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Therapeutic Delivery of Inhaled Nitric Oxide

Nitric Oxide:

Nitric oxide (NO) is a colorless, highly diffusible, and very toxic gas. It is also a promising new treatment in the battle against respiratory distress syndrome (RDS) and persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide was first used on animals inflicted with pulmonary hypertension in 1991. Then in 1992, NO was used with some success in infants with PPHN . Although NO has been shown to be beneficial in some cases of RDS and PPHN, it is still considered to be an investigational drug by the FDA. All candidates for NO therapy must meet certain criteria passed down by the FDA.

NO is naturally formed within the vascular endothelial cells from L-arginine and molecular oxygen in a reaction catalyzed by NO synthase. The NO activates chemicals which lead to the relaxation of vascular smooth muscle. Scientists believe that NO production is impaired in the patient suffering from PPHN. Studies have shown that inhaled NO diffuses from the alveoli into smooth muscle causing relaxation. Thus proving that inhaled NO could be the potent pulmonary vasodilator that is needed.

Indications for inhaled Nitric Oxide:

Inhaled nitric oxide is indicated for the treatment of RDS and various other lung disorders characterized by pulmonary hypertension and hypoxemia. Other indications include pediatric patients with g.a. > 35 weeks through age 18 years that meet one or more of the following criteria:

  1. Acute hypoxemic respiratory failure as defined by an oxygenation index ³ 15 x 2 within six hours.
  2. Documentation of pulmonary hypertension by a pediatric cardiologist as determined by right to left shunting and flattening or reverse curvature of the intraventricular septum
  3. A 5-15 percent difference between pre- and postductal oxygen saturations

  4. Informed consent by a parent

Contraindications for inhaled Nitric Oxide:

There are certain contraindications to the delivery of nitric oxide for the RDS patient and the infant with pulmonary hypertension. Listed below are a few of the contraindications:

  1. Refractory hypotension despite adequate volume and vasopressor support
  2. Lethal congenital anomaly
  3. Life-threatening bleeding diathesis such as:
    1. Intraventricular hemorrhage, grade III or higher
    2. Active pulmonary or gastrointestinal hemorrhage
    3. Disseminated intravascular coagulation (DIC)
    4. Thrombocytopenia
  4. Patients with a disease process that is refractory to any further medical support

Equipment needed for delivery:

1. Ventilator

 

2. A cylinder filled with 400ppm nitric oxide, balance nitrogen

 

3. NO/NO2 monitor with audible and visual alarms, and environmental NO monitor

 

4. Required blenders, flowmeters/rotameters

 

5. Scavenger system attached to exhalation port
  1. Pulse oximeter
  2. End tidal CO2 monitor

View a powerpoint presentation of setting up the iNO delivery device by Scott Richey, RRT

 

Normal Doses of Delivered Nitric Oxide:

Most hospitals across the country start NO doses between 5-6ppm initially. The normal dose used throughout treatment is between 5-20ppm. If no response is recorded the dose may be increased gradually to a maximum dose of 80ppm. When the maximum dose is achieved and no response is noted then the patient is discontinued from this course of therapy and is considered a nonresponder to inhaled Nitric Oxide.

Complications of Inhaled Nitric Oxide:

Nitric oxide in the presence of oxygen will in most instances combine to become nitrogen dioxide. Nitrogen dioxide can bring on respiratory distress even when delivered in low doses. The monitoring of NO/NO2 is very important for this reason. High levels of NO2 have produced pulmonary edema when extremely high doses of inhaled nitric oxide are used.

Another critical value to monitor is the formation of methemoglobin. Nitric oxide has been found to have an affinity for hemoglobin that is 280 times faster than carbon monoxide, therefore, continuous monitoring is essential. High levels of methemoglobin can potentially interfere with tissue oxygen delivery and result in hypoxia. At some hospitals, methemoglobin levels < 4% are considered acceptable. If at any time the level rises above that point then the concentration of inhaled NO should be reduced or discontinued completely.

One other potential complication that should be mentioned is the possible effect on coagulation caused by decreased platelet aggregation. Although not fully understood, researchers do know that NO plays an important role in platelet aggregation and could have significant effects on coagulation.

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