Inhaled Nitric Oxide

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Linda Melchor

I have been in the respiratory therapy field for over 30 years. I have worked as a staff therapist, clinical educator, and manager. I worked in all aspects of respiratory therapy from critical care staff therapist, nicu transport team, to air ambulance. My passion is teaching and organizing lecture series. In my off hours, you can find me at comic-con.

The Pre-brief

We ask, what is Nitric Oxide? Well, we can say that it’s a simple molecule that is composed of 1 atom of oxygen and 1 atom of nitrogen.  It is a colorless gas, known as NO, which has a very short half-life and is considered a free radical, which makes it volatile and reactive.  It reacts with metals and salts, such as iron and copper.  Inhaled Nitric Oxide (iNO) can be delivered via aerosol mask, nasal cannula, endotracheal tube, or tracheostomy.  iNO relaxes pulmonary vessels decreasing pulmonary vascular resistance and pulmonary arterial pressure. 

During iNO use, it’s important to keep an eye out for potential toxicity from the production of Nitric Dioxide (NO2) and methemoglobin levels.  NO can convert to NO2 in high areas of high oxygen concentration.  It is a good rule of thumb to keep the NO2 levels low around 2 parts per million (ppm).  While using NO, we need to monitor the patient’s blood at least once daily by checking the patient’s methemoglobin.  The reason for this is that NO binds to the red cells in the hemoglobin creating methemoglobinemia, which needs to be treated immediately due to its affinity to take up space for oxygen to bind to hemoglobin. 

Mechanism of Action

The mechanism of action for NO is that it diffuses rapidly across the alveolar-capillary membrane to the smooth muscle of the pulmonary vessels.  It can increase the intracellular concentration of cGMP, a messenger molecule, resulting in the relaxation of smooth muscle.  This muscle relaxation affects the muscles in the lungs which results in bronchodilation, anti-inflammatory, and anti-proliferative effects. Our bodies self-regulate keeping the ventilation and blood flow about equal in the lungs.   Inhaled NO is more effective than intravenous agents due to its delivery directly to the lungs and also helps to reduce intrapulmonary shunting.  

Treatment

We, as clinicians, use iNO to treat patients with pulmonary hypertension such as primary pulmonary hypertension and persistent pulmonary hypertension of the newborn. iNO was originally used for infants with PPHN and infants with a diaphragmatic hernia. Most recently it has been used in patients suffering from COVID-19 in combination with High-Frequency Oscillatory Ventilation (HFOV) (such as the 3100 series Oscillator) or High Frequency Percussive Ventilation (HFPV) (such as the VDR).  iNO can also be used to treat ischemia-reperfusion injury, post-op cardiac transplant, insertion of LVAD, ARDS, and COPD.

Selecting the dose for iNO usually is about 20ppm and can go up to as high as 40ppm.  As oxygenation improves, weaning can begin.  Once the FIO2 is 0.5 or less, iNO can be weaned in increments of 5ppm every hour. You will know if a patient is responding to iNO by monitoring their PaO2. iNO is rapidly metabolized in the body so be mindful when weaning to wean slowly or the patient could have a rebound pulmonary hypertension effect and instead of getting better, they worsen.  

Contraindications

Contradictions to iNO are those patients with congenital cardiac anomalies (ductal-dependent systemic blood flow), critical aortic stenosis, hypoplastic left heart and severe, left ventricular dysfunction, and methemoglobinemia.

The Debrief

  • iNO relaxes smooth muscles, increasing bronchodilation, and has anti-inflammatory effects
  • iNO has many uses in respiratory care, including PHTN, COVID-19, ARDS, and COPD
  • iNO should be weaned slowly to prevent rebound PHTN

References

  1. Dellinger RP, Zimmerman JL, Taylor RW, Straube RC, Hauser DL, Criner GJ, et al. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled nitric oxide in ARDS Study Group. Crit Care Med 1998; 26(1):15-23. 
  2. Branson RD, Hess DR, Campbell RS, Johannigman JA. Inhaled nitric oxide: delivery systems and monitoring. Resp Care 1999;44:281-306. 
  3. Hess DR. Adverse effects of toxicity of inhaled nitric oxide. Resp Care 1999;44:315-329. Bigatello LM. Strategies to enhance the efficacy of nitric oxide therapy. Resp Care 1999;44:331-337. 

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