Mechanisms and Efficacy of Intravenous Lipid Emulsion Treatment for Systemic Toxicity From Local Anesthetics

Abstract

Local anesthetics are widely used clinically for perioperative analgesia to achieve comfort in medical treatment. However, when the concentration of local anesthetics in the blood exceeds the tolerance of the body, local anesthetic systemic toxicity (LAST) will occur. With the development and popularization of positioning technology under direct ultrasound, the risks and cases of LAST associated with direct entry of the anesthetic into the blood vessel have been reduced. Clinical occurrence of LAST usually presents as a series of severe toxic reactions such as myocardial depression, which is life-threatening. In addition to basic life support (airway management, advanced cardiac life support, etc.), intravenous lipid emulsion (ILE) has been introduced as a treatment option in recent years and has gradually become the first-line treatment for LAST. This review introduces the mechanisms of LAST and identifies the clinical symptoms displayed by the central nervous system and cardiovascular system. The paper features the multimodal mechanism of LAST reversal by ILE, describes research progress in the field, and identifies other anesthetics involved in the resuscitation process of LAST. Finally, the review presents key issues in lipid therapy. Although ILE has achieved notable success in the treatment of LAST, adverse reactions and contraindications also exist; therefore, ILE requires a high degree of attention during use. More in-depth research on the treatment mechanism of ILE, the resuscitation dosage and method of ILE, and the combined use with other resuscitation measures is needed to improve the efficacy and safety of clinical resuscitation after LAST in the future.

Keywords: bupivacaine; lipid emulsion; local anesthetic systemic toxicity; mechanism; resuscitation.

Figure 1

Lipid emulsion enters the blood system to form “lipid sink” and wrap local anesthetics and remove them from various tissues and organs. Lipid emulsion is like a shuttle subway. It combines local anesthetics in the heart and the brain, which are most sensitive to the decline of blood oxygen, and is distributed to the liver and muscle tissue to begin detoxification and digestion.

Figure 2

Local anesthetics act on Na⁺, K⁺, Ca²⁺ channels, interfere with signal transduction in cells and transmembrane cells, and inhibit the metabolic processes of PKB, AMPK, and other molecules related to cell survival and apoptosis. Local anesthetics increase the release of cytochrome c from mitochondria to cytoplasm, increased apoptosis, and impaired mitochondrial function. Lipid emulsion inhibited the opening of MPTP to restore mitochondrial function. Lipid emulsion can activate Ca²⁺ channels, increase the intracellular calcium level, and activate upstream kinase PI3K, and PKB-mediated downstream kinase GSK-3β Phosphorylation leads to the inhibition of MPTP opening, thereby reversing cardiomyocyte apoptosis induced by local anesthetics. Lipid emulsion inhibits the activation of eNOS, reduces the production and release of NO, and reverses the severe vasodilation caused by LAST.