A case of severe hypoglycemia due to pimobendan

Several drugs are reported to cause severe hypo142 mmol / l, potassium 4.6 mmol / l, creatinine 1.6 glycemia. We report here a case of severe hypomg/dl (141 mmol / l), calcium 9.3 mg/dl (2.3 mmol / glycemia during treatment of heart failure, which was l). Plasma glucose was only 9 mg/dl (0.49 mmol / l). presumably caused by a novel inotropic agent, His consciousness became clear soon after intravenpimobendan. ous infusion of glucose. He had no episode of A 74-year-old man had been diagnosed as having hypoglycemia after pimobendan was discontinued. severe congestive heart failure due to aortic insufSevere hypoglycemia due to medications has been ficiency with severe left ventricular dysfunction. The reported. The causative agents include cardiovascular chest X-ray showed mild pulmonary congestion with drugs, such as a-blockers, b-blockers, disopyramide, a cardio-thoracic ratio of 71%. The echocardiography angiotensin converting enzyme (ACE) inhibitors [1]. demonstrated severe aortic regurgitation and severely Pimobendan belongs to a novel class of non-digitalis impaired left ventricular function (LVDd 71 mm, oral inotropic drug and is clinically effective for the LVDs 60 mm, ejection fraction 33%). He was not treatment of heart failure [2]. The agent inhibits diabetic. He was receiving 2.5 mg enalapril, 30 mg mainly phosphodiesterase III activity and elevates 21 furosemide, and 0.125 mg digoxin. After the worsenintracellular cAMP concentration. It also has a Ca ing of heart failure, pimobendan 2.5 mg daily was sensitizing effect, increasing myocardial contractility initiated and increased to a dose of 5 mg 4 weeks by generating more force per given amount of 21 21 later. No other medication was added. His symptoms cytoplasmic Ca . Intracellular Ca plays an imof heart failure were significantly improved after the portant role as a key second messenger in various initiation of pimobendan. organs including the heart and the pancreas. 21 Five weeks after pimobendan was increased to a Pimobendan, as a Ca sensitizer, not only acts on dose of 5 mg, he was urgently transferred to our cardiac myocytes but also acts on pancreatic b-cells. hospital. He was totally unconscious, blood pressure It is reported to enhance insulin release from pan21 was 126/80 mmHg and pulse rate was 88 beats /min. creatic b-cells by directly sensitizing the Ca -sensiAdmission laboratory tests were as follows: sodium tive exocytotic mechanism [3]. Enalapril causes severe hypoglycemia in diabetic patients treated with sulfonylurea, presumably via improving insulin sen*Corresponding author. Tel.: 181-3-5800-8652; fax: 181-3-5800sitivity [4]. Enalapril alone, however, is not reported 6530. E-mail address: ako-ger@h.u-tokyo.ac.jp (J. Ako). to cause severe hypoglycemia in non diabetic pa-