Podtlenek Azotu Medihni Air Liquide

Leaflet accompanying the packaging: patient information

Medical Nitrous Oxide Air Liquide, 100%, liquefied medical gas
Dinitrogenii oxidum
You should carefully read the contents of the leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so that you can read it again if you need to.
• If you have any doubts, you should consult a doctor or pharmacist.
• The medicine may harm another person, even if their disease symptoms are the same.
• If the patient experiences any side effects, including any side effects not listed in this leaflet, they should tell their doctor or pharmacist. See section 4.

Table of contents of the leaflet:

• 1. What is Medical Nitrous Oxide Air Liquide and what is it used for
• 2. Important information before using Medical Nitrous Oxide Air Liquide
• 3. How to use Medical Nitrous Oxide Air Liquide
• 4. Possible side effects
• 5. How to store Medical Nitrous Oxide Air Liquide
• 6. Contents of the packaging and other information

1. What is Medical Nitrous Oxide Air Liquide and what is it used for

Medical Nitrous Oxide Air Liquidebelongs to the group of general anesthetics (nervous system and central nervous system) and is an inhalation gas.
The medicine is intended for use only in hospitals.
The use of this medicine is indicated in the following cases:

• auxiliary medicine for general anesthesia, in combination with other anesthetics administered intravenously or by inhalation.
• auxiliary medicine for pain relief in shallow anesthesia without loss of consciousness during short, painful procedures, such as after an accident, with burns, dental procedures, childbirth, and otolaryngological surgery (related to the ear).

2. Important information before using Medical Nitrous Oxide Air Liquide

When not to use Medical Nitrous Oxide Air Liquide:

• if the patient requires 100% oxygen ventilation.
• in any conditions where air is trapped inside the body and its expansion may pose a risk, for example: head injuries, maxillofacial injuries, pneumothorax, gas embolism, decompression sickness, in patients who have recently dived, in patients who have undergone pneumoencephalography, in cases of bullous emphysema, during middle ear or inner ear surgery, in cases of significant abdominal distension (e.g. intestinal obstruction), when air has been injected into the epidural space to determine the position of the needle during epidural anesthesia.
• patients who have recently undergone intraocular gas injection (such as sulfur hexafluoride, octafluoropropane, hexafluoroethane), as long as the gas bubble remains in the eyeball or for a period of 3 months after the last gas injection into the eyeball. Expansion of the gas bubble in the eyeball under the influence of nitrous oxide can cause serious vision damage.
• do not use for more than 24 hours.
• in case of any change in the state of consciousness that disrupts cooperation with the patient during the use of nitrous oxide for pain relief.

Warnings and precautions

• nitrous oxide should always be administered with at least 21% oxygen.
• nitrous oxide causes inactivation of vitamin B12 (a cofactor of methionine synthase) which affects folate metabolism. As a result, DNA synthesis is disrupted after prolonged administration of nitrous oxide. Frequent or prolonged use of nitrous oxide may cause megaloblastic changes in bone marrow cells and potentially megaloblastic anemia and subacute combined degeneration of the spinal cord (see also section 4).
• in patients with undiagnosed asymptomatic vitamin B12 deficiency during general anesthesia, neurological toxicity has been observed after single exposure to nitrous oxide.
• before using nitrous oxide for anesthesia in patients with risk factors for vitamin B12 deficiency, it is necessary to check the level of vitamin B12. Risk factors may include alcohol dependence, patients suffering from anemia or atrophic gastritis, people following a vegetarian diet. Risk factors also include megaloblastic anemia, stomach cancer, post-gastrectomy, intestinal diseases, malabsorption, long-term use of proton pump inhibitors, and others. In appropriate cases, especially with prolonged and repeated use of nitrous oxide, it is necessary to administer vitamin B12 to the patient.

When nitrous oxide is used for pain relief:

• self-administration of the medicine should be preferred to allow for assessment of the level of consciousness
• careful monitoring of patients taking medications that impair the function of the central nervous system, especially opioids and benzodiazepines, is necessary due to the increased risk of deep sedation
• nitrous oxide is an oxidizing gas that facilitates and accelerates combustion.
• special caution should be exercised in patients with heart failure, if the administration of nitrous oxide leads to the occurrence of hypotension (low blood pressure) or heart failure, the administration of the gas should be stopped immediately.
• special caution should be exercised in patients who have undergone nasal or middle ear surgery.
• -rooms where N2O is used must be equipped with an appropriate gas disposal or ventilation system to maintain the nitrogen concentration at a minimal level and below established national occupational exposure limits. In case of Eustachian tube obstruction, increased pressure in the middle ear cavity may result in ear pain and/or middle ear disorders and/or eardrum rupture

Children and adolescents
Nitrous oxide can rarely cause respiratory depression in newborns.
A newborn should be examined for the possibility of respiratory depression if nitrous oxide was used during the perinatal period.

Medical Nitrous Oxide Air Liquide and other medicines

You should tell your doctor about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
In appropriate cases, especially with prolonged and repeated use of nitrous oxide, it is necessary to administer vitamin B12 to the patient (see "Warnings and precautions" above and section 4).
Medicines that interfere with vitamin B12 and/or folate metabolism may enhance the inactivation of vitamin B12 by nitrous oxide.
Patients who have recently undergone intraocular gas injection (such as sulfur hexafluoride, octafluoropropane, hexafluoroethane), as long as the gas bubble remains in the eyeball or for a period of 3 months after the last gas injection into the eyeball. Expansion of the gas bubble in the eyeball under the influence of nitrous oxide can cause serious vision damage.
Nitrous oxide enhances the sedative effect (drowsiness, sleep disorders) of anesthetics that impair the function of the central nervous system administered intravenously or by inhalation (thiopental, benzodiazepines, morphine derivatives, fluorinated anesthetics, or other psychotropic drugs), so the dose of these medicines should be reduced if they are administered simultaneously.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult your doctor before using this medicine.
Pregnancy:
Multiple data on pregnant women who have used a single dose of nitrous oxide in the first trimester (over 1000 exposure results) indicate no toxicity causing developmental anomalies. Additionally, exposure to nitrous oxide during pregnancy is not directly associated with toxicity to the fetus or newborn. Nitrous oxide can therefore be used during pregnancy in cases of clinically justified need. If nitrous oxide is used shortly before delivery, newborns should be monitored for potential side effects.
Pregnant women should be given nitrous oxide at a concentration not exceeding 50% of nitrous oxide in the inhaled mixture.
Fertility:
There is no relevant human data.
Breastfeeding
It is not known to what extent nitrous oxide passes into breast milk. After short-term use of nitrous oxide, considering the very short half-life, it is not necessary to interrupt breastfeeding.

Driving and using machines

After stopping the administration of nitrous oxide, especially after prolonged use, outpatients who are forced to drive or operate machines should be under medical supervision until they regain the same level of alertness as before the administration of the medicine.

3. How to use Medical Nitrous Oxide Air Liquide

Medical Nitrous Oxide Air Liquide can only be administered in hospitals by medical personnel, in accordance with the doctor's recommendations. In case of doubts, you should consult a doctor.
Nitrous oxide should only be administered during surgical procedures or in the delivery room, after mixing it with oxygen.
The doctor will determine the appropriate dose of nitrous oxide, which will be administered in an appropriate manner, depending on the patient's needs, ensuring an adequate amount of oxygen for the patient's body.

Using a higher dose of Medical Nitrous Oxide Air Liquide than recommended

• During analgesic use, an overdose may result in dizziness, loss of consciousness, cyanosis, and death due to too little oxygen. In such a situation, the doctor will immediately stop the administration of nitrous oxide and take appropriate actions.
• In the case of an overdose in general anesthesia (inhalation of nitrous oxide at a concentration above 70%), symptoms of hypoxia may occur. In such a situation, the fraction of inhaled nitrous oxide should be reduced, and the anesthesiologist should take actions according to the needs. In case of any further doubts related to the use of the medicine, you should consult a doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although they may not occur in everyone.
Main side effects:
Regarding pain relief
Not very common (occurs in no more than 1 in 10 patients ):
excessive sedation, agitation, anxiety, hallucinations, dreams.
Frequency not known (cannot be estimated from available data):
headache.
Common to both pain relief and general anesthesia
Nitrous oxide penetrates gas-containing spaces in the body faster than nitrogen is released from them. The use of nitrous oxide may cause expansion of body cavities where non-excreted gas is present.
Common (occurs in no more than 1 in 10 patients ):
nausea, vomiting.
Not very common (occurs in no more than 1 in 100 patients ):
Paresthesia (tingling, numbness), euphoria, psycho-dyslexic disorders not related to another anesthetic.
Frequency not known (cannot be estimated from available data):
dizziness, myelopathy (paresis, weakness), neuropathy (nerve damage - sensory disturbances), subacute combined degeneration of the spinal cord (a syndrome of neurological symptoms such as spastic paralysis, exaggerated deep reflexes, positive Babinski sign, absence of some deep reflexes, decreased superficial and deep sensation, coordination disorders), increased intracranial pressure, megaloblastic anemia (decrease in red blood cell count due to vitamin B12 deficiency), pancytopenia (a hematological disorder characterized by a deficiency of all normal morphological elements of blood: erythrocytes, leukocytes, and platelets) observed in the presence of predisposing factors (cobalamin deficiency, substance abuse), leukopenia or granulocytopenia (observed after significant and prolonged exposure to antitetanus therapy in the 1950s), serious vision damage (caused by gas expansion in the eye), ear pain, middle ear disorders, eardrum rupture (in case of Eustachian tube obstruction), respiratory depression (decreased breathing frequency and volume (in newborns, when nitrous oxide was used during delivery and in the perinatal period)), vitamin B12 deficiency, disorientation.

Generalized seizures of unknown frequency

Reporting side effects

If you experience any side effects, including any side effects not listed in the leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reactions to Medicinal Products of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, tel.: 22 49-21-301, fax: 22 49-21-309, e-mail: ndl@urpl.gov.pl.
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, more information can be collected on the safety of the medicine.

5. How to store Medical Nitrous Oxide Air Liquide

The medicine should be stored in a place that is out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after EXP.
The expiry date refers to the last day of the given month.
When storing and transporting the medicine, the following information should be taken into account:

• Store in the original gas cylinder.
• Store the gas cylinder tightly closed, in a vertical position.
• Do not transfer gas from one cylinder to another.
• Cylinders should be stored in well-ventilated or ventilated external storage rooms, where they are protected from rain and direct sunlight.
• Cylinders should be protected from shock, fall, oxidizing substances, and flammable substances, moisture, heat sources, or ignition sources.

Storage of gas cylinders in a warehouse:

• Cylinders should be stored in a ventilated or well-ventilated area, protected from adverse weather conditions and frost, clean, free from flammable materials, intended exclusively for the storage of medical gases, and locked.

Storage of gas cylinders during use:

• Before use, cylinders should be stored with the valve closed; it is recommended to avoid storing a large number of them.

6. Contents of the packaging and other information

What Medical Nitrous Oxide Air Liquide contains

• The active substance of the medicine is nitrous oxide (liquefied gas under pressure of 44 bar at 15°C).
• The medicine does not contain any other ingredients.

What Medical Nitrous Oxide Air Liquide looks like and what the packaging contains

Medical Nitrous Oxide Air Liquide is packaged in cylinders available in the following sizes:
A 3-liter cylinder containing 2.25 kg and delivering 1.22 m of gas at a pressure of 1 bar at 15°C,
a 10-liter cylinder containing 7.5 kg and delivering 4.06 m of gas at a pressure of 1 bar at 15°C,
a 13.33-liter cylinder containing 10 kg and delivering 5.41 m of gas at a pressure of 1 bar at 15°C,
a 40-liter cylinder containing 30 kg and delivering 16.23 m of gas at a pressure of 1 bar at 15°C,
a 53.33-liter cylinder containing 40 kg and delivering 21.65 m of gas at a pressure of 1 bar at 15°C,
a bundle of 12 cylinders of 53.33 liters containing 480 kg and delivering 259.8 m of gas at a pressure of 1 bar at 15°C.

Marketing authorization holder and manufacturer

Marketing authorization holder:
Air Liquide Santé International
75 quai d’Orsay
75007 Paris
France
Manufacturer:
Air Liquide Medical
Tolhuisstraat 46
2627 Schelle
Belgium

Date of last update of the leaflet:

April 24, 2019
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Information intended only for healthcare professionals:

Please refer to the Summary of Product Characteristics available on the website of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products (www.urpl.gov.pl).

Dosage and method of administration

Nitrous oxide can only be administered on the operating block or in the delivery room.
(Outside the operating rooms and delivery rooms, if nitrous oxide is to be used for anesthesia, a ready-made mixture of equal parts of nitrous oxide and oxygen 50%/50% should be used).
In accordance with existing regulations, the administration of the medicine requires:
nitrous oxide - a nitrous oxide and oxygen mixer should be used, which always guarantees oxygen concentrations (FiO2) greater than or equal to 21%, with the possibility of achieving an oxygen concentration (FiO2) of 100%, equipped with a check valve and an alarm system that operates in the event of a failure in the oxygen supply.
in the case of artificial ventilation, the oxygen concentration (FiO2) in the exhaled air should be monitored.
Dosage
Nitrous oxide should be administered by inhalation, in a mixture with oxygen, at a concentration between 50% and 70%.
Pregnant women can be given nitrous oxide only in case of absolute necessity at a concentration not exceeding 50% (see section 4.6).
Nitrous oxide should not be administered for a period longer than 24 hours due to its toxic effect on the spinal cord (see section 4.8).

Special warnings and precautions for use

• Nitrous oxide should always be administered with at least 21% oxygen.
• Nitrous oxide causes inactivation of vitamin B12 (a cofactor of methionine synthase) which affects folate metabolism. As a result, DNA synthesis is disrupted after prolonged administration of nitrous oxide. Frequent or prolonged use of nitrous oxide may cause megaloblastic changes in bone marrow cells and potentially megaloblastic anemia and subacute combined degeneration of the spinal cord (see also section 4).
• In patients with undiagnosed subclinical vitamin B12 deficiency during general anesthesia, neurological toxicity has been observed after single exposure to nitrous oxide.
• Before using nitrous oxide for anesthesia in patients with risk factors for vitamin B12 deficiency, it is necessary to check the level of vitamin B12. Risk factors may include alcohol dependence, patients suffering from anemia or atrophic gastritis, people following a vegetarian diet. Risk factors also include megaloblastic anemia, stomach cancer, post-gastrectomy, intestinal diseases, malabsorption, long-term use of proton pump inhibitors, and others. In appropriate cases, especially with prolonged and repeated use of nitrous oxide, it is necessary to administer vitamin B12 to the patient. When nitrous oxide is used for pain relief:
• self-administration of the medicine should be preferred to allow for assessment of the level of consciousness
• careful monitoring of patients taking medications that impair the function of the central nervous system, especially opioids and benzodiazepines, is necessary due to the increased risk of deep sedation
• nitrous oxide is an oxidizing gas that facilitates and accelerates combustion.
• special caution should be exercised in patients with heart failure, if the administration of nitrous oxide leads to the occurrence of hypotension or heart failure, the administration of the gas should be stopped immediately.
• special caution should be exercised in patients who have undergone nasal or middle ear surgery.
• Premises where N2O is used must be equipped with an appropriate gas disposal or ventilation system to maintain the nitrogen concentration at a minimal level and below established national occupational exposure limits.

In the case of women exposed to chronic inhalation of nitrous oxide during pregnancy in premises without an appropriate gas disposal or ventilation system, an increase in the number of spontaneous abortions and anomalies has been noted. These findings are questionable due to methodological errors and exposure conditions, as well as the fact that no risk has been observed in subsequent studies where an appropriate gas disposal or ventilation system was used.
This is a non-flammable gas, but it can support combustion of other gases, heavier than air, accumulating in low-lying areas.
Nitrous oxide facilitates and accelerates combustion. The greatest risk of ignition in the presence of nitrous oxide concerns flammable materials, and in particular fatty substances (oils, greases) and organic substances (fabrics, wood, paper, plastics, etc.), which can ignite in contact with nitrous oxide, both spontaneously and as a result of contact with a spark, flame, or ignition source.
Nitrous oxide can form explosive mixtures with flammable gases or vapors used for anesthesia, even in the absence of oxygen; it can also form toxic nitrogen oxides in the event of a fire.
The administration of nitrous oxide can increase the pressure in the balloons of endotracheal tubes.
When introducing nitrous oxide into the breathing circuit, it can increase the concentration of fluorinated anesthetics (second gas effect), facilitating the induction of anesthesia.
Adding nitrous oxide to the circuit reduces the flow of fluorinated anesthetics released during spraying. And vice versa, stopping the administration of nitrous oxide increases the concentration of the released fluorinated anesthetic. Therefore, it is recommended to stop the administration of the fluorinated anesthetic before administering nitrous oxide.
In anesthesia, in the first minutes after stopping the administration of nitrous oxide, diffusion hypoxia occurs. During this period, the oxygen concentration (FiO2) in the air inhaled by the patient should be increased.
If unexpected cyanosis occurs during anesthesia using a device powered by nitrous oxide and oxygen, it is essential to first stop the administration of nitrous oxide, and if the cyanosis does not resolve very quickly, the patient should be ventilated using a manual resuscitator filled with ambient air.
In the case of Eustachian tube obstruction, increased pressure in the middle ear cavity may result in ear pain and/or middle ear disorders and/or eardrum rupture.
In patients at risk of increased intracranial pressure, intracranial pressure should be carefully monitored, as an increase in intracranial pressure has been observed in some patients with intracranial disorders during the administration of nitrous oxide.
Abuse, misuse, and use inconsistent with the intended purpose: due to the fact that nitrous oxide causes a state of euphoria, it can be used and abused for recreational purposes.
Special precautions for use
When administering nitrous oxide, special precautions should be taken:
in patients with heart failure, if the administration of nitrous oxide leads to the occurrence of hypotension or heart failure, the administration of the gas should be stopped immediately.
after nasal or middle ear surgery.
In the case of women exposed to chronic inhalation of nitrous oxide during pregnancy in premises without an appropriate gas disposal or ventilation system, an increase in the number of spontaneous abortions and anomalies has been noted. These findings are questionable due to methodological errors and exposure conditions, as well as the fact that no risk has been observed in subsequent studies where an appropriate gas disposal or ventilation system was used.
Children and adolescents
Nitrous oxide can rarely cause respiratory depression in newborns.
A newborn should be examined for the possibility of respiratory depression if nitrous oxide was used during the perinatal period.

Special precautions for disposal of the medicinal product and preparation for use

Cylinders with medical nitrous oxide are intended for use only in hospitals.
Medical nitrous oxide should only be used in a mixture with medical oxygen.

The oxygen concentration in the breathing mixture (FiO2) should not be less than 30%.

To avoid potential accidents, the following instructions should be followed:

Cylinders should always be stored in a vertical position to prevent the risk of liquid splashing, which can cause serious cryogenic burns.

In case of frostbite (cryogenic burns), rinse with plenty of water.

• cylinders supplied by the manufacturer must be equipped with a safety system that guarantees they have not been tampered with.
• it should be taken into account that the gas pressure in the cylinder remains constant (44 bar at 15°C), regardless of the level of the remaining liquid, and does not reflect the amount of gas remaining in the cylinder. Only when the cylinder is empty does the pressure drop very quickly. Only the mass of the cylinder allows its contents to be calculated during use,
• before use, check the proper condition of the cylinder and valves,
• do not handle any cylinder whose valve is not protected by a cap or protective cover,
• handle cylinders with clean, non-greasy hands,
• when handling cylinders, wear gloves and protective footwear,
• cylinders should be secured using suitable fasteners (chains, hooks, etc.) to keep them in a vertical position and prevent them from falling,
• never place a cylinder on a holder that is too small,
• do not lift cylinders by the valve,
• use a special connection for nitrous oxide,
• use a pressure regulator equipped with a flowmeter that can withstand a pressure at least 1.5 times higher than the maximum working pressure in the cylinder,
• in the case of cylinder bundles, only regulators calibrated for at least 315 bar should be used,
• use flexible connections to wall sockets specifically designed for medical nitrous oxide,
• do not use intermediate connections that allow two devices that do not fit together to be connected,
• open the valve gradually,
• never use force to open the valve,
• empty the outlet connection of the cylinder before connecting the pressure regulator to remove dirt.
• never stand in front of the valve outlet; always stand on the opposite side of the pressure regulator, behind the cylinder, at a safe distance from it. Never expose the patient to the gas stream,
• previously, the compatibility (conformity) of materials in contact with medical nitrous oxide should be checked, and in particular, gaskets for the pressure regulator intended for this gas should be used. Check the condition of the gaskets.

Do not smoke or use open flames near the cylinder.
Do not use lubricants.
In particular:
a) never introduce gas into a device that may contain flammable substances, and in particular fatty substances,
b) never clean containers containing gas, valves, gaskets, inserts, closing devices, and circuits using flammable products, in particular fatty substances,

• do not use fatty substances (vaseline, ointments, etc.) on the patient's face,
• do not use aerosol generators (hair sprays, deodorants, etc.), solvents (alcohol, gasoline, etc.) on cylinders or near them,
• after use, close the cylinder valve, allow the pressure regulator to reduce the pressure, leaving the flowmeter open, close the flowmeter, and then loosen the pressure regulator adjustment screw.

Do not attempt to repair a damaged valve.
In case of a gas leak, close the damaged valve supplying the gas. Quickly ventilate the room and evacuate people. Without oxygen supply, it can cause asphyxiation in humans.
Nitrous oxide is a colorless, odorless gas, heavier than air, accumulating in low-lying areas.
never use cylinders that show signs of leakage; check the operation of the spare cylinder.
If, after opening the valve, the flow is large and frost forms on the pressure regulator, do not use the cylinder and return it to the pharmacy.

• when the ambient temperature is low or in case of high consumption, which causes cooling of the cylinder, the flow may decrease or even stop due to insufficient pressure in the cylinder,
• avoid using cylinders at temperatures below 0°C to prevent a drop in pressure in case of intense use,
• never use medical nitrous oxide for leak testing, for powering pneumatic devices, or for blowing through pipes,
• the average limit value for exposure (over 8 hours) to nitrous oxide is set at 25 ppm for personnel,
• systematic ventilation (ventilation) of the place where nitrous oxide is used should be carried out, removing gases to the outside and avoiding places where gases may accumulate. Before each use, it should be ensured that gases can be removed in case of accidental or premature leakage.
• if the pressure in the cylinder drops significantly (to about 3-5 bar), it should be considered empty, the valve should be closed (to prevent corrosion caused by moisture), and the equipment should be disconnected. The residual pressure should be left in the cylinder to prevent contamination.
• empty and full cylinders must be stored separately.
• empty cylinders should be stored in a vertical position, with the valve closed, to prevent corrosion caused by moisture.

Transport of gas cylinders:
Cylinders must be transported in a vertical position and secured using suitable devices (such as a cart equipped with chains, barriers, or rims) to protect them from shocks and falls, and thus prevent the risk of cryogenic burns to people in case of valve opening.
Particular attention should be paid when connecting the pressure regulator valve to prevent accidental damage.