Introduction
Noradrenaline (Norepinephrine) is a potent vasopressor and sympathomimetic agent primarily used in the management of severe hypotension and shock, especially septic shock. It is an endogenous catecholamine that acts mainly on alpha-adrenergic receptors, causing vasoconstriction, but also has some beta-adrenergic effects, which contribute to its inotropic actions. Noradrenaline is administered intravenously and is widely used in critical care settings to maintain blood pressure and tissue perfusion in shock states.
Pharmacokinetics
Noradrenaline is administered as a continuous intravenous infusion due to its short half-life and rapid onset of action. The onset of action occurs within 1 to 2 minutes of infusion, with effects disappearing within 1 to 2 minutes after discontinuation. The drug is rapidly metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) in the liver and kidneys.
Noradrenaline has a plasma half-life of approximately 2 to 3 minutes, making it necessary to be administered continuously in critically ill patients. It is excreted primarily via the urine as inactive metabolites (normetanephrine and vanillylmandelic acid).
Mechanism of Action
Noradrenaline predominantly stimulates alpha-1 adrenergic receptors located on vascular smooth muscle, leading to vasoconstriction and an increase in systemic vascular resistance (SVR). This vasoconstriction results in increased blood pressure, making Noradrenaline highly effective in treating hypotension during shock.
Noradrenaline also stimulates beta-1 adrenergic receptors in the heart, leading to a mild increase in heart rate and myocardial contractility. However, its primary action is vasoconstriction, with minimal effect on beta-2 adrenergic receptors, which are responsible for vasodilation. This combination of effects helps improve cardiac output and maintain adequate perfusion pressure in patients with circulatory shock.
Pharmacodynamics
Noradrenaline causes a marked increase in blood pressure due to its vasoconstrictive effects on peripheral vasculature. It increases both systolic and diastolic blood pressure, improving perfusion pressure to vital organs. The slight beta-1 adrenergic stimulation may enhance cardiac output in patients with shock, though the increase in myocardial oxygen demand is minimal compared to other inotropes.
In patients with septic or vasodilatory shock, Noradrenaline is particularly useful because it restores vascular tone and increases systemic vascular resistance, allowing for improved tissue perfusion and oxygen delivery.
Adverse Effects
Ischemia: Due to potent vasoconstriction, Noradrenaline can cause ischemia in peripheral tissues, including the skin, digits, and organs such as the kidneys. Prolonged use may lead to tissue necrosis if circulation is compromised.
Arrhythmias: Noradrenaline can increase the risk of arrhythmias, particularly tachycardia and ventricular arrhythmias, especially in patients with underlying cardiac conditions.
Hypertension: Excessive doses or prolonged use can result in severe hypertension, which may cause acute complications such as stroke or myocardial infarction.
Bradycardia: Reflex bradycardia can occur due to increased blood pressure, which activates baroreceptor reflexes that slow the heart rate.
Extravasation Injury: If Noradrenaline extravasates into surrounding tissues during IV administration, it can cause severe local tissue damage and necrosis. Immediate treatment with phentolamine or other vasodilators is required in such cases.
Drug Interactions
MAO Inhibitors and Tricyclic Antidepressants: Concurrent use of MAO inhibitors or tricyclic antidepressants can potentiate the vasopressor effects of Noradrenaline, leading to severe hypertension and arrhythmias.
Beta-blockers: Beta-blockers may reduce the positive inotropic effects of Noradrenaline on the heart, potentially leading to unopposed vasoconstriction and excessive hypertension.
General Anesthetics: Inhalation anesthetics such as halothane may sensitize the myocardium to catecholamines like Noradrenaline, increasing the risk of arrhythmias.
Sympathomimetics: Other sympathomimetics, such as epinephrine or dopamine, when used concurrently with Noradrenaline, may exacerbate vasoconstriction and increase the risk of severe hypertension and tissue ischemia.
Dosages
Adults (Shock): Noradrenaline is typically initiated at 0.01 to 0.05 mcg/kg/min, with the dose titrated based on blood pressure response. In severe shock, the dose may be increased to a maximum of 3 mcg/kg/min. The goal is to maintain a mean arterial pressure (MAP) of 65 mmHg or higher.
Children: The pediatric dose is generally 0.05 to 0.1 mcg/kg/min, titrated based on the clinical response. Close monitoring is required due to the risk of rapid changes in blood pressure and heart rate.
Renal Impairment: Noradrenaline is metabolized primarily by the liver and excreted as inactive metabolites, so no dose adjustment is required for renal impairment. However, its effects on renal perfusion may need close monitoring in patients with kidney dysfunction.
Hepatic Impairment: No specific dose adjustments are typically required in hepatic impairment. However, caution is advised due to potential alterations in drug metabolism.