Introduction
Nitrous oxide (NO) was first used as an endogenous endothelial-derived vasodilator in 1987. NO is a colorless, odorless gas that is used in a variety of respiratory therapies, particularly in the treatment of pulmonary hypertension.
Mechanism of Action
After inhalation, NO is rapidly absorbed from the alveolar space into the adjacent capillary where it activates guanylate cyclase in the pulmonary vascular smooth muscles. Activated guanylate cyclase then promotes the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (c-GMP), which causes relaxation of vascular smooth muscle.
A key feature of inhaled NO therapy is pulmonary bed vascular selectivity secondary to the rapid binding of NO by hemoglobin. Once in the blood, NO reacts with oxyhemoglobin to form methemoglobin and with deoxyhemoglobin to form iron-nitrosyl-hemoglobin. Ultimately, 70% of the inhaled NO is excreted in the urine as nitrate.
Clinical Use
Inhaled NO can be administered via a ventilator, face mask, or nasal cannula. Generally, the maximum current dose is 20 ppm as higher doses have not shown greater hemodynamic effects.
One of the most common uses of inhaled NO is for the treatment of pulmonary hypertension of the newborn (PPHN). In this setting, inhaled NO has been shown to improve oxygenation and to reduce the need for extracorporeal membrane oxygenation 9ECMO).
Other clinical applications for inhaled NO include acute respiratory distress syndrome, postoperative cardiac surgery, and post-lung transplantation. In cardiac surgery, cardiopulmonary bypass causes endothelial dysfunction and diminished endogenous NO production that leads to potentially lethal dysfunction and pulmonary hypertension.
The role for inhaled NO in patients with severe respiratory disease is less certain. The predominant mechanisms in respiratory disease with hypoxemia are intrapulmonary shunting and parenchymal lung disease. Some clinical evidence exists that show inhaled NO improves oxygenation but no differences in days of mechanical ventilation or improved mortality have been reported.
Inhaled NO is also used in the cardiac catheterization laboratory to selectively evaluate the pulmonary vascular reactivity potential in patients with known pulmonary hypertension as an indicator of the patient’s ability to respond to other vasodilating agents.
Side Effects
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