Inalossin

Italy
Brand name Inalossin
Form gas, compressed
Active substance / Dosage
NITRIC OXIDE
Prescription type Restricted prescription – hospital or equivalent facility use only
ATC code
R07AX01
Registration number 040635
Manufacturer SOCIETA' ITALIANA ACETILENE & DERIVATI -S.I.A.D.- S.P.A.

Table of Contents

Patient and user information leaflet

INALOSSIN 400 ppm mol/mol compressed medicinal gas, 800 ppm mol/mol compressed medicinal gas

nitrous oxide
Please read this leaflet carefully before using this medicine as it contains
important information for you.

  • Keep this leaflet. You may need to read it again.
  • If you have any questions, consult your doctor or nurse.
  • If you experience any side effects, including those not listed in this leaflet, consult your doctor or nurse. See section 4.

Contents of this leaflet:

  1. What INALOSSIN is and what it is used for
  2. What you need to know before using INALOSSIN
  3. How to use INALOSSIN
  4. Possible side effects
  5. How to store INALOSSIN
  6. Contents of the pack and other information

1. What INALOSSIN is and what it is used for

INALOSSIN is a medicinal gas containing nitric oxide. Nitric oxide is a substance produced by cells in the human body and is involved in many processes occurring within the body; for example, it promotes the dilation of blood vessels.

INALOSSIN is used to treat:

  • respiratory failure in newborns (neonatal respiratory failure), including cases associated with high blood pressure in the lungs (persistent pulmonary hypertension of the newborn, PPHN);
  • respiratory failure in children and adults, associated with high blood pressure in the lungs (pulmonary hypertension of various etiologies), thereby increasing the amount of circulating oxygen (improvement of oxygenation).

INALOSSIN is administered only in hospitals by medical personnel or healthcare professionals with expertise.

2. What you need to know before using INALOSSIN

Do not use INALOSSIN if:

  • you are allergic to the active substance or to nitrogen (another component of this medicinal product);
  • you have a heart condition called left ventricular dysfunction;
  • the newborn has abnormal blood circulation within the heart (right-to-left shunt or significant left-to-right shunt);
  • the newborn suffers from a disease known as favism or fava bean disease, which causes a reduction in red blood cells (glucose-6-phosphate dehydrogenase deficiency);
  • high blood pressure in the lungs (pulmonary hypertension) is caused by increased blood flow to the lungs (pulmonary hyperperfusion);
  • you are pregnant or breastfeeding.

Warnings and precautions
Inform your doctor if:

  • you have heart problems, for example, issues with the heart ventricle, or suffer from diseases causing blood to pass from the left side to the right side of the heart (left-to-right shunt), increasing the amount of blood reaching the lungs (pulmonary hyperperfusion). In such cases, your doctor will perform specific tests, such as an echocardiogram, before administering INALOSSIN.

Exercise caution with INALOSSIN
INALOSSIN contains nitric oxide:

  • nitric oxide may cause an increase in blood levels of a protein called methemoglobin. If this occurs, the blood is no longer able to carry oxygen effectively;
  • nitric oxide, when in contact with oxygen, can be converted into nitrogen dioxide, an irritant to the bronchi that may cause lung injury. During treatment with INALOSSIN, your doctor will regularly perform blood tests to monitor methemoglobin levels and check nitrogen dioxide levels. If these parameters are found to be abnormal, your doctor will adjust the treatment appropriately, including reducing the dose of INALOSSIN.
  • Inhaled nitric oxide may have a mild effect on platelets (components involved in blood clotting). During treatment with INALOSSIN, your doctor will monitor for any signs of bleeding or bruising. If you notice any symptoms suggestive of bleeding, inform your doctor immediately.

No effect of inhaled nitric oxide has been documented in neonates with malformations due to incomplete diaphragm, so-called "congenital diaphragmatic hernia".
In neonates with specific heart malformations, known by doctors as "congenital heart defects", inhaled nitric oxide may cause worsening of circulation.

Children
The safety and efficacy of INALOSSIN in premature neonates with less than 34 weeks of gestation have not yet been established.

Other medicines and INALOSSIN
Inform your doctor if you are taking, have recently taken, or might take any other medicines, as certain drugs may interact with INALOSSIN or increase the risk of adverse events, even serious ones.
In particular, inform your doctor if you are taking:

  • medicines called "nitric oxide donors" such as sodium nitroprusside or nitroglycerin, used to dilate blood vessels;
  • medicines that may cause methemoglobin formation, such as alkyl nitrates, sulfonamides (a type of antibiotic), prilocaine (a type of local anesthetic used to relieve pain);
  • zaprinast or other medicines that dilate blood vessels;
  • dipyridamole, a medicine that affects blood coagulation;
  • sildenafil, a medicine used for erectile dysfunction;
  • prostacyclin and its analogues, medicines that dilate blood vessels and affect blood coagulation.

Pregnancy and breastfeeding
INALOSSIN must not be used during pregnancy and breastfeeding. If you are pregnant, suspect you may be pregnant, or are breastfeeding, inform your doctor.

Driving and using machines
Not applicable.

3. How to use INALOSSIN

INALOSSIN will be administered by medical personnel or experienced healthcare professionals who are familiar with the correct way to use this medicine. Your doctor will determine the dose and duration of treatment based on the severity of your illness and your age.

The usual dose of INALOSSIN ranges from 2 ppm (i.e. parts per million to be inhaled) up to a maximum of 20 ppm. Your doctor will use the lowest effective dose for the time necessary to achieve improvement in your respiratory condition.

During treatment with INALOSSIN, your doctor will regularly perform blood tests to monitor methemoglobin levels and will check nitrogen dioxide levels. If these parameters are found to be abnormal, your doctor will adjust the therapy appropriately by reducing the dose of INALOSSIN (see section 2, “Faccia attenzione con INALOSSIN”).

Method of administration
INALOSSIN is a medicine administered to the lungs through the mouth and nose (inhalation route), for example by using a mask.

INALOSSIN is delivered via a specific system called mechanical ventilation, which delivers the correct amount of nitric oxide by diluting INALOSSIN with an oxygen/air mixture immediately before administration. The mechanical ventilation system is equipped with devices that continuously monitor the levels of nitric oxide, oxygen, and nitrogen dioxide being inhaled, to ensure the safety of the treatment.

In certain clinical situations, nitric oxide administration may be performed using CPAP (continuous positive airway pressure) ventilation. The inhaled amount of nitric oxide aims to achieve the same effects as those obtained with mechanical ventilation.

If you are given more INALOSSIN than you should
Excessive administration of INALOSSIN may impair the blood's ability to carry oxygen (due to increased methemoglobin levels). Lung injury or accumulation of fluid in the lungs (pulmonary edema) may also occur (due to elevated nitrogen dioxide levels).

If excessively high doses of INALOSSIN are administered, your doctor will perform blood tests and, if necessary, take appropriate measures to improve the blood's ability to carry oxygen (symptomatic treatment of breathing problems, administration of medicines such as vitamin C or methylene blue, blood transfusion).

If you stop INALOSSIN treatment
Treatment with INALOSSIN must not be stopped abruptly. Sudden discontinuation may lead to a drop in blood oxygen concentration and/or an increase in pulmonary pressure. At the end of treatment, your doctor will gradually reduce (approximately every 30–60 minutes) the amount of INALOSSIN administered, allowing pulmonary circulation to return to normal without INALOSSIN.

If you have any doubts about how to use this medicine, consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Inform your doctor if, during treatment with INALOSSIN, you experience any of the following:

Very common side effects (may affect more than 1 in 10 people)

  • decrease in the number of platelets in the blood (thrombocytopenia).

Common side effects (may affect up to 1 in 10 people)

  • increased levels of sugar (hyperglycemia) or bilirubin (hyperbilirubinemia) in the blood,
  • decreased levels of potassium in the blood (hypokalemia);
  • decreased blood pressure (hypotension);
  • reduction of air in the lungs (atelectasis);
  • inflammation of the tissue beneath the skin (cellulitis);
  • presence of blood in the urine (hematuria).

Uncommon side effects (may affect between 1 in 100 and 1 in 1,000 people)

  • increased levels in the blood of a protein called methemoglobin, leading to reduced oxygen-carrying capacity.

Side effects with unknown frequency (frequency cannot be estimated from the available data)

  • bradycardia (slow heart rate) or too low oxygen levels in the blood (oxygen desaturation/hypoxemia) when treatment is suddenly stopped;
  • headache (cephalalgia), dizziness, dry throat, or lack of oxygen (hypoxia), or breathing difficulties (dyspnea) following accidental environmental exposure to nitric oxide (e.g. due to leakage from equipment or cylinder).

Immediately inform medical staff if you experience headaches when near a child undergoing treatment with INALOSSIN.
If any side effect worsens, or if you notice any side effect not listed in this leaflet, even after discharge of yourself or the child, inform your doctor.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at:
“https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse”. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store INALOSSIN

Keep this medicinal product out of the sight and reach of children.
Storage of INALOSSIN cylinders is the responsibility of the hospital.
The cylinder must be protected to prevent breakage or falling and must be kept away from
flammable or combustible materials and moisture, protected from rain and direct sunlight.
Keep the cylinder at a temperature between –10°C and +50°C.
Cylinders must be secured so as to remain in an upright position and must be stored in a clean,
well-ventilated, and locked area reserved exclusively for the storage of medicinal gases.
Do not use this medicinal product after the expiry date stated on the label. The expiry date refers
to the last day of that month.
When the cylinder is empty, do not dispose of it. Empty cylinders are collected by the supplier.

6. Package contents and other information

What INALOSSIN contains
The active substance is: nitric oxide.
INALOSSIN 400 - 800 ppm mol/mol compressed medicinal gas contains: 400 - 800 ppm mol/mol
of nitric oxide.
The other component is: nitrogen.

Description of the appearance of INALOSSIN and contents of the pack
INALOSSIN 400 - 800 ppm mol/mol compressed medicinal gas is available in aluminum cylinders of 2 - 5 - 10 - 20 litres, equipped with a valve.
A 2-litre INALOSSIN cylinder delivers 0.3 m³ of gas at a pressure of 1 bar at 15°C.
A 5-litre INALOSSIN cylinder delivers 0.75 m³ of gas at a pressure of 1 bar at 15°C.
A 10-litre INALOSSIN cylinder delivers 1.5 m³ of gas at a pressure of 1 bar at 15°C.
A 20-litre INALOSSIN cylinder delivers 3 m³ of gas at a pressure of 1 bar at 15°C.

Marketing Authorization Holder
Società Italiana Acetilene & Derivati "S.I.A.D." S.p.A. – Via S. Bernardino, 92 – Bergamo

Manufacturer
Società Italiana Acetilene & Derivati “S.I.A.D.” S.p.A. - S.S. 525 del Brembo, 1 - Osio Sopra (Bergamo)

INFORMATION INTENDED EXCLUSIVELY FOR PHYSICIANS OR HEALTHCARE PROFESSIONALS. FOR

FURTHER DETAILS, PLEASE CONSULT THE PRODUCT CHARACTERISTICS SUMMARY.
Discontinuation of Therapy
Nitric oxide administration must not be abruptly interrupted to avoid the risk of rebound hypoxemia and/or increased pulmonary arterial pressure (PAP) and/or worsening of blood oxygenation (PaO₂). Deterioration of oxygenation and increased PAP may occur even in patients without an evident response to treatment.
Gradual withdrawal of nitric oxide therapy should be performed cautiously. In patients receiving inhaled nitric oxide who require further medical care involving transfer to another hospital, administration of inhaled nitric oxide should be maintained during transport. The physician should have access to a backup nitric oxide delivery system at the patient’s bedside.

Formation of NO₂
Nitrogen dioxide (NO₂) forms rapidly within gaseous mixtures containing nitric oxide and oxygen (O₂), and thus nitric oxide may cause respiratory tract inflammation and injury. The dose of nitric oxide should be reduced if NO₂ concentration exceeds 0.5 ppm.
Prescription of nitric oxide must be supervised by an expert. It should be restricted to units that have received adequate training in the use of nitric oxide delivery systems.

Administration
Nitric oxide is delivered to the patient via mechanical ventilation, after dilution with an oxygen/air mixture, using an approved nitric oxide delivery system (bearing the CE mark). Before initiating therapy and during preparation, ensure that device settings match the gas concentration in the cylinder. The delivery system must allow inhalation of a stable concentration of nitric oxide regardless of the ventilator used. Additionally, contact time between nitric oxide and oxygen in the inspiratory circuit should be minimized to reduce the risk of formation of toxic oxidation by-products of the inhaled gas (see section 4.4).

In the presence of "continuous flow" ventilators (conventional or high-frequency oscillatory) recommended in neonatology, nitric oxide can be administered as a continuous flow into the inspiratory limb or at the Y-piece, and in all cases as close as possible to the patient and distal to the humidifier. The flow rate of a continuous-flow ventilator must be sufficient to minimize the formation of toxic by-products. For high-flow intermittent sequential ventilators, the nitric oxide delivery system must be capable of managing peak gas concentrations.

During the inspiratory phase, synchronized sequential administration is recommended to avoid peaks in nitric oxide concentration and the bolus effect induced by continuous gas administration.

In certain clinical situations, nitric oxide administration may be possible via CPAP (continuous positive airway pressure). The amount of inhaled nitric oxide aims to achieve the same effects as those obtained with mechanical ventilation.

Direct intratracheal administration should be avoided to minimize local injuries that may occur due to contact between nitric oxide and the mucosal membrane.

Monitoring of Treatment
The inspired concentration of nitric oxide must be continuously measured at the inspiratory limb of the circuit near the patient. Measurement of nitrogen dioxide (NO₂) and FiO₂ at the same site is also necessary, using calibrated and CE-marked monitoring equipment. For patient safety, appropriate alarms must be set for nitric oxide (±2 ppm from the prescribed dose), NO₂ (1 ppm), and FiO₂ (±0.05). The pressure of the nitric oxide cylinder must be continuously displayed to allow prompt replacement without interrupting therapy. Reserve cylinders must be available to ensure rapid replacement. Nitric oxide therapy must remain available for manual ventilation, e.g., during suctioning, patient transport, or resuscitation.

In the event of system failure or electrical power interruption, a battery backup supply and a reserve nitric oxide delivery system must be available. Power supply for monitoring devices must be independent of the delivery device function.

The upper exposure limit (time-weighted average) for nitric oxide for healthcare personnel, as defined by occupational safety legislation, is 25 ppm over 8 hours (30 mg/m³) in most countries worldwide, while the corresponding limit for NO₂ is 2–3 ppm (4–6 mg/m³).

Training for Administration
Key elements to be covered in hospital staff training are listed below.

Proper Setup and Connections

  • Connection to the gas cylinder and to the patient’s ventilator circuit.

Operation

  • Pre-use checklist procedure (a series of necessary steps immediately before initiating therapy for each patient, ensuring proper system function and removal of NO₂ from the system).
  • Device setting according to the correct nitric oxide concentration to be administered.
  • Setting up monitors for NO, NO₂, and O₂, including high and low alarm limits.
  • Use of the manual backup delivery system.
  • Procedures for correct gas cylinder replacement and system purging.
  • Alarm troubleshooting.
  • Calibration of NO, NO₂, and O₂ monitoring devices.
  • Procedures for monthly system performance checks.

Monitoring of Methemoglobin (MetHb) Formation
After inhalation, the main systemic metabolites of nitric oxide are methemoglobin (MetHb) and nitrate.
It is well known that neonates and infants have lower methemoglobin reductase activity compared to adults.

Methemoglobin concentration in blood should be monitored within one hour after initiation of INALOSSIN therapy, using an analyzer capable of reliably distinguishing fetal hemoglobin from methemoglobin. Although significant increases in methemoglobin are uncommon when baseline levels are low, methemoglobin levels should nevertheless be checked before treatment and then regularly during administration.

If methemoglobin levels exceed 2.5%, the nitric oxide dose should be reduced. Administration of reducing agents such as methylene blue may also be considered. Although significant increases in methemoglobin levels are uncommon when baseline levels are low, it is prudent to repeat methemoglobin measurements every day or every other day.

In adults undergoing cardiac surgery, methemoglobin levels should be measured within one hour after initiation of INALOSSIN therapy. If the methemoglobin fraction rises to a level that potentially compromises adequate oxygen delivery, the dose of INALOSSIN should be reduced, and administration of reducing agents such as methylene blue may be considered.

Monitoring of Nitrogen Dioxide (NO₂) Formation
Immediately before delivery to each patient, follow the correct procedure to remove NO₂ from the system. Maintain NO₂ concentration at the lowest possible level and in any case always <0.5 ppm. If NO₂ exceeds 0.5 ppm, inspect the delivery system for malfunctions, recalibrate the NO₂ analyzer, and reduce the amount of nitric oxide and/or FiO₂ if possible. If an unexpected change in nitric oxide concentration is observed, verify that the delivery system is not faulty and recalibrate the analyzer.

Gradual Discontinuation of Therapy
INALOSSIN treatment must not be abruptly discontinued to avoid rebound effects. The following weaning technique may be considered: reduce the dose gradually by 1 ppm every 30 minutes to 1 hour, while continuously monitoring pulmonary arterial pressure. If an increase in pulmonary arterial pressure occurs after discontinuation, nitric oxide should be re-administered at 5 ppm, and the weaning procedure may then be repeated. This method is applicable regardless of patient age.

Overdose
Nitric oxide overdose leads to increased levels of methemoglobin and NO₂. High NO₂ concentrations may cause acute lung injury, and cases of pulmonary edema have been reported following administration of high nitric oxide concentrations. Elevated methemoglobin levels reduce the oxygen-carrying capacity of the circulation.

In clinical studies, NO₂ levels >3 ppm or methemoglobin levels >7% were managed by reducing or completely discontinuing INALOSSIN treatment.

Actions to Take in Case of Accidental Overdose

  • Symptomatic treatment of respiratory disturbances.
  • In case of persistent methemoglobinemia despite dose reduction or treatment interruption, intravenous administration of vitamin C or methylene blue, or blood transfusion, should be considered depending on the patient’s clinical condition.

Actions to Take in Case of Massive Inhalation Due to Accidental Leak

  • Maintain medical observation of the patient for at least 24 hours in case of respiratory symptoms; administer symptomatic treatment. In case of methemoglobinemia, specific treatment (methylene blue) should be administered.

Instructions for Use and Handling
All personnel handling nitric oxide cylinders must have adequate knowledge of:

  • gas properties;
  • correct operational procedures for cylinders;
  • precautions and emergency actions.

Nitric oxide cylinders are intended exclusively for containing/transporting this gas for inhalation, for therapeutic use.
Strictly follow these instructions:

  • Carefully read the cylinder instruction and use manual (package insert).
  • Verify that all equipment is in good condition before use.
  • Securely fasten gas cylinders with chains or locks on a rack to maintain them in an upright position (especially smaller cylinders), prevent falls, protect from impact, and keep them below 50°C. Ensure adequate ventilation in rooms where the product is used. Cylinders must be fitted with a closed or tulip-shaped cap to protect the valve. Cylinders must be stored with valves closed.
  • Never open the cylinder valve abruptly.
  • Do not handle or use a cylinder whose valve lacks a protective cap.
  • At each new use, purge the flowmeter/pressure reducer three times using nitric oxide.
  • Handle equipment with clean, dry hands.
  • Lift and move cylinders only using an appropriate trolley; never lift by the valve.
  • Use specific, compatible connectors, tubing, or coupling hoses.
  • Pay particular attention to securing pressure reducers to cylinders by proper screwing to avoid accidental breakage or disconnection from the valve thread.
  • Absolutely no modifications are permitted on cylinder connectors, delivery equipment, or their accessories or components.
  • Do not attempt to repair defective valves or taps. Return such cylinders to the distributor/manufacturer.
  • Do not force the pressure reducer/flowmeter onto the valve thread using inappropriate tools, as this may break the seal and damage the delivery device.
  • Vent exhaled gases outdoors to prevent accumulation in confined areas. Before use, ensure the room has adequate ventilation in case of accidents or accidental leaks.
  • Since nitric oxide is colorless and odorless, a gas detection system is recommended in all rooms where it is used or stored.
  • Exposure limits for personnel (see section 4.2).

General Instructions for Use

  1. Remove the seal and protective cap from the outlet valve.
  2. Set aside the cap so it can be reinstalled after use.
  3. Do not remove, damage, or discard labels attached to the cylinder.
  4. Ensure the cylinder is equipped with a pressure regulator/reducer specifically designed for nitric oxide and that the connector is compatible with the cylinder valve.
  5. Ensure the connector on the pressure regulator/reducer is clean.
  6. Screw on the pressure regulator/reducer using moderate force, and connect tubing to the outlet of the regulator/reducer. Connect the flowmeter.
  7. When in use, the valve must be fully opened without forcing. Open the cylinder valve slowly and gradually (without forcing) and check for leaks. Leaks may be indicated by a hissing sound. Soapy water may be used to detect minor leaks. If a leak occurs between the valve outlet and the pressure reducer, remove the latter and check for correct, clean seals. Clean seals if necessary and reconnect the regulator/reducer. Never use sealing compounds or adhesives to stop a leak. If the leak persists, label the cylinder indicating the problem and return it to the manufacturer.

WARNING

  • Ensure the cylinder contains sufficient nitric oxide to complete the prescribed administration.
  • Check that the regulator connection is clean and in good condition before attaching it to the valve.
  • Verify that the pressure regulator is properly tightened before opening the valve.
  • Open the valve gradually to avoid pressure surges.
  • Do not force taps or valves during opening or closing.
  • Do not attempt to open or repair defective valves or reducers.
  • Never stand directly in front of the gas outlet of the tap/valve; always stand to the side. Do not expose yourself or the patient to direct gas flow.
  • Do not completely empty the container.
  • After use, close the cylinder valve.
  • In case of gas leakage, close the valve and notify the supplier’s technical service.
  • Use only cylinders suitable for nitric oxide, maintained at the specified pressures and temperatures, pressure regulators designed for medical air, and devices designed for medical air delivery.

During Use
When nitric oxide cylinders are in use, ensure that:

  • they are used only as medicinal gases (not for purposes other than those prescribed by the physician).
  • they are handled carefully without violent movements to prevent falls.
  • they are securely fastened in an upright position on a support.
  • markings, labels, or attached stickers are not altered or removed.
  • they are not used near smokers or near heat sources.

After Use
When the nitric oxide cylinder is empty, ensure that:

  • valves are manually closed without forcing, using only moderate force.
  • the pressure regulator and/or connection is depressurized.
  • the protective cap is reinstalled on the valve, properly seated.
  • empty cylinders with closed valves and protective caps are placed in a designated storage area prior to return to the manufacturer.

Disposal
Nitric oxide cylinders should not be disposed of as waste. Do not discharge into sewers, basements, or pits where gas accumulation could be hazardous.
Do not discard empty gas cylinders, as empty cylinders will be collected by the supplier.
Cylinders must be returned to the supplier with a slight residual gas content (residual pressure prevents cylinder contamination).
Any unused medicinal product residue remaining in the pressurized cylinder will be removed through appropriate procedures by the company responsible for subsequent refilling.
If, for safety reasons, a cylinder must be emptied after use, the gas should be released into the atmosphere in a well-ventilated area.
Contact the supplier for further information on cylinder emptying.
Unused medicinal product and waste derived from such medicinal product must be disposed of in accordance with applicable local regulations.

Fire Safety Measures
In case of risk of fire involvement:

  • Remove cylinders from areas that could be affected by fire.
  • Close cylinder valves to prevent gas flow.
  • Move cylinders away from heat sources.

In case of fire involvement:

  • Immediately remove cylinders from the heat source. If this is not possible, cool them with water from a safe position; move cylinders only after they have cooled to ambient temperature.
  • All types of fire extinguishers may be used in case of fire involving medical gas cylinders. No toxic combustion products are released by the medicinal gas.

Measures in Case of Accidental Opening
Close the cylinder valve immediately.

Cylinder Transport
Cylinders must be transported using appropriate equipment to protect them from impact and falls (e.g., trolley equipped with chains, barriers, or rings).
Particular attention must be paid to ensure there are no leaks and that cylinder valves are securely closed.
During vehicle transport, cylinders must be securely fastened, preferably in an upright position, in a compartment separate from the driver’s cabin. Permanent vehicle ventilation and a no-smoking policy must be ensured.
Ensure the driver is aware of the hazards associated with the load and knows what to do in case of accidents or emergencies. It is advisable to provide the driver with written instructions detailing actions to take in case of accident or emergency.

Incompatibilities
All equipment, including connectors, tubing, and circuits, used in nitric oxide delivery must be made of materials compatible with the gas. From a corrosion standpoint, the delivery system can be divided into two zones:

  1. from the cylinder valve to the humidifier (dry gas)
  2. from the humidifier to the outlet (humid gas that may contain NO₂).
    Tests show that "dry" nitric oxide can be used with most materials. However, the presence of nitrogen dioxide and moisture creates an aggressive environment. Therefore, only stainless steel is recommended among metallic construction materials.
    Polymers tested and found suitable for use in nitric oxide delivery systems include polyethylene (PE) and polypropylene (PP).
    Do not use butyl rubber, polyamide, or polyurethane.
    Polychlorotrifluoroethylene, hexafluoropropylene-vinylidene copolymer, and polytetrafluoroethylene have been extensively used with pure nitric oxide and other corrosive gases. These materials are considered inert and do not require specific testing.

Storage
Observe all applicable rules for the use and handling of pressurized cylinders.
Store cylinders at temperatures between -10°C and 50°C, in well-ventilated, cool-light illuminated areas equipped with appropriate emergency systems, in an upright position with valves closed, protected from rain, weather, direct sunlight, heat or ignition sources (including static electricity), and combustible materials.
Empty cylinders or those containing other types of gases must be stored separately.
Cylinders should be used in such a way that cylinders with earlier filling dates are used first.
Protect gas cylinders from impact, falls, oxidation, flammable materials, moisture, heat sources, or ignition sources.

Storage in Pharmacy Department
Store cylinders in a well-ventilated, clean, locked area reserved exclusively for storage of medicinal gases. Within this area, designate a separate section for nitric oxide cylinders.

Storage in Medical Department
Place the cylinder in a properly equipped site with appropriate material to keep it in an upright position.

Transport of Gas Cylinders
Transport gas cylinders using appropriate tools to protect them from impact and falls. During intra- or inter-hospital transfers of patients treated with nitric oxide, securely fasten cylinders in an upright position. Pay particular attention to securing the pressure regulator/reducer to prevent accidental damage.