Abstract 191: During Lipid Resuscitation, Lipid-Blood-Fraction Rapidly Transports Radiolabeled-Bupivacaine From Highly Perfused Organs to Liver for Accelerated Processing and Excretion
Objective: Lipid emulsions (LE) reverse local anesthetic cardiotoxicity but the mechanism of reversal is not completely understood. We tested the hypothesis that LE accelerates removal of radiolabeled-bupivacaine from highly perfused tissue and transports it to the liver for conjugation and excretion.
Methods: Animals were anesthetized using 1.5-2% isoflurane. Jugular veins and right carotid artery were cannulated; a flow probe was hooked around the left common carotid. Flow, pressure and EKG were monitored continuously. Sixty Sprague-dawley rats received a 10mg/kg i.v. bolus of tritium-radiolabeled bupivacaine over 20-seconds with the end of infusion signaling t=0. Animals were assigned to eight sacrifice time-points (t=0.5, 1.5, 2.5, 4.5, 5.5, 8, 12, 60 minutes) and two treatment groups (i.v.LE, null). At t=0.5, animals in the test-group received 10mL/kg i.v.-LE over one minute. After sacrifice, tissues and fluids were collected and analyzed for radiolabeled-bupivacaine concentration.
Results: Concentrations in heart, cerebellum, and kidney dropped more rapidly in i.v.-LE-treated animals (Figure 1) while concentrations in blood, liver and urine rose in a sequential order. Elevated whole blood concentration of radiolabelled-bupivacaine was driven by the LE component. The drops in organ concentration were associated with improvements in cardiovascular (CV) parameters (flow, RPP, mean arterial pressure) but improvements in i.v.-LE treated animals were greater than the improvements seen in null animals with comparable cardiac bupivacaine concentrations.
Conclusion: The study confirms LE’s ability to sequester bupivacaine in vivo, reducing the concentration in vital organs and elevating liver concentrations. Further it is the first to demonstrate that LE accelerates processing and excretion into the urine. Finally, it builds on a growing body of evidence that LE improves CV dynamics that are beyond the pure removal of bupivacaine for CV tissue.
- © 2013 by American Heart Association, Inc.