Noradrenaline

Noradrenaline is the main neurotransmitter of postganglionic sympathetic nerves and the first line vasopressor for septic and other vasodilatory shock. It raises blood pressure mainly by vasoconstriction, with modest cardiac stimulation. Dosing errors arise from base versus salt strengths.

Classification. Catecholamine; alpha 1 predominant adrenergic agonist with beta 1 activity.

Mechanism. Alpha 1 stimulation constricts arterial and venous smooth muscle, raising systemic vascular resistance and venous return. Beta 1 stimulation gives mild positive inotropy; reflex vagal tone offsets tachycardia.

Pharmacodynamics. Onset within 1 to 2 minutes; effect stops within 5 to 10 minutes of stopping the infusion. Cardiac output may rise slightly or stay unchanged; renal, hepatic and mesenteric flow can fall at high doses.

Pharmacokinetics. Inactive orally. Half life about 2 to 3 minutes. Metabolised by monoamine oxidase and catechol O methyltransferase, with urinary excretion of metabolites.

Septic shock and vasodilatory shock, adult (first line).

• Start infusion at 0.05 to 0.1 micrograms/kg/min (about 2 to 5 micrograms/minute of base).

• Titrate every 5 minutes to a mean arterial pressure of at least 65 mmHg, with the aim of the lowest dose that restores perfusion.

• Usual range 0.05 to 0.5 micrograms/kg/min.

• Doses over 0.25 to 0.5 micrograms/kg/min mean refractory shock: add vasopressin 0.03 units/minute, and consider hydrocortisone 50 mg IV every 6 hours. Maximum: practice varies; rarely over 1 to 3 micrograms/kg/min.

• Give fluids first; start the vasopressor early rather than waiting for large volumes in profound hypotension.

Cardiogenic shock with hypotension, adult. Same starting range; add an inotrope (such as dobutamine) when cardiac output is low.

Neurogenic shock, vasoplegia after cardiac surgery, hepatorenal syndrome (specialist). Infusion 0.05 to 0.5 micrograms/kg/min. In hepatorenal syndrome, doses are titrated to mean arterial pressure rise of 10 to 15 mmHg, in intensive care.

Hypotension after spinal anaesthesia at caesarean delivery. Prophylactic infusion 0.05 micrograms/kg/min, or boluses 4 to 6 micrograms IV; titrate.

Children, shock. Infusion 0.05 to 2 micrograms/kg/min, titrated; specialist.

Strengths. Noradrenaline base 1 mg is equivalent to noradrenaline tartrate (bitartrate) 2 mg. Always prescribe in terms of base and check the ampoule label.

Contraindications. Hypovolaemia not yet corrected (relative); mesenteric or peripheral vascular thrombosis (relative); halothane or cyclopropane anaesthesia (arrhythmia).

Warnings. Extravasation causes severe local necrosis and gangrene. Peripheral and splanchnic ischaemia, arrhythmias, hypertension, reflex bradycardia, reduced renal perfusion and lactic acidosis. Tolerance with prolonged infusion.

Adverse effects. Headache, bradycardia or tachycardia, arrhythmia, hypertension, digital and gut ischaemia, urinary retention.

Interactions. Monoamine oxidase inhibitors, tricyclic antidepressants and linezolid give severe hypertension. Oxytocic drugs and ergometrine add to the pressor effect. Halogenated anaesthetics increase arrhythmia risk. Beta blockers and alpha blockers alter response.

Special groups.

• Pregnancy: acceptable in life threatening hypotension; may reduce uterine blood flow at high doses.

• Breastfeeding: compatible; given only in intensive care.

• Children: dose by weight.

• Older adults: start low; ischaemia risk.

• Kidney and liver impairment: no adjustment; liver failure may raise sensitivity.

Extravasation. Stop the infusion, aspirate the line, and infiltrate phentolamine 5 to 10 mg in 10 mL 0.9% sodium chloride around the site; elevate the limb and seek surgical review.

Formulations. Ampoules 1 mg/mL base (2 mg/mL tartrate); some markets use 4 mg/4 mL.

Preparation. For example 4 mg base in 50 mL of 5% glucose or 0.9% sodium chloride (80 micrograms/mL), through a dedicated central venous line. In an emergency, peripheral infusion through a large proximal vein cannula at a lower concentration is accepted for a short time (usually under 24 hours) while central access is arranged, with hourly site checks. Protect from light if discoloured; discard solutions that are pink or brown.

Baseline. Arterial or non-invasive blood pressure, lactate, central venous oxygen saturation, urine output, ECG.

Monitoring. Continuous arterial pressure where possible; heart rate and rhythm; lactate every 2 to 6 hours; skin perfusion and digits; urine output; infusion site.

Weaning. Reduce by 0.02 to 0.05 micrograms/kg/min as pressure allows; when vasopressin is also running, the order of weaning is directed by the intensive care team.

Common prescribing errors. Confusing base and tartrate strengths; prescribing in mL/hour without stating the concentration; running through a cannula in a small vein; stopping the infusion abruptly.