3.30 Glucocorticoid response to surgery

The stress response to injury may be important in patients who are receiving corticosteroids. The traditional concern relates to the danger of precipitating an Addisonian crisis in patients whose HPA axis is suppressed. Many clinicians believe that these anxieties are overstated. Certainly there is now little justification for the use of potentially dangerous supraphysiological replacement regimens.

The viva may be introduced by a question about the problems of anaesthetizing patients who are being treated with steroids (glucocorticoids). It will go on to the normal steroid response to surgery.

Patients who are receiving corticosteroids are often assumed to have suppression of the HPA axis. This occurs via a feedback inhibition of hypothalamic and pituitary function. This adrenal suppression means that patients cannot mount a normal steroid response to surgery, and may develop an Addisonian crisis in the postoperative period. This is characterized by cardiovascular instability and electrolyte derangement. Patients have hypotension, which may be refractory to routine treatment, can be hypokalaemic, hyponatraemic and hypoglycaemic.

• Sympathoadrenal response: • HPA Axis response • Cortisol production

this is an autonomic response which is mediated via the hypothalamus, and which results in an increase in medullary catecholamines. There is also an increase in the presynaptic release of noradrenaline. Aldosterone release is stimulated by the renin–angiotensin system, leading to sodium and water retention.

hypothalamic releasing factors stimulate the anterior pituitary, with resultant increases in ACTH via corticotrophin-releasing hormone (CRH).

ACTH stimulates adrenal glucocorticoid release. This is mediated by a cell-surface receptor, with G protein activation, adenyl cyclase stimulation and increased intracellular cAMP. The effects of cortisol are catabolic, with protein breakdown, gluconeogenesis, inhibition of glucose utilization and lipolysis. The hormone is also anti-inflammatory; it inhibits leucocyte migration into damaged areas and decreases the synthesis of inflammatory mediators such as prostaglandins

This varies according to the degree of surgical stress. There is normally a maximal rise at 4–6 hours with peak cortisol usually subsiding within 24 hours. After major surgery it may be sustained for up to 72 hours. Normal blood levels are around 200 nmol l but the increase following surgery may range from 800 to more than 1500 nmol l Normal 24 hour cortisol output is around 150 mg; minor surgery such as hernia repair will stimulate extra production of less than 50 mg in 24 hours, whereas following thoracotomy or laparotomy, between 75 and 100 mg will be released

Ideally a replacement regimen should be based on laboratory evaluation of the HPA axis (by conducting short synacthen or insulin tolerance tests if possible) a nd an assessment of the likely degree of surgical stress. Corticosteroid supplementation minimizes the risk of perioperative cardiovascular instability. Patients who are taking less than prednisolone 10 mg daily (or the equivalent) have a normal response to HPA testing and require no supplementation. Patients who have previously been taking an HPA suppressant dose, but have discontinued this within 3 months from surgery, should be assumed to have residual suppression. They should be tested wherever possible because exogenous steroid supplementation is not innocuous. Patients on high immunosuppressant doses must continue these perioperatively.

If taking more than 10 mg prednisolone daily and undergoing minor to moderate surgery: — Continue the usual dose preoperatively. — Give hydrocortisone 25 mg iv at induction. — Prescribe hydrocortisone 100 mg in the first 24 hours (by continuous infusion).

If taking more than 10 mg daily and undergoing major surgery: — Continue the usual dose preoperatively. — Give hydrocortisone 25 mg iv at induction. — Prescribe hydrocortisone 100 mg per day for 48–72 hours (by continuous infusion).

Complications of acute therapy: increased catabolism, hyperglycaemia, immunosuppression, peptic ulceration, delayed wound healing, myopathy (which can occur acutely), steroid psychosis (which is related to sudden large increases in blood levels), fluid retention and electrolyte disturbance, including hypokalaemia.

in addition to the above, these include immunosuppression, hypertension, increased skin fragility, posterior subcapsular cataract formation, osteoporosis, hypocalcaemia caused by reduced gastrointestinal absorption; negative nitrogen balance and Cushing’s syndrome.