Management of β-Adrenergic Blocker and Calcium Channel Antagonist Toxicity

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State-of-the-art therapy for β-adrenergic receptor blocker and calcium channel antagonist toxicity is reviewed in the light of new insights into drug-induced shock. A brief discussion of pathophysiology, including cardiac, hemodynamic, and metabolic effects of cardiac drug toxicity, provides a foundation for understanding the basis of therapy. The major focus of this review is a critical evaluation of antidotal use of calcium, glucagon, catecholamines, insulin-euglycemia, and other novel therapies based on investigational studies and cumulative clinical experience.

Section snippets

Initial resuscitation

Attention to airway, breathing, and circulation is paramount in improving patient survival following BB and CCA overdose. Although some patients maintain surprising alertness despite significant cardiovascular compromise, many will have abrupt central nervous system depression with loss of airway protective reflexes and require intubation and mechanical ventilation. For patients that present with hallmark bradycardia and hypotension, atropine and normal saline fluid bolus are reasonable initial

Calcium

Calcium is a logical therapy for CCA toxicity. In theory, augmentation of extracellular calcium may overcome competitive antagonism of the calcium channel or maximize calcium entry through unblocked channels. From animal investigations, calcium is expected to increase inotropy and improve blood pressure, but have little effect on conduction blocks and heart rate [38], [39], [40]. Calcium affords some survival effect in these studies [14], [40].

Clinical experience is mixed. Calcium infusion

Hemodialysis

Extracorporeal drug removal has limited usefulness following BB and CCA overdose. All three classes of CCAs are lipophilic, highly protein bound, and primarily undergo hepatic metabolism [1], [12]. Thus, one would predict little drug removal with dialysis. The same is true for most BBs, with a few exceptions. Atenolol, nadolol, and sotalol have properties that render them amenable to hemodialysis including: protein binding less than 25%, volume of distribution less than 2 L/kg, and renal

Continued research

There are several recent investigations of novel therapies for BBs and CCAs. Immunotherapy has been explored for CCA toxicity. In a model using rat ventricular tissue, verapamil-specific IgG attenuated decreases in myocardial contractility [148]. Intralipid has also been evaluated for CCAs. In theory, administration of an exogenous lipid compound provides an additional pharmacologic compartment in which highly lipid-soluble drugs can partition, thus reducing drug burden at target tissues. In

Therapeutic goals

The overall objective of therapy is to improve organ perfusion with subsequent increases in survival. Reasonable clinical and physiologic markers of the efficacy of therapy include improvement in myocardial ejection fraction (EF) (≥50% EF); increased blood pressure (≥ 90 mm Hg in adult); adequate heart rate (≥ 60 bpm); resolution of acidemia, euglycemia, adequate urine flow (1–2 mL/kg/hour); reversal of cardiac conduction abnormalities (QRS≤120 milliseconds); and improved mentation. It is

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