Why this drug is interesting

Noradrenaline is the default vasopressor for shock in modern practice, and the pharmacology is not the difficult part. Three practical issues account for nearly all the harm associated with it, and none of them is about receptors.

The first is that UK preparations express strength two different ways — as noradrenaline base or as noradrenaline tartrate — with a twofold difference between them. The second is that it is contraindicated in hypotension from hypovolaemia, which is exactly the situation where it is most tempting. The third is that extravasation causes tissue necrosis, and the antidote is one most clinicians have never drawn up.

The base versus tartrate problem

A twofold difference, expressed inconsistently between products

Noradrenaline is formulated as the tartrate salt, but its potency is conventionally expressed as base. UK SmPCs handle this differently:

Product wording	What 1 mL contains
"noradrenaline tartrate equivalent to 1 mg noradrenaline"	1 mg base (= 2 mg tartrate)
"2 mg noradrenaline tartrate, equivalent to 1 mg noradrenaline"	The same thing, stated explicitly
"2 mg noradrenaline tartrate equivalent to 1 mg noradrenaline base"	The same thing again

All three describe an identical ampoule. The risk arises when a protocol, a pump library entry and an ampoule label do not all use the same convention — a dose intended as base and delivered as tartrate, or the reverse, is out by a factor of two.

Doses in guidelines and in this monograph are expressed as base, which is the convention in critical care. When checking a local protocol or a prepared bag, confirm which the number refers to rather than assuming.

Pharmacology

Mechanism

Noradrenaline is a potent α₁ agonist with meaningful β₁ but minimal β₂ activity. The dominant effect is arterial and venous vasoconstriction, raising systemic vascular resistance and therefore mean arterial pressure. β₁ stimulation provides modest inotropic support, so cardiac output is generally maintained rather than falling as afterload rises.

The absence of significant β₂ activity is what distinguishes it from adrenaline: no bronchodilatation, no β₂-mediated vasodilatation to offset the pressor effect, and less tachycardia and lactataemia.

Kinetics

Onset: Rapid — within a minute of reaching the circulation
Half-life: Approximately 2 minutes
Metabolism: COMT and MAO, as for other catecholamines
Implication: Effects are governed almost entirely by the infusion rate; stopping the infusion produces a rapid fall in pressure

Indications and dosing

Licensed for use in adults as an emergency measure in the restoration of blood pressure in cases of acute hypotension.¹ In practice its dominant use is as the first-line vasopressor in septic shock, and in other distributive and vasoplegic states.

Dosing

Dilute before use; a common working concentration is 40 micrograms/mL of base
At that concentration, a typical starting rate is 10–20 mL/hour, equivalent to 0.4–0.8 mg/hour of base
Titrate in steps of 0.05–0.1 micrograms/kg/min of base according to the pressor effect observed¹
Targets: systolic 100–120 mmHg, or MAP 65–80 mmHg — adjusted to the individual patient

Route — the SmPC and current practice diverge

The SmPC specifies administration via a central venous catheter after dilution, using a syringe pump, infusion pump or drip counter.¹

Extravasation

Noradrenaline extravasation causes local necrosis through its vasoconstrictive action.¹ This is the specific risk that makes line choice matter, and it is entirely treatable if recognised.

Know whether your department stocks phentolamine and where it is. If it does not, that is worth raising before it is needed — the same argument as for lipid emulsion in lidocaine toxicity.

Contraindications, adverse effects and interactions

Contraindications

Hypersensitivity to noradrenaline or excipients
Hypotension due to blood volume deficit (hypovolaemia)
Concurrent cyclopropane and halothane anaesthesia — myocardial sensitisation to catecholamines

Adverse effects

Peripheral ischaemia — including, rarely, gangrene of the extremities
Hypertension if over-titrated, with associated bradycardia and headache
Reduced splanchnic and renal perfusion at higher doses
Arrhythmia — less than with adrenaline, but present
Extravasation necrosis
Anxiety, tremor, palpitations

Interactions

MAO inhibitors and tricyclic antidepressants — markedly potentiate the pressor response
Volatile anaesthetic agents — sensitise the myocardium to catecholamine-induced arrhythmia
Beta-blockers — may produce unopposed α effects with severe hypertension
Other vasopressors — additive peripheral ischaemia

Critical appraisal

The evidence for noradrenaline as first-line vasopressor in septic shock is good. It outperformed dopamine on arrhythmia and, in some analyses, mortality, and is recommended first-line by the Surviving Sepsis Campaign. This is a settled question in a field with plenty of unsettled ones.
The MAP target of 65 mmHg is a floor derived from trial populations, not a physiological truth. SEPSISPAM found no overall mortality difference between a higher and lower target, with a signal of benefit in chronic hypertension and more atrial fibrillation at the higher target. Individualising rather than reflexively targeting 65 is defensible.
Peripheral administration is an area where practice has moved ahead of the label, supported by a reasonable but not definitive observational literature. The honest position is that the risk is low with a good line and careful monitoring, and lower than the risk of delaying vasopressors — but that it is off-label and needs a protocol.
The base/tartrate issue is a genuine, documented medication-safety problem and not a pedantic one. It has produced real dosing errors and is a strong argument for standardised concentrations rather than local improvisation.
Blood pressure is a surrogate. Noradrenaline reliably raises the number; whether it improves tissue perfusion depends on the cause of the shock and on adequate filling. Lactate clearance, capillary refill and urine output matter more than the arterial line reading.

References

1
Noradrenaline (Norepinephrine) 1 mg/ml concentrate for solution for infusion — Summary of Product Characteristics. electronic Medicines Compendium. Sections 4.1–4.4. Verified 20 Aug 2026. Compare the wording of other UK products at emc and emc for the base/tartrate expressions described above.
2
Noradrenaline/norepinephrine — dosing and safety monograph. BNF, NICE. bnf.nice.org.uk
3
Evans L, Rhodes A, Alhazzani W, et al. Surviving Sepsis Campaign: international guidelines for management of sepsis and septic shock 2021. Crit Care Med 2021;49(11):e1063–143.
4
Asfar P, Meziani F, Hamel JF, et al. High versus low blood-pressure target in patients with septic shock (SEPSISPAM). N Engl J Med 2014;370(17):1583–93.
5
De Backer D, Biston P, Devriendt J, et al. Comparison of dopamine and norepinephrine in the treatment of shock. N Engl J Med 2010;362(9):779–89.
6
Resuscitation Council UK. Refractory anaphylaxis algorithm, 2021. resus.org.uk — mirrored at lifesupport.resusdoc.uk. Noradrenaline listed among second vasopressors alongside vasopressin and metaraminol.

Noradrenaline

At a glance