Background
Liposomal bupivacaine has been studied and applied in clinical practice in order to provide long lasting pain relief after a single dose1. Exparel is a formulation of bupivacaine encapsulated in multi-vesicular liposomes, developed for surgical wound infiltration for post-surgical anesthesia2. The liposomes have been shown to increase the drug’s stability and extend its duration of action, with recent studies showing bimodal kinetics and rapid uptake during the first few hours and prolonged release over 96 hours3. Exparel may prevent accumulation of bupivacaine in blood and/or tissues; thus, it may decrease the risk of central nervous or cardiovascular toxicities. Administration of Exparel has its risks. There is concern that non-bupivacaine based local anesthetics may cause immediate release of bupivacaine from Exparel when administered concomitantly4. The cross-reactivity may potentially place the patient at risk for local anesthetic toxicity especially when total local anesthetic use is unclear. Because Exparel is a white solution, another concern is inadvertent intravenous injection of the local anesthetic if mistaken for propofol leading to systemic toxicity. The maximum dosage of Exparel for adults is ~266 mg; however, the maximum mg/kg dosing limit is not known. There have been no formal studies conducted on Exparel’s actual toxic dose in mg/kg and if use of Intralipid 20% can reverse its toxicity. The study’s aim is to determine Exparel’s toxic dose in mg/kg and if Intralipid 20% can reverse its cardiotoxic effects.
Methods
Female rats (200-300 gm) were used for the study. Asystole was attempted with different IV dosages of Exparel (25 mg/kg, 15 mg/kg, 7.5mg/kg over 10 seconds). For the second part of the experiment, asystole was induced with Exparel (15 mg/kg over 10 seconds, IV), and resuscitation with Intralipid 20% (5 ml/kg bolus and 0.5 ml/kg/min maintenance) was started immediately along with chest compressions. Heart rates and ejection fractions (EF) were measured using continuous transthoracic echocardiography at 1, 5, and 10 minutes after cardiac arrest.
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 was still enough to cause immediate cardiovascular collapse. Exparel 7.5mg/kg did not induce cardiovascular collapse; instead, it caused wide complex tachycardia which resolved in 5 minutes with no intervention. Intralipid rescue of Exparel cardiotoxicity was found to be unpredictable. EF, HR, EKG were improved from cardiac arrest the most at 1min after Intralipid rescue and continued to deteriorate when measured at 5min and 10min after the initial bolus dose
Conclusion
We found a dose of Exparel that reliably induced cardiotoxicity in rats. More experiments are needed to determine Intralipid’s dosage that can reliably reverse Exparel toxicity. Based on our results, Intralipid is unreliable in rescuing Exparel induced cardiotoxicity at the dosage regimen used.
