Noradrenaline hydrochloride

What is noradrenaline hydrochloride?

Noradrenaline hydrochloride, also known as norepinephrine, is a chemical substance classified as a sympathomimetic amine.^[2] It is a precursor of adrenaline that is naturally secreted by the adrenal medulla and acts widely in the central and peripheral nervous system.^[2] Other names for the same substance include arterenol, levarterenol, and norepinephrine bitartrate.^[2] It is an authorised medicine available as a concentrate for solution for infusion, for example as a 1 mg/ml product.^[3]

How does noradrenaline hydrochloride work?

Noradrenaline acts on adrenergic receptors in the body. On peripheral noradrenergic nerve endings, activation of presynaptic beta-adrenoreceptors can enhance the release of noradrenaline in response to nerve stimulation.^[5] These presynaptic beta-adrenoreceptors do not appear to be activated by neuronally released noradrenaline itself, but adrenaline may act as a physiological activator during enhanced adrenal secretion.^[5] In the central nervous system, noradrenaline has a regulatory role in human attention, and drugs that increase noradrenaline tone have been shown to improve attention in experimental settings.^[4] Clinically, noradrenaline is used as a vasopressor: it narrows blood vessels, which raises blood pressure in patients with dangerously low blood pressure.

Which conditions is noradrenaline hydrochloride used or studied for?

• Shock – a life-threatening condition where blood pressure drops so low that organs do not get enough blood. The VASOSHOCK trial is studying whether early noradrenaline can control shock faster.^[1]
• Hypotension – abnormally low blood pressure. The same trial includes non-bleeding hypotensive patients presenting in the emergency department.^[1]

How is noradrenaline hydrochloride given?

Noradrenaline hydrochloride is available as a concentrate for solution for infusion and is given by intravenous infusion.^[3] In the VASOSHOCK trial, the intervention is described as an intravenous infusion of norepinephrine.^[1]

What do the clinical trials show?

One trial is registered for noradrenaline hydrochloride in shock and hypotension. The VASOSHOCK trial is a Phase 3, multi-centre, randomised controlled trial that plans to enrol 280 participants.^[1] It is currently authorised.^[1]

What is the trial measuring?

The primary outcome is the proportion of patients achieving either a systolic blood pressure (SBP) greater than 100 mmHg, a mean arterial pressure (MAP) greater than 65 mmHg, or a target blood pressure set by the treating physician at 90 minutes (plus or minus 15 minutes) after inclusion.^[1] The aim is to investigate whether early vasopressor therapy, compared to fluid therapy alone, can improve the time to shock control and reduce the need for intensive care unit admission.^[1]

Who can take part in the trial?

The trial includes non-bleeding hypotensive patients presenting in the emergency department.^[1] It compares early initiated vasopressor therapy with noradrenaline against fluid therapy alone.^[1]