Vasopressor
Angiotensin II (Giapreza)
Also called Giapreza
Indications
- Septic or other distributive shock still hypotensive despite fluids and vasopressors (label)
- Catecholamine-refractory vasodilatory shock: ATHOS-3 enrolled patients on more than 0.2 mcg/kg/min of norepinephrine equivalent
- Vasoplegia after cardiopulmonary bypass, as a rescue (observational data)
- Shock with high renin, the subgroup with lower mortality in a post hoc ATHOS-3 analysis (Bellomo 2020)
Dosing
Angiotensin II drip card and mL/h converterStart: 20 ng/kg/min
Mechanism of action
Angiotensin II is the effector peptide of the renin–angiotensin system. It binds AT1 receptors on vascular smooth muscle, which couple to Gq: IP3 and DAG raise calcium, and calcium–calmodulin-dependent myosin phosphorylation contracts the vessel. AT1 stimulation also releases aldosterone and vasopressin and constricts efferent more than afferent arterioles. Septic shock can leave patients short of angiotensin II when endothelial injury lowers ACE activity, and the drug adds a vasoconstrictor pathway independent of adrenergic and vasopressin receptors.
Pharmacology
- Cardiovascular: raises SVR and MAP within minutes and lets catecholamine doses fall; little direct effect on heart rate or contractility
- Renal: efferent constriction maintains filtration pressure; aldosterone retains sodium and wastes potassium
- Metabolic: hyperglycemia and acidosis were more common than with placebo (label)
- Other: releases vasopressin and drives thirst; feedback suppresses renin, so serum angiotensin I falls about 40% after 3 h (label)
Pharmacokinetics
| Onset | Minutes IV; median time to target MAP about 5 min in ATHOS-3 (label) |
|---|---|
| Duration | Ends within minutes of stopping, so wean in steps (label) |
| Half-life | Under 1 min (label) |
| Metabolism | Aminopeptidase A (to angiotensin III) and ACE2 (to angiotensin-(1-7)) in plasma, red cells and major organs (label) |
| Elimination | As peptide fragments; independent of kidney and liver function (label) |
| Routes | IV infusion through a central line, diluted in 0.9% saline only (label) |
Chemistry
- A linear octapeptide, Asp-Arg-Val-Tyr-Ile-His-Pro-Phe (MW 1046), identical to human angiotensin II; unlike vasopressin it has no disulfide bond
- In the body, ACE (largely on pulmonary endothelium) cuts it from the decapeptide angiotensin I
- Synthetic acetate salt in 2.5 mg/mL and 0.5 mg/mL vials with mannitol, pH 5.5; refrigerate vials; diluted bags last 24 h (label)
Adverse effects and cautions
In the one-pagers
- Vasopressors and InotropesReceptors and effects: Angiotensin II: AT1: ↔ / ↔ / ↑↑
- Shock Types at a GlanceResuscitation endpoints, mixed and late shock: Refractory shock, loosely a norepinephrine-equivalent dose above 0.5–1 mcg/kg/min with persistent hypoperfusion, calls for a checklist: confirm the infusion is running and the arterial line is accurate, repeat the echo, give hydrocortisone, add vasopressin, correct ionized calcium, severe acidosis and hypothermia, consider angiotensin II or methylene
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Sources
- FDA label: Giapreza (2021)
- ATHOS-3 (Khanna, NEJM 2017)
- Bellomo 2020 (renin and survival)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.