NEW Written to fill a gap — Cuthbertson's ebb and flow phases and the whole metabolic response to surgery.

The stress response — ebb & flow

Cuthbertson's two phases, the hormones and cytokines that drive them, and how anaesthesia modifies the whole thing.

The time course

Cuthbertson described this in 1932 in patients with long bone fractures. The terms are still the ones examiners use.

Ebb versus flow

	EBB	FLOW (catabolic)
Timing	First 24–48 hours	Days 3–10, then anabolic recovery over weeks
Metabolic rate	↓ REDUCED	↑↑ RAISED — up to 50% above baseline in severe burns
Oxygen consumption	↓	↑
Cardiac output	↓	↑
Temperature	Hypothermia	Pyrexia
Volume state	Hypovolaemia, vasoconstriction	Restored, often vasodilated
Nitrogen balance	Slightly negative	Markedly NEGATIVE
Dominant hormone	Catecholamines	Cortisol, glucagon, cytokines
Biological purpose	Survive — conserve volume and perfuse the vital organs	Repair — mobilise substrate for healing and immunity

Getting the direction right

The intuitive error is to assume the stress response starts hypermetabolic. It does not — the EBB is hypometabolic. Think of the tide going out: perfusion, temperature and metabolic rate all ebb away.
The catecholamine surge in the ebb phase is intense, but it is directed at maintaining blood pressure and volume, not at burning fuel.
The flow phase is the tide coming back in — and overshooting.

The hormonal response

Increased	Decreased	Unchanged / variable
Cortisol · ACTH · catecholamines · glucagon · growth hormone · ADH · aldosterone · renin · prolactin · β-endorphin	Insulin (early) · testosterone · oestrogen · T3 (sick euthyroid)	TSH · T4 · LH · FSH

Cortisol rises within minutes; normal output of 25–30 mg/day can reach 75–150 mg/day after major surgery. Crucially, the normal negative feedback is lost — cortisol keeps rising despite high levels.
ADH rises from pain, hypovolaemia, positive pressure ventilation and opioids — driving water retention and postoperative hyponatraemia if hypotonic fluid is given.
Aldosterone rises via renin–angiotensin — sodium and water retention, potassium loss.
Insulin falls early (alpha-2 mediated suppression of the beta cell) and then there is peripheral resistance — the "diabetes of injury".
The four counter-regulatory hormones — cortisol, catecholamines, glucagon and growth hormone — all oppose insulin. This is why perioperative hyperglycaemia happens even in the non-diabetic.

The cytokine and acute phase response

Released from the site of injury by macrophages and monocytes: IL-1, IL-6 and TNF-α, then IL-8.
IL-6 is the principal driver of the hepatic acute phase response, and its peak correlates with the severity of the insult.
Cytokines also cause fever (via hypothalamic prostaglandin E₂), leucocytosis and the malaise of the postoperative period.
A compensatory anti-inflammatory response (IL-10, IL-4, TGF-β) follows — an excessive one leaves the patient immunoparalysed and prone to infection.

Positive acute phase proteins (↑)	Negative acute phase proteins (↓)
CRP · fibrinogen · ferritin · haptoglobin · caeruloplasmin · α₁-antitrypsin · complement · procalcitonin	Albumin · transferrin · prealbumin · retinol-binding protein

This is why a low albumin postoperatively is not a nutritional statement. Albumin is a negative acute phase protein — it falls because the liver has switched to making CRP and fibrinogen, and because capillary leak redistributes it. Feeding will not correct it in the acute phase.

Metabolic consequences

Substrate	What happens	Consequence
Carbohydrate	Glycogenolysis, then gluconeogenesis; insulin resistance	Hyperglycaemia — associated with infection and poor wound healing
Protein	Skeletal muscle proteolysis, up to 0.5 kg lean mass/day in severe injury	Negative nitrogen balance (up to 40–80 g protein/day), weakness, delayed rehabilitation
Fat	Lipolysis and ketogenesis	Free fatty acids become the main fuel
Water & sodium	Retained (ADH and aldosterone)	Weight gain, oedema, hyponatraemia if given hypotonic fluid
Potassium	Lost in urine; released from damaged cells	Variable — check it rather than assume

The catabolism cannot be reversed by feeding during the flow phase. Nutrition limits the deficit; it does not abolish it. Anabolism only resumes when the inflammatory drive settles.
Magnitude tracks severity: minor surgery produces a barely detectable response; major abdominal, cardiac or burn injury produces a large and prolonged one.

Modifying the response — the anaesthetist's contribution

Regional and neuraxial blockade is the single most effective modifier. It blocks the afferent limb — the nociceptive signal never reaches the hypothalamus. It works best for lower body surgery (a block to T4 largely abolishes the response to lower abdominal and limb surgery) and poorly for upper abdominal and thoracic surgery, where vagal and phrenic afferents escape the block.
High-dose opioid (classically fentanyl in cardiac anaesthesia) suppresses the hypothalamic–pituitary response — at the cost of prolonged ventilation.
Minimally invasive surgery — less tissue injury, so a smaller cytokine signal.
Etomidate blunts the cortisol response by inhibiting 11-β-hydroxylase — an unwanted version of the same effect.
Volatiles and propofol have little effect on the stress response at usual doses. Depth of anaesthesia alone does not abolish it.

The ERAS elements that target it directly

Preoperative carbohydrate loading — reduces insulin resistance by putting the patient in a fed rather than starved state.
Avoid prolonged fasting; clear fluids to 2 hours.
Maintain normothermia — hypothermia amplifies the catecholamine response and causes shivering.
Multimodal opioid-sparing analgesia and regional techniques.
Early feeding and early mobilisation — shorten the catabolic phase.
Goal-directed fluid therapy — avoid both hypovolaemia and salt-and-water overload on top of an already retaining patient.

Is the response good or bad?

It evolved as a survival mechanism for injury without medical care — conserve volume, mobilise fuel, fight infection, heal.
In modern practice, where we replace volume and provide nutrition, an excessive or prolonged response is harmful: hyperglycaemia, immunosuppression, muscle wasting, delayed recovery and fluid overload.
So the goal is attenuation, not abolition — enough response to heal, not enough to harm. That nuance is what a viva is looking for.

Quick recall

Cuthbertson 1932, long bone fracture

EBB 24–48 h · hypoMETABOLIC

FLOW catabolic then anabolic

Ebb cold, hypovolaemic, ↓CO

Flow pyrexial, ↑CO, −N balance

IL-6 drives acute phase

Albumin NEGATIVE acute phase protein

Insulin ↓ everything else ↑

Neuraxial best modifier, lower body

Etomidate blunts cortisol