Local Anesthetic Systemic Toxicity

Definition

Local anesthetics inhibit the ability to generate and propagate electrical impulses in excitable tissues via binding of voltage-gated sodium channels. Interaction of local anesthetics with a specific region of the alpha subunit on the inner pore of these channels acts to prevent conformational changes of channel activation and results in physical occlusion of the channel. This impedes the sodium influx normally associated with membrane depolarization. Local anesthetics differ from medications given via parenteral or enteral administration, as they are deposited in close proximity to their intended site of action and removed via systemic absorption into the circulation. Local anesthetics may be injected directly into perineural tissues or joint spaces, infiltrated into subcutaneous tissues, or applied topically to the skin and mucosal surfaces to provide anesthesia and analgesia. They are administered intravenously to produce regional anesthesia, to attenuate the rise in intracranial pressure that may be seen with intubation, and to treat cardiac dysrhythmias.

The toxic effects of local anesthetics have been described since cocaine was introduced into clinical practice in 1884, and the search for compounds with an improved safety profile has had a significant impact on the evolution of this class of drugs. Adverse reactions to local anesthetics can be localized or systemic. Local anesthetic–induced myotoxicity and neurotoxicity will not be discussed. Local anesthetic systemic toxicity (LAST) results from excessive plasma concentrations of local anesthetics and predominantly involves the central nervous system (CNS) and the cardiovascular system (CVS). The potential for toxicity parallels the intrinsic anesthetic potency of the local anesthetic, with more potent, more lipid-soluble compounds posing the greatest risk. Decreased protein binding and reduced drug clearance also increase the potential for toxicity. The clinical presentation of LAST is highly variable and ranges on a spectrum from mild symptoms caused by the systemic absorption of local anesthetic from the site of administration to catastrophic cardiovascular collapse (CC) after inadvertent intravascular injection. Less common systemic toxicities include allergic reactions and methemoglobinemia.