Noradrenaline (Norepinephrine): Pharmacology and Clinical Applications
Noradrenaline (norepinephrine) is a potent vasoconstrictor and first-line vasopressor agent used primarily to treat severe hypotension in shock states, particularly when characterized by low systemic vascular resistance. 1
Pharmacology and Mechanism of Action
- Chemical Structure: Norepinephrine is a catecholamine that differs from epinephrine by the absence of a methyl group on the nitrogen atom 2
- Endogenous Role: Functions as both a hormone and neurotransmitter in the body 3
- Receptor Activity: Acts primarily on α-adrenergic receptors causing vasoconstriction, with minimal β-adrenergic effects 4
- Physiologic Effects:
- Increases systemic vascular resistance
- Raises blood pressure (particularly diastolic)
- Has mild inotropic properties
- Minimal effect on heart rate compared to other vasopressors
Clinical Applications
Primary Indications
- Septic Shock: First-line vasopressor for fluid-refractory hypotensive shock 1
- Cardiogenic Shock: Used when combination of inotropes and fluid challenge fails 4
- Post-cardiac Arrest: Maintains adequate perfusion pressure 4
- Neurogenic Orthostatic Hypotension: Used in treatment of symptomatic cases 5
Dosing Guidelines
- Initial Dose: 0.05-0.1 μg/kg/min (7-35 μg/min in a 70kg adult) 4, 1
- Titration: Increase by 0.05-0.1 μg/kg/min every 5-15 minutes based on blood pressure response 1
- Administration: Must be given as continuous intravenous infusion, preferably via central line 4
Clinical Considerations and Precautions
Administration Considerations
- Central Line Preferred: Administration through a central line is recommended to prevent tissue necrosis from extravasation 4
- Extravasation Management: If extravasation occurs, infiltrate 5-10 mg of phentolamine diluted in 10-15 mL of saline into the site to prevent tissue necrosis 4
- Incompatibilities: Should not be mixed with sodium bicarbonate or other alkaline solutions as adrenergic agents are inactivated in alkaline environments 4
Monitoring Parameters
- Blood Pressure: Continuous monitoring recommended
- Target MAP: At least 65 mmHg (higher in patients with chronic hypertension) 1, 6
- Other Parameters: Heart rate, urine output, skin perfusion, mental status, lactate clearance 1
Special Populations
- Pediatric Patients: Historically, dopamine was first-line, but evidence now supports norepinephrine's efficacy and safety 1, 7
- Neonates: Studies show improved mean blood pressure and urine output with norepinephrine without significant adverse effects 7
Potential Adverse Effects
- Excessive Vasoconstriction: May reduce end-organ perfusion if dosed too aggressively
- Cardiac Effects: May increase myocardial oxygen requirements (use cautiously in ischemic heart disease) 4
- Renal Effects: Traditionally feared to decrease renal blood flow, but in vasodilated states may actually improve renal perfusion 8
Combination Therapy
- With Dobutamine: When cardiac output needs support alongside vasoconstriction 4, 1
- With Vasopressin: In refractory shock, as vasopressin acts independently of adrenergic receptors 4, 1
Practical Considerations
- Fluid Status: Ensure adequate volume resuscitation before or concurrent with norepinephrine initiation 1
- Early Administration: Recent evidence supports early administration of norepinephrine in septic shock to restore organ perfusion 6
- Refractory Hypotension: Consider adding vasopressin (up to 0.03 U/min) when high doses of norepinephrine are required 1
Norepinephrine remains a cornerstone of vasopressor therapy in critical care settings, with a well-established safety and efficacy profile when used appropriately with proper monitoring.