Aspirin Intoxication in a Child Associated with Myocardial Necrosis: Is this a Drug-related Lesion?

Abstract

A 5-year-old girl with a mild upper airways infection was admitted to the hospital because of sudden vomiting and drowsiness that evolved to stupor; she was dehydrated, hypotensive, and tachypneic; laboratory tests revealed noncompensated lactic acidosis. She also had hypoglycemia followed by hyperglycemia, and progressive bradycardia leading to reversible cardiac arrest. Her clinical condition complicated by sinus bradycardia, ventricular tachycardia, third-degree atrioventricular blockage and lethal asystole. At the final stage of her illness, the serum salicylate concentration was 383.8 mcg/mL. Based on this single data, a retrospective toxicological analysis estimated a theoretical peak level of serum salicylate of approximately 1570 mcg/mL (therapeutic range, 20-250 mcg/mL) although the real amount of aspirin that this child ingested is difficult to calculate because aspirin is a drug that shows a so-called zero order kinetics. At autopsy, the most striking finding was multiple foci of coagulative necrosis involving the entire thickness of the myocardium with scant inflammatory infiltrate composed mainly of macrophages and polymorphonuclear leukocytes. The morphologic characteristics of the myocardial lesion in addition to salicylate blood levels suggests the possibility of an adverse drug reaction of the type acute toxic myocarditis.

Emergency Department Management of the Salicylate-Poisoned Patient

“…Mean postmortem salicylate serum levels on 16 patients who presented dead on arrival after aspirin overdose were 51 mg/dL (range 17 to 101 mg/dL) [55]. Postmortem examination of salicylate-poisoned patients demonstrated several unique findings including myocardial necrosis suggestive of toxic myocarditis [57], pulmonary congestion, hemorrhagic gastritis with unabsorbed salicylate and GI ulceration, cerebral edema, and paratonia (extreme muscle rigidity) [55,56].…”

Effect of Salicylate on the Elasticity, Bending Stiffness, and Strength of SOPC Membranes

“…The physiological effects of salicylate resulting from normal aspirin consumption occur at concentrations between 0.l and 2 mM (42). When the blood serum level of salicylate reaches 10 mM, diverse pathological effects occur, including myocardial necrosis (43). The minimum amount of salicylate required to change the apparent membrane compressibility (K app ) was ;1 mM.…”

Acidosis slows electrical conduction through the atrio-ventricular node

“…Further evidence for sensitivity of the AVN to acidosis comes from the observation that experimental hypoxaemic/hypercapnic hyperventilation and apnoea produced in cats by inhalation of increased CO 2 is accompanied by acidosis and high-level AV conduction block (Tomori et al, 1997). Furthermore, non-compensated lactic acidosis associated with salicylic acid (aspirin) poisoning has been associated with third degree AV block, whilst toxic adenoma of the thyroid gland has been associated, albeit rarely, with complete heart block accompanied by metabolic acidosis (Pena-Alonso et al, 2003). …”