Abstract 21323: Intralipid Fails to Rescue Bupivacaine-Induced Cardiac Arrest in Pregnant Rats

Abstract

Background: Pregnant patients routinely get neuraxial anesthesia. Bupivacaine is one of the most commonly used local anesthetics in obstetric anesthesia. Studies have suggested that pregnancy increases Bupivacaine cardiotoxicity. We and others have previously shown that Intralipid (ILP) rescues the heart from Bupivacaine cardiotoxicity in male rats. ILP mediates its cardioprotective effects via glycogen synthase kinase-3b (GSK-3b) phosphorylation. We aimed to investigate Bupivacaine cardiotoxicity and potential for ILP’s rescue in pregnant rats, that has not been studied before. Methods: Late pregnant rats (200-300 g, n=12) at day 20 of pregnancy were used for the study. A group of pregnant rats received Bupivacaine bolus (10 mg/kg, IV over ~20 seconds, n=7) to induce asystole under anesthesia. Resuscitation with ILP 20% (5 ml/kg bolus, and 0.5 ml/kg/min maintenance, n=7) and chest compressions were initiated. The ejection-fraction (EF%), and heart rate (HR) were calculated from echocardiography and EKG at baseline and at 1, 5, and 10 min after ILP treatment. A group of pregnant rats that did not undergo Bupivacaine-induced cardiac arrest and ILP rescue served as sham controls (n=5). Hearts were collected and Western blot was performed to assess GSK-3b phosphorylation. Results: All 7 late pregnant rats developed cardiac arrest a few seconds after Bupivacaine. Interestingly, 6 out of the 7 rats were not rescued with ILP using the same dose as in male rats. In these 6 rats, the average baseline EF and HR were 67.344.47% and 34130.44 bpm. One, five and ten minutes after ILP administration, the EF and HR were 0. Western blots showed that pregnant rats which were not rescued by ILP failed to have GSK-3b activation (pGSK/GSK=0.80±0.51 vs. 1.00±0.56 in late pregnant sham controls; p=0.578). In the late pregnant rat that recovered with ILP, baseline EF and HR (66.302.99% and 31034 bpm), were not different than the rats that did not recover. Conclusions: ILP failed to rescue Bupivacaine-induced cardiac arrest in pregnant rats. This failure of rescue is most likely attributed to the inability of ILP to activate GSK-3b, a known mediator of ILP’s cardioprotection.