Levosimendan combined with epinephrine improves rescue outcomes in a rat model of lipid-based resuscitation from bupivacaine-induced cardiac arrest

Fubei Nan, Xixi Cai, Yingchao Ye, Xuzhong Xu, Zhengqian Li, Min Li, Limei Chen

The effectiveness of a combination of a lipid emulsion with epinephrine in reversing local anesthetic-induced cardiac arrest has been confirmed. The combination of a lipid emulsion with levosimendan, was shown to be superior to administration of a lipid emulsion alone with regard to successful resuscitation. In this study, we compared the reversal effects of levosimendan, epinephrine, and a combination of the two agents in lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest. Fifty-four adult male Sprague-Dawley rats were subjected to bupivacaine (15 mg·kg(-1)) -induced asystole and were then randomly divided into 3 groups. A lipid emulsion was used as the basic treatment, and administration of drug combinations varied in each group as follows: (1) levosimendan combined with epinephrine (LiEL); (2) epinephrine (LiE); and (3) levosimendan (LiL). The resuscitation outcomes were recorded and included the rate of return of spontaneous circulation (ROSC) and survival at 40 min, time to first heartbeat, time to ROSC, and cumulative dose of epinephrine. We calculated the wet-to-dry ratio of the lung, blood gas values at 40 min and bupivacaine concentration of cardiac tissue and plasma. The rates of ROSC in LiEL and LiE groups were higher than LiL group (P < 0.001; LiEL vs LiL, P = 0.001; LiE vs LiL, P = 0.007). The survival rate in LiEL group was higher than LiE group (P = 0.003; LiEL vs LiE, P = 0.008; LiEL vs LiL, P = 0.001). The time to first heart beat in LiEL group was shorter than LiE, LiL groups. (P < 0.001; LiE vs LiEL, P = 0.001; LiL vs LiEL, P < 0.001). The time to ROSC in LiEL group was shorter than LiE, LiL groups (P < 0.001; LiEL vs LiE, P < 0.001; LiEL vs LiL, P < 0.001). The result was similar for the bupivacaine concentration of cardiac tissue and plasma (cardiac tissue: P = 0.002; plasma: P = 0.011). Furthermore, there were significant differences in the blood-gas values at 40 min, wet-to-dry lung weight ratio, and ratio of damaged alveoli among groups. The LiEL group had the best result for all parameters (P < 0.01, P = 0.008, P < 0.001, respectively). Additionally, significantly less epinephrine was used in the LiEL group (P < 0.001). Levosimendan combined with epinephrine may be superior to either drug alone for lipid-based resuscitation in a rat model of bupivacaine-induced cardiac arrest. The drug combination was associated with a higher survival rate as well as decreased epinephrine consumption and lung damage.