Chapter 58

### INTRODUCTION

Local anesthetics can have several adverse side effects, including allergic reactions, methemoglobinemia, and direct nerve toxicity. Local anesthetic systemic toxicity (LAST) is perhaps the most devastating complication and can lead to significant morbidity and mortality, particularly cardiovascular and neurologic.

By definition, LAST is characterized by excessive plasma concentrations of local anesthetic that lead to systemic symptoms. Toxic local anesthetic levels occur either due to (1) accidental direct intravascular injection or (2) systemic absorption during and after regional anesthesia. Unintentional intravascular injection of an appropriately dosed nerve block will produce a rapid increase in plasma levels due to the large volumes and/or high concentrations of local anesthetic. Less commonly, the slow vascular absorption of inappropriately dosed local anesthetic at the site of injection can cause LAST. The extent of systemic absorption depends on the specific agent, dose given, presence of epinephrine in the solution, and the vascularity of the tissue injection site (Table 58-1). Whether by direct intravascular injection or systemic vascular absorption, LAST ultimately depends on the quantity of free local anesthetic on the plasma, which is determined by the dose and the rate of injection.

TABLE 58-1Rate of Local Anesthetic Systemic Absorption Based on Injection Site

### MANIFESTATIONS

To produce local and regional anesthesia, local anesthetics inhibit voltage-gated sodium channels in the axons of peripheral nerves and decrease action potential conduction velocity. These agents can block potassium and calcium channels as well. The variety of clinical problems due to LAST result from blockade of all of these ion channels in multiple organ systems. In addition, local anesthetics have been shown to inhibit electron transport and uncouple oxidative phosphorylation in mitochondria, thus interrupting ATP synthesis. This effect may be the reason why the brain and heart, two organs highly intolerant of anaerobic metabolism, are most affected by local anesthetic toxicity.

#### Central Nervous System

The signs of LAST occur on a spectrum that almost always begins with effects on the central nervous system (CNS). Initial signs and symptoms of CNS toxicity may be subtle or nonspecific, such as subjective reports of lightheadedness, dizziness, circumoral paresthesias, and metallic taste. These symptoms are usually followed by visual and auditory disturbances, such as tinnitus, diplopia, and nystagmus. As plasma concentrations rise, local anesthetics then produce greater blockade of sodium channels of GABA-ergic inhibitory cortical interneurons, principally in the temporal lobe. The now-unopposed excitatory neurons have a higher discharge rate that leads to agitation, confusion, muscle twitches (usually of the face and distal extremities), and finally tonic–clonic seizures. Higher plasma levels of local anesthetic are necessary to block the more resistant excitatory neurons. At this later stage, inhibition of excitatory ...

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