Case Presentation:

A 48 year-old Chinese man with background history of major depression, presented 7 hours after ingestion of unknown amount of multiple drugs including immediate-release gliclazide, simvastatin, fluvoxamine and pacofen (paracetamol, codeine and caffeine). He denied suicidal ideation or intent but said he felt stress. He had no hallucinations or delusions. His Glasgow coma scale was 15, appeared anxious and maintained minimal eye contact. His respiratory rate was 16 breaths per minute and oxygen saturation was 95% on ambient air. Physical examination was otherwise unremarkable. His glucose level was 5.8mmol/L at presentation and capillary blood glucose was regularly monitored. Serum transaminases, bilirubin, prothrombin time, creatinine, creatine kinase, paracetamol levels were normal. Later, he developed hypoglycemic episodes, requiring repeated oral glucose drinks and intravenous dextrose 50%. He was started on intravenous dextrose 10% infusion. Despite that, the patient developed severe hypoglycemia of 1.6mmol/L, resulting in generalized tonic clonic seizures which resolve with intravenous dextrose 50%. A central venous catheter was inserted and he was given intravenous D20% infusion and octreotide. There were no further episodes of hypoglycemia and dextrose infusion was later titrated down before reduction of dose and frequency of octreotide. He was discharged well one week into his admission.

Discussion:

Sulfonylurea overdose is a condition commonly encountered by hospitalist. Most are asymptomatic patients with normal glucose and they do not require treatment or hospital admission. However, some can present with severe recurrent hypoglycemia, and, if not treated promptly, could lead to permanent neurological sequelae and even death. Fluvoxamine, a selective serotonin reuptake inhibitor, may enhance hypoglycemic effect of sulfonylurea by increasing its serum concentration. Octreotide, a synthetic peptide hormone analogous to somatostatin, suppresses insulin secretion from pancreatic beta cells. It binds to G protein-coupled somatostatin-2 receptors, resulting in decreased calcium influx and inhibition of insulin secretion. It acts as specific sulfonylurea antidote for the treatment of sulfonylurea induced hypoglycemia.

Conclusions:

Sulfonylurea overdose can be difficult to manage; hospitalist should be familiar with pharmacological treatment of severe recalcitrant hypoglycemia. In symptomatic intentional sulfonylurea overdose, intravenous dextrose monotherapy causes transient hyperglycemia which triggers insulin secretion, leading to recurrent episodes of hypoglycemia. Octreotide should be given with intravenous dextrose to minimize this effect.  Short duration of action of glucagon limits its use to temporarily raise serum glucose level; while hypotensive side effect of diazoxide limits its use in sulfonylurea overdose.