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GUIDELINES

Guideline for Steroid Replacement in Children with Adrenal Insufficiency or at Risk of Adrenal Suppression who Require Surgery or a Procedure Requiring Sedation or General Anaesthetic
  • Flowchart
  • Introduction
  • Scope
  • Purpose
  • Definitions​​
  • Background
  • Steroid Doseing Before, During and After Surgery​
  • Governance​
  • ​​​References​
  • Appendices
    • Equivalent Doses of Commonly Used Glucocorticoids in Relation to Prednisolone
    • ​Signs and Symptoms of Adrenal Insufficiency
    • ​Mosteller Formula for BSA
    • Hydrocortisone Infusion
    • Stat Doses of IM Hydrocortisone Based on Age
Flowchart
Picture
BSA Calculator
Introduction

Children with adrenal insufficiency or at risk of adrenal suppression are frequently admitted to hospital for routine and complex surgical procedures. These conditions and their specific management during times of increased stress may be unfamiliar to the attending staff. If managed incorrectly, this can put the child at risk of a life-threatening adrenal crisis.
 
This guideline provides information for health care professionals for the safe use of steroids peri-operatively. The dose and duration of increased steroid requirement depends on the type of surgical procedure. This guideline refers to the following 3 categories:
  • major surgery under general anaesthetic
  • minor surgery or procedures under general anaesthetic e.g. endoscopy, bronchoscopy, MRI under GA
  • minor surgery under local anaesthetic or sedation e.g. dental extraction in older children
 
The local paediatrician with a special interest in endocrinology or the regional paediatric endocrinology team at Southampton can be contacted for additional advice. During normal working hours the Southampton Childrens Hospital on call paediatric endocrinology consultant can be contacted via the switchboard. The registrar carries bleep 2027 and the paediatric endocrine nurse specialists (PENS) are on extension 8719. Both are contactable via the hospital switchboard.
 
This guideline has been developed based on national and international current best practice and expert opinion. It is summarised in the accompanying flow chart on the PIER website

Scope

All staff working in Child Health within the Wessex region, anaesthetists, surgeons and theatre staff involved in perioperative care of children up to the age of 18 years
Purpose

This guideline is intended for use in managing all children and young people up to the age of 18 years with adrenal insufficiency or at risk of adrenal suppression that require surgery.
 
It provides advice on the perioperative steroid management of children with the following conditions:
  • primary, secondary and tertiary adrenal insufficiency
  • congenital adrenal hyperplasia (CAH)
  • adrenal suppression due to exogenous steroid use
Definitions

Adrenal Insufficiency (AI)
Inadequate production of glucocorticoid +/- mineralocorticoid by the patient’s adrenal gland due to a problem at the level of the adrenal gland (primary), pituitary gland (secondary) or hypothalamus (tertiary).

Adrenal Suppression (AS)
Exogenous steroid use leading to atrophy of the adrenal gland and inadequate production of endogenous glucocorticoid.

Minor Surgery and Minor Procedures
Short procedures lasting <1 hour with rapid recovery post procedure so that the child is expected to eat and drink by the next meal. For example dental extraction, endoscopy, central line insertion, lumbar puncture or MRI.

Major Surgery
​
Longer and more complex procedures lasting >1 hour or a procedure that is likely to cause post operative nausea and vomiting and will significantly delay the patient eating and drinking after the procedure.
 
If you are unsure about the length of anaesthetic or risk of slow post-operative recovery, please discuss with the anaesthetist involved.

Background

The Hypothalamic-Pituitary-Adrenal (HPA) Axis

Corticotrophin Releasing Hormone (CRH) secreted by the hypothalamus stimulates the secretion of Adrenocorticotrophic Hormone (ACTH) from the anterior pituitary which in turn causes the release of cortisol from the adrenal cortex. Negative feedback occurs at the level of both the pituitary and hypothalamus in response to raised cortisol levels. Exogenous steroids also cause inhibition of CRH and ACTH release which, if prolonged, causes adrenal atrophy and suppresses the ability of the adrenal glands to increase the production of cortisol in response to stress. Cortisol has many important functions including maintenance of blood pressure and blood glucose levels.
 
In adults with an intact HPA, the production of cortisol increases from a concentration of 10 mg/day (5.7mg/m2/day) (1,2) to 50 mg/day after minor surgery and 75-150 mg/day after major surgery(3). The cortisol concentration increases during the operation and reaches a peak in the early post-operative period, at the time of anaesthesia reversal and extubation (4,5).

 
Children with Adrenal Insufficiency
 
Children with AI, who are known to have a problem with their HPA axis, will be on maintenance doses of hydrocortisone +/- fludrocortisone. Typical maintenance doses of hydrocortisone for CAH are 10-15 mg/m2/day and for other causes of adrenal insufficiency are 8-10 mg/m2/day.
 
Children with Adrenal Suppression
 
What is Adrenal Suppression?
 
Adrenal Suppression (AS) caused by exogenous glucocorticoid use is the most common cause of AI in children. The estimated incidence in the paediatric population is 0.35/100000 (6) but is much higher in the 'at risk' population with 1 in 5 children on long term steroids for Inflammatory Bowel Disease demonstrating biochemical evidence of AS (7). Children on long term glucocorticoid therapy are frequently admitted to hospital for elective surgical procedures such as endoscopy, and require appropriate steroid cover. Children with AS are at risk of an adrenal crisis if they do not receive adequate steroid replacement during stressful events.
 
Children at risk of AS will typically be on once daily steroids, such as prednisolone, for treatment of their underlying illness and will require conversion to oral hydrocortisone around the time of surgery. This is administered in multiple daily doses and provides a more consistent level of steroid cover.


Who is at risk of Adrenal Suppression?

The following factors have been identified as increasing the risk of AS in children on glucocorticoid therapy and can be used to help decide which patients need steroid cover:
 
  1. Steroid potency
    • Steroid formulations with a more potent glucocorticoid effect and longer half life increase the risk of AS (see appendix 1).
  2. Route of administration
    1. Oral steroids increase the risk of AS compared with topical steroids (6).
    2. High dose inhaled corticosteroids (Beclomethasone and Fluticasone >400mcg daily dose) for more than 3 months have been shown to cause adrenal suppression (8,9).
  3. Daily dosage
    1. In adults it is generally accepted that a daily dose of prednisolone >5mg for more than 4 weeks increases the risk for AS (10)
    2. Supraphysiological doses of glucocorticoid in children would be the equivalent of >10mg/m2/day of hydrocortisone (11).
  4. Divided and nocturnal doses:
    1. Multiple daily dosing and administration in the evening increase the risk of AS.
  5. Duration of treatment
    1. AS has been documented in children treated for as little as 14 days with oral glucocorticoids12. The risk increases with longer duration of treatment but >4 weeks is significant (13).
    2. The duration of AS following discontinuation of steroids is variable and can range from between 3 to 18 months (14).
    3. It is recommended that anyone who has completed a prolonged course of steroids within the last 12 months and has had further short courses of steroids should be considered at risk of AS (15).
  6. Cushingoid features on examination or features of AI/AS on history (see appendix 2).

​If you are unsure whether or not a child requires perioperative steroid cover based on the above, please discuss with your local paediatrician with a special interest in endocrinology or the regional team in Southampton.
Steroid Dosing Before, During and After Surgery

Pre-operative assessment

When the decision is made to undertake surgery, the surgical team needs to inform the local paediatrician with a special interest in endocrinology or the regional paediatric endocrinology team and the anaesthetist about the date and time of the planned procedure, the type of procedure and whether it is judged to be major or minor surgery (see definitions above).
The child should be given first on the list priority to minimise fasting and dehydration which children with AI or AS tolerate poorly. No child with AI or AS should be fasted for more than 6 hours.
If possible, the parents should be contacted prior to surgery to let them know how to manage their child’s steroids at this time (see tables below).


Pre-operative Fasting

  • No solid food should be consumed for 6 hours before elective surgery in children.
  • In infants, breast milk is safe for up to 4 hours and other milks up to 6 hours. Thereafter, clear fluids should be given as in older children.
  • Children should be encouraged to drink clear fluids containing sugar (e.g. sugar containing squash or cranberry juice) up to 1 hour before elective surgery.
  • The child’s usual morning dose of hydrocortisone can be given with clear fluids on the morning of surgery and will not interfere with fasting times.

If there is a delay of more than 2 hours in taking the child to theatre, IV maintenance fluids (0.9% sodium chloride plus 5% dextrose) should be started.
 
General Advice

Children with AI on multiple daily doses of oral hydrocortisone should take their usual dose at 06:00 on the morning of surgery. If the child is taking fludrocortisone this should be given at the same time.
 
If the child is due any further doses of hydrocortisone routinely while they are in hospital and NBM for the procedure, these should be given intravenously at the usual dose. Please ensure these are prescribed on the drug chart at the time of admission to anticipate any delays.   
 
Children at risk of AS on daily oral prednisolone should be converted to oral hydrocortisone on the day of surgery to provide more consistent cortisol replacement. The first dose should be given at 06:00 prior to theatre.
  • For minor surgery a stress dose would be 30 mg/m2/day of hydrocortisone in 4 divided doses (16).
  • For major surgery a stress dose would be 50 mg/m2/day of hydrocortisone in 4 divided doses (17).
BSA can be calculated using the formula in appendix 3 or the BSA tables in the BNF for Children.  
​
Minor surgery or minor procedure under GA, morning list
Day Before Surgery
​Advise usual oral steroid treatment and diet 
Morning of Surgery
  1. ​All children should be placed first on the morning list, if possible, to minimise dehydration and fasting time
  2. Take oral hydrocortisone pre-operatively (see general advice)
  3. Record weight and height on admission to calculate body surface area (see appendix 3)
  4. Record blood pressure
  5. Insert IV cannula
  6. Monitor Capillary Blood Glucose (CBG) hourly once fasting time exceeds 4 hours
 
Hypoglycaemia and hypotension in this setting may suggest inadequate hydrocortisone replacement.
 
If CBG <3.5mmol/L give 2ml/kg 10% dextrose IV to treat hypoglycaemia followed by maintenance IV fluids (0.9% saline + 5% dextrose). Give a stress dose of IV hydrocortisone (2mg/kg up to 100mg).
 
Record blood pressure on admission and only check again if symptomatic before going to theatre (i.e. dizzy, lethargic, syncope). If the patient is hypotensive (systolic blood pressure below recommended threshold on appropriate age PEWS chart) then give a 10ml/kg fluid bolus and stress dose IV hydrocortisone (2mg/kg, max 100mg).
 
A stress dose of hydrocortisone should only be given once for hypoglycaemia and/or hypotension pre-operatively. The patient should then be discussed with the local endocrinology team about further management.
During Surgery
​At induction of anaesthesia give 1mg/kg IV hydrocortisone (max 100mg) (18).

An induction dose of hydrocortisone should be given in addition to any pre-operative stress dose of IV hydrocortisone. This is to cover the additional stress of induction of anaesthesia, surgery and recovery.

​Monitor blood glucose levels hourly.
After Surgery
​Once the child is eating and drinking they can be converted to oral hydrocortisone at 30mg/m2/day in 4 divided doses for 24 hours (16).After this time they can resume their usual steroid medication.

​Major Surgery under GA, morning list
Day Before Surgery
​Advise usual oral steroid treatment and diet 
Morning of Surgery
  1. All children should be placed first on the morning list, if possible, to minimise dehydration and fasting time
  2. Take oral hydrocortisone pre-operatively (see general advice)
  3. Record weight and height on admission to calculate body surface area (see appendix 3)
  4. Record blood pressure
  5. Insert IV cannula
  6. Monitor Capillary Blood Glucose (CBG) hourly once fasting time exceeds 4 hours
 
Hypoglycaemia and hypotension in this setting may suggest inadequate hydrocortisone replacement.
 
If CBG <3.5 mmol/L give 2ml/kg 10% dextrose to treat hypoglycaemia followed by maintenance IV fluids (0.9% saline + 5% dextrose). Give a stress dose of IV hydrocortisone (2mg/kg - max 100mg)
 
Record blood pressure on admission and if symptomatic (i.e. dizzy, lethargic, syncope) before going to theatre. If the patient is hypotensive (systolic blood pressure below recommended threshold on appropriate age PEWS chart) then give a 10ml/kg fluid bolus and stress dose IV hydrocortisone (2mg/kg - max 100mg).
 
A stress dose of hydrocortisone should only be given once for hypoglycaemia and/or hypotension pre-operatively. The patient should then be discussed with the local endocrinology team about further management.
During Surgery
At induction of anaesthesia give 2mg/kg IV hydrocortisone (max 100mg) (19).

Start maintenance IV fluids (0.9% saline and 5% dextrose).​
After Surgery
​Continue 2mg/kg IV hydrocortisone (max 100mg) 6 hourly until the child is eating and drinking (19).

If the child is seriously unwell, septic or haemodynamically unstable then consider an IV hydrocortisone infusion, for example children admitted to PICU post-operatively (appendix 4) (16,20).

Monitor CBG 2 hourly until the child is eating and drinking.

Monitor blood pressure hourly.

Once the child is eating and drinking they can be converted to oral hydrocortisone 50mg/m2/day in 4 divided doses for 48 hours (17).

After this time they can restart their usual steroid medication.​

Minor Surgery or minor procedure under LA or sedation, morning list e.g. dental extraction
Day Before Surgery
​Advise usual oral steroid treatment and diet 
Morning of Surgery
Children should be placed first on the morning list, if possible, to minimise dehydration and fasting times.

Children with AI on maintenance hydrocortisone: Take an increased dose of oral hydrocortisone pre-operatively at 30mg/m2/day in 4 divided doses.

Children at risk of AS on daily oral prednisolone: Take a double dose of prednisolone on the morning of surgery.

Children at risk of AS on inhaled glucocorticoids or other oral formulation: Take stress dose hydrocortisone at 30mg/m2/day in 4 divided doses starting at 0600 on the morning of surgery.
During Surgery
N/A
After Surgery
​Once the child is eating and drinking they can take oral hydrocortisone 30mg/m2/day in 4 divided doses for 24 hours.

After this time they can restart their usual steroid medication.

Children on oral prednisolone can resume their normal dose the following day.

If at any point during or after the procedure the child is unwell or vomiting, give emergency intramuscular hydrocortisone (appendix 5) and arrange transfer to hospital for further assessment.​

Surgery or Procedures Occurring in the Afternoon

If a procedure is delayed from the morning list and subsequently takes place in the afternoon please remember the following:
  • Any further usual doses of hydrocortisone should be given intravenously while the child is NBM in hospital waiting for the procedure.
  • Start IV maintenance fluids if the procedure is delayed for more than 2 hours.
  • Follow above instructions for major and minor surgery in terms of pre-surgery observations, dosing of hydrocortisone at induction and post-operatively.
 
If a procedure is scheduled for the afternoon the above advice can still be applied with the following adjustments:
  • The child can eat breakfast between 0600-0700 and then follow normal fasting guidelines for milk and clear fluids before the procedure.
  • Children should take their usual dose of hydrocortisone (and fludrocortisone) at 0600 on the morning of the procedure.
  • Subsequent doses of hydrocortisone, for example the midday dose, should be given intravenously in hospital.
  • The child should then have a further dose of IV hydrocortisone at induction of anaesthesia, based on the above dosing.
Emergency Surgery
 
There will be some situations where children with AI or suspected AS require emergency surgery, for example with appendicitis or treatment of an acute fracture. In these situations they should be fluid resuscitated and started on stress doses of IV hydrocortisone at the time of admission using the doses in the BNFC (2-4mg/kg IV hydrocortisone 6 hourly - max 100mg). The patient should be resuscitated and stable before going to theatre.
 
After surgery it would be appropriate to follow the guidance above for major surgery under GA.

 
 
Fludrocortisone Replacement

 
The above stress doses of hydrocortisone will provide full mineralocorticoid effect. There is no need for additional cover during surgery. Children should take their usual fludrocortisone on the morning of surgery.

Governance

Implementation

The guideline will be displayed on the PIER website and can be accessed by all healthcare professionals working in Wessex. This guideline will be disseminated to consultant paediatric endocrinologists and consultant paediatricians with an interest in endocrinology across Wessex, to share with clinical teams in their hospital.
 
 
Process for Monitoring Effectiveness

Compliance with the guideline will be monitored by annual audit at Southampton Childrens Hospital. This will determine whether the guideline is user friendly and identify any changes that need to be made as a result of staff and patient feedback. Audit results will be shared with local and regional endocrinology teams.
 
The guideline will be reviewed every 3 years or sooner because of audit results or new published evidence.

References
  1. Esteban NV, Loughlin T et al. Daily cortisol production rate in man determined by stable isotope dilution/mass spectrometry. J Clin Endocrinol Metab 1991; 72: 39-45.
  2. Kerrigan JR, Veldhuis JD et al. Estimation of daily cortisol production and clearance rates in normal pubertal males by deconvolution analysis. J Clin Endocrinol Metab 1993; 76: 1505-1510.
  3. Salem M, Tanish RE et al. Perioperative glucocorticoid coverage. A reassessment 42 years after emergence of a problem. Ann Surg 1994; 219: 416-425.
  4. Udelsman R, Norton JA et al. Responses of the hypothalamic-pituitary-adrenal and renin-angiotensin axes and the sympathetic system during controlled surgical and anesthetic stress. J Clin Endocrinol Metab 1987: 64; 986-994.
  5. Jung C, Inder WJ. Management of adrenal insufficiency during the stress of medical illness and surgery. MJA 2008; 188 (7): 409-411.
  6. Goldbloom E, et al. Symptomatic adrenal suppression among children in Canada. Arch Dis Child. 2017; 102: 340-345.
  7. Sidoroff M, Kolho K. Screening for adrenal suppression in children with inflammatory bowel disease discontinuing glucocorticoid therapy. BMC Gastroenterology 2014; 14: 51-55.
  8. Schwartz RH, Neacsu O, Ascher DP, Alpan O. Moderate dose inhaled corticosteroid induced symptomatic adrenal suppression: case report and review of the literature. Clin Pediatr (Phila) 2012; 51: 1184–1190
  9. Issa-El-Khoury K, Kim H et al. CSACI position statement: systemic effect of inhaled corticosteroids on adrenal suppression in the management of pediatric asthma. Allergy Asthma Clin Immunol 2015; 11: 9.
  10. Wass JAH, Arlt W. How to avoid precipitating an acute adrenal crisis. BMJ 2012; 345: e6333.
  11. Goldbloom E, Ahmet A. Adrenal suppression: an under-recognized complication of a common therapy. Paediatr Child Health 2010; 15(7): 411-412.
  12. Aljebab F et al. Systematic review of the toxicity of short-course oral corticosteroids in children. Arch Dis Child 2016; 101: 365-370.
  13. Kao J. Adrenal suppression secondary to exogenous glucocorticoids [Internet]. Melbourne, Australia: Royal Children’s Hospital ; August 2015. Available from: www.rch.org.au/uploadedFiles/Main/Content/endo.
  14. Gordijn MS, Gemke RJ et al. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia. Cochrane Database Syst Rev 2012; 5: CD008727.
  15. Hamrahian AH, The management of the surgical patient taking glucocorticoids [Internet]. USA: UpToDate: February 2017. Available from: www.uptodate.com/contents.
  16. Webb EA, Krone N. Current and novel approaches to children and young people with congenital adrenal hyperplasia and adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2015 Jun; 29(3): 449-68
  17. Park J, Didi M, Blair J. The diagnosis and treatment of adrenal insufficiency during childhood and adolescence. Arch Dis Child 2016; 101: 860-865.
  18. Great Ormond Street Hospital Clinical Guideline: Perioperative management of children on hydrocortisone replacement.
  19. Bornstein SR et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2015; 1710: 1-26.
  20. Chamandari E et al. Congenital adrenal hyperplasia: management during critical illness. Arch Dis Child 2001; 85: 26-28.
Appendix 1:
Equivalent Doses of Commonly Used Glucocorticoids in Relation to Prednisolone
Prednisolone 1mg/kg =
  • ​Betamethasone 150mcg
  • Deflazacort 1.2mg
  • Dexamethasone 150mcg
  • Hydrocortisone 4mg
  • Methylprednisolone 800mcg
  • Triamcinolone 800mcg
Appendix 2:
Signs and Symptoms of Adrenal Insufficiency


Cushingoid features for patients on high dose steroids include:
  • moon face
  • buffalo hump
  • abdominal obesity with thin arms and legs
  • acne
  • fragile skin
  • abdominal striae
  • hypertension
 
The triad of adrenal crisis is hyponatremia, hyperkalaemia and hypotension.
 
Clinical features of adrenal insufficiency could include:
 
Non-specific symptoms
  • Fatigue, vomiting, nausea, abdominal pain, weakness, morning headaches and failure to thrive
Symptoms of hypoglycaemia
  • Pallor, sweatiness, disorientation and mood swings
Symptoms of mineralocorticoid deficiency
  • Dehydration, collapse, hypotension, tachycardia, weight loss, dizziness and salt craving
Features of elevated ACTH concentrations (for primary adrenal insufficiency only)
  • Hyperpigmentation of nail beds, mucous membranes, palmer creases and scars
 
Adapted from Park J et al. Arch Dis Child 2016; 101: 860-86517.


Appendix 3:
Mosteller Formula for BSA


BSA (m2) = √ (weight in kg x height in cm/3600)
 
For quick reference use BSA tables in the appendix section of BNFc
Appendix 4:
Hydrocortisone Infusion


Mix 50mls 0.9% Sodium Chloride with 50mg hydrocortisone to give a 1mg/ml solution. A stress dose IV infusion should provide the following doses in 24 hours according to the weight/age of the child: 
cf
Total dose over 24 hours (mg)
Infusion rate (ml/hr)
Up to 10kg
25
1
11-20kg
50
2
Over 20kg
Pre-Pubertal
Pubertal
100
​150
4.1
6.2

These doses equate to between 50-100mg/m2/day
 
Adapted from:
  1. Walker J, Davis E. Emergency Management of Adrenal Failure – Guide for Parents/Community and Ward Professionals. Portsmouth Hospitals NHS Trust.
  2. Perioperative management of children on hydrocortisone replacement. Great Ormond Street Hospital clinical guideline.
  3. Webb EA, Krone N. Current and novel approaches to children and young people with congenital adrenal hyperplasia and adrenal insufficiency. Best Pract Res Clin Endocrinol Metab. 2015 Jun; 29(3): 449-68
Appendix 5:
Stat Doses of Intramuscular Hydrocortisone Based on Age
Age
IM Hydrocortisone Dose (mg)
<1 year
25
1-5 years
50
>5 years
​100
Adapted from the British National Formulary for Children 2018
Document Version: 
1.0

Lead Author: 

Dr Anitha Kumaran, Consultant in Paediatric Endocrinology and Diabetes

Additional Author:
Dr Gemma Watts, ST6 Paediatrics
Approving Network:
Wessex Paediatric Endocrine Network

Date of Approval: 
02/2023

Review Date:
02/2024

PIER Contact

Admin@piernetwork.org

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