PURPOSE: Intravenous lipid emulsions have been used to treat the systemic toxicity of local anesthetics. The goal of this in vitro study was to examine the effects of lipid emulsions on the norepinephrine-mediated reversal of vasodilation induced by high doses of levobupivacaine, ropivacaine, and mepivacaine in isolated endothelium-denuded rat aorta, and to determine whether such effects are associated with the lipid solubility of local anesthetics. MATERIALS AND METHODS: The effects of lipid emulsions (0.30, 0.49, 1.40, and 2.61%) on norepinephrine concentration-responses in high-dose local anesthetic (6x10-4 M levobupivacaine, 2x10-3 M ropivacaine, and 7x10-3 M mepivacaine)-induced vasodilation of isolated aorta precontracted with 60 mM KCl were assessed. The effects of lipid emulsions on local anesthetic- and diltiazem-induced vasodilation in isolated aorta precontracted with phenylephrine were also assessed. RESULTS: Lipid emulsions (0.30%) enhanced norepinephrine-induced contraction in levobupivacaine-induced vasodilation, whereas 1.40 and 2.61% lipid emulsions enhanced norepinephrine-induced contraction in both ropivacaine- and mepivacaine-induced vasodilation, respectively. Lipid emulsions (0.20, 0.49 and 1.40%) inhibited vasodilation induced by levobupivacaine and ropivacaine, whereas 1.40 and 2.61% lipid emulsions slightly attenuated mepivacaine (3x10-3 M)-induced vasodilation. In addition, lipid emulsions attenuated diltiazem-induced vasodilation. Lipid emulsions enhanced norepinephrine-induced contraction in endothelium-denuded aorta without pretreatment with local anesthetics. CONCLUSION: Taken together, these results suggest that lipid emulsions enhance the norepinephrine-mediated reversal of local anesthetic-induced vasodilation at toxic anesthetic doses and inhibit local anesthetic-induced vasodilation in a manner correlated with the lipid solubility of a particular local anesthetic.
Amides/adverse effects ; Anesthetics, Local/*adverse effects ; Animals ; Bupivacaine/adverse effects/analogs & derivatives ; Emulsions/*chemistry/*therapeutic use ; Lipids/*chemistry ; Male ; Mepivacaine/adverse effects ; Norepinephrine/*therapeutic use ; Rats ; Rats, Sprague-Dawley ; Vasodilation/*drug effects

The mechanism of chronic pain is very complicated. Memory, pain, and opioid dependence appear to share common mechanism, including synaptic plasticity, and anatomical structures. A 48-yr-old woman with severe pain caused by bone metastasis of breast cancer received epidural block. After local anesthetics were injected, she had a seizure and then went into cardiac arrest. Following cardiopulmonary resuscitation, her cardiac rhythm returned to normal, but her memory had disappeared. Also, her excruciating pain and opioid dependence had disappeared. This complication, although uncommon, gives us a lot to think about a role of memory for chronic pain and opioid dependence.
Amnesia/*diagnosis ; Anesthesia, Local/adverse effects ; Bone Neoplasms/drug therapy/radiotherapy/secondary ; Breast Neoplasms/drug therapy/pathology/radiotherapy ; *Cardiopulmonary Resuscitation ; Electroencephalography ; Female ; Heart Arrest/etiology ; Humans ; Magnetic Resonance Imaging ; Mepivacaine/adverse effects ; Middle Aged ; *Pain Management ; Seizures/etiology ; Tomography, X-Ray Computed