II. Definitions
- Norepinephrine
- Natural Catecholamine, released from Adrenal Medulla as a stress response (along with Epinephrine)
- Also the primary postganglionic Neurotransmitter of the Sympathetic Nervous System
- Strong Vasoconstriction and increased arterial pressure (a1) and reflex Bradycardia
- Unlike Epinephrine, only small effects on contractility and NO beta effect (no bronchodilation or metabolic effects)
III. History
- Ulf Von Euler won 1970 Nobel Prize for its discovery
- Swedish Chemist also discovered Prostaglandins
IV. Mechanism
- Naturally occurring Catecholamine
- Potent Alpha Adrenergic ReceptorAgonist
- Potent arterial and venous Vasoconstriction
- Weak Beta 1 Adrenergic ReceptorAgonist
- Only small effects on contractility (contrast with Epinephrine which increases contractility)
- Reflex Bradycardia (contrast with Epinephrine, which increases Heart Rate)
- No Beta 2 Adrenergic Receptor Activity
- No bronchodilation or metabolic effects (contrast with Epinephrine)
V. Indications
- First line Vasopressor in fluid refractory, hemodynamically significant Hypotension (esp. Septic Shock)
- Useful in Low Systemic Vascular Resistance (e.g. Septic Shock, Neurogenic Shock)
VI. Contraindications: Relative
- Acute Myocardial Infarction
- Risk of worsening coronary perfusion
VII. Monitoring
- Monitor Blood Pressure accurately
- Consider Arterial Line with continuous monitoring
- Blood Pressure cuff monitoring every 5 minutes
- Consider advanced hemodynamic monitoring
- Cardiac Output
- Pulmonary wedge pressure
- Peripheral arterial resistance
VIII. Precautions
- Maximize management of other Hypotension Causes first
- Maximize fluid Resuscitation in Sepsis
- Replace Blood Products in Trauma
- Use with caution in Myocardial Ischemia
- Increases myocardial oxygen requirements
- No compensatory increase in coronary perfusion
- Observe for Arrhythmias
- Volume depleted patents
- Limited myocardial reserve
- Norepinephrine is safest to use via central venous catheter
- However reliable large bore peripheral IV may be used safely with caution initially (e.g. first 24 hours)
- Extravasation may cause severe local tissue damage
- Antidote for extravasation
- Phentolamine 5-10 mg diluted in 10-15 ml NS
- Infiltrate area of extravasation with Phentolamine
IX. Preparation
- Start with Norepinephrine (1 mg/ml) 4 ml ampule
- Option 1: Mix 4 mg (4 ml) Norepinephrine in 500 ml D5W or Normal Saline
- Final Concentration: 8 mcg/ml Norepinephrine (rate 22.5 ml/h delivers 3 mcg/min)
- Option 2: Mix 4 mg (4 ml) Norepinephrine in 250 ml D5W or Normal Saline
- Final Concentration: 16 mcg/ml Norepinephrine (rate 11.25 ml/h delivers 3 mcg/min)
X. Dosing: Infusion via Central Venous Catheter
- May start via reliable large bore peripheral line during stabilization, but should be transitioned to Central Line within hours (<24 hours)
- Child (off label)
- Start 0.05 to 0.1 mcg/kg/min IV
- Titrate to mean arterial pressure or systolic Blood Pressure target up to max rate (2 mcg/kg/min)
- Adult: Weight Based (preferred, adults)
- Start at 0.05 mcg/kg/min
- Unlikely to benefit from titration above 0.3 mcg/kg/min
- Adult: Non-weight based
- Start at 5 mcg/min up to 8 to 12 mcg/min
- Typical dose range (adults): 2 to 4 mcg/min (up to 30 mcg/min or 0.3 mcg/kg/min)
- Adult: Titrate to Systolic Blood Pressure >90 mmHg or MAP >65 mmHg
- Average Adult Dose: 2 to 12 mcg/min
- Refractory Shock: up to 30 mcg/min
XI. Adverse Effects
- Tissue extravasation
- Risk of tissue ischemia, necrosis, gangrene
- Infuse via central venous catheter
- May use reliable large bore peripheral IV initially during stabilization
XII. Resources
- Norepinephrine Bitartrate Injection Solution (DailyMed)
XIII. References
- McCollum in Herbert (2019) EM:Rap 19(7):4-6