Question
A 55-year-old woman is admitted to ICU with septic shock due to an ascending urinary tract infection. She has already received several litres of IV crystalloid but remains profoundly hypotensive. She is on noradrenaline and vasopressin, but her MAP is still around 50 mmHg, lactate is rising, and urine output is very poor. The ICU consultant advises adding an IV adrenaline infusion.
Which metabolic change is most likely after starting IV adrenaline?
A. Raised serum potassium
B. Low blood glucose
C. Raised serum sodium
D. Increased lactate generation
E. Raised serum calcium
Answer: D. Increased lactate generation
Explanation
Adrenaline can increase lactate production, even when tissue oxygenation is not necessarily worsening. This is very important in ICU and sepsis because a rising lactate after starting adrenaline may partly reflect adrenaline-driven metabolism rather than only worsening shock.
Adrenaline acts on both alpha and beta adrenergic receptors. Through beta-2 stimulation in skeletal muscle, it increases glycogenolysis and glycolysis. This drives pyruvate production, and much of this pyruvate is converted into lactate. Therefore, adrenaline can cause hyperlactataemia.
Adrenaline also causes hyperglycaemia. It increases hepatic glycogenolysis and gluconeogenesis. It also inhibits insulin secretion through alpha-adrenergic stimulation and increases glucagon release through beta stimulation. So hypoglycaemia is not expected; hyperglycaemia is more typical.
Adrenaline usually causes hypokalaemia, not hyperkalaemia. This is because beta-2 receptor stimulation increases Na+/K+ ATPase activity, pushing potassium into cells. This is the same physiological principle used when nebulised salbutamol is given to temporarily lower potassium in hyperkalaemia.
Hypernatraemia is not a characteristic acute biochemical effect of adrenaline infusion. Serum sodium may change in critically ill patients for many reasons, but adrenaline itself is not classically associated with hypernatraemia.
Hypercalcaemia is also not an expected effect. Adrenaline has major cardiovascular and metabolic effects, but raising serum calcium is not one of its classic biochemical consequences.
So the key adverse biochemical pattern of adrenaline is:
Adrenaline → hyperglycaemia + hyperlactataemia + hypokalaemia.
Cheat sheet for exam
Adrenaline is a sympathomimetic catecholamine acting on alpha-1, alpha-2, beta-1 and beta-2 receptors.
Main emergency uses:
Anaphylaxis
Cardiac arrest
Refractory shock, usually ICU setting
Adult doses to remember:
Anaphylaxis: 0.5 mg IM, usually 0.5 mL of 1:1000 adrenaline
Cardiac arrest: 1 mg IV, usually 10 mL of 1:10,000 adrenaline
Accidental digital adrenaline injection:
Treat with local phentolamine infiltration.
Adrenaline metabolic effects:
Increases glycogenolysis
Increases gluconeogenesis
Increases glycolysis in skeletal muscle
Increases lipolysis
Inhibits insulin secretion via alpha stimulation
Stimulates glucagon secretion via beta stimulation
Biochemical effects:
Hyperglycaemia
Hyperlactataemia
Hypokalaemia
Why lactate rises:
Beta-2 stimulation in skeletal muscle increases glycolysis. More pyruvate is generated and converted to lactate. Lactate then travels to the liver and can be used for gluconeogenesis via the Cori cycle.
Important exam trap:
A rising lactate after starting adrenaline does not always mean worsening hypoperfusion. It may be partly due to adrenaline-induced aerobic glycolysis.
Flash cards
Q: What are the three classic biochemical effects of adrenaline infusion?
A: Hyperglycaemia, hyperlactataemia and hypokalaemia.
Q: Why does adrenaline increase lactate?
A: Beta-2 stimulation increases skeletal muscle glycolysis, producing more pyruvate and lactate.
Q: Does adrenaline usually cause hyperkalaemia or hypokalaemia?
A: Hypokalaemia, due to beta-2-mediated intracellular potassium shift.
Q: Why does adrenaline cause hyperglycaemia?
A: It increases glycogenolysis and gluconeogenesis, inhibits insulin secretion, and stimulates glucagon release.
Q: Which receptor effect of adrenaline inhibits insulin secretion?
A: Alpha-adrenergic stimulation.
Q: Which receptor effect of adrenaline promotes potassium entry into cells?
A: Beta-2 receptor stimulation.
Q: What is the first-line route and dose of adrenaline in adult anaphylaxis?
A: 0.5 mg IM, usually 0.5 mL of 1:1000 adrenaline.
Q: What is the standard adult cardiac arrest dose of adrenaline?
A: 1 mg IV, usually 10 mL of 1:10,000 adrenaline.
Q: What drug can reverse accidental adrenaline-induced digital ischaemia?
A: Phentolamine.
MCQs
- A patient in refractory septic shock is started on an adrenaline infusion. Lactate rises from 3.5 to 6 mmol/L, but perfusion and MAP improve. What is the most likely explanation?
A. Adrenaline-induced skeletal muscle glycolysis
B. Adrenaline-induced renal lactate retention
C. Adrenaline-induced hepatic failure
D. Adrenaline-induced inhibition of glycogenolysis
Answer: A. Adrenaline-induced skeletal muscle glycolysis
Explanation: Adrenaline stimulates beta-2 receptors in skeletal muscle, increasing glycogenolysis and glycolysis. This increases pyruvate generation and lactate production. Therefore, lactate can rise after adrenaline even when haemodynamics improve. This is a classic ICU exam point.
- Which biochemical pattern is most typical after IV adrenaline?
A. Hypoglycaemia, hyperkalaemia, low lactate
B. Hyperglycaemia, hypokalaemia, high lactate
C. Hyponatraemia, hypercalcaemia, low lactate
D. Hypoglycaemia, hypokalaemia, low lactate
Answer: B. Hyperglycaemia, hypokalaemia, high lactate
Explanation: Adrenaline increases glucose production, suppresses insulin release, increases skeletal muscle glycolysis and promotes intracellular potassium shift. The expected pattern is therefore hyperglycaemia, hyperlactataemia and hypokalaemia.
- Which of the following statements about adrenaline is false?
A. It stimulates beta-1 receptors and increases cardiac output
B. It can increase lactate production
C. It commonly causes hypoglycaemia
D. It can cause hypokalaemia
Answer: C. It commonly causes hypoglycaemia
Explanation: This is false. Adrenaline usually causes hyperglycaemia, not hypoglycaemia. It increases glycogenolysis and gluconeogenesis, suppresses insulin secretion and stimulates glucagon release.
- The hypokalaemic effect of adrenaline is mainly due to which mechanism?
A. Increased urinary potassium loss due to aldosterone release
B. Reduced dietary potassium absorption
C. Potassium binding to plasma proteins
D. Beta-2-mediated intracellular potassium shift
Answer: D. Beta-2-mediated intracellular potassium shift
Explanation: Beta-2 receptor stimulation activates Na+/K+ ATPase activity, pushing potassium from the extracellular space into cells. This lowers serum potassium.
- In accidental injection of adrenaline into a finger causing digital ischaemia, which treatment may be used locally?
A. Phentolamine
B. Atropine
C. Protamine
D. Naloxone
Answer: A. Phentolamine
Explanation: Phentolamine is an alpha-blocker. It reverses adrenaline-mediated alpha-adrenergic vasoconstriction and can be infiltrated locally in cases of adrenaline-induced digital ischaemia.
- In adult anaphylaxis, the recommended adrenaline dose is closest to:
A. 1 mg IV as 10 mL of 1:10,000
B. 0.5 mg IM as 0.5 mL of 1:1000
C. 5 mg nebulised adrenaline
D. 0.05 mg subcutaneous adrenaline
Answer: B. 0.5 mg IM as 0.5 mL of 1:1000
Explanation: In adult anaphylaxis, adrenaline is given intramuscularly, usually into the anterolateral thigh. The standard adult dose is 0.5 mg IM, equivalent to 0.5 mL of 1:1000 adrenaline.
- In adult cardiac arrest, the standard adrenaline dose is:
A. 0.5 mg IM
B. 0.1 mg IV
C. 1 mg IV
D. 10 mg IV
Answer: C. 1 mg IV
Explanation: During adult cardiac arrest, adrenaline is given as 1 mg IV, commonly 10 mL of 1:10,000 adrenaline. This differs from anaphylaxis, where the standard route is IM.
- Which receptor action contributes to adrenaline-induced hyperglycaemia by suppressing insulin release?
A. Alpha-adrenergic stimulation
B. Muscarinic stimulation
C. Histamine H1 stimulation
D. Dopamine D2 blockade
Answer: A. Alpha-adrenergic stimulation
Explanation: Alpha-adrenergic stimulation inhibits pancreatic insulin secretion. Reduced insulin allows glucose to remain elevated. Adrenaline also increases hepatic glucose output and stimulates glucagon secretion.
- Which of the following is false regarding adrenaline metabolism?
A. It increases hepatic glycogenolysis
B. It increases gluconeogenesis
C. It reduces skeletal muscle glycolysis
D. It increases lipolysis
Answer: C. It reduces skeletal muscle glycolysis
Explanation: This is false. Adrenaline increases, not reduces, skeletal muscle glycolysis. This is the key reason it can increase lactate production.
- Why can lactate rise after adrenaline even without worsening tissue hypoxia?
A. Adrenaline causes aerobic glycolysis in skeletal muscle
B. Adrenaline blocks lactate assay detection
C. Adrenaline directly damages red cells
D. Adrenaline causes acute calcium release from bone
Answer: A. Adrenaline causes aerobic glycolysis in skeletal muscle
Explanation: Adrenaline-induced lactate is not always due to anaerobic metabolism. Beta-2 stimulation can increase glycolytic flux in skeletal muscle under aerobic conditions, generating lactate despite adequate oxygen delivery.
- A septic shock patient is already on noradrenaline and vasopressin. Adrenaline is added as an additional vasopressor. Which lab result should be interpreted cautiously afterwards?
A. Serum lactate
B. Serum albumin
C. Serum phosphate
D. Serum urea
Answer: A. Serum lactate
Explanation: Lactate remains important in shock monitoring, but adrenaline can independently increase lactate production. A rising lactate after adrenaline must therefore be interpreted in the full clinical context, including MAP, urine output, capillary refill, vasopressor dose and acid-base status.
- Which of the following best describes adrenaline?
A. Pure alpha-1 agonist
B. Pure beta-2 agonist
C. Mixed alpha and beta adrenergic agonist
D. Selective dopamine receptor agonist
Answer: C. Mixed alpha and beta adrenergic agonist
Explanation: Adrenaline acts on alpha-1, alpha-2, beta-1 and beta-2 receptors. This explains its broad cardiovascular and metabolic effects.
Summary for quick exam revision
Adrenaline is a mixed alpha and beta adrenergic agonist used in anaphylaxis, cardiac arrest and sometimes refractory shock. Its key exam biochemical effects are hyperglycaemia, hyperlactataemia and hypokalaemia. Hyperglycaemia occurs because adrenaline increases hepatic glycogenolysis and gluconeogenesis, suppresses insulin secretion through alpha stimulation and increases glucagon release through beta stimulation. Hyperlactataemia occurs mainly through beta-2 stimulation in skeletal muscle, which increases glycogenolysis and glycolysis, generating excess pyruvate that is converted into lactate. Therefore, after adrenaline is started, a rise in lactate may reflect adrenaline-driven aerobic glycolysis and not necessarily worsening tissue hypoxia. Hypokalaemia occurs because beta-2 stimulation drives potassium into cells through Na+/K+ ATPase activation. Adrenaline does not classically cause hypoglycaemia, hyperkalaemia, hypernatraemia or hypercalcaemia. In adult anaphylaxis, adrenaline is given as 0.5 mg IM, usually 0.5 mL of 1:1000 adrenaline. In adult cardiac arrest, the dose is 1 mg IV, usually 10 mL of 1:10,000 adrenaline. Accidental digital injection can cause severe vasoconstriction and digital ischaemia, which may be treated with local phentolamine.