Nitric Resource Manual

OBJECTIVES Describe the biologic basis for inhaled nitric oxide therapy Describe the indications for inhaled nitric oxide therapy Describe the potential hazards, side effects and contraindications of inhaled nitric oxide therapy Understand the charting and charging of inhaled nitric oxide Understand the setup and delivery of inhaled nitric oxide administration in conventional and HFOV Understand the policy and procedure for delivering inhaled nitric oxide Have a working understanding of the operation and troubleshooting of the INOvent This manual is intended as a resource for staff to understand the use and application of Nitric Oxide. This is not meant as a sole guide for Nitric Oxide application and use. Please refer to additional resources under References at the back of this manual.

Inhaled Nitric Oxide Biological Basis for the use of Inhaled Nitric Oxide Overview Interest in nitric oxide has been intense. More than 14,300 papers have been published on the subject of nitric oxide since 1966. The journal Science named nitric oxide Molecule of the Year in 1992. The initial studies of inhaled nitric oxide (ino) were conducted in the laboratory and in adult patients with primary pulmonary hypertension. Since that time there have been several hundred studies to determine the potential uses for ino. In selected groups of critically ill adult and pediatric patients, ino has shown to improve arterial oxygenation (Pa02) and in some cases, selectively reduced pulmonary artery hypertension (PAH). As a result of these and other ongoing studies, there are substantial indications for the use of ino for treating hypoxic respiratory failure in the newborn and for the assessment of pulmonary vascular reactivity in patients with pulmonary hypertension. Currently, there are several investigational studies for the use of ino for treating ARDS, lung and cardiac transplants, congenital and acquired heart disease, chronic pulmonary hypertension (PAH), meconium aspiration syndrome (MAS), and the treatment of acute chest syndrome in sickle cell disease. Until recently, the U.S. Food and Drug Administration (FDA) had approved the use of ino only for the treatment of hypoxic respiratory failure associated with Persistent Pulmonary Hypertension of the Newborn (PPHN). In January of 2004, the FDA gave approval for the use of ino in the treatment of Respiratory Distress Syndrome (RDS) and Acute Respiratory Failure (ARF).

ino A Selective Pulmonary Vasodilator Nitric oxide is a lipophilic, endogenous free radical molecule with biologic activity identical to endothelium-derived relaxing factor (EDRF). Nitric oxide is a naturally occurring molecule that is commonly found during volcanic reactions. It is a common pollutant found in cigarette smoke and the incomplete combustion of fossil fuels. Nitric oxide causes several reactions at the cellular level. Nitric oxide activates Guanylate Cyclase, which converts to cgmp. cgmp at the smooth muscle causes relaxation. When this occurs in the pulmonary vasculature, the result is a reduced pulmonary vascular resistance, redistribution of pulmonary circulation, and a reduction in right heart work. When ino is inhaled, this redistribution of pulmonary circulation is directed to the areas of the lung where ventilation is effective; and the improved matching of ventilation and perfusion can result in improved oxygenation. Nitric oxide, when inhaled, will diffuse rapidly across the alveolar capillary membrane into the vascular epithelium and adjacent smooth muscle. It almost instantly combines with hemoglobin and forms methemoglobin, preventing any systemic effect making it a selective pulmonary vasodilator. Even though ino is thought to be specific to the pulmonary vasculature, the fact is that the half life of ino in tissues is a few seconds thus preventing it from providing any systemic vasodilation. ino is rapidly oxidized to nitrite and nitrates and are eliminated in the urine.

Pathway for pulmonary bronchi dilation Reference:WWW.wellesley.edu/.../bindprotns/0199nobel4.gif

Research In studies using pre-term lambs, endogenous nitric oxide (NO) regulated the pulmonary vascular tone and helped with the normal fall in pulmonary vascular resistance (PVR) at birth. Additional studies with pre-term lambs showed that when endogenous NO was blocked; there was a significant increase in PVR. Furthermore, when NO production was inhibited during the delivery of the preterm lambs, the normal increase in pulmonary blood flow associated with mechanical ventilation and lung inflation was decreased markedly. Additionally, ino is thought to act as a second messenger in other naturally occurring physiologic processes such as neurotransmission, immune function and platelet aggregation.

Indications As stated previously, the FDA has approved the use of ino in neonates with Persistent Pulmonary Hypertension of the Newborn (PPHN), Respiratory Distress Syndrome (RDS), and Acute Respiratory Failure (ARF). Persistent Pulmonary Hypertension of the Newborn (PPHN) is a clinical syndrome that may result when pulmonary vascular resistance remains elevated rather that rapidly falling as it should during early postnatal period. Respiratory Distress Syndrome is a disease primarily of premature infants with a decreased surfactant production and/or release resulting in pulmonary hyaline membranes, atelectasis, and poor lung compliance. Respiratory failure is the inability to maintain gas exchange at a rate that matches the body s metabolic demands. Acute respiratory failure (ARF) is diagnosed when the patient loses the ability to ventilate or to adequately provide enough oxygen to the blood and systemic organs. Some centers have been proponents of using ino in treating pulmonary artery hypertension (PAH) associated with congenital diaphragmatic hernia. There are a limited number of studies associated with this modality of therapy and the results do not support the use of ino in this disease process. There are several other potential uses for ino, but use of ino in these cases is considered off label use. Off label use refers to use of a product/drug which does not have approval by the FDA. Several studies are underway to determine the usefulness of ino for relieving symptoms associated with sickle cell chest syndrome, acute respiratory distress syndrome, status asthmaticus, lung and cardiac transplants, congenital cardiac anomalies and acquired cardiac diseases.

Contraindications There are few true contraindications for the use of ino but one that is an absolute is in infants which are known to be dependent on right to left shunting. The use of ino is contraindicated when there is an existing methemoglobinemia. The use of ino however can cause methmoglobinemia. As stated previously, NO is a naturally occurring molecule. The body produces a small amount NO, (4-6 parts per billion) and is responsible for smooth muscle relaxation in the pulmonary vasculature. NO has a tremendous affinity for binding to hemoglobin. NO has an affinity that is 200 times greater than carbon monoxide (CO) for biding to hemoglobin. CO has an affinity that is 200 times greater than oxygen (O2) for binding to hemoglobin. Premature infants do not tolerate excessive levels of Met Hb very well. Due to their prematurity, premature infants have an extremely difficult time breaking down Met Hb. Patients suffering from Met Hb levels >10%, demonstrate a chocolate brown colored blood. Patients who have an initial baseline Met Hb of 1.5% have been shown to be at risk for developing methmoglobinemia. A level change of greater than 3% from baseline is considered a sign of developing methmoglobinemia and should be reported to either the fellow or the attending physician immediately. The primary hazard of using ino is the development of nitrogen dioxide (NO2). NO2 is a caustic gas that can cause damage to lung tissue and must be considered hazardous. NO2 is formed when NO and O2 are combined. NO2 formation may increase as oxygen and/or NO levels are increased. NO2 levels of greater than 1 ppm are considered critical and require immediate physician notification. WARNING: you MUST purge the regulator assembly immediately before (within 5 minutes of use on patient or changing of NO tank) using the INOvent to make sure the patient receives the correct NO concentration and does not receive high NO2 concentrations.

Documentation Choose Flowsheets

Documentation

Documentation (cont)

Fax your Nitric Log to Tessie Q- shift

Dosing Clinical Guidelines suggest an initial recommended dose of ino to be 20 ppm. If the patient does not respond When you set the ordered dose of nitric oxide, the INOvent uses a specifically designed injector module that injects a proportional amount of nitric oxide, based on ventilator flow rate and mode, ensuring the delivery of a constant concentration of nitric oxide throughout the inspired breath.

Injector Module

When ino is discontinued, the therapist discontinuing the therapy must do the following:

Alarm Settings Alarm settings should be set as follows: High/low FiO2 alarms at 5% above/below ordered FiO2. Remember to set alarm limits and document FiO2 measured at INOvent, not from the ventilator. Set the high NO2 at 1 ppm. Set the high/low NO alarm 2-3 ppm above/below the ordered NO. When delivering 5 ppm or less, the low alarm should be set at 0.5 to 1 ppm.

NO, NO2, and O2 Sensor low range calibration Done Q shift

NO, NO2, and O2 Sensor low range calibration (cont)

O2, NO, NO2, High Range Calibration The high range calibration must be done the 1st Tuesday of every month. This is normally done by the pediatric and adult team leaders.

Oxygen Sensor High Cal (cont)

Nitric Oxide (NO) High Calibration

Nitric Dioxide (NO2) High Calibration

System Purge and Performance WARNING: Make sure a purge has been completed within five (5) minutes before the start of NO therapy. If not, repeat the performance test as described here, making sure the NO2 is less than the value listed for the cylinder concentration being used. 1. 2. Connect the Injector Module to an O2 flowmeter using O2 tubing, a 4.5mm to 15mm adapter and breathing circuit adapter to condition the flow before the Injector Module. Connect a sample tee to the outlet of the injector module with a 6 length of 22 mm corrugated tubing to ensure gas mixing prior to gas sampling. Attach a sampling line from the sample tee to the sample connector on the front panel. 3. Do a low range calibration of the NO, NO2, and O2 monitors. 4. Make sure both NO cylinders are turned off after being turned on. 5. Set the oxygen flow to 15 lpm and the set NO concentration to its maximum setting.

System Purge and Performance (cont) 6. Make sure both cylinder high pressure gauges go to zero to purge both high pressure circuits. 7. Check that the NO2 value is higher than 0.2ppm to verify that the NO2 monitor is functional. 8. Make sure these two alarms occur: 9. Low NO/N2 Pressure 10. Delivery Failure - This may take a few minutes depending on cylinder pressures at the start of the test. 11. When the alarms have occurred, turn one of the tanks on and leave the other off. 12. Set the O2 flow on the auxiliary flowmeter to 15 lpm and set the NO to 40ppm. 13. Wait 3 minutes or until the monitor readings are stable 14. Make sure that the O2, NO2, and NO readings are within the acceptable ranges given below. Note: These acceptable readings include the errors of the NO delivery system and the NO gas Set NO 40ppm O2% (+/- 3%) 95 NO2ppm (max) 1.5 NO ppm (min/max) 32/48 You may refer to the Purge and Performance Test card located on the side of the machine.

Make sure and connect the INO connector to the blender.

Conventional Ventilator (Setup) Make sure that the arrow on the injector module is pointing away from the ventilator. Connect the Injector Module close to the ventilator on the Inspiratory Limb Place your sample line at least 6 inches away from the wye of the circuit.

High Frequency Oscillatory Ventilation - HFOV (Setup)