Severe metabolic alkalosis, hypokalemia, and respiratory acidosis induced by the Chinese herbal medicine yokukansan in an elderly patient with muscle weakness and drowsiness

Abstract

Yokukansan is a Chinese herbal medicine containing licorice that has been shown to alleviate the behavioral and psychological symptoms of Alzheimer's disease, with few adverse effects. Increasing numbers of patients with Alzheimer's disease in Japan are now being treated with this drug. However, yokukansan should be used with caution because of its potential to induce pseudoaldosteronism through the inhibition of 11-betahydroxysteroid dehydrogenase type 2, which metabolizes cortisol into cortisone. We present the case of an 88-yearold woman with a history of Alzheimer's disease who was transferred to our emergency department because of drowsiness, anorexia, and muscle weakness. Her blood pressure was 168/90 mmHg. Laboratory data showed serum potassium of 1.9 mmol/l, metabolic alkalosis (pH 7.54; HCO 3 -, 50.5 mmol/l; chloride, 81 mmol/l; sodium, 140 mmol/l), and respiratory disorders (pCO 2 , 60.5 mmHg; pO 2 , 63.8 mmHg). Plasma renin activity and aldosterone concentration were suppressed, and urinary potassium excretion was 22 mmol/l (calculated transtubular potassium gradient 12.9). An electrocardiogram showed flat T-waves and U-waves with ventricular premature contractions.Echocardiography denied volume depletion. Medical interview disclosed that she had been treated with a Chinese herbal medicine (yokukansan) containing licorice. The final diagnosis was pseudoaldosteronism and respiratory acidosis induced by licorice. Hypokalemia, metabolic alkalosis, and respiratory acidosis all subsided shortly after the discontinuation of yokukansan and initiation of intravenous potassium replacement. This case highlights the need for nephrologists to consider the possible involvement of Chinese herbal medicines, including yokukansan, when they encounter hypokalemia in elderly patients.

A review on phytochemicals, pharmacological activities, drug interactions, and associated toxicities of licorice (Glycyrrhizasp.)

“…Wang et al (2014) stated that it is clearly mentioned in TCM that concomitant consumption of licorice with Sargassum (macroalgae), Cirsii japonica, Euphorbia kansui, and Flos genkwa (Daphne genkwa flower bud) may affect the hepatic function and induce cardiac toxicity. Yokukansan, a Chinese herbal preparation that contains 4.5 g of licorice and 7.5 g of Yokukansan, was used to alleviate the behavioral and psychological symptoms of Alzheimer's (Yamada et al, 2013). With the continuous clinical use of F I G U R E 8 Pure phytochemicals of licorice inhibit the activity of 11β-hydroxysteroid dehydrogenase (11β-HSD).…”

“…Simultaneously, glycyrrhizin and its derivative cabenoxolone also inhibit the catalytic activity of 11β-HSD1 this medicine, patients suffered from hypokalemia with a 6.6% incidence rate (Iwasaki et al, 2011). The other mild to fatal side effects include muscle weakness, paralytic ileus, polyuria, and rhabdomyolysis (Yamada et al, 2013). There are several other TCM preparations containing licorice as an ingredient and have the potential to cause pseudoaldosteronism.…”

“…Recently, the Ministry of Health, Labour and Wealth, Japan, has reported several cases of severe liver dysfunction and lethal interstitial pneumonia that are associated with the consumption of Yokukansan. Further, they issued a recommendation for careful use of Yokukansan (Yamada et al, 2013).…”