Unexplained severe hypoglycaemia in hospital: a difficult diagnostic challenge

Abstract

We report a case of severe unexplained hypoglycaemia occurring in a surgical patient during a routine hospital admission. This case caused significant diagnostic problems and highlights a number of important learning points.A 66-year-old male inpatient on a surgical ward was found unrousable by a member of staff after a visit from a friend. Until this episode he had been making an uneventful recovery from a complicated open cholecystectomy 13 days earlier. He had Type 2 diabetes that was treated with diet alone, and during the admission his blood sugars were in the range of 4.7-7.7 mmol l -1 . He was known to have chronic renal insufficiency secondary to hypertension and had had a renal transplant 5 years earlier. A recent serum creatinine concentration was 372 mmol l -1 (normal range 70-150).His blood glucose concentration was found to be 1.7 mmol l -1 . He was treated initially with 50 ml of 50% intravenous glucose, but became symptomatically hypoglycaemic again within 1 h. He was normotensive throughout. The endocrinology team was contacted and they recommended that insulin, pro insulin, C-peptide and glucose concentrations should be measured and the presence of a sulphonylurea excluded by analysis. They also advised that all current infusions should be changed. It soon became apparent that the patient required repeated injections of 50% glucose to maintain euglycaemia. A continuous infusion of 20% glucose was started after he had received 300 ml of 50% glucose. His blood glucose concentration stabilized only after treatment with 650 g of i.v. glucose over 41 h. Results showed raised insulin (364 pmol l -1 ) and C-peptide (7.67 nmol l -1 ) concentrations in the presence of a low blood glucose concentration (1.1 mmol l -1 ). The sulphonylurea screen was strongly positive.Using selective and sensitive high-performance liquid chromatogrphy mass spectrometry, the Regional Laboratory for Toxicology, Birmingham, confirmed the presence of gliclazide.The plasma concentration 20 h after the initial hypoglycaemic event was 3.44 mg l -1 . As our patient weighed 80 kg and the apparent volume of distribution of gliclazide is 0.28 l kg -1 , there was approximately 77 mg gliclazide in his body at the time the sample was taken. Although it is difficult to assess accurately the half-life of gliclazide in renal impairment, extrapolation of this plasma concentration using a half-life of approximately 10 h [1] showed that the presenting hypoglycaemia could have been the result of a single oral dose of approximately 320 mg gliclazide given at 14.00 h.Although the cause of the hypoglycaemia was now clear, the circumstances leading to the ingestion of the gliclazide were not. As the patient had not been prescribed gliclazide during this admission, the possible causes were considered to be a medication dispensing error, a medication administration error, deliberate self-harm or malicious intent. This prompted a thorough investigation by a multidisciplinary team, which included a clinical pharmacologist, hospital pharmacist and senio...