3.29 Stress Response to Surgery

is the term used to describe the widespread metabolic and hormonal changes which occur in response to trauma, including surgical trauma. It is a complex neuroendocrine response whose net effect is to increase catabolism and release endogenous fuel stores while conserving body fluids. In evolutionary terms, it is a natural mechanism which increases an injured animal’s chances of survival.

The degree of catabolism is related to the severity of the surgical insult or traumatic tissue injury. In practice, the plasma concentrations of most substances increase, and it is unlikely that the examiner will ask you specifically about a single hormone. If this does happen, and you do not immediately know the answer, or you suspect that it is a trick question, then try to answer it from first principles. Do not be concerned if your reply does not seem that logical; it is not clear, for example, why prolactin concentrations should increase while thyroid hormone should rise little, if at all

1 Autonomic nervous system – sympathoadrenal response 2 Hypothalamic–pituitary–adrenal (HPA) axis • Cortisol • Insulin • Inflammatory response

This is mediated via the hypothalamus with the stimulation of adrenal medullary catecholamines. There is also increased presynaptic noradrenaline release. This leads to cardiovascular stimulation with tachycardia and peripheral vasoconstriction. The renin–angiotensin system stimulates aldosterone release, leading to sodium and water retention.

Hypothalamic releasing factors respond to major surgical trauma by stimulating the anterior pituitary. This in turn leads to increases in adrenocorticotrophic hormone (ACTH) which stimulates adrenal glucocorticoid release, and somatotrophin (growth hormone). This enhances protein synthesis and inhibits breakdown, stimulates lipolysis and antagonizes insulin. Prolactin release is also evident, although its purpose is not obvious. The other anterior pituitary hormones, including thyroid hormone, change little. The posterior pituitary produces increased amounts of arginine vasopressin (antidiuretic hormone, ADH).

Release from the adrenal cortex after stimulation by ACTH may increase fourfold, and this leads to intense catabolism in which there is protein breakdown, increased gluconeogenesis and lipolysis, with inhibition of glucose utilization. Cortisol is anti-inflammatory: it inhibits leucocyte migration into damaged areas and inhibits synthesis of various inflammatory mediators, including prostaglandins.

This is the major anabolic hormone of which there is a relative perioperative deficiency. Its effects are unable to match the catabolic response.

After major tissue trauma, a number of cytokines are released (including IL-1, IL-6, TNF and interferons). IL-6 is the cytokine mainly responsible for the development of the systemic ‘acute phase response’.

Catabolism provides endogenous fuel from carbohydrate, fatty acids and amino acids, with the loss of body nitrogen. The process is accompanied by sodium and water retention. As an evolutionary process this may have conferred a survival benefit, but this must apply less in the context of modern surgery and anaesthesia. In the elderly surgical population with patients with significant co-morbidity, the stress response may have obvious adverse effects. Whether or not anaesthetists should be trying to ablate the response, however, remains contentious.

these suppress hypothalamic and pituitary secretion, and high-dose opiates (for example, morphine in a dose of 4mg/kg or fentanyl in a dose of 100 ug/kg may attenuate the response substantially, but this is at the cost of profound sedation and respiratory depression. The effect does not endure.

Etomidate: this drug is an effective inhibitor of cortisol and aldosterone synthesis via its inhibition of the 11-b and 17-a hydroxylase steps of steroid synthesis. This inhibition persists for 6–12 hours after a single dose.

Benzodiazepines: these also inhibit cortisol production, probably via a central effect. a-2 agonists: these attenuate the sympathoadrenal responses, and lead indirectly to a decrease in cortisol production.

This is of continued interest because it has been demonstrated that extensive extradural block ablates the adrenocortical and glycaemic responses to surgery. It may be more difficult to achieve in upper gastrointestinal tract and thoracic surgery, but there is increasing acceptance of the claim that targeted and sustained regional anaesthesia has beneficial effect on surgical outcome. This, however, may be related as much to earlier ambulation and improvements in respiratory function as to the abolition of the stress response itself.