Data from various animal studies in the late '90's and early 2000's indicated that lipid infusion increases resistance to local anesthetic toxicity and improves success of resuscitation from local anesthetic overdose. Additional data show similar beneficial effects in animal models of other lipophilic drug overdoses including tricyclic antidepressants, calcium channel blockers and beta blockers.
This work was originally initiated by a chance observation made during a series of experiments testing whether a lipid infusion would increase arrhythmias during bupivacaine toxicity. The investigators had noted that a patient with carnitine deficiency exhibited extreme sensitivity to bupivacaine induced cardiac arrhythmias. They postulated that bupivacaine might interfere with carnitine metabolism. Carnitine is an essential component of the biochemical pathways that transport fatty acids into mitochondria where, under normal aerobic conditions, they provide the majority of cardiac energy needs. Other investigators had shown that intracellular fatty acid derivatives accumulate during myocardial ischemia and postulated that they contribute to ischemia-induced arrhythmias. The reasoning was that if bupivacaine induced arrhythmias by inhibiting carnitine-mediated mitochondrial fatty-acid uptake, then a pretreating infusion of lipids might aggravate such arrhythmias. The exact opposite was found: infusing lipids into rats made them more resistant to bupivacaine-induced asystole.
The next series of experiments confirmed in anesthetized rats that lipid infusion improves the success of resuscitation from bupivacaine toxicity. Subsequent studies in dogs showed that whether given immediately after the bupivacaine, or several minutes later, lipid infusion significantly improved recovery from an otherwise fatal dose of bupivacaine (10mg/kg). In those experiments all six treated animals rapidly recovered normal hemodynamic parameters while none of the controls survived.
The question of using this treatment in patients originally sparked some controversy in the anesthesia literature. The hallmark of local anesthetic-induced cardiac arrest is relative resistance to standard resuscitative measures, hence there would seem to be little to lose in trying the method in someone who has failed ACLS and is effectively dead. Since the first clinical report of a patient saved by LipidRescue in 2006 a large number of compelling case reports and general clinical experience from many sources have indicated that the method has very high efficacay as an antidote to treating local anesthetic systemic toxicity (LAST) when given in combination with the primary elements of good Basic Life Support (BLS): oxygenation, ventilation and, when needed, high quality chest compressions. These features of LAST treatment are brought together in the most current recommendations and practice advisories of key professional societies including ASRA, AAGBI and AHA.
As mentioned in the 'Welcome' section, LipidRescue resuscitation has also been used successfully in certain types of non-LAST drug overdoses, especially involving lipid soluble drugs. Perhaps the most interesting aspect of this development is that the beneficial effects of lipid emulsion infusion extend beyond acting as a simple 'sponge' to soak up the toxic drug and likely involves the important contributions of a variety of other effects inside cells, at the cell membrane and in the plasma. Stay tuned, things are getting interesting.