From the FDA Drug Label
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action Norepinephrine is a peripheral vasoconstrictor (alpha-adrenergic action) and an inotropic stimulator of the heart and dilator of coronary arteries (beta-adrenergic action).
- 2 Pharmacodynamics The primary pharmacodynamic effects of norepinephrine are cardiac stimulation and vasoconstriction. Cardiac output is generally unaffected, although it can be decreased, and total peripheral resistance is also elevated.
The effect of norepinephrine on pulmonary hypertension is not directly addressed in the provided drug label.
- The label discusses the drug's mechanism of action and pharmacodynamic effects, including vasoconstriction and increased total peripheral resistance.
- However, it does not explicitly mention pulmonary hypertension. 1
From the Research
Noradrenaline (norepinephrine) should be used cautiously in patients with pulmonary hypertension as it can worsen the condition by increasing pulmonary vascular resistance. When treating hypotension in patients with pulmonary hypertension, alternative vasopressors like vasopressin (0.01-0.04 units/minute) or low-dose dobutamine (2-5 mcg/kg/minute) may be preferable, as suggested by a study published in 2020 2. If noradrenaline must be used, start at a low dose (0.01-0.05 mcg/kg/minute) and titrate carefully while monitoring pulmonary artery pressures. Noradrenaline primarily activates alpha-1 receptors causing systemic vasoconstriction, but this effect also occurs in the pulmonary circulation, potentially increasing right ventricular afterload and worsening right heart function. In pulmonary hypertension patients, the right ventricle is already strained, and further increases in pulmonary vascular resistance can precipitate right heart failure. Some studies, such as one published in 2016 3, have investigated the hemodynamic effects of various vasopressors in pediatric patients with pulmonary hypertension, but the most recent and relevant guidance for managing pulmonary hypertension is provided by the 2020 study 2. Inhaled pulmonary vasodilators like nitric oxide (5-40 ppm) or inhaled prostacyclins may be beneficial adjuncts when vasopressor support is needed in these patients to counterbalance the pulmonary vasoconstriction caused by systemic vasopressors. Key considerations in managing patients with pulmonary hypertension include:
- Avoiding hypoxia and hypercarbia
- Maintaining right ventricular preload support
- Judicious use of vasopressors and inotropes
- Restarting oral or intravenous PH medications that may have been discontinued
- Early imaging with chest radiograph, bedside echocardiogram, and computed tomography to determine the underlying etiology of PH exacerbation. Overall, the management of pulmonary hypertension requires careful consideration of the potential effects of various medications on pulmonary vascular resistance and right heart function, with a focus on minimizing morbidity, mortality, and improving quality of life.