Sulfonylurea toxicity

Hypoglycaemia can occur at therapeutic doses especially in those who develop renal impairment. In overdose these drugs cause a profound and prolonged hypoglycaemia, usually apparent within 8 hours post ingestion of a standard preparation. The sulfonylureas consist of glibenclamide, gliclazide, glimepiride and gliplizide.

Toxic Mechanism:

They inhibit potassium efflux in the beta cells of the pancreas. As a result insulin is released resulting in a hyperinsulinaemic state.

Toxicokinetics: 

  • Well absorbed
  • Peak levels at 4 – 8 hours
  • Volumes of distribution are variable but small
  • Elimination half life is also variable but prolonged in overdose
  • Metabolised in the liver and renal excretion

Resuscitation:

  • Hypoglycaemia (<4.0 mmol/L):
    • Adult: 50ml bolus of 50% dextrose IV, repeat as required
    • Children: 2 ml/kg of 10% dextrose IV, repeat as required
    • Repeated hypoglycaemia: commence 10% glucose infusion, starting at 100ml and hour and monitor the blood glucose (children start maintenance fluids with o.9% saline and 5% dextrose +/- potassium). If further episodes of hypoglycaemia occur, treat with another bolus.
    • Ultimately the dextrose is partly a temporising measure until octreotide can be given to halt the process
    • Supplement potassium to a low-to-normal range.

Risk Assessment

  • Ingestion of one tablet in the non-diabetic patient can cause a profound hypoglycaemia
  • Onset of hypoglycaemia is usually within 8 hours (longer if extended release preparations, 18 hours and can be delayed up to 48 hours later)
  • Hypoglycaemia is profound and prolonged (up to several days)
  • Recent impairment of hepatic or renal function will predispose patients to hypoglycaemia even at therapeutic doses (the elderly are particularly vulnerable).
  • Children: One tablet can cause fatal hypoglycaemia

Supportive Care

  • Hypoglycaemia, if present can be managed with dextrose.
  • It is rare that higher doses of dextrose will be required once octreotide has commenced, however if greater than 100ml of 10% dextrose in adults or maintenance in paediatrics (0.9% saline + 5% dextrose solution) is required consider a central line to administer higher concentrations of dextrose.

Investigations

  • Screening: 12 lead ECG, BSL, Paracetamol level
  • Specific:
    • Regular blood glucose at least hourly until the patient is stable on octreotide
    • EUC – monitor potassium and renal function

Decontamination:

  • 50 grams of charcoal to the co-operative patient who presents <1 hour with a standard preparation or <4 hours with a modified release preparation.
  • Paediatric dose 1 g/kg

Enhanced Elimination

  • Not clinically useful

Antidote

  • Octreotide
  • Do not start the antidote until a documented hypoglycaemia has occurred, equally giving boluses of dextrose without an episode of hypoglycaemia complicates the risk assessment.
  • Once hypoglycaemia does occur may sure you have enough supply of octreotide

Disposition

  • All children require blood sugar level monitoring for 18 hours before medical clearance with advice to the parents.
  • Adults require 8 hours of monitoring for standard preparations and 12 hours of monitoring for modified release. If asymptomatic and euglycaemic they can be medically cleared with advice (do not discharge at night)
  • All symptomatic patients and those receiving treatment require admission and can be medically cleared once they can maintain euglycaemia on a normal diet for 12 hours post octreotide discontinuation.
  • If hypoglycaemia occurred on therapeutic dosing they require management of any underlying disease and an endocrine review for ongoing therapy.

References and Additional Resources:

Additional Resources:

References:


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Dr Neil Long BMBS FACEM FRCEM FRCPC. Emergency Physician at Burnaby Hospital in Vancouver. Loves the misery of alpine climbing and working in austere environments. Supporter of FOAMed, toxicology, tropical medicine, sim and ultrasound

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