norepinephrine
vasopressor· Brands: Levophed, ArterenolIV
Mechanism of action
Norepinephrine is a catecholamine that acts as a potent vasopressor. It stimulates alpha-1 adrenergic receptors, causing vasoconstriction of peripheral blood vessels, and has some beta-1 activity, which increases cardiac contractility and heart rate. The net effect is a rise in blood pressure, primarily through increased systemic vascular resistance.
Pharmacokinetics
Norepinephrine is administered intravenously and has a short half-life of approximately 2 to 3 minutes. It is rapidly metabolised by catechol-O-methyltransferase and monoamine oxidase, and its metabolites are excreted in urine. The drug is titrated according to its immediate haemodynamic effects.
Indications & dosing
Septic shock
Titrate to target MAP of >=65 mmHg. Use in combination with fluids.
- adult · IV: 0.05–0.5 mcg/kg/min continuous · Titrate to target MAP of >=65 mmHg. Use in combination with fluids.
Cardiogenic shock
Titrate to maintain haemodynamic stability. Monitor cardiac output.
- adult · IV: 0.05–0.5 mcg/kg/min continuous · Titrate to maintain haemodynamic stability. Monitor cardiac output.
Neurogenic shock
Use after spinal cord injury with hypotension. Titrate to blood pressure target.
- adult · IV: 0.05–0.5 mcg/kg/min continuous · Use after spinal cord injury with hypotension. Titrate to blood pressure target.
Intraoperative hypotension
Titrate to maintain adequate organ perfusion during surgery.
- adult · IV: 0.05–0.2 mcg/kg/min continuous · Titrate to maintain adequate organ perfusion during surgery.
Contraindications & precautions
- Hypersensitivity to norepinephrine or any component of the formulation
- Peripheral or mesenteric vascular thrombosis · Vasoconstriction may exacerbate ischaemia and thrombosis.
- Hypovolaemic shock without adequate volume replacement · Volume resuscitation should be undertaken first; norepinephrine may worsen tissue ischaemia if hypovolaemia is uncorrected.
- Administer through a large peripheral or central venous line; monitor the infusion site closely for extravasation.
- Use continuous blood pressure and heart rate monitoring; titrate to target organ perfusion.
- Correct hypovolaemia prior to or during infusion to prevent worsening of haemodynamic instability.
- Use with caution in patients with coronary artery disease, myocardial ischaemia, or arrhythmias, as these may be exacerbated.
- Withdraw the infusion gradually to avoid rebound hypotension.
- Store and dilute according to local protocols; do not mix with alkaline solutions.
Adverse effects
- Hypertensionserious
- Reflex bradycardia
- Arrhythmias (e.g., ventricular tachycardia)serious
- Tissue ischaemia or necrosis at infusion site (extravasation)serious
- Headache
- Anxiety or restlessness
- Reduced renal blood flow or oliguriaserious
Renal & hepatic adjustment
- eGFR 0+: No dosage adjustment required; titrate to target blood pressure.
- Hepatic impairment (severe): Use with caution; consider a lower initial dose and titrate slowly due to reduced metabolism.
Monitoring, pregnancy & toxicity
- Blood pressure · Continuous (intra-arterial preferred)
- Heart rate and rhythm · Continuous ECG
- Urine output · Hourly
- Peripheral perfusion · Regularly
- Extravasation site · Frequently if peripheral
- Pregnancy: Use in pregnancy only for serious maternal indications when benefits outweigh potential fetal risks. Norepinephrine may reduce uterine blood flow, but is acceptable in life-threatening hypotension. Fetal monitoring is advised if feasible.
- Toxicity: Hypertension (excessive vasoconstriction) · Discontinue or reduce infusion; administer afterload reduction if severe.
- Toxicity: Bradycardia (reflex vagal stimulation) · Reduce dose; atropine if symptomatically compromised.
- Toxicity: Cardiac arrhythmias · Stop infusion, correct electrolytes, consider antiarrhythmics.
- Toxicity: Tissue extravasation/ischemia · Stop infusion; infiltrate with phentolamine and elevate limb.
Antidotes & reversal
- Phentolamine (local infiltration) · Extravasation ischaemia: phentolamine 5-10 mg in 10 mL saline infiltrated subcutaneously around the site.
Clinical notes
Norepinephrine is used to manage hypotension, particularly in septic shock, cardiogenic shock, and other distributive shock states. It is a first-line vasopressor in many guidelines. It should be infused via a central line when possible to minimise the risk of extravasation injury. Continuous blood pressure monitoring and careful titration are essential. Hypovolaemia should be corrected before starting vasopressor therapy.
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BNF; local formulary