title: Analysis of the temporal regression of the QRS widening induced by bupivacaine after Intralipid administration. Study in an experimental porcine model.
abstract: OBJECTIVE
  The principal mechanism of cardiac toxicity of bupivacaine relates to the blockade of myocardial sodium channels, which leads to an increase in the QRS duration. Recently, experimental studies suggest that lipid emulsion is effective in reversing bupivacaine cardiac toxicity. We aimed to evaluate the temporal evolution of the QRS widening induced by bupivacaine with the administration of Intralipid.
  
  
  METHODS
  Twelve pigs were anesthetized with intravenous sodium thiopental 5mg kg(-1) and sevoflurane 1 MAC (2.6%). Femoral artery and vein were canalized for invasive monitoring, analysis of blood gases and determination of bupivacaine levels. After instrumentation and monitoring, a bupivacaine bolus of 4-6 mg kg(-1) was administered in order to induce a 150% increase in QRS duration (defined as the toxic point). The pigs were randomized into two groups of six individuals. Intralipid group (IL) received 1.5 mL kg(-1)of IL over one minute, followed by an infusion of 0.25 mL kg min(-1). Control group (C) received the same volume of a saline solution. The electrocardiographic parameters were recorded, and blood samples were taken after bupivacaine and 1, 5, 10 and 30 minutes after Intralipid/saline administration.
  
  
  RESULTS
  Bupivacaine (4.33±0.81 mg/kg in IL group and 4.66±1.15 mg/kg in C group) induced similar electrocardiographic changes in both groups; mean maximal percent increase in QRS interval was 184±62% in IL group, and 230±56% in control group (NS). Lipid administration reversed the QRS widening previously impaired by bupivacaine. After ten minutes of the administration of IL, the mean QRS interval decreased to 132±56% vs. 15±76% relative to the maximum widening induced by bupivacaine, in IL and C group, respectively.
  
  
  CONCLUSIONS
  Intralipid reversed the lengthening of QRS interval induced by the injection of bupivacaine. Time to normalization of electrocardiographic parameters can last more than 10 minutes. While the phenomena of cardiac toxicity persist, resuscitation measures and adequate monitoring should be continued until adequate heart conduction parameters are restored.
authors: Servicio de Anestesiología, Reanimación y Terapéutica del Dolor, Hospital Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, España. Electronic address: mati@plagaro.net.
authors: M
authors: M
authors: Zaballos
authors: Servicio de Anestesiología, Reanimación y Terapéutica del Dolor, Hospital Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, España.
authors: R
authors: R
authors: Sevilla
authors: Servicio de Cardiología, Hospital Universitario de Getafe, Madrid, España.
authors: J
authors: J
authors: González
authors: Servicio de Anestesiología, Reanimación y Terapéutica del Dolor, Hospital Universitario Gregorio Marañón, Universidad Complutense de Madrid, Madrid, España.
authors: D
authors: D
authors: Callejo
authors: Servicio de Cardiología, Hospital de Torrejón, Torrejón de Ardoz, Madrid, España.
authors: C
authors: C
authors: de Diego
authors: Unidad de Electrofisiología Cardíaca y Arritmología Clínica, Grupo HM Hospitales, Universidad CEU-San Pablo, Madrid, España.
authors: J
authors: J
authors: Almendral
authors: Instituto Nacional de Toxicología y Ciencias Forenses, Universidad Complutense de Madrid, Madrid, España.
authors: O
authors: O
authors: Quintela
authors: Departamento de Toxicología y Legislación Sanitaria, Universidad Complutense de Madrid, Madrid, España.
authors: M J
authors: MJ
authors: Anadón
mesh_terms: D000779:Anesthetics, Local; D000818:Animals; D001784:Blood Gas Analysis; D002045:Bupivacaine / Q000494:pharmacology*; D004562:Electrocardiography; D006339:Heart Rate; D012151:Resuscitation; D013552:Swine
chemical_list: D000779:Anesthetics, Local; D002045:Bupivacaine
keywords: Antidote; Antídoto; Bupivacaine; Bupivacaína; Cardiac toxicity; Intervalo QRS; Intralipid; QRS interval; Toxicidad cardiaca