Investigations and Initial Management of Hypoglycaemia
Published by PIER Network Clinical Review Group • Ratified by Child Health Governance • Last updated: 10-2026
Flowchart Algorithm: Pediatric Acute Wheeze Escalation Pathway. Standardized assessment and stepwise escalation protocol for children presenting with acute w...
Flowchart
Introduction
This guideline is intended to provide doctors with a clear structure for the initial investigations and management of babies, infants and children who present with hypoglycaemia. It incorporates recently published guidance and consensus.
This guideline excludes those with insulin dependent diabetes or a known metabolic disorder and babies with early onset hypoglycaemia <72 hours of birth for which there is separate neonatal guidance.
There is a separate PIER guideline for the Initial Assessment and Management of Congenital Hyperinsulinism in Neonates.
Scope
Paediatricians working across Wessex. Children with hypoglycaemia should be discussed with the DGH lead for paediatric endocrinology at each DGH during working hours
Purpose
To provide an agreed clinical approach to managing hypoglycaemia, provide a structured overview of underlying disorders that can result in hypoglycaemia and guide clinicians to the appropriate investigations including those that are time critical and must be carried out at the time of hypoglycaemia and prior to initiating treatment.
Definitions
Normoglycaemia
Other than the first 2-3 days of life normal fasting blood glucose is kept within a narrow physiological range 3.5-5.5 mmol/l.
Hypoglycaemia
Clinical hypoglycaemia is defined as blood glucose (BG) concentration low enough to cause symptoms and or signs of impaired brain function. It cannot be defined by a specific BG level as thresholds for specific brain responses to hypoglycaemia occur across a range of BG levels and can be influenced by the presence of alternative fuels such as ketones or lactate.
Neurogenic symptoms are perceived at a BG concentration < 3.0mmol/l, which in older children and adults triggers a search for food or assistance.
Cognitive function is impaired at a BG concentration < 2.8mmol/l.
Young infants and children often cannot dependably recognize and or communicate their symptoms.
A BG < 2.6 mmol/l is generally regarded as a level at which prompt investigation and treatment is required regardless of the presence of symptoms.
Glucose homeostasis
The key hormones that regulate glucose homeostasis are insulin, glucagon, adrenaline, noradrenaline, cortisol and growth hormone. Insulin regulates glucose homeostasis in the post prandial state whereas the other hormones (counter regulatory hormones) control glucose levels during the fasting state. Glucagon and adrenaline are the main line of defence against hypoglycaemia whereas cortisol and GH have a permissive role in regulating blood glucose levels.
Hypoglycaemia associated autonomic failure (HAAF)
Reduced or absent awareness of hypoglycaemia and impaired hepatic glucose release due to impaired neurogenic responses to hypoglycaemia. This can persist for > 24 hours after a single episode of hypoglycaemia and longer after repeated episodes.
Transitional hypoglycaemia
After birth the continuous glucose delivery to the foetus is disrupted and for the first few hours, after birth there is a transitional phase of physiologically low normal blood glucose levels (transitional hypoglycaemia) which normalises around 72 hours after birth.
Ketone bodies
Acetoacetate and Beta – hydroxybutyrate are produced by beta oxidation of free fatty acids and can be utilised as an alternative energy source. Free fatty acids are released during lipolysis in the fasting state when insulin levels are low. The presence or absence of ketones during hypoglycaemia is key to considering the diagnosis and appropriate further investigations.
Clinical Features of Hypoglycaemia
Hypoglycaemia may be associated with symptoms and signs or may be asymptomatic.
Clinical features associated with symptomatic hypoglycaemia are as follows:
Neonates | Infant/Older Child |
Pallor | Anxiety |
Important Points to Guide the History
The history must be thorough and should include:
Timing of the episode of hypoglycaemia and its relationship to food (i.e. how long was the fasting episode)
Features and timing or previous episodes of suspected hypoglycaemia
Ability to cope with intercurrent illness
Birth history and weight
Neonatal jaundice and or hypoglycaemia
Tolerance to fasting/illness
Drug ingestion
Family history parental consanguinity
History of neonatal or unexplained deaths in the family
Important Points to Guide the Clinical Examination
Features of sepsis, hepatomegaly, encephalopathy, cardiac failure
Optic atrophy, cataracts, nystagmus, failure to fix and follow
Appearance of external genitalia (micropenis)
Midline defects (cleft lip, cleft palate, bifid uvula)
Skin pigmentation (gums, scars, skin creases)
Hemihypertrophy, macroglossia, omphalocoele
Causes of Hypoglycaemia
Hypoglycaemia arises from an imbalance between glucose production and consumption and can be caused by either endocrine or metabolic disorders or may be secondary to other disorders or organ dysfunction.
Endocrine | Hyperinsulinism |
Metabolic | Fat oxidation defects |
Other | Sepsis |
Investigations
Clinical practice point
A key clinical practice point is to take blood and next urine for ketones at the time of hypoglycaemia and before treatment with glucose. The presence or absence of ketones at the time of hypoglycaemia is diagnostically crucial to aid diagnosis and subsequent management.
ALWAYS request laboratory serum glucose even if a finger prick glucose has been taken.
Laboratory measurement for glucose is essential as point of care testing can be unreliable at low blood glucose levels.
ALWAYS contact biochemistry to inform them that samples are to be sent; SOME TESTS NEED TO REACH THE LAB URGENTLY FOR ANALYSIS.
It is important to collect and save blood when the infant is hypoglycaemic for any specialist tests which may be subsequently required.
Time critical investigations
If sampling is difficult, the most important tests to collect at the time of hypoglycaemia are:
Blood glucose
Ketone level (request B-hydroxybutyrate)
Blood gas
Insulin level
C-Peptide
Cortisol
Lactate
1st Urine passed
Point of care testing for B hydroxybutyrate is now widely available.
Major categories of hypoglycaemia can be determined simply from analysis of a blood gas and ketone levels at the time of hypoglycaemia. This can help tailor any subsequent investigations.
Hypoglycaemia with inappropriately low or absent ketones usually indicates hyperinsulinism as the underlying cause with the exception of fatty acid oxidation defects and defects of ketone metabolism.
Clinical practice point
A key practice point for interpreting the results of a hypoglycaemia screen is to interpret the episode of hypoglycaemia in the presence or absence of ketones and acidaemia.
This is diagnostically crucial to aid diagnosis and subsequent management and reinforces the need to take the appropriate time critical samples.
Flow Chart
Investigations Required for a Complete Hypoglycaemia Screen
Specimen | Test | Bottle | Instructions | Time for result (days) |
|---|---|---|---|---|
Should be taken prior to correction of glucose | ||||
Bedside | Capillary blood gas | Immediate | ||
Glucose | Immediate | |||
Ketones | Immediate | |||
Laboratory Blood test | Glucose | Flu Ox | <1 | |
Lactate | Flu Ox | Rush to Lab | <1 | |
Insulin | Serum or EDTA | Rush to Lab | 5 | |
C-Peptide | Serum or Li Hep | Rush to Lab | 5 | |
3 Hydroxybutyrate | Flu Ox | 5 | ||
Free Fatty Acids | Flu Ox | Rush to Lab | 5 | |
Cortisol | Serum | <1 | ||
First urine passed after episodes | ||||
Urine Diptest | Glucose | White cap sterile univeral container | Immediate | |
Ketones | Immediate | |||
Reducing substances | Immediate | |||
Laboratory Tests (urine) | Organic acids | 10 | ||
Toxicology screen (if factitious or accidental ingestion suspected) | Discuss with lab | |||
May be taken after correction of glucose | ||||
Laboratory blood test | Plasma or blood sport carnitine | Li Help or Guthrie Card | 10 | |
Plasma amino acids | Serum or Li Hep | 10 | ||
Ammonia | EDTA | Rush to lab on ice | <1 | |
Urea and Electrolytes | Serum or Li Hep | <1 | ||
Liver Function tests | Serum or Li Hep | <1 | ||
Alcohol | Li Hep | <1 | ||
Salicylates | Li Hep | <1 | ||
Blood Culture | Blood culture bottle | 2 | ||
Growth Hormone | Serum or Li Hep | 1 | ||
Bottles required:
2 x 2ml flu ox
2 x 2ml EDTA
6 x 2ml Li Hep
Plain universal bottle 25 ml (10 mls urine).
Note: Bottles required for samples may vary slightly between laboratories
Turnaround time may be longer if transport to the laboratory is required
Hypoglycaemia: Grab bag/emergency box
Some units will have pre made emergency hypo boxes available in ED or on the paediatric wards which will include the bottles required for a hypoglycaemia screen.
Clinical practice point
If hypoglycaemia is though to the presenting feature of adrenal insufficiency, please see the following PIER guideline - Adrenal Crisis (new presentation or pre-existing adrenal insufficiency)
Interpretation of Hypoglycaemia Screening Tests
Test | |
|---|---|
Blood/plasma glucose | Without accurate confirmation of hypoglycaemia the results of specialised endocrine and metabolic investigations may be difficult to interpret and potentially misleading. |
Ketones | The absence of ketones in hypoglycaemic patients is suggestive of hyperinsulinism or a fatty acid oxidation defect |
Blood gases | An unexplained metabolic acidosis is suggestive of a ketoacidosis/lactic acidosis or an organic acidaemia |
Liver funciton tests | Evidence of liver dysfunction, i.e. hyperbilirubinemia, abnormal enzymes, clotting maa suggest specific disorders |
Urea | May be increased if there is pre-renal uraemia due to dehydration as a consequence of prolonged vomiting. |
Electrolytes (Sodium and Potassium) | Hyponatraemia and hyperkalaemia are observed in either primary adrenal insufficiency or adrenal steroid biosynthesis dirosers. |
Lactate | Increased in metabolic liver disease, secondary to prolonged convulsions or glycogen storage disorders. |
Ammonia | Increased in liver dysfunction, hyperinsulinism with hyper ammonaemia. |
Amino acids (plasma and urine) | Tyrosinemia, maple syrup urine disease |
Urine reducing substances | The presence of non-glucose reducing substances suggests galactosaemia |
Acyl carnitine (plasma) Guthrie card | Fatty acid oxidation and organic acid disorders |
Free Fatty Acids Hydroxybutyrate (plasma) | Fatty acid oxidation defects |
Insulin and C-Peptide (plasma) | Inappropriately increased in hyperinsulinism. C-Peptide to look for exogenous sources of insulin |
Cortisol (plasma) | Diagnostic of Addison's disease and defects of adrenal steroid biosynthesis. May represent hypopituitarism |
Paired ACTH/Cortisol | Pituitary Disorders |
Growth Hormone (plasma) | Reduced in panhypopituitarism and isolated GH deficiency |
Alcohol level, salicylate level | Drugs most commonly associated with hypoglycaemia include insulin, sulphonyl ureas, alcohol, betablockers and salicylates |
Controlled fasts
Children who present with hypoglycaemia and have not had investigations carried out at the time of hypoglycaemia may require a controlled fast to help make a diagnosis.
This is potentially dangerous and must be performed according to strict protocol in the hospital setting and should be discussed with the local DGH lead for endocrinology or tertiary centre at Southampton.
It is important to exclude fatty acid oxidation defects and hyperinsulinism before subjecting a child to a controlled fast.
Suspected adrenal insufficiency should be assessed by a short synacthen test prior to the fast.
Management
The correction of hypoglycaemia should follow standard practice guidelines (APLS) using intravenous glucose, glucagon injection or oral glucose (in the non-drowsy conscious patient).
Assess patient using ABC framework
Confirm Blood sugar < 2.6 mmol/l
Insert IV cannula
Take blood tests for hypoglycaemia screen
Ensure lab glucose sent to confirm hypoglycaemia
Put urine bag on to collect next urine passed
DO NOT DELAY TREATMENT WHILST AWAITING CONFIRMATION OF LAB GLUCOSE
No IV Access | |
|---|---|
Child not drowsy | Child drowsy |
<1 year give milk feed >1 year give oral hypoglycaemia treatment* | IM glucagon (<25kg 0.5mg, >25kg 1.0mg) |
Recheck BG at 10 minutes post IM glucagon or post oral treatment | |
IV Access |
|---|
IV bolus 10% glucose 2ml/kg |
Recheck capillary BG (blood glucose) at 10 minutes interval until GD (blood glucose) stable >3 mmol/L |
If following initial treatment child unable to recommence feeds or remains unwell: start IV glucose infusion using 10% glucose/0/9% sodium chloride solution at a rate of 2.4-4.8 ml/kg/hr equivalent to giving 4-8mg/kg/min dextrose. Recheck capillary BG (blood glucose) at 10 minutes interval until GD (blood glucose) stable >3 mmol/L If BM remains below 2.6mmol/l Repeat bolus dextrose 2ml/kg Increase IV glucose infusion rate to 6ml/kg/hr 10% glucose/ 0/9% sodium chloride (or 10mg/kg/min). If BMs remain low increase concentration of glucose to IV fluids - note the glucose concentrations >12.5%, central access required. Do not exceed 50% glucose infusions. Monitor electrolytes regularly. If adrenal insufficiency is suspected give 4mg/kg hydrocortisone to a max 100mg. If congenital hyperinsulinism suspected (GIR typically > 12 mg/kg/min) and unable to increase blood glucose levels with dextrose consider IG glucagon infusion (1-18mcg/kg/hr). Specialist endocrine advice should be sought at an early stage. Note: Glucagon can cause hypokalaemia, vomiting and rebound hypoglycaemia (monitor blood sugars carefully). Consider starting continuous glucagon infusions at 19mcg/kg/hr and decrease carefully, monitoring blood glucose, until the minimum effective dose is reached. |
See SORT guidelines for preparation of non-standard isotonic glucose concentrations and for glucose delivery calculations.
Blood glucose treatment targets
Treatment targets for blood glucose levels are aimed at avoiding activation of neuro endocrine responses and hypoglycaemia – associated autonomic failure (HAAF).
For children and adults with diabetes, neonates with a confirmed hypoglycaemia disorder and infants and children with a persistent hypoglycaemia disorder blood glucose levels should be kept above 3.9 mmol/l.
Glucose Infusion Rate (GIR)
Calculating the amount of glucose required (glucose infusion rate, GIR) to maintain normoglycaemia is helpful when considering the diagnosis.
Most infants will be normoglycaemic on an initial GIR of 5 – 8 mg/kg/min.
Infants who are hyperinsulinaemic or have minimal glycogen stores may need a higher glucose infusion rate than 5 – 8 mg/kg/min to maintain normoglycaemia.
Infants with congenital hyperinsulinism usually require a GIR greater than 12 mg/kg/min.
The glucose infusion rate (mg/kg/min) can be calculated using the following formulae:
GIR = % of glucose being infused x rate of infusion (ml/hr)/ Body weight (in kg) x 6
or
GIR = Rate of IV fluids (in ml/kg/day) x % of glucose infused/144
or
GIR = Rate of IV fluids (in ml/kg/day) x % of glucose infused x 0.007
Oral hypoglycaemia treatment options
5-20g of fast acting oral carbohydrate should be given (approx. 0.3g/kg) see table below:
Age | Carbohydrate | LiftR (15g/60ml) | Dextrose Tablets (3.3g) | Dextrose tablets (3.5g) | Fruit juice or non diet cola (10g/100ml) |
|---|---|---|---|---|---|
<4 years | 5 g | 20 ml | 1.5 | 1.5 | 50 ml |
4-12 years | 10 g | 40 ml | 3 | 2.5 | 100 ml |
13 years + | 15 g | 60 ml | 4.5 | 4 | 150 ml |
IV Glucagon infusion preparation
SINGLE STRENGTH infusion
Add 1 mL of diluent provided (water) to the 1 mg vial (1000 microgram of glucagon). Draw up 0.5 mL/kg (0.5 mg/kg of glucagon) and make up to a final volume of 50 mL with glucose 5% or 0.9% sodium chloride to give a concentration of 10 microgram/kg/mL.
Infusing at 1 mL/hour = 10 microgram/kg/hour.
DOUBLE STRENGTH infusion
Add 1 mL of diluent provided (water) to the 1 mg vial (1000 microgram of glucagon). Draw up 1 mL/kg (1 mg/kg of glucagon) and make up to a final volume of 50 mL with glucose 5% or 0.9% sodium chloride with a concentration of 20 microgram/kg/mL.
Infusing at 1 mL/hour = 20 microgram/kg/hour.
Discharge Planning
It is important that a cause for the hypoglycaemia is established before the patient is discharged home and appropriate treatment and follow up plans arranged.
If hypoglycaemia unexplained or at risk of hypoglycaemia, prior to discharge:
Determine how long the child can safely remain normoglycaemic (see below)
arrange open access to the ward
train parents in monitoring blood sugars and treating hypoglycaemia
arrange follow-up appointment
A reasonable time between meals or feeds should be safely tolerated without blood sugar dropping below 3.0mmol/l. A controlled fast may be required and this should be discussed with the local DGH endocrine lead or tertiary centre.
The details of treatment for specific conditions is beyond the scope of this guideline but may include involvement of the paediatric dietitians, training on hypoglycaemia management, home glucose monitoring and open access arrangements to the local centre.
Hypoglycaemia Results Log
Governance
Implementation
The guideline will be displayed on the PIER website and can be accessed by all healthcare professionals working within Wessex. This guideline will be disseminated to network centre leads within the Wessex Paediatric Endocrine Network.
Process for Monitoring Effectiveness
Compliance with the guideline will be audited and results disseminated to the Wessex Paediatric Endocrine Network. A service evaluation of parental satisfaction of initial management will be undertaken.
References
APLS Manual 6e 2016.
Southampton Oxford Retrieval Team guidelines SORT: https://www.sort.nhs.uk/Media/Guidelines/Glucose-concentrations-and-calculator.pdf
BNFc, BNF.NICE.org.uk
Medusa Injectable medicines guide: Glucagon, Version 6 published 07/12/2018
ISPAD Clinical Practice Consensus Guidelines 2014. Assessment and management of hypoglycemia in children and adolescents with diabetes. Ly TT et al Pediatr Diabetes. 2014 Sep;15 Suppl 20:180-92. doi: 10.1111/pedi.12174. Epub 2014 Jul 12.
ACDC clinical guideline: Management of hypoglycaemia in children with Type 1 diabetes 2016.
Recognition, assessment and management of hypoglycaemia in childhood. Ghosh A, Banerjee I, Morris AAM, Arch Dis Child 2016; 101:575-580
What is normal blood glucose? Güemes M, Rahman SA, Hussain K. Arch Dis Child 2016; 101: 569–574.
Recommendations from the Paediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycaemia in Neonates, Infants and Children. Thornton PS et al. The Journal of Paediatrics 2015, 167(2), May 2015
How to use a controlled fast to investigate hypoglycaemia. Streekantam S, Preece MA, Vijay S et al Arc Dis Child Educ Pract Ed 2017; 102:28-36
Investigation of the child with acute metabolic disorder. Cook P, Walker V. J Clin Pathol 2011; 64:181-191.
Re-evaluating “Transitional Neonatal Hypoglycaemia”: Mechanism and implications for management. Stanley CA. J Pediatr. 2015 June; 166(6): 1520–5.