Hypoglycaemia on the Neonatal Unit - Guideline for the Management of

Publication: 01/05/2004  --
Last review: 12/11/2018  
Next review: 12/11/2021  
Clinical Guideline
CURRENT 
ID: 524 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2018  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for the Management of Hypoglycaemia on the Neonatal Unit

Summary of Guideline
Background
Diagnosis
Treatment / Management
Glossary of Terms

Summary of Guideline

Pertinent aspects of history and examination& Key diagnostic criteria:

Symptoms of hypoglycaemia may include:

jitteriness

lethargy

respiratory distress

irritability

poor suck

tachypnoea

temperature instability

tachycardia or bradycardia

seizures

apnoeas

Table 1: Infants ‘at-risk’ of hypoglycaemia

Maternal factors:

Diabetes (pre-gestational and gestational)
Drug treatment- ß-blockers, oral hypoglycaemic agents
Intrapartum glucose administration

Neonatal factors:

Preterm (<37 weeks)
Intrauterine growth restriction (<2nd centile for weight) Low birth weight (<2.5 Kg)
Perinatal hypoxic-ischaemia
Hypothermia (<36.0º C) Infection
Polycythaemia
Infants on parenteral nutrition
Syndromes such as Beckwith-Wiedemann or mid-line defects (eg. cleft-lip, cleft- palate, micropenis)
Suspected Endocrine or metabolic disorder
Fetal hydrops

Investigations required- refer to table 4

Treatment & Management: refer to management algorithms

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Background

Introduction:

Hypoglycaemia is a common problem in the neonatal period. In the majority of healthy neonates, low blood glucose concentrations are not problematic and merely reflect the normal process of metabolic adaptation to extra uterine life 1. For this adaptation to occur, there must be adequate glycogen stores, intact and functional glycogenolytic, gluconeogenic and lipogenic mechanisms and appropriate counter-regulatory hormonal responses. Breast feeding has been shown to promote ketogenesis and normal adaptive processes and should be the milk of choice wherever possible 2. Breastfed infants have lower blood glucose and higher ketone body concentrations than formula-fed infants 3.

The neonatal brain is critically dependent on a continuous supply of glucose. In addition, fetal and neonatal brains also have the capacity to oxidize ketone bodies, lactate, and possibly amino acids. Recurrent and persistent hypoglycaemia is associated with significant morbidity and mortality with the risk of sudden death or long term neurological damage 4. The investigation and treatment of symptomatic hypoglycaemia is a clinical emergency. Controversy remains as to whether asymptomatic hypoglycaemia actually causes brain damage.

When compared to term babies, preterm babies have lower hepatic glycogen reserves, lower activities of key gluconeogenic enzymes, an initially limited hormonal response and lower blood glucose values with a slower rise 5.

Plasma blood glucose values tend to be about 10-18% higher than the whole blood values due to the higher water content of plasma compared to erythrocytes 1. This must be borne in mind when comparing glucose measurements made using the point of care equipment, which uses whole blood, as opposed to laboratory plasma glucose. This guidance is based upon whole blood glucose measurements as that is what would be most frequently used on the neonatal unit.

Definition:

The definition of what constitutes a threshold hypoglycaemic blood glucose(BG) level in infants remains controversial but there is no evidence to support a level higher than 2.6mmol/L 1.

For infants with hyperinsulinism, an operational threshold of 3.5 mmol/L has been suggested, as these infants have very low levels of alternative fuels such as ketones and lactate at low blood glucose concentrations 6.

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Diagnosis

Symptoms of hypoglycaemia:

Symptomatic hypoglycaemia must be treated urgently, irrespective of the blood glucose (BG) level. In infants admitted to ICU, symptoms maybe masked for various reasons including sedation and paralysis.

Table 1: Symptoms of hypoglycaemia may include:

jitteriness

lethargy

respiratory distress

irritability

poor suck

tachypnoea

temperature instability

tachycardia or bradycardia

seizures

apnoeas

Which babies should be monitored?
Routine monitoring of blood glucose concentrations in term infants should only be undertaken in those who have clinical manifestations or are at risk of compromised metabolic adaptation. (Table 2)

A normal infant at term shows an immediate postnatal fall in blood glucose concentrations during the first 1-2 hours. Therefore, even if a term baby is known to be at risk of hypoglycaemia, blood glucose measurement is best avoided in babies <3hours of age1.

All babies admitted to ICU and HDU should have blood sugar monitoring on admission and then subsequently as required. Those on I/V fluids or TPN should be monitored 8 hourly and an hour after any change in fluids or after starting a new bag of TPN.

Table 2: Infants ‘at-risk’ of hypoglycaemia 1,7,8

Maternal factors:

Diabetes (pre-gestational and gestational)
Drug treatment- ß-blockers, oral hypoglycaemic agents
Intrapartum glucose administration

Neonatal factors:

Preterm (<37 weeks)
Intrauterine growth restriction (<2nd centile for weight) Low birth weight (<2.5 Kg)
Perinatal hypoxic-ischaemia
Hypothermia (<36.0º C) Infection
Polycythaemia
Infants on parenteral nutrition
Syndromes such as Beckwith-Wiedemann or mid-line defects (eg. cleft-lip, cleft- palate, micropenis)
Suspected Endocrine or metabolic disorder
Fetal hydrops

 

Table 3: Endocrine and metabolic causes of neonatal hypoglycaemia1

Hyperinsulinism:

Congenital hyperinsulinism, Beckwith-Wiedemann syndrome

Counter-regulatory hormonal deficiency:

eg. Hypopituitarism, Growth hormone deficiency, Adrenal steroid disorders

Fatty acid oxidation disorders:

eg. Medium and long-chain fatty acid oxidation disorders

Gluconeogenic disorders:

eg. Fructose-1,6- bisphosphatase deficiency

Glycogen storage disorders:

Glucose-6-phosphatase deficiency, Glycogen synthase deficiency

Others:

Galactosaemia, Maple syrup urine disease, Propionic acidaemia

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Investigation

Refer to table 4

Treatment / Management

Management:

A. Management of babies <33 weeks and deemed suitable for full enteral feeds: To be used in conjunction with the Enteral Feeding Guideline for the Preterm Infant within the Neonatal Service, Leeds Clinical guidelines.

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B. Management of babies =/> 34 weeks and >1.5Kg and deemed suitable for full enteral feeds:
To be used in conjunction with Leeds Clinical guidelines on (i) Breastfeeding - The prevention and management of hypoglycaemia of the newborn and (ii) Postnatal care of the Term infant of a diabetic mother

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C. Management of babies on I/V fluids:

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Consider a 10% glucose bolus of 2.5 ml/Kg at A), B), C) or D) if BG<1 or continuing to drop

  • Central venous access is required if glucose concentration exceeds 10%
  • A glucose bolus should always be followed by an increase in the rate of glucose infusion.
    Frequent and large glucose boluses should be avoided.
  • The BG should be checked an hour after any change in volume or concentration.
  • If BG<1, recheck on gas machine and send a lab glucose.
  • Check glucose infusion site and apparatus to ensure glucose delivery in cases of persistent hypoglycaemia.
  • Enteral feeds should be initiated when clinically appropriate and should not be delayed for the treatment of hypoglycaemia.
  • In infants of diabetic mothers, excessive I/V fluids should be avoided. Early enteral feeding with breast milk is recommended.
  • Glucose infusion rate:

Formula=% glucose x fluid rate (ml/Kg/day)/ 144= mg/Kg/min

Normal glucose requirement: 4-6 mg/Kg/min Moderate hypoglycaemia: 6-10 mg/Kg/min
Severe hypoglycaemia: >10 mg/Kg/min

Worked example: If a baby is on 12.5% dextrose at 100mls/kg/day the glucose requirement is 12.5 x 100/ 144 = 8.68 mg/kg/min

Drug treatment:
Some patients may require drug treatment. A Paediatric endocrinologist may have to be consulted in such a situation.

The following drugs may be considered in acute hypoglycaemia: 9, 10

  1. Glucagon - 100micrograms/Kg IV or IM bolus (if no I/V access). IUGR babies may require 30-200micrograms/Kg
  2. Hydrocortisone (if known or suspected cortisol deficiency)

The following drugs may be considered in chronic hypoglycaemia:

  1. Diazoxide - 5mg/Kg/day in 3 divided doses and Chlorthiazide- 7mg/Kg/day in 2 divided doses
  2. Octreotide - 10micrograms/Kg/day S/C

Current evidence does not support the use of Hypostop in neonates but this maybe considered 1.

Which babies should have a hypoglycemia screen?
A screen should be considered in any baby with severe or persistent hypoglycaemia if:

  • Not in the ‘at risk’ (Table 2) group, except in cases where an underlying metabolic or endocrine disorder is strongly suspected (Table 3)
  • Symptomatic / severe hypoglycaemia (requiring >10mg/Kg/min glucose). If glucose requirement rate >10mg/Kg/min, then likely hyperinsulinism1
  • ≥ 2-3 days old and continuing to have blood sugars <2.6

The hypoglycaemia screen must be sent at the time of the hypoglycaemic episode. However, do not delay correcting hypoglycaemia if there are any difficulties in obtaining bloods. Do not wait for the results of the screen to correct hypoglycaemia.

Table 4: What constitutes a hypoglycaemia screen?

Lab glucose

2ml fluoride oxalate

Free fatty acids

3-OH butyrate

lactate

Plasma amino acids

2ml lithium heparin

Plasma cortisol

Plasma insulin and C- peptide

Plasma growth hormone

Acyl-carnitines

2-3 blood spots on Guthrie card (stating acyl carnitine assay)

Blood gas

These samples can be taken after glucose has been given.
For ammonia, a minimum of 0.5mls of blood should be obtained in a lithium heparin bottle. The lab must be informed and sample sent immediately.

Liver function tests

Urea

Electrolytes

Ammonia

Organic acids

First passed urine sample (5mls or more)

Amino acids

Sugar

Ketones

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Provenance

Record: 524
Objective:

Aims
To improve the diagnosis and management of Hypoglycaemia on the neonatal unit.

Objectives
To provide evidence-based recommendations for appropriate diagnosis, investigation and management of Hypoglycaemia on the neonatal unit.

Clinical condition:

Neonatal Hypoglycaemia

Target patient group: Neonates
Target professional group(s): Midwives
Secondary Care Doctors
Secondary Care Nurses
Adapted from:

N/A


Evidence base

  1. Deshpande S, Ward Platt M. (2005). The investigation and management of neonatal hypoglycaemia. Seminars in Fetal and Neonatal Medicine; 10, 351-361.
  2. Hypoglycaemia of the Newborn- Unicef 2011
  3. Hawdon J, Ward Platt M, Aynsley-Green A. Patterns of metabolic adaptation for preterm and term infants in the first neonatal week. Arch Dis Child 1992; 67: 357-65.
  4. Khalid Hussain. Investigations for neonatal hypoglycaemia. Clinical Biochemistry 44(2011) 465-466
  5. Robert Hume et al. Glucose Homeostasis in the newborn. Early Human Development (2005) 81, 95-101.
  6. Hussain K. Congenital hyperinsulinism. Seminars in Fetal Neonatal Med 2005
  7. Marvin Cornblath et al. Controversies regarding definition of neonatal hypoglycaemia: suggested operational thresholds. Pediatrics 2000;105;1141
  8. Jane M Hawdon (2012) Investigation, prevention and management of neonatal hypoglycaemia (impaired postnatal metabolic adaptation). Paediatrics and Child Health Vol22, issue 4-131-135.
  9. Robertons Textbook of Neonatology. Fifth Edition
  10. British National Formulary for children 2014

A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)

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Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.0

Related information

Glossary of Terms

BG- blood glucose
I/V- intravenous
I/M- intramuscular
S/C- subcutaneous
ICU- intensive care unit
HDU- High dependency Unit
TPN- total parenteral nutrition
IUGR- intrauterine growth retardation

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