Intravenous lipid emulsion: Why wait to save a life?

Here is a most improbable story connecting a near cardiac arrest in a young patient having liposuction with the dramatic save of another young patient in cardiac arrest following an attempted suicide. The saving medicine? Implausibly, it was an oil emulsion normally intended to improve a patient’s nutritional status. How did a nutritional supplement turn into an antidote for lipophilic drug overdose? Neither by accident, nor intent, but by a stranger path still – one leading to two papers in this issue of Emergency Medicine Australasia (EMA). More than a decade ago, I learned of a patient with carnitine deficiency who exhibited extreme sensitivity to bupivacaine, a lipophilic local anaesthetic known to cause severe cardiac toxicity. I wondered if carnitine deficiency lowers the threshold for local anaesthetic toxicity and later determined that bupivacaine inhibits a carnitine-dependent mitochondrial enzyme that is necessary for metabolizing fats, the hearts preferred fuel. We hypothesized that this effect contributed to the wellknown cardiotoxicity of bupivacaine and only needed a laboratory model of carnitine deficiency to prove the theory. This proved difficult, or in our hands, impossible. The alternative was to recreate the metabolic context of impaired fatty acid oxidation, which was known to enhance arrhythmias through accumulation of cytoplasmic fatty acids. What better way to reproduce this than loading the test subject with a lipid emulsion? Our hypothesis predicted that this would make the rat more susceptible to bupivacaine . the experiment proved exactly the opposite: infusion of lipid emulsion made the animal resistant to bupivacaine. Follow-up experiments showed that administering the same lipid emulsion after an otherwise fatal dose of bupivacaine rapidly reversed the signs of local anaesthetic toxicity. Later, we published a paper showing the same effect in dogs: resuscitation was always successful after a huge dose of bupivacaine, when an i.v. bolus of lipid emulsion was given. An accompanying editorial asked, ‘Could this be the silver bullet? ’ to the problem of local anaesthetic toxicity, a potentially life-threatening complication of regional anaesthesia that had been vexing anaesthesiologists for decades. But lipid resuscitation would remain forever a laboratory phenomenon unless someone who had read these papers (probably rare) was present when a case of bupivacaine toxicity occurred (definitely rare) and had the courage (rarer still) to try something that had never been done in a human. That vanishingly unlikely occurrence transpired when Dr Meg Rosenblatt at Mount Sinai in New York City happened upon a team of anaesthesiologists 20 min into the resuscitation of a patient who had arrested shortly after a bupivacaine-based brachial plexus block. She knew the literature and after ascertaining that the resuscitation was going nowhere, ran to the pharmacy, picked up 20% lipid emulsion, ran it back to the Code Blue team and instructed them to give 100 mL as an i.v. bolus. Within 1 min, the patient had a pulse and quickly recovered normal vital signs. He was ultimately discharged with no neurological or cardiac sequelae. A nearly identical case of ILE reversing ropivacaine-induced cardiac arrest was published shortly afterward by Rainer Litz and colleagues from Dresden, Germany. Meg and Rainier’s courageous action saved lives and ushered in the clinical translation of lipid resuscitation. Dozens of reports of successful saves from local anaesthetic overdose have now followed in the literature, including that of bupivacaine toxicity published in this issue of EMA.