. 2011; 21: 1103-1108
        • Juurlink D.N.
        • McGuigan M.A.
        • Paton T.W.
        • Redelmeier D.A.
        Availability of antidotes at acute care hospitals in Ontario.
        CMAJ. 2001; 165: 27-30