BSPED Adrenal Insufficiency Consensus Guidelines

Emergency and peri-operative management of adrenal insufficiency in children and young people: BSPED consensus guidelines

Developed by the Paediatric Adrenal Insufficiency Group On Behalf of the British Society of Paediatric Endocrinology & Diabetes

Adrenal insufficiency (AI) is characterised by lack of cortisol production from the adrenal glands. This can be a primary adrenal disorder or secondary to adrenocorticotropic hormone (ACTH) deficiency or suppression from exogenous glucocorticoids. Symptoms of AI in children may initially be non-specific and include growth faltering, lethargy, poor feeding, abdominal pains, vomiting and lingering illnesses. AI is treated with replacement doses of hydrocortisone. At times of physiological stress such as illness, trauma or surgery there is an increased requirement for exogenous glucocorticoids, which if untreated can lead to an adrenal crisis and death.

This national project sets out standardised guidance to manage children and young people with AI or adrenal crisis during intercurrent illness, as well as recommendations for medical, dental and surgical procedures.

This page has specifically been designed to be the link to share the guidelines and will not change should updates to the guideline occur. Therefore the URL for this page should be used at your local website to link to the guidelines. The links below to the actual documents should not be used as these could be subject to change.

Section 1: Emergency management of adrenal crisis

If you suspect a child is in adrenal crisis (acutely unwell with tachycardia, hypotension, hypoglycaemia, hyponatraemia, hyperkalaemia, or altered consciousness not attributable to another illness) they should be treated immediately with glucocorticoids without delay +/- additional fluids as follows:

Emergency Management of Paediatric Adrenal Crisis In the COMMUNITY
Intramuscular (IM) hydrocortisone doses or initial IV dose
Age	IM hydrocortisone Dose	Indications
Less than 1 year	25mg	Acutely unwell and unable to get IV access Acutely unwell with diarrhoea and vomiting and unable to tolerate oral treatment Reduced responsiveness or loss of consciousness. Hypoglycaemic or new onset seizure in known or suspected adrenal insufficiency. Fracture / significant burn
1 to 5 years	50mg
6 years and over	100mg

Emergency Management of Paediatric Adrenal Crisis in HOSPITAL
Children (>28 days)*	Hydrocortisone dose and frequency
Severe illness	Age based doses given IM or IV (25mg < 1year, 50mg 1 to 5 years, 100mg for 6 years and over - subsequent doses as in 2 below) or 2mg/kg (max 100mg) IV bolus initially then bolus dose 6 hourly (*can consider giving 4 hourly or as an infusion (see “Major Surgery”)
Stable and improving	1mg/kg (max 50mg) IV 6 hourly (can consider giving 4 hourly or as an infusion (see “Major surgery”)
Stable and tolerating drinks / diet	Oral sick day steroids: 30mg/m2/day in 4 equally divided doses Restart fludrocortisone if indicated
Neonates (<28 days)	Hydrocortisone dose and frequency
Severe illness	4mg/kg IV initially 6 hourly (*can consider giving 4 hourly or as an infusion (see “Major surgery”)
Stable and improving	2mg/kg IV 6 hourly (can consider giving 4 hourly or as an infusion (see “Major surgery”)
Stable and tolerating drinks / diet	Oral sick day steroids: 30mg/m2/day in 4 equally divided doses Restart fludrocortisone if indicated

* Consider using neonatal doses if small or failing to thrive

Fluid type and volume
Blood Glucose < 3mmol/L	2ml/kg of 10% dextrose as IV bolus Recheck blood glucose after 15 minutes and repeat bolus if necessary.
Shock or moderate to severe dehydration	Give 10ml/kg of 0.9% sodium chloride as a bolus and repeat if necessary Check electrolytes immediately at presentation to inform fluid usage (see "Fluid and electrolyte management")
Maintenance fluids type and amount	0.9% sodium chloride / 5% dextrose is usually an appropriate starting point: 100ml/kg/day for 1st 10kg, 50ml/kg/day for 2nd 10kg, 20mls/kg/day >20kg

All patients requiring a dose of IM or IV hydrocortisone should be observed until they are tolerating oral steroids at sick day dosing. Contact your acute paediatric or paediatric endocrine team if admission is required.

Section 2: Peri- and post-operative management – major surgery

Major surgery is defined as any procedure lasting >90 minutes with variable recovery periods and an expected delay in restarting oral intake. In all cases, an initial bolus of hydrocortisone is given at induction, followed by either a hydrocortisone infusion or regular bolus doses (as preferred).

Major surgery: continuous intravenous infusion (IVI) hydrocortisone doses
Induction	IV bolus of hydrocortisone 2mg/kg (max 100mg) (premature infants and neonates < 28 days corrected gestational age: 4mg/kg)
Intraoperative	IV hydrocortisone infusion as below
Weight	Total dose in 24 hours	Infusion rate (50mg hydrocortisone in 50ml 0.9% sodium chloride)	Additional considerations
$10kg	25 mg	1 ml/hr	- Consider more concentrated infusion in those needing fluid restriction (e.g. 100mg hydrocortisone in 50mls 0.9% saline). - The hydrocortisone infusion can be run alongside 0.9% sodium chloride, 5% glucose and PlasmaLyte solutions
10.1 to 20kg	50 mg	2 ml/hr
20.1 to 40kg	100 mg	4 ml/hr
40.1 to 70kg	150 mg	6 ml/hr
Over 70kg	200 mg	8 ml/hr
Post-operative	Continue hydrocortisone infusion Change to oral sick day hydrocortisone when stable and tolerating oral fluids / diet

Major surgery: child (>28 days corrected gestational age) with intravenous hydrocortisone boluses
	Hydrocortisone bolus dose	Frequency	Additional considerations
Induction	2mg / kg (max 100mg)		- Consider neonatal doses for infants who are significantly small for gestational age or with growth faltering
Intraoperative	2mg / kg (max 100mg)	Given at 6 hours IV	- Consider infusion for prolonged procedures - 4 hourly if unstable
Post-operative	1mg / kg (max 50mg)	Every 6 hours IV Change to oral sick day hydrocortisone when stable and tolerating oral fluids / diet	- In severe obesity consider substituting 50 mg hydrocortisone with 100 mg hydrocortisone

Major surgery: premature infants & neonates (<28 days corrected gestational age) with intravenous hydrocortisone boluses
	Hydrocortisone bolus dose	Frequency	Additional considerations
Induction	4mg / kg
Intraoperative	2mg / kg	Given at 6 hours IV	- Consider infusion for prolonged procedures - 4mg/kg if unstable or consider 4 hourly doses
Post-operative	2mg / kg	Every 6 hours IV Change to oral sick day steroids when stable and tolerating oral feeds	- The oral dose can be given IV if not tolerating feeds

Section 3: Peri- and post-operative management – minor procedures

Minor procedures are defined as any procedure lasting <90 minutes and the patient is expected to be eating and drinking by the next meal (e.g. MRI scans, endoscopies, dental extractions under general anaesthetic or sedation). If the procedure exceeds >90 minutes management should proceed as per major surgery, with a further bolus of IV hydrocortisone given 4-6 hours after the initial dose.

Hydrocortisone dose for minor procedures requiring general anaesthesia
	Hydrocortisone bolus dose	Post-operative
Induction	2mg /kg (max 100mg) * (4mg/kg in neonates)	Oral sick day steroid doses for 24 hours
* It would seem prudent to use the neonatal dosing for infants who are significantly small for gestational age or failing to thrive and as such, whilst not neonates, are a neonatal size

Hydrocortisone advice for minor procedures NOT requiring general anaesthesia
Medical procedures (local anaesthetic or sedation)	Oral hydrocortisone dose
Minor procedure – local anaesthetic (e.g. skin biopsy) Minor dental procedures e.g. filling, tooth extraction	Give oral sick day steroid dose prior to procedure. Continue for up to 24 hours if in pain or unwell
MRI scans (using sedation) Non-anaesthetic sedation (e.g. chloral hydrate) does not merit use of IV hydrocortisone. Sick day dosing with oral hydrocortisone is sufficient	Give oral sick day steroid dose prior to procedure and continue for the day

Section 4: Sick day rules – when to give additional steroids

Situation	Change to usual steroid dose	Length of change	When to get help?
Minor Illness
Mild cold / runny nose with no fever. Minor playground bumps and bruises	No change
Moderate or severe illness
Fever, flu, infection, childhood illnesses (usually not well not enough to go to school)	Sick day doses required	For as long as the illness lasts	Contact GP or medical team if not improving after 24-48 hours
Vomiting or diarrhoea	Sick day doses required
	If sick day dose tolerated (kept down for at least 30 minutes with no frequent diarrhoea or vomiting), then continue oral sick day dosing
	If sick day dose not tolerated, give intramuscular (IM) hydrocortisone injection		If an IM injection of hydrocortisone is required then dial 999 and inform them that the patient is having an adrenal crisis
Drowsy and unresponsive	Give IM hydrocortisone injection
Major trauma or severe shock (e.g. suspected fracture, road traffic accident, head injury with loss of consciousness).	Give IM hydrocortisone injection
Other (discuss with medical team)
Routine or travel vaccinations	Consider 1 or 2 doses of sick day steroids.	Continue if unwell
Long haul flights	Give usual morning dose at 6 to 8 hourly intervals
Surgical and dental procedures
Minor surgery (e.g. tooth extraction under local anaesthetic)	Sick day dose prior to procedure. Return to usual dose immediately afterwards.	Continue sick day doses for up to 24 hours if in pain or unwell	Inform medical staff including dentist and anaesthetist that you/your child have adrenal insufficiency and takes steroids

Section 5: Pre-calculated oral hydrocortisone sick day doses

A total daily hydrocortisone dose of around 30/mg/m2/day given as four evenly spaced doses is recommended for illness. A guide to the doses is provided below; however the actual dose may vary depending on the strength and preparation of the available hydrocortisone medication.

Weight(kg)	BNFc surface area	Total daily sick day steroid dose (mg) (30/m²/day)	Sick day hydrocortisone: Dose	Frequency
1	0.1	3	0.8	4 x a day
2	0.16	5	1.2	4 x a day
3	0.21	6	1.5	4 x a day
4	0.26	8	2	4 x a day
5	0.3	9	2.5	4 x a day
6	0.34	10	2.5	4 x a day
7	0.38	11	3	4 x a day
8	0.42	13	3	4 x a day
9	0.46	14	3.5	4 x a day
10	0.49	15	4	4 x a day
15	0.65	20	5	4 x a day
20	0.79	24	6	4 x a day
25	0.92	28	7.5	4 x a day
30	1.1	33	7.5	4 x a day
35	1.2	36	10	4 x a day
40	1.3	39	10	4 x a day
45	1.4	42	10	4 x a day
50	1.5	45	10	4 x a day
55	1.6	48	12.5	4 x a day
60	1.7	51	12.5	4 x a day
65	1.8	54	12.5	4 x a day
70	1.9	57	15	4 x a day
75	1.9	57	15	4 x a day
80	2.1	63	15	4 x a day
90	2.2	66	15	4 x a day

Section 6: Fluid and electrolyte management

- Initial shock, dehydration or hypoglycaemia should be treated as in Section 1

- Sodium chloride 0.9%/5% glucose is usually a good starting point for initial fluid management if the clinical and biochemical pictures suggest that the low sodium has arisen primarily because of salt wasting. In primary AI insufficiency, mineralocorticoid deficiency will cause hyponatraemia due to renal losses. In secondary AI, cortisol deficiency can lead to a lack of free water clearance which can contribute to hyponatraemia. In this latter scenario (those with secondary AI), a degree of fluid restriction may be more appropriate.

- Further information about electrolytes and hyponatraemia is provided in the table below

	Primary adrenal insufficiency (elevated ACTH levels)	Secondary adrenal insufficiency (suppressed ACTH)
Glucocorticoid treatment	Usually Hydrocortisone	Usually Hydrocortisone (or Prednisolone)
Mineralocorticoid treatment	Fludrocortisone	Not required
	Acute illness (primary AI)	Acute illness (secondary AI)
Possible abnormality of sodium and potassium	May have hyponatraemia and hyperkalaemia. Dehydration is due to mineralocorticoid deficiency causing salt and water loss.	ACTH and hence cortisol deficiency is associated with an inability to excrete a water load. Hyponatraemia, if present may be due to excess water. Potassium is usually normal. Thus patients may not be significantly fluid deplete.
Other possible electrolyte abnormalities	Hypoglycaemia Hypercalcaemia Metabolic acidosis	Hypoglycaemia
Treatment	Correct hypoglycaemia Glucocorticoids in stress doses have some mineralocorticoid action. Sick day oral hydrocortisone or intravenous hydrocortisone along with IV 0.9% NaCl will usually result in resolution of biochemical abnormality. In some cases, specific treatment for hyperkalaemia is required (see below)	Correct hypoglycaemia The volume and type of IV fluid may need to be adapted to the individual circumstance. This may include checking that adequate glucocorticoids have been provided For further details see below
Features warranting slow or particularly careful rehydration in hyponatraemia
Rapid correction of acute and chronic hyponatraemia can be associated with a significant risk of cerebral oedema and / or osmotic demyelination syndrome. There is a substantial risk of seizures with plasma Na <110 mmol/l and an elevated risk of the osmotic demyelination syndrome if plasma Na concentration <105 mmol/l. A careful approach to rehydration is therefore needed in children with: Severe hyponatraemia; plasma sodium < 120 mmol/l. Reduced consciousness, seizures or other signs compatible with cerebral oedema. Diabetes insipidus When duration of illness or being unwell is more than one day
Key considerations in severe hyponatraemia
Avoid increasing plasma Na concentration by >10 mmol/l/day (~0.5 mmol/l/hr) in these circumstances. Normal (0.9%) saline with stress doses of glucocorticoid can increase sodium concentrations more rapidly than this. Therefore, the IV fluid may need to be changed to one containing less sodium. A slow, measured, increase in serum sodium can be achieved by linking sodium input (fluid) to output (urine). (i.e. giving a little more sodium than that present in the urine.) In patients in adrenal crisis careful monitoring of electrolytes is required. This is particularly important when hydrocortisone treatment is started because in addition to its’ mineralocorticoid action, hydrocortisone will also switch off ADH secretion leading to a diuresis and potentially a rapid rise in plasma sodium concentration. 1 ml /kg of 3% saline will increase the plasma Na concentration by about 1 mmol/l. This can be considered especially in the context of abnormal neurology or on-going severe symptomatic hyponatraemia. This bolus may need to be repeated. Close supervision and regular clinical assessment and monitoring of electrolytes is required. Consider admission to PHDU/PICU The rate of correction of hyponatraemia may be dependent on the underlying aetiology. The sodium should not rise >10mmol/l in 24 hours.
g) Hyperkalaemia treatment
Rehydration with sodium chloride and the administration of hydrocortisone are key measures that will reduce potassium in the context of AC If plasma potassium is > 7.0 nmol/L or there are ECG changes – IV 10% calcium gluconate: 0.5 ml/kg (0.11 mmol/kg) slow IV administration over 10 minutes with ECG monitoring to stabilise myocardium. Maximum single dose 4.5 mmol (20 ml) Nebulised salbutamol is a quick and readily available treatment that drives potassium into cells – 0 - 5 years: 2.5 mg; 5 years: 5 mg (three doses back-to-back). If persistent hyperkalaemia - Insulin and Dextrose – short-acting insulin (Actrapid or Novorapid): 0.1 units/kg in 5 to 10 ml/kg of 10% dextrose IV over 30 minutes If significant metabolic acidosis, consider sodium bicarbonate 1 mmol/kg IV over 30 minutes Consider cation exchange resins – calcium or sodium polystyrene sulfonate (resonium) – 125 to 250 mg/kg QDS orally or PR in neonates. Consider admission to PHDU/PICU. Potassium levels must be checked within 15 minutes post treatment and 1-2 hours after treatment.

Resources

Download BSPED adrenal insufficiency card

Patient information on sick day rules and dosing

Checklist for information, education and training of new patients prior to discharge

Society for Endocrinology/ NHS Steroid Emergency Card (adults)

Translations of BSPED adrenal insufficiency card

BSPED

Useful websites

Addison's Disease Self-Help Group

Living with CAH Support Group

Pituitary Foundation Adrenal Insufficiency web page