To the Editor: 

We read with interest the work of Ruan et al.  1in the February 2012 issue of ANESTHESIOLOGY; the article explored the effect of both triglyceride chain length and pH modulation on lipid sequestration of cardiotoxic local anesthetics in human serum in vitro . The authors are to be lauded for their efforts to expound the physicochemical interaction known widely as the “sink,” purported to be primarily responsible for the beneficial effects demonstrated in animal models and human subjects suffering local anesthetic systemic toxicity. Their results in many respects epitomize the difficulties associated with forwarding a therapy such as lipid rescue – itself a product of a chance laboratory observation, when definitive knowledge of mechanistic action for lipid remains to be fully elucidated.

Ruan et al.  demonstrated the superiority of mixed medium and long-chain triglyceride preparations in sequestration of lipophilioc local anesthetics, seemingly independent of pH, when compared with long-chain triglyceride in in vitro  human serum. These results, nevertheless, conflict with the findings of Li et al.  2(from the December 2011 issue of ANESTHESIOLOGY), who demonstrated advantages with long-chain triglycerides in an intact animal model. The observed disparity in outcomes between such bench-top and whole animal experiments was discussed expertly in an accompanying editorial.3 

Although the advancement of any therapy is necessarily paved with conjecture and discourse, such as evidenced in microcosm with these two papers, conclusions drawn from such work must be tempered against the findings of prior investigators' and the associated relevant (and, in the case of lipid therapy, substantial) bodies of work. It is therefore concerning that in their concluding remarks Ruan et al. “call into question the current advanced cardiac life support guidelines specifying use of a long-chain triglyceride emulsion” in local anesthetic systemic toxicity on the basis of their findings alone, before the existence of a body of work supporting alternative lipid emulsion preparations as clearly superior. The work of Ruan et al.  clearly represents one step of many in the evolution of lipid emulsion therapy. Their results, however, are insufficient to alter current recommendations4for lipid infusion in local anesthetic systemic toxicity.

Ruan W, French D, Wong A, Drasner K, Wu AH: A mixed (long- and medium-chain) triglyceride lipid emulsion extracts local anesthetic from human serum in vitro  more effectively than a long-chain emulsion. ANESTHESIOLOGY 2012; 116:334–9
Li Z, Xia Y, Dong X, Chen H, Xia F, Wang X, Dong H, Jin Z, Ding X, Papadimos TJ, Xu X: Lipid resuscitation of bupivacaine toxicity: Long-chain triglyceride emulsion provides benefits over long- and medium-chain triglyceride emulsion. ANESTHESIOLOGY 2011; 115:1219–28
Killoran PV, Cattano D: From bedside to bench and back: Perfecting lipid emulsion therapy for local anesthetic toxicity. ANESTHESIOLOGY 2011; 115:1151–2
Neal JM, Bernards CM, Butterworth JF 4th, Di Gregorio G, Drasner K, Hejtmanek MR, Mulroy MF, Rosenquist RW, Weinberg GL: ASRA practice advisory on local anesthetic systemic toxicity. Reg Anesth Pain Med 2010; 35:152–61