HYPOGLYCAEMIA DEFINITION Hypoglycaemia is a blood glucose concentration below the normal range of 3.3 to 6.3 mmol/L (60 to 115 mg/dL). Symptoms are likely when the blood glucose concentration falls below 2.5 mmol/L (45 mg/dL). TOXIC CAUSES Common Ethanol Insulin Sulfonylurea and related hypoglycaemic drugs * Acetohexamide Chlorpropamide Glibenclamide Glibornuride Gliclazide Glipizide Gliquidone Glisentide Glisolamide Glisoxapide Glyburide Glybuzole Glycopyramide Glycyclamide Glymidine Tolazamide Tolbutamide Uncommon Ackee fruit (Jamaican vomiting sickness) Alcohols (isopropyl, methanol) Beta-adrenergic blockers Cocaine Disopyramide Ethionamide Haloperidol Herbal/plant remedies (several) Mebanazine (MAO inhibitor) Opioids Orphenadrine Oxytetracycline Pentamidine Perhexiline Pertussis vaccine Propoxyphene Quinine Ritodrine Salicylates Sulfonamides Vacor (PNU) - transient effect * Oral biguanides (metformin, phenformin) can cause severe lactic acidosis but do not normally cause severe hypoglycaemia. NON-TOXIC CAUSES Endocrine disorders Hepatic failure Insulinoma Starvation CLINICAL FEATURES The clinical manifestations of hypoglycaemia are highly variable, and it is essential to consider the diagnosis in any patient with altered consciousness. Victims with mild hypoglycaemia may be agitated, mute, or confused, while those with severe effects may present with deep coma or convulsions. Focal neurologic deficits resembling an acute cerebrovascular accident may occur. Associated findings may include tremor, tachycardia and diaphoresis, and in some patients, hypothermia. DIFFERENTIAL DIAGNOSIS In patients with confusion, stupor, or coma, consider the possibility of overdose by sedative-hypnotic drugs, anticholinergic agents, opioids, or ethanol. Tremor, tachycardia, and sweating may be associated with stimulant drugs such as cocaine or amphetamines. Seizures may be caused by a variety of drugs or poisons. RELEVANT INVESTIGATIONS Rapid bedside glucose measurement can be obtained within 1 to 2 minutes using fingerstick capillary blood and a portable battery-operated analyzer or a test strip. Ideally, blood should be obtained for laboratory analysis before exogenous dextrose is administered however this should not unduly delay dextrose administration. Serum electrolytes Liver function tests Serum concentrations of oral sulfonylureas or insulin are not widely available, but may occasionally be useful in documenting the cause of hypoglycaemia. Exogenous administration of insulin results in elevated concentrations of insulin but low concentrations of C-peptide, whereas after oral hypoglycaemic agent overdose, and with insulinoma, both C-peptide and insulin levels are increased. TREATMENT There should be no delay in treating patients with suspected hypoglycaemia, as permanent cerebral damage may occur. Administer a bolus of concentrated dextrose, 25 to 50 g (0.5 to 1 g/kg as 25% dextrose in children) intravenously through a secure line. Give repeated doses if needed. Start a continuous infusion of 5 to 10% dextrose in water. In cases of severe hypoglycaemia from overdose of insulin or sulphonylureas, continuous infusion of large volumes of concentrated (25 or 50 %) dextrose solutions via a central line may be necessary to maintain euglycaemia. Antidotes: Glucagon is not recommended because it requires the presence of hepatic glycogen stores and these are often depleted in patients with acute hypoglycaemia. Diazoxide (0.1 to 2 mg/kg/hr) intravenous infusion inhibits pancreatic insulin secretion and has been useful for patients with oral sulfonylurea overdose. Octreotide (30 nanograms/kg/min) has also been recommended. CLINICAL COURSE AND MONITORING Obtain frequent measurements of the serum or capillary glucose. Patients with insulin overdose may have prolonged hypoglycaemia, depending on the amount, type, and route of administration. Injection of a large quantity of insulin into the subcutaneous space may produce a "depot" from which prolonged absorption occurs. The duration of action of oral sulfonylurea agents varies from 6 to 72 hours, and recurrent hypoglycaemia has been reported as long as 1 week after chlorpropamide ingestion. Moreover, the onset of hypoglycaemia may be delayed in patients with acute oral hypoglycaemic or insulin overdose. Some authors advise hospital admission for all patients with suspected serious hypoglycaemic agent exposure. One study suggested that asymptomatic individuals who are not receiving oral or intravenous dextrose should be observed for a minimum of 8 hours. LONG TERM COMPLICATIONS Permanent cerebral cortical damage may result from prolonged or severe hypoglycaemia. AUTHOR(S)/REVIEWERS Author: Dr KR Olson, University of California, San Francisco. Peer review: Cardiff 9/96: V. Afanasiev, M Burger, T Della Puppa, L Fruchtengarten, K Olsen, J Szajewski.