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Unexplained hypoglycaemia – Emergency

Unexplained hypoglycaemia – Emergency management in children

Key points

  • Hypoglycaemia is defined as a blood glucose level (BGL) of 2.6 mmol/L using a blood gas machine, iSTAT, or formal laboratory testing.
  • Ketotic hypoglycaemia (KH) of childhood is the most common cause of hypoglycaemia in children.
  • In the absence of a history of prolonged fasting (over 30 hours) and blood ketones >4, all children with a formal BGL ≤2.6mmuol/L should be investigated for an underlying disorder.
  • Management of hypoglycaemia includes administration of a 10% glucose bolus followed by a 10% glucose + 0.9% NaCl IV infusion (which needs to be mixed onsite).
  • Fluids containing less than 10% glucose (such as 5% glucose + 0.9% NaCl) are unsuitable.
  • Hypoglycaemia is a medical emergency. If left untreated it can cause convulsions, irreversible brain damage and death.

Purpose

This document provides clinical guidance for all staff involved in the care and management of a child presenting to an Emergency Department (ED) in Queensland with unexplained hypoglycaemia.

This guideline has been developed by the department of Metabolic Medicine at the Queensland Children’s Hospital in consultation with senior ED clinicians and Paediatricians across Queensland. It has been endorsed for statewide use by the Queensland Emergency Care of Children Working Group in partnership with the Queensland Emergency Department Strategic Advisory Panel and the Healthcare Improvement Unit, Clinical Excellence Division.

Introduction

Maintaining glucose homeostasis relies on:

  • an intact system of endocrine hormones (insulin, glucagon, growth hormone, cortisol)
  • a system of intact metabolic pathways to be able to use fat, protein and glucose
  • suitable substrates that are able to be metabolised to produce glucose/ketones for energy in times of fasting e.g. glycogen, protein, fat.

Some children become symptomatic of hypoglycaemia or hypoglycaemic faster than others.

Hypoglycaemia is defined as a blood glucose measurement (BGL) of ≤2.6 mmol/L using a blood gas machine, iSTAT, or formal laboratory testing.

As glucometers are unreliable at measuring low levels of glucose it is suggested that 3.0mmol/L be considered a reasonable level to begin formal investigations.

Possible causes of hypoglycaemia
Severe vomiting or diarrhoeal illness
Prolonged fasting
Underlying medical conditions including:

  • liver disease (i.e. end stage liver failure)
  • hyperinsulinism
  • hormone deficiencies such as hypopituitarism
  • neonatal sepsis
  • metabolic causes
Ingestions (in younger children)
Drugs and alcohol (in an adolescent)

The most common cause of hypoglycaemia in children is ketotic hypoglycaemia (KH) of childhood. This is a physiological condition that is a variant of normal and expected in a fasting state. Most children grow out of KH by mid-late primary school age.

In the absence of a history of prolonged fasting (over 30 hours) and blood ketones >4, all children with a BGL ≤2.6mmuol/L should be investigated for an underlying disorder.

This is a critical time to obtain samples and gain a diagnosis.

Refer to the Queensland Newborn Hypoglycaemia Guideline for the management of newborns prior to initial discharge from hospital. The management of children with a diagnosis known to present with hypoglycaemia is beyond the scope of this gudieline. Manage these children as per their emergency sick day management plan.

Assessment

A child with hypoglycaemia may appear drowsy, listless and lethargic.

A thorough history and examination is important to identify other precipitating causes that need further investigation.

History

History taking should include the following:

  • How long has the child fasted before becoming hypoglycaemic?
  • Has the child suffered symptoms of vomiting, diarrhoea or fasted in the last three days?
  • Is the child sometimes difficult to wake in the morning?
  • How long does the child usually fast overnight?
  • Was the hypoglycaemia precipitated by a protein meal?
  • Has the child had recent exposure to fruit or honey (consider hereditary fructose intolerance)?
  • Could the child have had any medications or alcohol? (especially insulin, metformin, beta-blockers, quinine, chloroquine, salicylates and valproate)

Examination

Red flags to suggest an underlying disorder

  • midline defects – consider pituitary hormone deficiencies
  • organomegaly – consider storage disorders such as glycogen storage disease
  • small genitalia in a male child – consider pituitary hormone deficiencies
  • hyperpigmentation – consider adrenal insufficiency
  • short stature
  • macrosomia
  • growth hormone deficiency or overgrowth syndrome
  • hyperinsulinism – especially in an infant
  • hypoglycaemia precipitated by shorter (<6 hour) fasting period
  • Seek senior emergency/paediatric advice as per local practice if suspect an underlying disorder.

Investigations

The presence of blood or urinary ketones at the time of presentation is essential to differentiating possible causes of the hypoglycaemia and obtaining a final diagnosis. Blood ketones can be rapidly performed in ED and should be measured at the same time as formal confirmation of blood glucose. If testing urinary ketones, it is important to obtain the first urine passed after the hypoglycaemia is confirmed.

Blood collection

Ideal blood collection for the initial investigation of unexplained hypoglycaemia

Preferred blood collection (volume 5mL)
Tube type Tube description Volume required Tests required
Serum Red or yellow pedi-pot Red or yellow pedi-pot 3mL
  • free fatty acids
  • βhydroxybutyrate
  • cortisol
  • growth hormone
  • insulin
  • E/LFTs
Lithium heparin no gel Green pedi-pot or adult pot green or adult pedi-pot 0.5mL
  • acylcarnitine
  • plasma amino acids
Fluoro-oxalate Grey pedi-pot grey pedi-pot 1mL
  • glucose
  • lactate

Can be performed on VBG

EDTA Purple pedi-pot purple pedi-pot 0.5mL
  • ammonium

Notify and send to lab urgently. Check with lab if needs to be on ice.

Prioritised blood collection for child with blood collection difficulties

Essential blood collection (required volume 2mL)
Tube type Tube description Volume Tests required
Lithium heparin- no gel Green pedi-pot or adult pot
(see image above)
0.5mL
  • acylcarnitine
  • plasma amino acids – may be done from a newborn screening card if collection is difficult.
Fluoro-oxalate Grey pedi-pot (see image above) 1mL
  • glucose
  • lactate

Can be performed on VBG

Serum Red or yellow pedi-pot
(see image above)
0.5mL
  • cortisol
  • insulin
Second priority investigations (2 mL volume)
Tube type Tube description Volume Tests required
Serum Red or yellow pedi-pot
(see image above)
0.5mL
  • growth hormone
EDTA Purple pedi-pot (see image above)
  • 0.5mL
  • ammonium

Notify and send to lab urgently (check if needs to be on ice)

Serum Red or yellow pedi-pot
(see image above)
1.0mL
  • E/LFTs

Urine

A urine metabolic screen includes urine amino acids and organic acids.

Critical urine sample

The first urine passed after the episode of hypoglycaemia (BGL ≤2.6mmol/L) is the CRITICAL SAMPLE. It must be collected and sent for a urine metabolic screen regardless of age and time since hypoglycaemic episode.

Management

Refer to flowchart for a summary of the management of a child presenting to ED with hypoglycaemia.

  • ALERT – Hypoglycaemia is a medical emergency. If left untreated it can cause convulsions, irreversible brain damage and death.

Acute management

Obtain IV/IO access rapidly for child with BGL <3.0 mmol/L on a glucometer.

Upon obtaining IV access:

  • obtain formal BGL on blood gas machine, iSTAT or formal laboratory testing
  • draw 5 mL of blood (ideally) for further investigations (See Investigations section)
  • measure blood ketones using a blood ketone monitor

Management of child with formal BGL >2.6 mmol/L

  • If low normal BGL, push fluids with initial high sugar content (apple juice, flavoured ice block) followed by more complex carbohydrates.
  • If formal BGL is greater than 3.0mmol/L, do not send bloods for further investigation

Management of child with hypoglycaemia (formal BGL ≤2.6mmol/L)

Children with a history of prolonged fasting (over 30 hours) and blood ketones >4 can be managed as KH.

In addition to treating the hypoglycaemia, blood and urine should be collected from all remaining children to screen for an underlying disorder (refer to Investigation section).

  • ALERT – Hypoglycaemia should be treated with 10% glucose + 0.9% NaCl IV fluids. A 5% glucose infusion is usually not sufficient to maintain BGL or clear ketones.
Management of hypoglycaemia in children
Initial bolus dose (IV) 2 mL/kg of 10% glucose
Following IV bolus Commence an infusion of 10% glucose + 0.9% NaCl at maintenance rate.
Take a 1L bag of 5% glucose with 0.9% NaCl, withdraw 100mL of fluid from the bag and discard. Inject 100mL of 50% glucose into the bag and mix well. Refer to QCH IV Fluid Guideline.
If dehydrated, commence maintenance fluids plus replacement of deficit over 24 hours.
Monitoring IV site hourly for signs of extravasation due to the hyperosmolality of the infusion (see Insertion and management of peripheral and central venous access devices (QH only)

IM glucagon is unlikely to benefit a child with KH.
IO route is recommended if unable to obtain IV access.

  • Consider seeking senior emergency/paediatric advice as per local practice for child with a BGL ≤2.6, a history of fasting over 30 hours and blood ketones >4.
  • Seek senior emergency/paediatric advice as per local practice for child BGL ≤2.6 without a history of fasting over 30 hours and blood ketones >4. Additional investigations are required.

Ongoing management

  • Seek senior emergency/paediatric advice as per local practice if no clinical improvement following initial glucose bolus and IV fluid infusion.  Consider seeking paediatric metabolic advice.
  • Seek relevant specialist advice as clinically indicated by results of the hypoglycaemia screen for ongoing investigations and management.

Review the IV fluid calculation and glucose concentration for children with ongoing symptoms of clinical concern following initial bolus and IV infusion. Consider alternate/concurrent diagnoses.
On admission to the ward or SSU:

  • continue 10% glucose + 0.9% NaCl at maintenance rate (plus additional fluids to replace deficit if dehydrated).
  • administer Ondansetron for children over 12 months of age with nausea or vomiting (note ketones alone can cause nausea which may not settle until ketones have cleared).
  • encourage oral fluids (see below) and diet, preferably with foods containing carbohydrates.
  • once tolerating oral intake IV fluids may be discontinued or changed to 5% glucose with 0.9% NaCl at a reduced rate.
  • organise discharge medications (glucose gel and glucose 10% polymer, +/- ondansetron) early in admission.
Ondansetron for the management of nausea or vomiting in children
Dose Given orally or sublingually at a dose of 0.15mg/kg (maximum 8mg).

Tablets and wafers are available in 4mg and 8mg doses. Recommended doses are as follows:

  • 8-15 kg: 2mg
  • 15-30kg: 4mg
  • greater than 30kg: 8mg

Not recommended for children aged less than 6 months, weight less than 8kg or with ileus.

Considerations Ondansetron prolongs the QT interval in a dose–dependent manner. Exercise caution in children who have or may develop prolongation of QTc (such as those with electrolyte disturbances, heart failure or on medications that may lead to a prolongation of the QTc).

Fluids

Appropriate oral fluids include:

  • 10% glucose polymer (Polyjoule, CarbPlus, SOS formulas)
  • 100% apple juice

The following fluids are unsuitable:

  • glucolyte (2.5% glucose + 3% sucrose)
  • hydralyte ice blocks (1.6% glucose)

Monitoring

Children with hypoglycaemia require routine observation as dictated by their clinical condition.

BGL monitoring

BGL monitoring is not required for children receiving a 10% glucose infusion as the risk of hypoglycaemia is minimal unless hyperinsulinism is suspected.

Consider BGL monitoring for the following children:

  • symptoms of clinical concern such as pallor, vomiting, tachycardia or drowsiness
  • ketones that are absent or inappropriately low (consider hyperinsulinism and continue BGL monitoring until insulin level is known).

It is the treating doctor’s responsibility to document if BGL monitoring is required.

Ketone monitoring

Test urine for ketones after 12 – 24 hours of treatment to ensure urine ketones have cleared or are clearing. If ketones are present, continue to monitor 12 – 24-hourly until cleared.

Escalation outside of ED

Clinicians can contact the services below if escalation of care outside of senior clinicians within the ED is needed, as per local practices. Transfer is recommended if the child requires a higher level of care.

Reason for contact by clinician Contact
For specialist advice on the management, disposition and follow-up of the following children with unexplained hypoglycaemia:

  • if considering admission
  • as required for children admitted to a SSU
Onsite/local paediatric service as per local practice or the Queensland Lifespan Metabolic Medicine Service (07) 3068 1111 and ask for the metabolic clinician on-call
For assistance with local inter-hospital transfers of non-critical patients. Onsite/local paediatric service as per local practice
For assistance with inter-hospital transfer of non-critical patients into and out of Queensland Children’s Hospital.
View the QH Inter-hospital transfer request form (QH only).
Children’s Advice and Transport Coordination Hub (CATCH)
(07) 3068 4510 (24-hour service)
For assistance with decision making regarding safe and appropriate inter-hospital transfer of children in Queensland. View the Queensland Paediatric Transport Triage tool – Medical or call CATCH on (07) 3068 4510 (24 hours)
For access to generalist and specialist acute support and advice via videoconferencing, as per locally agreed pathways, in regional, rural and remote areas in Queensland. Telehealth Emergency Management Support Unit (TEMSU)
1800 11 44 14 (24-hour service)
TEMSU (access via QH intranet)
To request aeromedical inter-hospital transfer in Queensland. Retrieval Services Queensland (RSQ)
1300 799 127 (24-hour service)
RSQ (access via QH intranet)

Disposition

All patients with unexplained hypoglycaemia require a period of observation. Admission to an inpatient service is usually required but admission to an SSU (where relevant) may be considered.

Children with refactory BGLs despite IV therapy or rebound hypoglycaemia on cessation of fluids require admission to an inpatient service.

Discharge from the ward or SSU

On discharge, caregiver/s should be provided with:

  • script for the following:
    • 1 tube of glucose gel
    • +/- Ondansetron
    • +/- 1 can of 10% glucose polymer with the age-appropriate recipe (Lucozade is an appropriate alternative if more than 5 years of age)
  • education including:
    • signs, symptoms and emergency management of hypoglycaemia
    • written instructions on management to prevent a recurrent hypoglycaemic episode as per Sick Day Plan
    • advice against purchasing a glucometer or monitoring BGLs at home (as results can be inaccurate and misleading)

Follow-up

In the event that an overnight fast rather than an intercurrent vomiting illness precipitated the hypoglycaemic episode, discuss with the on-call Metabolic Physician, Queensland Children’s Hospital. The administration of night time cornstarch may be required on discharge.

First presentation of unexplained hypoglycaemia

  • formal written referral to the Department of Metabolic Medicine, Queensland Children’s Hospital to review results of initial metabolic screening. Consultation can be conducted via telehealth if required.

Subsequent presentations

  • liaise with Department of Metabolic Medicine, Queensland Children’s Hospital to determine the need for further outpatient follow-up and if needed book into local General Paediatric outpatient clinic.

Related documents

References

  1. Fernandes, J., Saudubray, J.M., van den Berghe, G. (1996), Inborn Metabolic Diseases: Diagnosis and Treatment. Springer: USA, p.43
  2. Harff, G.A., Janssen, W.C.M., Rooijakkers, L.J. (1997), ‘Evaluation of the Radiometer whole blood glucose measureing system’, European Journal of Clinical Chemistry and Clinical Biochemistry. Walter de Gruyter. Germany Vol. 35(3): pp. 241-242
  3. Hofmann, G.F., Nyham, W., Zschocke, J., Kahler, S.G., Mayatepek, E. (2002), Inherited Metabolic Diseases, Lippincott Williams & Wilkins: Philadelphia, pp.132-144.
  4. McGill, J. (2003), ’Inborn errors of metabolism,’ in Practical Paediatrics, 7th edn, Elsevier: Victoria,p. 318-
  5. Zschocke, J.,  Hoffmann,  G.  (2011),  ‘Vademecum  Metabolicum:  Manual  of  Metabolic  Paediatrics’,  Milupa  / Schattauer: Germany, p.5

Guideline approval

Guideline approval history
Document ID CHQ-GDL-60024 Version no. 1.0 Approval date 19/6/19
Executive sponsor Executive Director Medical Services Effective date 19/6/19
Author/custodian Queensland Emergency Care Children Working Group Review date 19/6/22
Supersedes CHQ-PROC-04100
Applicable to Queensland Health medical and nursing staff
Document source Internal (QHEPS) + External
Authorisation Executive Director Clinical Services QCH
Keywords Paediatric, guideline, metabolic, hypoglycaemia, ketotic hypoglycaemia, inborn errors or metabolism, investigation of hypoglycaemia, 04100, 60024
Accreditation references NSQHS Standards (1-8): 1, 4, 8

Disclaimer

This guideline is intended as a guide and provided for information purposes only. View full disclaimer.
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