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Current Concepts in Resuscitation of Patients With Local Anesthetic Cardiac Toxicity

Severe local anesthetic-induced cardiac toxicity during regional anesthesia is not common.1,2 Yet the prospect of such an event is daunting,3,4 thereby warranting interest in its prevention and treatment. Experimental studies of local anesthetics other than cocaine identify the 2 most important components of local anesthetic cardiac toxicity as arrhythmia and contractile depression.5-8 Cocaine overdose,9,10 which also manifests systemic and coronary vasoconstriction9 and myocardial ischemia or infarction,11-13 is not addressed in this review. Arrhythmias after local anesthetic overdose include conduction delay, ranging from bundle branch block and prolonged PR interval to complete heart block, sinus arrest, or asystole.14 Ventricular ectopy is common and may progress to more malignant arrhythmias such as ventricular tachycardia, torsades de pointes,15 and ventricular fibrillation.8 Local anesthetics can also depress myocardial contractility,16 thereby lowering cardiac output and further reducing the likelihood of successful resuscitation from overdose. In the extreme, all these effects can be resistant to treatment. Furthermore, local anesthetic overdose is likely to cause seizures, hypoxia,17 or acidosis,18,19 all of which may exacerbate cardiotoxicity. The resulting cycle of systemic and myocardial hypoperfusion, tissue acidosis, and worsening cardiac performance can lead to failed resuscitation. Severe local anesthetic toxicity is mechanistically complex. A comprehensive review of the chemistry and molecular actions of local anesthetics is beyond the scope of this article.20-26 Nevertheless, a simplistic explanation of their potential for causing harm is that virtually all local anesthetics are amphiphilic molecules. By having both lipophilic and hydrophilic properties, they can enter a variety of cell compartments and potentially interact with many different cell membranes, organelles, and a host of membrane-bound and cytosolic, charged molecules. When delivered to sensitive tissues (eg, heart, brain, or skeletal muscle) at therapeutic concentrations, they can interfere with cellular metabolism and homeostasis, particularly cell signalling systems and energy transduction pathways. Documented sites of toxic action include ionotropic signaling pathways (sodium,27,28 potassium,29,30 and calcium31 ion channels) and metabotropic pathways such as beta-adrenergic32 and lysophosphatidate33 signaling systems that confer information by second messengers rather than by changes in ion flux. Local anesthetics also interfere with G-protein modulation of Ca and K channels,34,35 cardiac bioenergetics,36 and mitochdondrial dynamics.37 Local anesthetics also impede adenosine triphosphate (ATP) synthase,38 the enzyme which converts adenosine diphosphate (ADP) to ATP at the mitochondrial inner membrane. The apparent ability to affect so many different cellular processes may account for the clinical complexity and potential severity of local anesthetic toxicity.39-41