Stress Dosing in Adrenal Insufficiency

Stress dosing is the temporary increase of glucocorticoid in a patient who cannot make cortisol, so that illness, injury, surgery or labour does not cause adrenal crisis. Adrenal crisis presents with vomiting, abdominal pain, hypotension, hypoglycaemia, hyponatraemia and hyperkalaemia, and kills quickly if not treated. It applies to adrenal insufficiency of any cause and to anyone whose own adrenal glands are suppressed by steroids.

Who is at risk. Primary or secondary adrenal insufficiency, congenital adrenal hyperplasia, and patients who have taken prednisolone 5 mg daily or more (or an equivalent) for more than 4 weeks, or high-dose inhaled fluticasone (1000 micrograms daily or more) for several months. Suppression can last 6 to 12 months after stopping.

Three levels of response. Oral dose increase for minor illness, intramuscular or intravenous hydrocortisone for vomiting or severe illness, and a planned infusion for surgery and labour.

Oral. Hydrocortisone tablets, doubled or tripled during illness.

Injectable. Hydrocortisone sodium succinate 100 mg by intramuscular or intravenous injection. It is the only injectable steroid with both glucocorticoid and mineralocorticoid action at these doses. Dexamethasone 4 mg is a second choice if hydrocortisone is unavailable, and prednisolone 20 mg orally is a bridge until injection can be given.

Fluid. 0.9% sodium chloride, with 5% or 10% glucose if glucose is under 4 mmol/L.

Emergency supply. Every patient should hold a steroid card, a medical alert, and an emergency injection kit with a trained relative. In East Africa, confirm where the nearest facility stocks hydrocortisone injection before travel or during rural stays.

Minor illness (adults). Applies to fever over 37.5 degrees Celsius, infection that needs antibiotics, or illness that keeps the patient in bed.

• Fever 37.5 to 39 degrees Celsius: double the usual daily hydrocortisone dose, for example 10 mg three times daily.
• Fever over 39 degrees Celsius: triple the usual daily dose, for example 20 mg three times daily.
• Continue until the fever is gone for 24 hours, usually 2 to 3 days, then return to the usual dose.
• Patients on prednisolone alone: double the daily dose and divide it into two doses, then change to injection if vomiting.

Vomiting, diarrhoea or unable to take tablets. Give hydrocortisone 100 mg intramuscularly at once, and take the patient to hospital. Repeat if vomiting continues.

Adrenal crisis (adults).

• Give hydrocortisone 100 mg intravenously or intramuscularly immediately. Do not wait for tests. Take blood for cortisol, ACTH, sodium, potassium and glucose first only if it causes no delay.
• Give 0.9% sodium chloride 1 litre intravenously over the first hour (500 mL over 10 to 15 minutes if shocked). Then continue by volume status, with 2 to 4 litres in the first 24 hours.
• Glucose: 10% glucose 150 to 200 mL or 20% glucose 75 to 100 mL for glucose under 4 mmol/L.
• Then give hydrocortisone 200 mg over 24 hours by continuous infusion, or 50 mg every 6 hours intravenously or intramuscularly.
• Treat the cause (infection, vomiting, drug withdrawal).
• When recovered and eating, change to oral hydrocortisone 20 mg every 6 hours for 24 hours. Then double the usual dose for 2 to 3 days, and then return to the usual dose.

Children. Emergency injection: hydrocortisone 25 mg for infants and children under 3 years, 50 mg for ages 3 to 11 years, and 100 mg from age 12 years. Then hydrocortisone 50 to 100 mg/m2/day by infusion or in 4 divided doses. Oral stress dose for illness: 30 to 50 mg/m2/day in 3 to 4 divided doses.

Procedures and surgery (adults).

• Dental work under local anaesthesia: usual dose, with an extra 5 to 10 mg hydrocortisone 1 hour before for extractions.
• Minor procedures under sedation or short anaesthesia: hydrocortisone 100 mg intravenously at induction, then double the usual oral dose for 24 hours.
• Major surgery: hydrocortisone 100 mg intravenously at induction, then 200 mg over 24 hours by infusion or 50 mg every 6 hours for 24 to 72 hours. Then double the oral dose until recovered, then the usual dose.
• Colonoscopy with bowel preparation: hydrocortisone 100 mg intravenously or intramuscularly at the start of the preparation, with fluids.

Labour. Hydrocortisone 100 mg intravenously at onset, then 200 mg over 24 hours or 50 mg every 6 hours, and the usual dose after delivery. For caesarean section, give the major surgery cover of hydrocortisone 100 mg intravenously at induction, then 200 mg over 24 hours.

Fludrocortisone. Continue at the usual dose. It may be paused when the hydrocortisone dose is 50 mg daily or more.

Special groups.

• Kidney impairment: no change in hydrocortisone dose; use smaller fluid boluses if oliguric.
• Liver disease: no routine change in the emergency dose; monitor glucose closely.
• Older adults: use the same emergency doses and give fluids cautiously in heart failure.
• Pregnancy: hyperemesis needs injection and admission, since vomiting prevents absorption.
• Breastfeeding: compatible.
• Weight: use the adult doses over 50 kg, and the children’s schedule under 40 kg.

Monitoring. Blood pressure, pulse, urine output, glucose hourly until stable, sodium and potassium every 4 to 6 hours, and temperature. Review daily during an infusion.

Return to usual dose. Once the patient is well and eating, reduce to the usual dose over 2 to 3 days. Longer high-dose cover is needed only after major illness.

Stopping. Stress cover stops when the cause has resolved and the patient is stable on the usual dose for 24 hours.

Referral and escalation. Admit any patient who vomits, has diarrhoea, collapses, or has a systolic pressure under 100 mmHg. Escalate to critical care for refractory hypotension, glucose under 3 mmol/L despite treatment, sodium under 120 mmol/L, or potassium over 6.5 mmol/L. Refer after any crisis for review of the education, the sick day plan and the emergency kit.