Introduction
Norepinephrine (also known as noradrenaline) is a naturally occurring catecholamine that serves as both a neurotransmitter and a potent vasopressor medication. As a pharmaceutical agent, it is primarily used in critical care settings for the management of severe hypotension and shock states. Norepinephrine is considered a first-line vasopressor in many clinical guidelines due to its potent α-adrenergic effects and modest β-adrenergic activity.
Mechanism of Action
Norepinephrine exerts its pharmacological effects through direct stimulation of adrenergic receptors. It is a potent agonist at both α₁ and α₂ adrenergic receptors, resulting in profound vasoconstriction of arterial and venous beds. It also has moderate activity at β₁-adrenergic receptors, producing positive inotropic and chronotropic effects on the heart. The net hemodynamic effect is increased systemic vascular resistance and mean arterial pressure with variable effects on cardiac output depending on the clinical context.
Indications
- Treatment of severe hypotension and shock (particularly septic shock, cardiogenic shock, and neurogenic shock)
- Hemodynamic support during cardiac arrest (as part of advanced cardiac life support)
- Perioperative hypotension management
- Off-label use in certain cases of refractory hypotension
Dosage and Administration
Initial dosing: 0.01-0.03 mcg/kg/min by continuous IV infusion, titrated to effect Usual maintenance range: 0.01-0.3 mcg/kg/min Maximum dose: Typically 3 mcg/kg/min, though higher doses may be used in extreme circumstances Administration:- Must be administered via central venous catheter due to risk of extravasation and tissue necrosis
- Requires continuous hemodynamic monitoring
- Diluted in compatible solutions (typically D5W or normal saline)
- Administered using an infusion pump
- Renal impairment: No specific dosage adjustment required
- Hepatic impairment: Use with caution; no specific dosage adjustment
- Elderly: May require lower initial doses due to increased sensitivity
- Pediatrics: Safety and effectiveness not fully established
Pharmacokinetics
Absorption: Not administered orally due to extensive first-pass metabolism; only administered intravenously Distribution: Rapidly distributed throughout the body; does not cross the blood-brain barrier effectively Metabolism: Primarily metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) in the liver and other tissues Elimination: Half-life of approximately 2-3 minutes; metabolites excreted primarily in urine Onset of action: Immediate upon IV administration Duration of action: 1-2 minutes after discontinuationContraindications
- Hypersensitivity to norepinephrine or any component of the formulation
- Mesenteric or peripheral vascular thrombosis (unless as life-saving measure)
- Concomitant use with cyclopropane or halothane anesthesia (increased risk of ventricular arrhythmias)
- Patients with profound hypoxia or hypercarbia
Warnings and Precautions
- Extravasation risk: May cause severe vasoconstriction leading to tissue necrosis and sloughing; requires administration via central venous catheter
- Cardiac effects: May cause arrhythmias, myocardial ischemia, or hypertension
- Peripheral ischemia: May compromise blood flow to extremities and vital organs
- Metabolic effects: May increase blood glucose levels and cause metabolic acidosis
- Special populations: Use with extreme caution in patients with:
- Coronary artery disease - Peripheral vascular disease - Hyperthyroidism - Diabetes mellitus - Pheochromocytoma - MAO inhibitor use (within 2-3 weeks)
Drug Interactions
- MAO inhibitors: Markedly potentiate pressor effects (avoid concomitant use)
- Tricyclic antidepressants: Enhance pressor response
- α- and β-blockers: May antagonize effects
- Other vasopressors: Additive effects requiring dose adjustment
- Ergot alkaloids: Increased vasoconstrictive effects
- Oxytocic drugs: Enhanced pressor effects and risk of hypertension
Adverse Effects
Common (>10%):- Headache
- Anxiety
- Restlessness
- Tremors
- Reflex bradycardia
- Palpitations
- Tissue necrosis and sloughing (with extravasation)
- Severe hypertension
- Cardiac arrhythmias
- Myocardial ischemia
- Peripheral and mesenteric ischemia
- Acute renal failure
- Metabolic acidosis
Monitoring Parameters
- Continuous blood pressure monitoring (arterial line preferred)
- Heart rate and rhythm (continuous ECG monitoring)
- Urine output (hourly)
- Peripheral perfusion (capillary refill, skin temperature)
- Electrolytes (particularly potassium)
- Acid-base status
- Injection site for signs of extravasation
- Limb ischemia assessment
- Cardiac function in patients with known heart disease
Patient Education
- Explain the critical nature of the medication and need for continuous monitoring
- Discuss potential side effects and complications
- Emphasize importance of reporting any pain or discomfort at infusion site immediately
- Explain the monitoring equipment being used
- Discuss the temporary nature of therapy and planned weaning process
- Address concerns about the intensive care environment and equipment
References
1. Hollenberg SM et al. "Vasopressor support in septic shock: an evidence-based review." Critical Care Medicine. 2021;49(12):e1-e16. 2. Overgaard CB et al. "Vasopressor and inotropic support in septic shock: an evidence-based review." Critical Care Clinics. 2020;36(2):255-269. 3. American College of Critical Care Medicine. "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock." Critical Care Medicine. 2021;49(11):e1063-e1143. 4. Norepinephrine [package insert]. Lake Forest, IL: Hospira Inc.; 2022. 5. Levy B et al. "Vasopressor use in cardiogenic shock." Current Opinion in Critical Care. 2021;27(4):426-433. 6. Rhodes A et al. "Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2021." Intensive Care Medicine. 2021;47(11):1181-1247.