t the very time that resident candidates grade the excellence of their potential training programs by the quality of the regional anesthesia rotations therein and while regional anesthesia/analgesia techniques are finding greater application in clinical practice worldwide, there comes growing evidence that there is a new and effective treatment for local anesthetic (LA) toxicity emerging. The first reported clinical applications of lipid therapy in humans are attributed to Rosenblatt et al. and Litz et al. Their patients had undergone an interscalene block with bupivacaine and mepivacaine and an axillary block with ropivacaine, respectively, with clinically appropriate doses of local anesthetics.^1,2 When the patients were failing to benefit from conventional cardiopulmonary resuscitation after manifesting LA toxicity (hypotension and arrhythmias leading to cardiac arrest), lipid emulsion therapy was administered. The use of this novel technique led to the patient’s rapid and successful response to resuscitative measures. These reports have triggered a cascade of similar reports, which are providing enthusiasm for this unique therapy, modifications in the original protocol described, and confidence that the risk of a patient suffering detrimental consequences from LA toxicity is less likely.

The concept of using a lipid emulsion to create a lipid bank into which wayward LAs could be deposited from (cardiac) tissues is not new. Weinberg et al. showed that this might occur, in that rats and dogs were easier to resuscitate from LA overdoses after lipid administration.^3,4 In commentary about the theoretic clinical application of this therapy, Groban and Butterworth stated in a 2003 editorial that lipid emulsion therapy (for bupivacaine overdose) should be used “…only after other, more conventional treatments have proven unsatisfactory.”⁵ That is exactly what occurred in the two reported cases cited above.

What, though, is the incidence of LA toxicity? In publishing the results of a survey of U.S. academic centers about their preparedness to manage patients with LA toxicity, Corcoran et al. projected that the incidence of LA toxicity (7.5 to 20 per 10,000 peripheral nerve blocks) was in decline, even as the total number of peripheral nerve blocks performed in today’s anesthetic practices was increasing.⁶ Because LA toxicity can be fatal, they assert that having a corporate plan to manage this clinical event is necessary. The plan needs to be known to practitioners and readily accessible in an emergency situation. Their survey documented the widely varying number of block procedures performed within institutions and a preference for choosing bupivacaine or ropivacaine for long-lasting effects and lidocaine or mepivacaine for shorter-duration blocks. The extent of the use of standard ASA monitoring varied among institutions, as did the choice of emergency drugs for treatment of ventricular tachycardia and hypotension. Fifty-nine percent of the responding programs declared that they had no established plan for using cardiopulmonary bypass, yet 84 percent of the programs stated that cardiothoracic surgeons would be available within 30 minutes to provide advanced circulatory support. At the time of the survey (prior to any reports of lipid therapy in human care), 74 percent of the programs said they would not consider using lipid emulsion therapy. Corcoran et al. concluded that there is a “…wide range of current practice patterns … in U.S. academic centers, and variability in nearly all aspects of treatment strategies for managing severe local anesthetic toxicity” and that “there is no consensus strategy for how to best treat severe local anesthetic toxicity.”⁶ The published case reports bode of new insights into experiences that might foster a modification of the last-mentioned conclusion.

Soon after the case report by Rosenblatt et al.¹ was published, Weinberg established a Web site www.lipidrescue.org to serve as an informational resource about LA toxicity and lipid therapy (the site now lists four published cases) as well as to provide a readily accessible forum for the exchange of ideas about the presentation, diagnosis and management of LA toxicity (and eventually toxicity from other drug classes) and the possible mechanisms of action of lipid therapy. There also is a section for the demographic accumulation of clinicians’ experiences with lipid emulsion therapy. While these particular submissions do not share the scientific rigor of published cases, per se, they do demonstrate a positive, if not remarkable, performance profile for lipid therapy in the face of a variety of presentations of LA toxicity. The current protocol listed on the Web site emphasizes its application in “…local anesthetic-induced cardiac arrest that is unresponsive to standard [resuscitation] therapy.” It recommends a bolus of Intralipid™ 20 percent 1.5 mL/kg over a minute, followed by an infusion at a rate of 0.25 mL/kg/min. The bolus can be repeated every three to five minutes up to a dose of 3 mL/kg total dose until circulation is restored. The infusion should be continued until hemodynamic stability is achieved and the rate increased to 0.5 mL/kg/min if the blood pressure drops. A total maximum dose of 8 mL/kg is recommended (www.lipidrescue.org).

We should admire the persistence of Dr. Weinberg and his associates in establishing the basic science rationale for lipid therapy to be of benefit in the face of local anesthetic toxicity with cardiac arrest. The challenge of Groban and Butterworth and Corcoran et al. that clinicians should have a departmental/institutional plan for managing LA toxicity seems easier to confront when one appreciates the growing number of reports of patients being “rescued,” as found at the Web site referenced above. This oracle of contemporary information raises lipid therapy to at least a high level of attention for the astute practitioner. Putting this new therapy in perspective, Picard et al. pointed out the similarity and evolution of our understanding and use of dantrolene for malignant hyperthermia (MH) to that of lipid therapy for LA toxicity. Both of these conditions are unpredictable and infrequent and associated with a potentially fatal outcome. In that vein, clinicians should consider co-locating lipid emulsion to areas where large doses of LAs are used, so that as with MH, lives can be saved if toxicity occurs because the most up-to-date treatment is readily available. The use of lipid emulsion therapy seems to be a circumstance about which we should learn from the experience of others and the wisdom of their decisions.

References:
1. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ, Eisencraft JB. Successful use of a 20% lipid emulsion to resuscitate a patient after presumed bupivacaine-related cardiac arrest. Anesthesiology. 2006; 105:217-218.
2. Litz RJ, Popp M, Stehr SN, Koch T. Successful resuscitation of a patient with ropivacaine-induced asystole after axillary plexus block using lipid emulsion. Anaesthesia. 2006; 61:800-801.
3. Weinberg GL, VadeBoncouer T, Ramaraju GA, Garcia-Amaro MF, Cwik MJ. Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats. Anesthesiology. 1998; 88:1071-1075.
4. Weinberg GL, Ripper R, Feinstein DL, Hoffman W. Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity. Reg Anesth Pain Med. 2003; 28:198-202.
5. Groban L, Butterworth J. Lipid reversal of bupivacaine toxicity: Has the silver bullet been identified? Reg Anesth Pain Med. 2003; 28:167-169.
6. Corcoran W, Butterworth J, Weller RS, et al. Local anesthetic-induced cardiac toxicity: A survey of contemporary practice strategies among academic anesthesiology departments. Anesth Analg. 2006; 103:1322-1326.
7. Picard J, Ward S, Meek T. Antidotes to anesthetic catastrophe: Lipid emulsion and dantrolene. Anesth Analg. 2007; 105:283-284.

John C. Rowlingson, M.D., is Cosmo A. DiFazio Professor of Anesthesiolgy and Director, Pain Medicine Services, University of Virginia Health System Department of Anesthesiology, Charlottesville, Virginia.