Pathophysiology

Isopropanol is a clear, volatile liquid with a bitter, burning taste and an aromatic odor. It is rapidly absorbed after being ingested, with 80 percent of an oral dose being absorbed after 30 min and complete absorption within 2 h. The substance has a volume of distribution of 0.6 to 0.7 L/kg. Small and clinically insignificant amounts are resecreted by the salivary glands and stomach.

The kidneys excrete 20 to 50 percent of an absorbed dose unchanged. However, the major pathway for metabolism of isopropanol is in the liver, where it is oxidized to acetone by alcohol dehydrogenase (Fig, 16.0.-1). Acetone is further metabolized to acetate, to formate, and then finally to carbon dioxide. Mild acidosis may result from the conversion of acetone to acetic acid and formic acid. However, unlike methanol and ethylene glycol, significant acidoses directly ascribed to isopropanol or its metabolites is not seen. A hallmark of isopropanol toxicity is ketonemia and ketonuria, but without elevated blood glucose or glycosuria. This feature helps differentiate isopropanol ingestion from poisoning with ethylene glycol or methanol.

FIG. 160-1. Metabolic pathway of isopropanol in the liver.

Isopropanol most closely follows concentration-dependent (first-order) kinetics. The half-life of isopropanol in the absence of ethanol is 6 to 7 h, while the half-life of acetone is 22 to 28 h. The long half-life of acetone may be the cause of the prolonged symptomatology often associated with isopropanol poisoning. Ethanol administration has not been used clinically to inhibit isopropanol metabolism to acetone.

The toxic dose of 70% isopropanol is approximately 1 mL/kg, with the lethal dose in an adult approximately 2 to 4 mL/kg. As little as 0.5 mL/kg may cause symptoms, but survival has been reported following ingestions of up to 1 L. Children are especially susceptible to toxic effects and may develop symptoms with as little as three swallows of 70% isopropanol.

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