Local anesthetic systemic toxicity (LAST) and allergy to local anesthetics (LAs) are potentially life-threatening complications of regional anesthesia.
The most common causes of LAST are the administration of an excessive dose of LAs, accidental intravascular injections, and the rapid absorption from tissue injection sites. Fortunately, incidence of LAST has decreased in recent years. This can be attributed to the use of ultrasound (US) to monitor the administration of nerve blocks, lower doses of LAs with ultrasound-guided regional anesthesia, and the implementation of safety checklists. It is estimated that approximately 1.8/1000 of the patients receiving a peripheral nerve block (PNB) may develop LAST. However, in one report, no severe cardiac toxicity was reported in 12,666 patients who received an ultrasound-guided PNB.
Allergy to LAs is uncommon. Most symptoms after LA injection are misintrepreted as an allergic reaction. Sympathetic stimulation, vasovagal syncope, or even LAST may be confused for an allergic reaction. True allergy occurs in less than 1% of all LA adverse reactions and is an immune-mediated response triggered by the LA molecule and/or its preservative compounds (metabisulphite or methylparaben). Both allergic and nonallergic adverse reactions require appropriate treatment.
This chapter will focus on the prevention, mechanisms, and treatment of LAST and allergy to LAs. The chapter includes also a practical algorithm for the evaluation and management of patients with suspected allergy to LAs.
LAs are generally safe and effective in therapeutic doses for tissue infiltration, fascial planes, or near a nerve/plexus of nerves. However, supratherapeutic plasma levels of LAs can result in LAST. High plasma concentration of LAs can be the result of accidental venous/arterial puncture, intravascular injection, or rapid vascular absorption from the injection site. Plasma levels of LAs are proportional to the rate of systemic absorption from the site of therapy. The rate of absorption varies among tissues, and it is often determined by the size of the absorptive surface and vascularization of the tissue planes where the injection is made. Clearly, higher doses of LA will yield higher plasma levels of LAs, independent of where the injection takes place.
LAs exert their inhibitory action on nerve conduction by inhibiting the movement of ions through voltage-gated ionotropic channels at the level of the cell membrane (refer to Chapter 2). The primary therapeutic target of LAs is the voltage-gated sodium channel where inhibition alters the transmission of sensory and motor signals in axons. In addition to the voltage-gated sodium channel, LAs also inhibit voltage-gated Ca2+ channels, K+ channels, the Na-K ATPase, and other channels and enzymes. This inhibition occurs from the intracellular side and requires LAs to cross the lipid bilayer first as unbound, non-ionized free molecules. At lower concentrations, LAs block protein kinase signaling induced by tumor necrosis factor α. At higher concentrations, LAs can inhibit other channels, enzymes, and receptors, including the ...