LAUSR

Methadone-induced hypoglycemia is uncommon and traditionally methadone is not on the list of differential diagnosis of drug-causing hypoglycemia. A 51-year-old normal build non-diabetic lady with history of schizophrenia and heroin dependence was presented to the emergency department within 1 hour after she deliberately drank 250mL methadone. She denied co-ingestion. Her body weight is around 55 kg; the estimated dose of methadone ingested was 18.2mg/kg. On arrival, she had a Glasgow Coma Score (GCS) of 14/15. Her blood pressure (BP) and pulse rate were 155/71mmHg and 113 beats per minute, respectively. Her respiratory rate (RR) was 8 breaths per minute with decreased depth. She had bilateral pinpoint pupils. Bedside glucose level was 7.8mmol/L (140.5mg/dL). Electrocardiogram showed sinus tachycardia with corrected QT interval (QTc) 410ms. Naloxone 0.4mg in total was given in small separate doses which her RR was brought up to 16 breaths per min and GCS up to 15/15. Her liver, renal function tests were normal; ethanol and acetaminophen were undetected. She was observed in the emergency medicine ward (EMW). At 4-h post-ingestion of methadone, she was found to have recurrence of CNS depression with GCS 8/15 and hypoventilation evidenced by RR 10 breaths per min and desaturation despite oxygen supplement. Further doses of naloxone were given and naloxone infusion was started. Her vital signs improved. Bedside glucose was repeated and found 2.6mmol/L (46.8mg/dL). Bolus dextrose was given intravenously and her GCS shortly improved. However, she developed refractory hypoglycemia, blood glucose 2.1mmol/L (37.8mg/dL) despite 10% dextrose infusion. She was transferred to intensive care unit (ICU) for further monitoring. During the ICU stay, titrated naloxone infusion at 0.1 to 0.4mg/h and 20% dextrose infusion were given. Endocrine screening including plasma insulin level were normal. No oral hypoglycemic agents were detected in her urine. Dextrose was weaned off at 54-h post ingestion and she was transferred back to EMW. Methadone has been reported to cause hypoglycemia in several case reports and animal study and the effect is believed to be dose related [1–3]. Acute methadone overdose induce hypoglycemia was firstly reported by Fung et al. [4]. The case has massive overdose (18mg/kg) and was resolved after single bolus of dextrose and 10% dextrose infusion. Our case has overdosed 18.2mg/kg of methadone and developed more refractory hypoglycemia. The exact mechanism of methadone-induced hypoglycemia is not known. Some postulate that methadone may have direct effect on islet insulin secretion through opioid receptors in pancreas [5]. It was interesting that in the animal study [3] some other opioids such as morphine and fentanyl did not induce hypoglycemia as methadone does and naloxone can prevent the hypoglycemia [3]. Further studies are needed to determine the relationship between the dose and hypoglycemia in acute methadone overdose. In conclusion, we report a case of acute massive methadone overdose complicated with refractory hypoglycemia. Although it is rare, it is important to recognize the possibility of methadone-induced hypoglycemia so as not to confuse it with opioid-induced CNS depression.