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What is this guide about?
This guide covers the Nitric Oxide Delivery System (iNO system) used in neonatal intensive care units (NICUs). It explains what the device is, how it works, how it is used, and what precautions are essential. This is a hospital-based device operated only by trained medical professionals.

Introduction

Inhaled nitric oxide (iNO) therapy is one of the most important advances in neonatal critical care. It is used to treat newborns who have serious breathing problems caused by high blood pressure in the lungs - a condition called Persistent Pulmonary Hypertension of the Newborn (PPHN).

A Nitric Oxide Delivery System (NODS) is a specialized medical device that delivers a precise, controlled amount of nitric oxide gas into a ventilator circuit. The gas travels into the baby's lungs and helps relax the tightened blood vessels there, making it easier for oxygen to pass into the bloodstream.

Nitric oxide (NO) is a gas that the body also produces naturally. When inhaled at controlled, low doses, it acts only on the blood vessels in the lungs without affecting the rest of the body. This selective action makes it a very effective and targeted treatment.

Purpose and Where It Is Used

Primary Medical Use

The nitric oxide delivery system is used to treat:

Persistent Pulmonary Hypertension of the Newborn (PPHN) - The most common and main indication
Hypoxic Respiratory Failure (HRF) - When a newborn cannot maintain enough oxygen levels
Meconium Aspiration Syndrome (MAS) - When a baby inhales meconium (first stool) before or during birth
Respiratory Distress Syndrome (RDS) - Lung immaturity in premature babies
Congenital Diaphragmatic Hernia (CDH) - A birth defect where organs push into the chest cavity
Neonatal Sepsis - Serious infections that affect lung circulation

Where Is It Used?

Setting	Details
Neonatal Intensive Care Unit (NICU)	Primary place of use, equipped with mechanical ventilators
Pediatric Intensive Care Unit (PICU)	For older children with pulmonary hypertension
Cardiac Surgery Units	Post-operative care for children with heart defects
Neonatal Transport	Portable systems used during inter-hospital transfer of sick neonates
MRI Suites	Special MRI-compatible systems available for this purpose

Key Fact: Inhaled nitric oxide is approved for use in term and near-term neonates (gestational age greater than 34 weeks). Its use in very premature babies is done under close monitoring and is considered investigational in many countries.

How It Works (Simple Explanation)

Normally, blood vessels in the lungs are relaxed and allow blood to flow through easily to pick up oxygen. In PPHN, these vessels become tight (constricted), so blood cannot flow well and the baby does not get enough oxygen.

When nitric oxide is inhaled, it goes directly into the small air sacs (alveoli) of the lungs. There, it relaxes the walls of the nearby blood vessels, allowing more blood to flow through and pick up oxygen. Because NO is rapidly broken down by hemoglobin in the blood, it does not travel to the rest of the body. This means it works only in the lungs - which is exactly what is needed.

Types of Nitric Oxide Delivery Systems

Several FDA-cleared or internationally approved systems exist. All are hospital-use-only devices operated by trained staff.

System Name	Manufacturer	Key Feature
INOmax DSIR Plus	Mallinckrodt Pharmaceuticals	Most widely used; validated with many ventilators; has MRI-compatible version
Genosyl DS	Vero Biotech	FDA-approved; alternative to INOmax; portable design
NOxBOX i	Linde/Air Products	Used widely in Europe; portable monitor; continuous and synchronous delivery modes
INOvent	Datex-Ohmeda/GE Healthcare	Older system, used in some NICUs globally
AeroNOx	International Biomedical	Transport-capable; can be used with high-frequency ventilators during neonatal transport

By Delivery Mode

Continuous flow systems: Deliver a constant amount of NO into the ventilator circuit. Most common type.
Demand or synchronized flow systems: Deliver NO only during the patient's inhalation phase. Reduces NO2 buildup.
Transport systems: Compact, battery-powered, designed for ambulance or helicopter use.
Non-invasive delivery systems: Deliver NO through nasal CPAP or high-flow nasal cannula (HFNC). Used when a baby is not on a full ventilator.

Components of a Nitric Oxide Delivery System

NO Gas Cylinder: A pressurized tank containing nitric oxide at a known concentration (commonly 800 ppm or 4,880 ppm). The gas is diluted before delivery.
Flow Control Valve: Controls exactly how much NO is released from the cylinder.
Mixing Chamber / Injector: Mixes NO precisely with the ventilator gas flow before it reaches the patient.
Flow Sensor / Transducer: Measures the total gas flow and adjusts NO delivery accordingly.
NO and NO2 Analyzers: Continuously monitor the actual concentration of nitric oxide (NO) and nitrogen dioxide (NO2) being delivered to the patient.
Oxygen Analyzer: Monitors oxygen levels in the circuit.
Central Processing Unit (CPU): Calculates and adjusts NO delivery in real time to maintain the set concentration.
Alarm System: Alerts when gas levels are too high or too low, or if equipment fails.
Backup Battery: Maintains function during power failure.
Reserve System: A backup NO delivery system is kept available at all times.

Step-by-Step: How the Nitric Oxide Delivery System Is Used

This device is used exclusively by trained clinical staff in a hospital setting. The following outlines the standard process:

1Patient Assessment: A physician confirms the clinical indication (e.g., PPHN, hypoxic respiratory failure). An echocardiogram (heart ultrasound) is done to rule out congenital heart disease that might be worsened by iNO (such as left ventricular dysfunction or ductal-dependent circulation).

2Ventilator Setup: The baby is placed on a mechanical ventilator first. Adequate lung inflation is confirmed before starting iNO - poor lung inflation reduces the effectiveness of the therapy.

3System Assembly and Calibration: The NO delivery system is assembled and connected to the ventilator circuit according to the manufacturer's instructions. The NO and NO2 analyzers are calibrated. Incorrect calibration can cause under- or over-dosing.

4Starting the Therapy: The standard starting dose is 20 ppm (parts per million). Doses above 20 ppm are not recommended. The device automatically controls and adjusts flow to maintain this concentration.

5Monitoring During Therapy: Continuous monitoring includes: oxygen saturation (SpO2), blood oxygen levels (PaO2), methemoglobin levels (measured in blood), NO concentration, NO2 levels (must remain very low), and vital signs. Methemoglobin should be checked within 4-8 hours of starting therapy and then regularly throughout.

6Duration of Treatment: Treatment is typically continued for up to 14 days or until the baby's oxygen levels improve and stabilize. Most babies improve within the first few days.

7Weaning (Gradual Reduction): The dose is never stopped abruptly. It is reduced step by step (e.g., from 20 ppm to 5 ppm to 1 ppm). At each step, the baby is observed for several hours for any drop in oxygen levels. Abrupt stopping can cause a dangerous rebound effect (sudden worsening of lung blood pressure).

8Discontinuation: Once the baby maintains good oxygen levels without iNO, the therapy is fully stopped. The baby remains on the ventilator and continues to be monitored closely.

Precautions and Risks

Important: This is a high-risk medical therapy. It must only be set up, adjusted, and monitored by trained healthcare professionals. It is never used outside a hospital.

Key Risks and Side Effects

Risk / Side Effect	What It Means
Methemoglobinemia	NO reacts with hemoglobin and reduces its ability to carry oxygen. Blood levels must be monitored regularly.
Rebound Pulmonary Hypertension	Abruptly stopping iNO causes a sudden spike in lung blood pressure. Always wean gradually.
Nitrogen Dioxide (NO2) Toxicity	NO reacts with oxygen to form NO2, which is toxic. High NO2 can damage lung tissue. Continuous monitoring is essential.
Worsening in Left Heart Failure	In babies with left ventricular dysfunction, iNO may increase pressure in the pulmonary veins (pulmonary capillary wedge pressure). Contraindicated in this situation.
Hypotension (low blood pressure)	The most common side effect. Blood pressure must be monitored throughout therapy.
Bleeding Risk	NO can reduce platelet aggregation (clotting). Monitor for signs of unusual bleeding.

Contraindications (When NOT to Use)

Newborns dependent on right-to-left blood shunting (certain complex heart conditions such as hypoplastic left heart syndrome)
Significant left ventricular failure
Elevated methemoglobin levels that do not improve

Staff Safety

Accidental exposure to nitric oxide gas in hospital staff has been associated with headache, dizziness, dry throat, chest discomfort, and breathing difficulty. Proper room ventilation and system leak checks are essential. Staff should not be exposed to high concentrations of NO or NO2.

Equipment Safety

Always keep a backup battery power supply ready
Always keep an independent reserve NO delivery system nearby
Calibrate analyzers before each use and regularly during treatment
Use only validated ventilator-NODS combinations specified by the manufacturer
In MRI suites, only MRI-compatible cylinders and systems should be used

Monitoring Summary

Parameter	How Often
Oxygen saturation (SpO2)	Continuous
NO concentration	Continuous
NO2 concentration	Continuous
Methemoglobin (blood test)	Within 4-8 hours of starting, then every 4-24 hours
Blood oxygen levels (PaO2)	Regular arterial blood gas monitoring
Blood pressure and heart rate	Continuous
Echocardiogram (heart ultrasound)	Before starting and as clinically needed

Frequently Asked Questions (FAQ)

What is the standard dose of inhaled nitric oxide for newborns?

The recommended starting dose is 20 ppm (parts per million). Doses above 20 ppm are not recommended because higher doses increase the risk of side effects without added benefit.

How long does nitric oxide therapy last?

Treatment is continued for up to 14 days. Most babies show improvement within 4 days. Therapy is stopped gradually once the baby maintains stable oxygen levels.

Can nitric oxide therapy be stopped suddenly?

No. Abrupt stopping can cause rebound pulmonary hypertension - a sudden dangerous worsening of lung blood pressure. The dose must always be reduced step by step with careful monitoring at each step.

What is methemoglobin and why is it monitored?

Methemoglobin is a form of hemoglobin that cannot carry oxygen properly. Nitric oxide reacts with hemoglobin to form methemoglobin as a side effect. If levels become too high, oxygen delivery to the body is reduced. That is why blood tests are done regularly during iNO therapy. If levels are elevated, the dose is reduced or stopped, and additional treatment may be needed.

Is inhaled nitric oxide used for premature babies?

It is approved for use in neonates born at more than 34 weeks of gestation. Its use in very preterm babies (less than 34 weeks) has been studied but has not shown a clear consistent benefit in preventing complications like chronic lung disease, and is considered investigational in most countries.

Is nitric oxide used only in newborns?

Primarily, yes - in the neonatal setting. In older children, it is used in PICUs and cardiac surgery units for pulmonary hypertension. In adults, while studied for conditions like ARDS, it has not been shown to improve survival and is not a standard adult treatment.

What happens if the power goes out during therapy?

All nitric oxide delivery systems are required to have a backup battery and an independent reserve delivery system on hand. Abrupt interruption of NO therapy is dangerous because of the rebound effect, so emergency backup is mandatory.

What is nitrogen dioxide (NO2) and why is it dangerous?

When nitric oxide mixes with oxygen, some of it converts to nitrogen dioxide (NO2). NO2 is a toxic gas that can irritate and damage lung tissue. The delivery system continuously monitors NO2 levels and keeps them as low as possible. Proper calibration and modern delivery systems minimize this risk.

What is the difference between different brands of iNO delivery systems?

All FDA-cleared or approved systems serve the same purpose - delivering precise, safe concentrations of NO. They differ in design, portability, compatible ventilators, and availability in different countries. Not all systems are compatible with all ventilators, so the correct validated combination must always be used.

Can nitric oxide therapy be given without a ventilator?

Usually, iNO is given through a mechanical ventilator via an endotracheal tube. In some cases, it can be delivered non-invasively through nasal CPAP or high-flow nasal cannula. However, the actual dose reaching the lungs through non-invasive routes can vary and requires careful monitoring.

How to Keep the Device Safe and Well-Maintained

Device Safety Checklist (for clinical staff):

Calibrate NO and NO2 analyzers before each new patient and regularly during treatment
Check all gas connections and tubing for leaks before use
Ensure backup battery is charged and functional at all times
Keep a reserve NO delivery system immediately available
Use only manufacturer-approved ventilator-NODS combinations
Never exceed recommended NO concentrations in the gas cylinder storage areas
Store NO cylinders upright in a well-ventilated area, away from heat and direct sunlight
Follow local hospital protocols for cylinder change procedures
Do not use the system if any alarm is sounding without first identifying and correcting the cause
Perform scheduled preventive maintenance as recommended by the manufacturer
Document all readings, calibrations, and any equipment issues
Ensure all staff are trained specifically for the brand of system in use

NO Gas Cylinder Storage

Store in a locked, well-ventilated area designated for compressed medical gases
Keep away from flammable materials, heat sources, and direct sunlight
Secure cylinders upright with chains or brackets to prevent falling
Label cylinders clearly and check expiry dates
Track cylinder levels - do not allow cylinders to run very low during therapy

Additional Information

Response to Therapy

A response to iNO therapy is considered positive if oxygen levels improve within 30-60 minutes of starting treatment. About 50-60% of babies with PPHN show a significant improvement. If there is no response after an adequate trial, other therapies such as ECMO (extracorporeal membrane oxygenation) may be considered.

Combination with High-Frequency Ventilation

Research shows that combining iNO with high-frequency oscillatory ventilation (HFOV) can improve results in certain babies, especially those with PPHN associated with meconium aspiration syndrome or significant lung disease. Better lung inflation during HFOV helps iNO reach more of the lung and work more effectively.

Global Availability

In high-income countries, iNO therapy is widely available in tertiary NICUs. In low- and middle-income countries, access is more limited due to cost of the gas, cylinders, and delivery systems. Efforts are ongoing to improve access globally. Different delivery systems have different regulatory approvals depending on the country or region - always use a system that is approved for use in the relevant jurisdiction.

Medical Device Guides

Nitric Oxide Delivery System