See also:

Key points

1. The two groups of oral hypoglycaemic agents used in adolescents are the Sulfonylureas and Biguanides. This review focuses on sulfonylurea overdose
2. Sulfonylurea overdose and symptomatic hypoglycaemia should be treated with both intravenous dextrose and octreotide
3. Any child with possible sulfonylurea exposure should be observed for 24 hours, as delayed hypoglycaemia may occur
4. A single sulfonylurea pill (as small as 2 mg) can cause hypoglycaemia in young children

For 24 hour advice, contact the Poisons Information Centre 13 11 26 

Background

Oral hypoglycaemic agents are used for managing type-II diabetes mellitus (non-insulin dependent diabetes)

Sulfonylureas

• Sulfonylurea agents increase pancreatic insulin secretion
• They are the most important cause of hypoglycaemic toxicity and may cause prolonged and profound life-threatening hypoglycaemia after accidental paediatric ingestion or deliberate self-poisoning
• A single tablet in a toddler can cause life-threatening hypoglycaemia
• Onset of hypoglycaemia may be delayed up to 18 hours after ingestion
• Large overdoses may require treatment for several days
• Admission for a minimum of 12–24 hours is indicated for blood glucose monitoring and discharge from hospital should only occur in daylight hours

Biguanides

• Metformin is a biguanide agent that acts by decreasing carbohydrate absorption from the gut, increasing glucose uptake in peripheral tissues in the presence of insulin, and reducing hepatic gluconeogenesis
• Metformin ingestion is not associated with hypoglycaemia in normal patients, but may cause life-threatening lactic acidosis in large overdoses in the presence of renal or cardiac failure, or when there are co-ingestants impairing renal perfusion
• Asymptomatic patients following accidental exposure to metformin do not require hospital assessment, decontamination or investigation
• Children who have taken an unintentional ingestion of up to 1700 mg do not require hospital assessment
• Nausea and vomiting may occur in smaller overdoses
• Haemodialysis therapy resolves the acidosis and removes metformin from the blood

Pharmacokinetics:
Sulfonylureas possess a broad range of pharmacokinetic properties

• In overdose, onset of action remains unchanged but duration of action increases
• Peak plasma concentrations are generally achieved within 8 hours of an acute ingestion but may be delayed in overdose
• Metabolized by the liver. Some agents have active metabolites that are renally excreted
• Extensively protein bound

Children requiring assessment

All children with deliberate self-poisoning or significant accidental ingestion
Any symptomatic child
Acute ingestion of unknown quantity
Any child whose developmental age is inconsistent with accidental poisoning as non-accidental poisoning should be considered 

Risk assessment

History

Intentional overdose or accidental
Focus on dose, timing and co-ingestants

Examination  

Manifestations of hypoglycaemia may include:

• Autonomic: tachycardia, sweating, anxiety
• CNS: drowsiness, altered mental status, coma, seizures

Always check for Medicalert bracelet in any unconscious patient, or any other signs of underlying medical condition (fingerprick marks etc)

Investigations

• Serial BSLs
• UEC
• Insulin levels may have some role (if available) for sulfonylurea overdoses on the advice of toxicology services
• VBG/ABG (including lactate) should be done in metformin overdoses to confirm lactic acidosis and monitor progress in any unwell patient or following clinical deterioration
• For possible co-ingestants consider paracetamol level and ECG

Acute Management

1. Resuscitation
Standard procedures and supportive care
Sulfonylurea

• Obtain IV access and administer concentrated IV glucose solutions if the patient is hypoglycemic
• Paediatric doses:
• 5 mL/kg of 10% glucose IV bolus
• Then commence 1-2 mL/kg/hour 10% glucose IV infusion
• Check BSL hourly
• Send other bloods including serum insulin level
• Commence octreotide infusion (see section 3 below)

2. Decontamination 
Consider charcoal if massive ingestion and within 1 hour, or after airway protection
Discuss with toxicologist

3. Specific treatment
Antidote:

• Octreotide is a long-acting synthetic analogue of somatostatin. It is a specific antidote for sulfonylurea agents, as it suppresses insulin release from pancreatic cells

• Dose:
• Children - 1 microgram/kg IV bolus (maximum 50 microgram) followed by 1 microgram/kg/hour continuous infusion (up to 25 microgram) for at least 24 hours. (Alternatively, 1-2 microgram SC (maximum 50 microgram) 8 hourly)
• Adolescents or adults - 50 microgram IV bolus followed by 25 microgram/hour continuous infusion for at least 24 hours. (Alternatively, 50 microgram SC 8 hourly may be preferred)

• Once octreotide infusion is running, normoglycaemia will likely be achieved without glucose supplementation. If hypoglycaemia recurs, it should be corrected with glucose and the infusion rate of octreotide doubled

Octreotide infusion may be ceased when all the following criteria have been met:

• 10% glucose infusion ceased at least 4 hours prior
• No symptoms of hypoglycaemia
• Bedside BSLs >2.5 mmol/L for more than 4 hours
• Daylight hours - octreotide should not be ceased during evening or night shifts

Following cessation of octroetide, BSLs should be checked every hour for a minimum of 12 hours post cessation of octerotide/dextrose before discharge. 

Consider consultation with local paediatric team when

• Any child or young person presents with intentional overdose as admission should be considered
• Any child with sulfonylurea exposure as admission for a minimum of 12–24 hours is indicated for blood glucose monitoring 

Consult Victorian Poisons Information Centre 13 11 26 for advice

Consider transfer when

Children require care beyond the comfort level of the current hospital  

For emergency advice and paediatric or neonatal ICU transfers, call the Paediatric Infant Perinatal Emergency Retrieval (PIPER) Service: 1300 137 650.  

Consider discharge when

• Normal BSLs are maintained for 12 hours post cessation of octreotide infusion and the patient is on a normal diet
• Plasma insulin level (if available) is within the normal range at 6 hours post cessation of octreotide infusion
• During daylight hours only for children exposed to sulfonylureas

Assessing risk and connecting to community services

• Prior to discharge, adolescents who present with deliberate ingestions need a risk assessment regarding the likelihood of further ingestions or other attempts to self-harm
• Assessment of other drug and alcohol use should also be undertaken
• If, after risk assessment, it is deemed safe to discharge a patient from hospital, but ongoing mental health or drug and alcohol needs are identified, the adolescent should be linked with appropriate services (see links below for services in the State of Victoria). 

Discharge information and follow-up

Parent Information: Poisoning prevention for children
Prevention of poisoning (Victorian Poisons Information Centre)

Poisons Information Centre: phone 13 11 26

Victoria
Poisons Information Centre
Child & Adolescent Mental Health Services (CAMHS): Victorian government mental health services are region-based
Orygen Youth Health: Specialist mental health services for people aged 15–25 years, residing in the western and north-western regions of metropolitan Melbourne. Triage/intake - 1800 888 320.
Headspace: National Youth Mental Health Foundation with local headspace centres

YSAS (Youth Support and Advocacy Service): Outreach teams across Melbourne and regional Victoria for young people experiencing significant problems with alcohol and/or drug use
YoDAA: Victoria’s Youth Drug and Alcohol Advice service - provides information and support for youth AOD needs or anyone concerned about a young person
Infoxchange Service Seeker: Search for local community support services eg local doctor, dentist, counselling services, drug and alcohol services. 

Last Updated December 2020