| Background: Local anesthetic (LA) toxicity may result in severe cardiovascular failure. It has been reported recently that lipid emulsion (LE) rapidly reverses such serious complication in both animal studies and clinical case reports. Recovery of heart function was accelerated by LE infusion in anesthetized animals or in-vivo hearts. In clinical cases, LE increase the success rate of cardiac resuscitation caused by LA.LE was also found to reverse central nervous system symptoms caused by LA toxicity. However, although LE holds great promise in decreasing clinical signs of LA toxicity, two questions remain unanswered. First, the LE mechanism of action is still unclear. The"Lipid sink effect and the metabolic mechanism are speculated to contribute to this protective effect10, but no definite conclusion can be made from the current literatures. Second, it was not well described whether epinephrine could be used in combination with LE. The present study was designed to try and solve these questions.Section One: Pretreatment effect of LE on cardiac arrest by bupivacaine intoxication and mechanism studyObjective: To investigate the pretreatment effect of lipid emulsion (LE) on cardiac arrest by bupivacaine intoxication and the mechanisms.Methods: Fourteen New Zealand rabbits were pretreated with lactate ringer solution (group A, n=7) or 20% Intralipid (group B, n=7), followed by 0.75% bupivacaine until the arterial wave turning to a straight line. Duration until adverse cardiac events and cardiac bupivacaine concentration was compared. Blood pressure (BP), electrocardiogram (ECG) and end-tidal CO2 (ETCO2) were all measured continuously. Arterial blood gas analysis was done. High performance liquid chromatography (HPLC) determined bupivacaine concentration in heart tissue. Bupivacaine was extracted by liquid-liquid extraction method and extraction liquid included equal amount of n-hexane and tert-butyl. The mobile phase consisting of a mixture of methanol and triethylamine buffer and pH was adjusted to 3.0 with phosphoric acid. Flow rate was 1.0ml/min. Chromatographic analysis was performed by a Dima C18 chromatographic column at 30?C and wavelength was set at 215nm. After clipping 0.5g heart sample into fragment and homogenate in 2ml 50% methanol. 200μl homogenate and 100μl 4% NaOH was mixed by vortex for 30 seconds and then mixed with 3ml extraction liquid for 3 minutes. The mixture was then centrifuged at 3000rpm for 10min and 2ml of organic phase was collected in a centrifuge tube. This was followed by evaporating of the solution to dryness in a water bath at 35℃under a gentle stream of nitrogen. The dried residue was reconstituted with 100μl mobile phase, followed by mixing by vortex for 30s and centrifuged at 12000rpm for 10min. The supernatant was transfer into a 250μl vial-insert and a volume of 25μl was drawn by the HPLC system automatically for each analysis.Results: Basic hemodynamic data (MAP, HR) was similar between group A and group B. Mean arterial BP was 94.4±5.9mmHg in group B and 96.4±4.2mmHg in group A (P=0.482); HR was 273±17bpm in group B and 278±15bpm in group A (P=0.522). The onset of ventricular arrhythmia or cardiac stand-still was significantly delayed in group B (P<0.001) . The concentration of bupivacaine in the myocardial tissue was comparable between the 2 groups (P=0.108), But the total dose of intra-venous bupivacaine needed to achieve this cardiac muscle concentration was significantly higher in group B (P<0.001). Conclusions: Lipid emulsion pretreatment reduces cardiac toxicity of bupivacaine. The main mechanism may be the"lipid pool"effect.Section two: Post-treatment effect of LE on resuscitation of cardiac arrest after bupivacaine intoxicationObjective: To investigate post-treatment effect of lipid emulsion in addition to routine cardiopulmonary resuscitation on cardiac arrest induced by bupivacaine overdose and epinephrine dosage during cardiopulmonary resuscitation in rabbits.Methods: Twenty-four New Zealand rabbits were randomly divided into 4 groups (n=6, in each group). Group C was treated with ringer solution (RS) and intrathoracic cardiac massage (ICM), group D with LE and ICM, group E with RS, ICM and epinephrine and group F with LE, ICM and epinephrine. After anesthesia and tracheal intubation, thoracotomy was performed and heart was exposed. Then 10 mg/kg bupivacaine was infused intravenously, followed by resuscitation as designed protocol for each group. Resuscitation outcome and epinephrine dosage in group E and F were recorded.Results: Resuscitation failed in all animals of group C and group D within 30min. Complete recovery of spontaneous heart rhythm and BP was obtained within 5min in all animals in group E and group F, but continuous epinephrine was needed to maintain the BP between 80 and 90mmHg. Cardiac arrest occurred in 4 rabbits in group E (66.7%) at 83.5±12.3min and only in 1 rabbit in group F (16.7%) at 102min. Survival study revealed that survival rate was significantly higher in group F than group E (P=0.0495) . Mean epinephrine utilization was 5.13±1.84μg?kg-1?min-1 in group E and 2.86±0.93μg?kg-1?min-1 in group F (P<0.001) .Conclusions: Lipid emulsion post-treatment in addition to routine cardiopulmonary resuscitation increases survival of resuscitation after bupivacaine-induced cardiac arrest and reduces epinephrine dosage.
|
PDF Full Text Request