Background: Exparel is a formulation of bupivacaine encapsulated in multi-vesicular liposomes, developed for post-surgical anesthesia. The liposomes have been shown to increase the drug’s stability and extend its duration of action. Exparel may prevent accumulation of bupivacaine in blood and/or tissue; thus, decreasing risk of central nervous or cardiovascular toxicities. However, administration of Exparel has its risks. The maximum dosage of Exparel for adults is ~266 mg, but the maximum mg/kg dosing limit is unknown. The role of Intralipid (ILP, 20%) for reversal of Exparel toxicity is not known. Our aim is to determine toxic dose of Exparel in mg/kg and if ILP can reverse its cardiotoxic effects in rats.
Methods: Female rats (~250 gm, n=6) were used for the study. Asystole was attempted with different IV doses of Exparel (25 mg/kg, 15 mg/kg, 7.5mg/kg over 10 seconds). For the second part of the study, asystole was induced with Exparel (15 mg/kg over 10 sec, IV), and resuscitation with ILP (5 ml/kg bolus and 0.5 ml/kg/min maintenance) was started immediately along with chest compressions. Heart rate (HR, beats per min) and ejection fraction (EF, %) were measured using echo at 1, 5, and 10 min.
Results: We found that a dose of 25 mg/kg of Exparel caused cardiac arrest immediately. Next we decreased the dose of Exparel to 15 mg/kg, that also caused immediate cardiovascular collapse. Exparel 7.5 mg/kg did not induce cardiac arrest; instead, it caused wide complex tachycardia that self resolved in 5 min. ILP rescue of Exparel cardiotoxicity was found to be unpredictable (n=3). EF, HR and EKG improved after cardiac arrest the most at 1 min after ILP. At 1 min, EF was 42.8+/-15% and HR was 169.3 +/- 25 bpm. ILP rescue of Exparel cardiotoxicity was not sustained contrary to ILP’s rescue of Bupivacaine cardiotoxicity in rats. EF and HR continued to deteriorate when measured at 5 and 10 min, with 2 out of 3 rats with EF=0 at 5 and 10 min.
Conclusion: We found a dose of Exparel that reliably induced cardiotoxicity in rats. ILP is unreliable in rescuing Exparel induced cardiotoxicity at the dosage regimen typically used for rats with Bupivacaine cardiotoxicity. More experiments are needed to determine ILP’s dosage that can reliably reverse Exparel cardiotoxicity.