Local Anesthetic Systemic Toxicity

The American Society of Regional Anesthesia and Pain Medicine's Third Practice Advisory on local anesthetic systemic toxicity is an interim update from its 2010 advisory. The advisory focuses on new information regarding the mechanisms of lipid resuscitation, updated frequency estimates, the preventative role of ultrasound guidance, changes to case presentation patterns, and limited information related to local infiltration anesthesia and liposomal bupivacaine. In addition to emerging information, the advisory updates recommendations pertaining to prevention, recognition, and treatment of local anesthetic systemic toxicity. WHAT'S NEW IN THIS UPDATE?: This interim update summarizes recent scientific findings that have enhanced our understanding of the mechanisms that lead to lipid emulsion reversal of LAST, including rapid partitioning, direct inotropy, and post-conditioning. Since the previous practice advisory, epidemiological data have emerged that suggest a lower frequency of LAST as reported by single institutions and some registries, nevertheless a considerable number of events still occur within the general community. Contemporary case reports suggest a trend toward delayed presentation, which may mirror the increased use of ultrasound guidance (fewer intravascular injections), local infiltration techniques (slower systemic uptake), and continuous local anesthetic infusions. Small patient size and sarcopenia are additional factors that increase potential risk for LAST. An increasing number of reported events occur outside of the traditional hospital setting and involve non-anesthesiologists.

Emergency clinicians utilize local anesthetics for a variety of procedures in the emergency department (ED) setting. Local anesthetic systemic toxicity (LAST) is a potentially deadly complication. This narrative review provides emergency clinicians with the most current evidence regarding the pathophysiology, evaluation, and management of patients with LAST. LAST is an uncommon but potentially life-threatening complication of local anesthetic use that may be encountered in the ED. Patients at extremes of age or with organ dysfunction are at higher risk. Inadvertent intra-arterial or intravenous injection, as well as repeated doses and higher doses of local anesthetics are associated with greater risk of developing LAST. Neurologic and cardiovascular manifestations can occur. Early recognition and intervention, including supportive care and intravenous lipid emulsion 20%, are the mainstays of treatment. Using ultrasound guidance, aspirating prior to injection, and utilizing the minimal local anesthetic dose needed are techniques that can reduce the risk of LAST. This focused review provides an update for the emergency clinician to manage patients with LAST.

Local anesthetic systemic toxicity (LAST) is a life-threatening adverse event that may occur after the administration of local anesthetic drugs through a variety of routes. Increasing use of local anesthetic techniques in various healthcare settings makes contemporary understanding of LAST highly relevant. Recent data have demonstrated that the underlying mechanisms of LAST are multifactorial, with diverse cellular effects in the central nervous system and cardiovascular system. Although neurological presentation is most common, LAST often presents atypically, and one-fifth of the reported cases present with isolated cardiovascular disturbance. There are several risk factors that are associated with the drug used and the administration technique. LAST can be mitigated by targeting the modifiable risk factors, including the use of ultrasound for regional anesthetic techniques and restricting drug dosage. There have been significant developments in our understanding of LAST treatment. Key advances include early administration of lipid emulsion therapy, prompt seizure management, and careful selection of cardiovascular supportive pharmacotherapy. Cognizance of the mechanisms, risk factors, prevention, and therapy of LAST is vital to any practitioner using local anesthetic drugs in their clinical practice.

Lipid emulsion has been shown to be an effective treatment for systemic toxicity induced by local anesthetics, which is reflected in case reports. A systemic review and meta-analysis confirm the efficacy of this treatment. Investigators have suggested mechanisms associated with the lipid emulsion-mediated recovery of cardiovascular collapse caused by local anesthetic systemic toxicity; these mechanisms include lipid sink, a widely accepted theory in which highly soluble local anesthetics (particularly bupivacaine) are absorbed into the lipid phase of plasma from tissues (e.g., the heart) affected by local-anesthetic-induced toxicity; enhanced redistribution (lipid shuttle); fatty acid supply; reversal of mitochondrial dysfunction; inotropic effects; glycogen synthase kinase-3β phosphorylation associated with inhibition of the mitochondrial permeability transition pore opening; inhibition of nitric oxide release; and reversal of cardiac sodium channel blockade. The current review includes the following: 1) an introduction, 2) a list of the proposed mechanisms, 3) a discussion of the best lipid emulsion treatment for reversal of local anesthetic toxicity, 4) a description of the effect of epinephrine on lipid emulsion-mediated resuscitation, 5) a description of the recommended lipid emulsion treatment, and 6) a conclusion.