Monitoring systemic effects of Glucocorticoids in children with a diagnosis of asthma

Publication: 22/02/2018  --
Last review: 01/01/1900  
Next review: 22/02/2021  
Clinical Guideline
CURRENT 
ID: 6273 
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.

Guidelines for monitoring systemic effects of Glucocorticoids in children with a diagnosis of asthma

Summary of Guideline

The majority of children with a diagnosis of asthma can achieve good symptom control with low dose inhaled steroids. There is a small group of children in whom symptom control can only be achieved with high dose inhaled and/or oral steroids in addition to maximal add-on therapies. These children will be investigated to determine that they have true high steroid requirements (severe asthma) rather than difficult to treat asthma as research has shown that 40% of children referred as severe asthma had modifiable factors[1] . Our aim is to achieve symptom control on the lowest dose of inhaled (and oral) steroid possible for each
individual however there are those who will require high dose treatment. In these children monitoring of the potential side effects of high dose steroids is necessary
and will be outlined in this guideline.
Definition of high dose steroids is age dependent:

The main potential side effects of steroids are on height velocity and suppressed adrenal function due to effects on the hypothalamic-pituitary-adrenal (HPA) axis. The rate of associated side effects continues to be high in those on high doses of steroids and has been underappreciated previously[3]. One study in children found a prevalence of adrenal axis suppression of 9.3% in those on inhaled corticosteroids(ICS) for asthma[4] where as other studies have reported incidences as high as 40%.
A recent study found cumulative steroid dose to have a correlation with effect on the HPA axis[5]. The peak cortisol level was significantly associated with the cumulative steroid dose but did not correlate with inhaled steroid dose alone regardless of how high the dose was. This evidence supports the need for investigation in children on inhaled steroids in whom multiple courses of oral
steroids have been used increasing the cumulative steroid dose.
The potential effects on bone mineral density are less clear. In adult studies[6] there has been shown to be an effect from steroids on bone mineral density and osteoporosis however this effect has not been shown in studies in children. Two large cohort studies of children with asthma found differing results with regard to effect on bone mineral density. The CAMP study[7] found that bone mineral density was affected in children with a low serum vitamin D level and high cumulative doses of ICS whereas the Helsinki study [8]found a reduction in bone mineral density which was greatest in the first 6 months of treatment and that height velocity can be used to determine if bone mineral density may be affected. There is no evidence for increased fracture rate in children associated with
steroid use.

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Background

In children with a diagnosis of asthma, adequate symptom control is achieved in the majority using low and safe doses of inhaled steroids. There is a small sub- group of children who require maximal conventional therapy up to stages 4/5 of
the BTS/SIGN guidelines[9] including high dose inhaled steroids, long acting beta agonists and leukotriene receptor antagonists. It is this second group of children who need particular close monitoring for the potential side effects of glucocorticoids.
Inhaled corticosteroids have been found to result in adrenal suppression in up to
40% of children on treatment. This includes those on treatment doses up to those recommended in the BTS/SIGN guideline. Close monitoring and consideration of the possible side effects is therefore essential.
Children seen in the tertiary asthma clinic will have adherence to treatment thoroughly investigated to ensure that they are concordant with treatment and appropriate doses of steroids are prescribed.

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Diagnosis

Diagnosis of asthma - at least one of the following criteria must be met

  • Documented wheeze by a healthcare professional
  • Documented bronchodilator reversibility
  • Airway hyper-responsiveness (confirmed by direct or indirect challenge)
  • Recorded evidence of spontaneous variation in FEV1 (≥12%) or peak flow (≥12%) in the past year

Exclusion of other diagnoses if there are features atypical of asthma.

Confirming the correct diagnosis is essential to ensure that increasing doses of potentially harmful medications are not used in a situation where they will be of little or no benefit.

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Investigation

Growth

  • At every clinic visit every child will have his/her height and weight checked and plotted on a growth chart regardless of treatment regimen.

Further investigations should be considered after 6 months of treatment with high dose steroids or if the threshold for number of courses of oral steroids has been reached.

Low Dose Synacthen Test (1mcg)
Monitoring for adrenal suppression should be performed in children who meet one or more of the criteria

  • Inhaled steroids >800mcg Beclomethosone daily equivalent (Fluticasone 400mcg/day) in 12-18 year olds, >500mcg Beclomethosone daily equivalent in children <12years
  • Multiple courses of oral steroids - >4 courses in 12 months
  • Regular Prednisolone - alternate days (see below for guidance) plan to wean and test when on less than 8mg/m2 . (Also plan to increase to daily steroids to cover duration of any acute illness)
  • Those on continuous steroids in whom there is a plan to wean off steroids

When to do the test if on regular oral Prednisolone

  • A Synacthen test is not indicated when on high dose Prednisolone
  • The aim is to wean to just below maintenance adrenal dose before testing
  • Adrenal steroid replacement dose is around 8mg/m2/day of Hydrocortisone split in 2/3 doses
  • Prednisolone 1mg = Hydrocortisone 4mg

Eg: If child is on Prednisolone 10mg alternate days and has surface of 1.5m2. Daily Pred dose is 5mg = Hydrocortisone 20mg /day = 13.3mg/m2/day - defer test Daily Pred dose is 2.5mg = Hydrocortisone 10mg /day = 6.7mg/m2/day - test now

Bone mineral density
Investigation of bone mineral density is not routinely considered. There is little evidence for effects in children with asthma with inhaled corticosteroids Investigations for bone mineral density should be considered in children

  • requiring regular daily/alternate day oral steroids (at least 6 months of treatment)
  • with confirmed adrenal suppression
  • Low vitamin D levels
  • Decreased height velocity on centiles

For those on regular oral corticosteroids:
Give advice about diabetes risk and check for Glycosuria in clinic
BP monitoring in clinic
Optician review in community if prolonged steroids

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Treatment / Management

Low Dose Synacthen Test (1mcg) test result

  • Normal initial cortisol level with rise in cortisol to >500 - normal result with no further intervention required
  • Low initial cortisol with rise to >500
    • No intervention required
    • Consider repeat morning ACTH and cortisol if clinically indicated
  • Cortisol rise to 450 - 500
    • Consider normal if no symptoms of adrenal insufficiency (eg prolonged recovery from illnesses)
  • Cortisol rise to between 350-450
    • Give steroid card (if not already supplied)
    • Steroid replacement with Hydrocortisone when unwell or
      undergoing surgery
    • May need daily Hydrocortisone if symptomatic
    • Discuss with Endocrine team
  • Cortisol rise <350
    • Abnormal result requiring endocrine team review and treatment
  • Low ACTH and low / undetectable baseline cortisol
    • Discuss with endocrine team

Low bone mineral density

  • Check levels of Vitamin D - consider Vit D replacement
  • Discuss with endocrine team

All children on high dose inhaled steroids and/or regular oral corticosteroids should carry a steroid card.

Provenance

Record: 6273
Objective:
  • To improve monitoring for potential significant side effects in asthmatic children requiring high dose steroids.
  • To provide evidence-based recommendations for monitoring of adverse systemic effects of steroids in children on high doses of inhaled steroids and/or parenteral treatment.
Clinical condition: Paediatric asthma
Target patient group: Children with severe asthma on high dose steroids.
Target professional group(s): Pharmacists
Secondary Care Doctors
Secondary Care Nurses
Tertiary care teams
Adapted from:

Evidence base

References and Evidence levels:

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 )

  1. M, B., et al., - The importance of nurse-led home visits in the assessment of children with. Arch Dis Child, 2009. 94(10): p. 780-4.
  2. A, B., et al., - Pharmacological treatment of severe, therapy-resistant asthma in children: what. Eur Respir J, 2011. 38(4): p. 947-58.
  3. Covar, R.A., et al., Risk factors associated with glucocorticoid-induced adverse effects in children with severe asthma. J Allergy Clin Immunol, 2000. 106(4): p.
    651-9.
  4. Campbell, L.S., et al., Hypothalamic-pituitary-adrenal axis suppression related to topical glucocorticoid therapy in a child with psoriatic exfoliative erythroderma. Pediatr Dermatol, 2012. 29(1): p. 101-4.
  5. Hawcutt, D.B., et al., Adrenal responses to a low-dose short synacthen test in children with asthma. Clin Endocrinol (Oxf), 2015. 82(5): p. 648-56.
  6. Mortimer, K.J., T.W. Harrison, and A.E. Tattersfield, Effects of inhaled corticosteroids on bone. Ann Allergy Asthma Immunol, 2005. 94(1): p. 15-21; quiz 22-3, 79.
  7. Tse, S.M., et al., Corticosteroid use and bone mineral accretion in children with asthma: effect modification by vitamin D. J Allergy Clin Immunol, 2012. 130(1): p. 53-60 e4.
  8. Turpeinen, M., et al., Bone mineral density in children treated with daily or periodical inhaled budesonide: the Helsinki Early Intervention Childhood Asthma study. Pediatr Res, 2010. 68(2): p. 169-73.
  9. Levy, M.L., et al., Summary of the 2008 BTS/SIGN British Guideline on the management of asthma. Prim Care Respir J, 2009. 18 Suppl 1: p. S1-16.

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.0

Related information

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