3.30 Glucocorticoid response to surgery

Question 1

Commentary

Answer 1

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.

Question 2

The viva

Answer 2

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.

Question 3

Problem with patients receiving corticosteroids

Answer 3

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.

Question 4

Steroid response to surgery

Answer 4

1. Sympathoadrenal response:
2. HPA Axis response
3. Cortisol production

Question 5

Sympathoadrenal response:

Answer 5

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.

Question 6

HPA axis response:

Answer 6

hypothalamic releasing factors stimulate the anterior pituitary,

with resultant increases in ACTH via corticotrophin-releasing hormone (CRH).

Question 7

Cortisol production:

Answer 7

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

Question 8

Cortisol output

Answer 8

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

Question 9

describe your approach to perioperative steroid replacement

Answer 9

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.

Question 10

What to do if >10mg Pred + min- moderate surgery

Answer 10

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).

Question 11

If taking more than 10 mg daily and undergoing major surgery:

Answer 11

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).

Question 12

dangers of supraphysiological doses of exogenous
corticosteroids

Answer 12

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.

Question 13

Complications of chronic therapy:

Answer 13

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.