title: The effect of levosimendan on bupivacaine-induced severe myocardial depression in anesthetized pigs.
abstract: OBJECTIVE
  Levosimendan, an inodilator without proarrhythmogenic properties, has been shown to reverse ropivacaine-induced negative inotropy in isolated heart preparations. In this randomized and blinded study, we investigated whether levosimendan is able to reverse rapidly bupivacaine-induced myocardial depression in pigs.
  
  
  METHODS
  Twenty invasively monitored pigs anesthetized with isoflurane 1% received bupivacaine 2 mg/kg per minute into a central vein until mean arterial pressure decreased to 55% of baseline. Thereafter, levosimendan 80 microg/kg for 10 mins, followed by 0.7 microg/kg per minute during the next 50 mins (L-SIM) or corresponding amounts of placebo were administered intravenously. Simultaneously, Ringer's acetate was infused intravenously, 20 mL/kg for 10 mins, followed by 20 mL/kg for 50 mins.
  
  
  RESULTS
  Two pigs in each group developed cardiac arrest immediately after bupivacaine and could not be resuscitated. Bupivacaine induced widening of the QRS complex in the electrocardiogram and bradycardia.In the remaining 16 pigs, 3 (2 in L-SIM group and 1 in placebo group) needed short-lasting manual cardiac compression and 1 dose of epinephrine. Cardiac output, ejection fraction, and stroke power/end-diastolic volume recovered initially very rapidly in the L-SIM group.However, there was no time x group effect difference in the overall recovery in the various parameters between the 2 groups, except in heart rate which was higher (P G 0.05) when levosimendan was administered.During the 50-min levosimendan infusion, mean arterial pressure and systemic vascular resistance stayed slightly lower in comparison with placebo infusion, but the difference was not statistically significant.
  
  
  CONCLUSIONS
  Levosimendan together with the infusion of Ringer's solution rapidly reversed the cardiac depression, but there was no difference in overall cardiovascular recovery in comparison to treatment with Ringer's solution alone. Levosimendan-induced increase in heart rate possibly facilitated the recovery from bupivacaine intoxication.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Helsinki University Hospital, Helsinki, Finland.
authors.forename: Juha
authors.initials: J
authors.lastname: Aittomäki
authors.forename: Sasu
authors.initials: S
authors.lastname: Liuhanen
authors.forename: Marko
authors.initials: M
authors.lastname: Sallisalmi
authors.forename: Markku T
authors.initials: MT
authors.lastname: Salmenperä
authors.forename: James E
authors.initials: JE
authors.lastname: Heavner
authors.forename: Per H
authors.initials: PH
authors.lastname: Rosenberg
mesh_terms: D000779:Anesthetics, Local / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D000818:Animals; D001919:Bradycardia / Q000139:chemically induced / Q000188:drug therapy; D002045:Bupivacaine / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002985:Clinical Protocols; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006323:Heart Arrest / Q000139:chemically induced / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006835:Hydrazones / Q000627:therapeutic use*; D007552:Isotonic Solutions / Q000627:therapeutic use; D008297:Male; D011724:Pyridazines / Q000627:therapeutic use*; D011897:Random Allocation; D000077331:Ringer's Solution; D000077464:Simendan; D013552:Swine; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000188:drug therapy*
chemical_list: D000779:Anesthetics, Local; D002316:Cardiotonic Agents; D006835:Hydrazones; D007552:Isotonic Solutions; D011724:Pyridazines; D000077464:Simendan; D000077331:Ringer's Solution; D002045:Bupivacaine