From the Guidelines
The most common intracellular change after intravenous norepinephrine is an increase in intracellular calcium due to its vasoconstrictive effects.
Mechanism of Action
- Norepinephrine increases mean arterial pressure (MAP) due to its vasoconstrictive effects on alpha-receptors, with little change in heart rate and less increase in stroke volume compared with dopamine 1.
- The increase in intracellular calcium is a result of the activation of alpha-receptors, which leads to the influx of calcium ions into the cell.
Clinical Use
- Norepinephrine is commonly used to treat septic shock, where it is favored over dopamine due to its ability to increase systemic vascular resistance without causing significant tachycardia or arrhythmias 1.
- The recommended dosing of norepinephrine varies depending on the clinical context, but a common starting dose is 0.5 mg/h, which can be increased every 4 hours by 0.5 mg/h to a maximum of 3 mg/h 1.
Important Considerations
- Norepinephrine may reduce end-organ perfusion, and its use should be carefully monitored to avoid adverse effects 1.
- The use of norepinephrine should be guided by the patient's clinical response, including changes in blood pressure, urine output, and other indicators of organ perfusion 1.
From the FDA Drug Label
The following reactions can occur: ... Ischemic injury due to potent vasoconstrictor action and tissue hypoxia. Prolonged administration of any potent vasopressor may result in plasma volume depletion which should be continuously corrected by appropriate fluid and electrolyte replacement therapy If plasma volumes are not corrected, hypotension may recur when LEVOPHED is discontinued, or blood pressure may be maintained at the risk of severe peripheral and visceral vasoconstriction (e.g., decreased renal perfusion) with diminution in blood flow and tissue perfusion with subsequent tissue hypoxia and lactic acidosis and possible ischemic injury.
The intracellular change most common after intravenous norepinephrine is tissue hypoxia and lactic acidosis, resulting from decreased blood flow and tissue perfusion due to the potent vasoconstrictor action of the drug 2 2.
From the Research
Intracellular Changes after Intravenous Norepinephrine
- The most common intracellular change after intravenous norepinephrine is an increase in intracellular Ca2+ concentration ([Ca2+]i) due to Ca2+ release from intracellular stores 3.
- This increase in [Ca2+]i is a well-recognized event involved in regulating several metabolic functions.
- Norepinephrine induces a transient increase in [Ca2+]i that precedes the known Ca2+ influx, and this novel [Ca2+]i response to norepinephrine is detected in cells bathed with Ca2+-free saline and prevented by TMB-8, a blocker of Ca2+ release from intracellular stores 3.
Mechanisms of Norepinephrine-Induced Intracellular Changes
- Norepinephrine increases [Ca2+]i in cells by two mechanisms: (1) phasic release from intracellular stores and (2) tonic influx through a mechanism activated by larger applications of norepinephrine than required to evoke the phasic release 3.
- The increase in [Ca2+]i is associated with metabolic neural activation, and a tight direct correlation between norepinephrine-induced changes in metabolic activity and intracellular levels of oxygen and glucose suggests that local cerebral vasodilation is triggered via a neurovascular coupling mechanism 4.
Other Effects of Norepinephrine
- Norepinephrine also has effects on the immune response, including attenuating the production of proinflammatory mediators and augmenting anti-inflammatory IL-10 production, which can compromise host defense during sepsis 5.
- The cerebrovascular response to norepinephrine is unclear, with some studies demonstrating a direct vasoconstriction effect and others showing increases or decreases in regional cerebral blood flow (rCBF) or global cerebral blood flow (CBF) 6.