Intravenous lipid emulsion is an established, effective treatment for local anesthetic-induced cardiovascular collapse. The predominant theory for its mechanism of action is that by creating an expanded, intravascular lipid phase, equilibria are established that drive the offending drug from target tissues into the newly formed 'lipid sink'. Based on this hypothesis, lipid emulsion has been considered a candidate for generic reversal of toxicity caused by overdose of any lipophilic drug. Recent case reports of successful resuscitation suggest the efficacy of lipid emulsion infusion for treating non-local anesthetic overdoses across a wide spectrum of drugs: beta blockers, calcium channel blockers, parasiticides, herbicides and several varieties of psychotropic agents. Lipid emulsion therapy is gaining acceptance in emergency rooms and other critical care settings as a possible treatment for lipophilic drug toxicity. While protocols exist for administration of lipid emulsion in the setting of local anesthetic toxicity, no optimal regimen has been established for treatment of acute non-local anesthetic poisonings. Future studies will shape the evolving recommendations for lipid emulsion in the setting of non-local anesthetic drug overdose.

Survival of chronic lymphocytic leukemia (CLL) cells in vivo is supported by the tissue microenvironment, which includes components of the extracellular matrix. Interactions between tumor cells and the extracellular matrix are in part mediated by CD44, whose principle ligand in this respect is hyaluronic acid. Purpose: to evaluate the effect of CD44 engagement on the survival of CLL cells. Experimental Design: CD44 in CLL cells was engaged by anti-CD44 monoclonal antibody, or hyaluronic acid, and the effects of CD44 activation on CLL cell viability and pro-survival pathways were evaluated. Results: engagement of CD44 activated the PI3K/AKT and MAPK/ERK pathways and increased MCL-1 protein expression. Consistent with the induction of these anti-apoptotic mechanisms, CD44 protected CLL cells from spontaneous and fludarabine-induced apoptosis. Leukemic cells of the more aggressive CLL subtype that express unmutated IgVH genes (U-CLL) showed higher CD44 expression than IgVH-mutated CLL (M-CLL) cells, and acquired a greater survival advantage via CD44 activation. Thus, CD44 activation in the tissue microenvironment may contribute to increased MCL-1 protein levels, resistance to apoptosis, and could contribute to the more progressive nature of U-CLL. Furthermore, PI3K or MEK inhibitors as well as obatoclax, an antagonist of MCL-1, blocked the pro-survival effect of CD44. In addition, obatoclax synergized with fludarabine to induce apoptosis of CLL cells. Conclusions: components of the extracellular matrix may provide survival signals to CLL cells through engagement of CD44. Inhibition of MCL-1, PI3K, and MAPK/ERK pathways are promising strategies to reduce the anti-apoptotic effect of the microenvironment on CLL cells.

As the obstetric demographic becomes older and more obese, new technologies and strategies can assist in controlling maternal death and major morbidity secondary to anesthesia complications. Lipid resuscitation appears to be an effective treatment for toxicity induced by lipophilic medications and may be useful in treating systemic toxicity in the pregnant patient. Obstetric care providers should be aware of lipid resuscitation and consider its use as described by American Society of Regional Anesthesia and Pain Medicine guidelines.