Lipid resuscitation: development in basic research and application to clinical practice

Abstract

It has been nearly 15 years since the effectiveness of intravenous lipid emulsion in resuscitation from bupivacaine-induced cardiac arrest was reported by Weinberg et al. [1]. Despite the outstanding novelty and originality of this finding, it was not until a 2006 case report of a patient resuscitated with lipid emulsion after bupivacaine-induced refractory dysrhythmia and cardiac arrest that its clinical effectiveness was acknowledged [2]. This event was followed by a large number of case reports that showed the effectiveness of lipid emulsion for treating the central nervous system as well as cardiac toxicity induced by various kinds of local anesthetics [3–8]. Treatment with intravenous lipid emulsion has been incorporated into practice advisories of the Association of Anesthesiologists of Great Britain and Ireland, the American Society of Regional Anesthesia and Pain Medicine [9], and endorsed by the American Heart Association Advanced Cardiac Life Support (ACLS) guidelines [10] (Table 1). In response to widespread interest, numerous studies have been undertaken using various animal models [8]. Notably, most of the animal experiments have been focused on examining the effect of lipid on local anesthetic-induced cardiac toxicity, not central nervous system toxicity, probably because of the primary concern of resuscitation and the entirely different animal models required for studying these two types of toxicity. Animals under mechanical ventilation with oxygen are needed to examine the effect of lipid emulsion on cardiac toxicity of local anesthetics while eliminating the influence of hypoxia induced by sedation and convulsions preceding circulatory collapse [11–14]. In contrast, awake, spontaneously breathing animals are needed to observe its effect on the central nervous system toxicity [15]. Randomized clinical trials are no longer ethically defensible for studying local anesthetic toxicity. Moreover, clinical data from healthy volunteers given nontoxic doses of bupivacaine would not precisely reflect the condition at the onset of the toxic effects [16].