Index of drugs

Together with respiratory support and other relevant active substances: for the treatment of newborns born ≥ 34. the week of pregnancy with hypoxic respiratory failure associated with clinically or echocardiographically confirmed pulmonary hypertension to improve oxygenation and reduce the need for in-vitro membrane oxidation; as part of perioperative and post-operative pulmonary hypertension in neonates, infants, children, adolescents and adults subjected to heart surgery, in order to selectively reduce pulmonary artery pressure and improve the function of the right ventricle and oxygenation.

Each cylinder contains nitrogen oxide 400 ppm mol / mol. From gas cylinders filled under an absolute pressure of 155 bar, we obtain: from a 2-liter gas cylinder - 307 liters of gas at a pressure of 1 bar at 15 ° C; from a 10-liter gas cylinder - 1535 liters of gas at a pressure of 1 bar at 15 ° C.

Pulmonary gas expanding gas. Nitric oxide increases the arterial pressure of arterial oxygen probably by expanding the pulmonary vasculature in better ventilated areas of the lungs, thereby moving the blood flow from areas of low ventilation to perfusion (V / Q) to areas with normal V / Q. After inhalation, it is absorbed into the bloodstream, the greater part penetrates through the capillaries in the lungs, where it binds with oxyhemoglobin. It can also be associated with oxygen and water or in the case of low oxygen saturation with deoxyhemoglobin. The final products of nitric oxide transformations that get into the systemic circulation are methemoglobin and nitrate. Nitrate accounts for> 70% of inhaled dose of nitric oxide, and is excreted in the urine.

Hypersensitivity to the active substance or any of the excipients. The drug is contraindicated in newborns addicted to right-left blood leak or a significant degree of left-right leakage.

The safety and efficacy of the drug in premature infants born before the 34th week of pregnancy have not yet been established. Clinical trials have not demonstrated the efficacy of treatment with inhaled nitric oxide in patients with congenital diaphragmatic hernia. Use with caution in patients with complex heart defects, when high pulmonary artery pressure is important for maintaining circulation; in patients with impaired left ventricular function and increased occlusal wedge pressure (PCWP) during the initial visit, as they may be more at risk of developing heart failure (eg pulmonary edema). Before administration of nitric oxide, pulmonary venous catheterisation or echocardiography of large haemodynamics should be performed. If the drug is administered for more than 24 hours in patients with platelet dysfunction or abnormalities, low blood clotting factor and in patients receiving anticoagulants, haemostasis and bleeding time should be monitored regularly. Nitric oxide treatment should not be stopped abruptly, as it may result in increased pulmonary artery pressure (PAP) and / or worsening of oxygenation of the blood (PaO₂). Deterioration of oxygenation and increase in PAP may also occur in newborns who do not expressly respond to the preparation. Discontinuation of inhaled nitric oxide should be carried out carefully. Patients should be kept continuously during the transport of patients. In case of permanent deterioration or lack of improvement, life saving measures such as extracorporeal membrane oxygenation (ECMO) should be considered.

Do not use during pregnancy and breast-feeding. There are no adequate data on the use of nitric oxide in pregnant women.

Very common: thrombocytopenia. Common: hypotension, atelectasis. Uncommon: methaemoglobinaemia. Not known: bradycardia (after sudden discontinuation of therapy), hypoxia, shortness of breath, chest discomfort, dry throat, headache and dizziness.There have been reports of violent recurrent reactions, such as increased pulmonary vasoconstriction and hypoxia following sudden discontinuation of inhaled nitric oxide therapy leading to cardiovascular collapse following post-marketing experience.

Persistent pulmonary hypertension in newborns (PPHN). Treatment should only be carried out in neonatal units under the supervision of an experienced neonatologist. The drug should be used in ventilated infants who are expected to support breathing longer than 24 hours and only when optimal respiratory support methods have been used, i.e. optimizing tidal volume / pressure and lung aeration (surfactant, high frequency ventilation and positive end pressure). tract). The maximum recommended dose is 20 ppm. In the main clinical trials, the starting dose was 20 ppm. Starting as early as possible, during the first 4-24 hours of treatment, the dose should be gradually reduced to 5 ppm, provided that if a lower dose is used, arterial oxygenation is appropriate. The therapy should be maintained at 5 ppm until achieving an oxygenation improvement that FiO₂ (oxygen concentration in the breathing mixture) will be <0.60. The treatment can be used for 96 hours or until the cause causing hypoxia is removed and the newborn is ready to stop treatment. The duration of treatment may vary, but usually lasts less than 4 days. Discontinuation should be started when respiratory support has been significantly reduced or after 96 hours of treatment. The dose should be reduced to 1 ppm within 30-60 min. If oxygenation does not change with the 1 ppm dose, increase FiO₂ by 10%, discontinue administration of nitric oxide and carefully monitor for signs of hypoxia. If oxygenation decreases by> 20%, therapy with 5 ppm nitric oxide should be resumed and treatment discontinuation should be considered again after 12 - 24 h. Newborns who fail to discontinue nitric oxide after 4 days should be subjected to thorough diagnostic tests in to detect other diseases.Pulmonary hypertension associated with heart surgery. Treatment should be under the supervision of a physician with relevant experience in anaesthesiology and intensive care after cardiac and surgical procedures, only in cardiotorax surgery departments. Nitric oxide should only be used after optimizing conservative treatment. In clinical trials, nitric oxide was given as an adjunct to standard treatment regimens in perioperative conditions, including inotropic and vasoactive drugs. Serve only strictly observing hemodynamics and oxygenation.Newborns, infants, children and adolescents up to 17 years old: the starting dose is 10 ppm and can be increased up to 20 ppm if the lower dose did not allow to achieve sufficient clinical effects. The lowest effective dose should be administered and should be reduced to 5 ppm, provided that pulmonary artery pressure and systemic arterial oxygenation remain appropriate at the lower dose. Clinical data justifying the suggested dose in the age range of 12-17 years are limited.Adults: the starting dose is 20 ppm and can be increased up to 40 ppm if the lower dose did not allow to achieve sufficient clinical effects. The lowest effective dose should be administered and should be reduced to 5 ppm, provided that pulmonary artery pressure and systemic arterial oxygenation remain appropriate at the lower dose. Reduction of pulmonary artery pressure and oxygenation improvement are visible within 5-20 min. If the answer is insufficient, the dose can be increased at the earliest after 10 min. Discontinuation of treatment should be considered if no beneficial physiological effects are observed after a 30 minute trial therapy. Treatment can be started at any time during the perioperative period. In clinical trials, it was usually started before disconnecting the extracorporeal circulation. Inhaled nitric oxide was administered for up to 7 days in perioperative conditions, but often the duration of treatment was 24-48 h. The withdrawal test should be initiated immediately after establishing haemodynamics in conjunction with disconnection from the ventilator and discontinuation of inotropic drugs. The withdrawal of inhalation therapy with nitric oxide should be carried out gradually.The dose should be gradually reduced to 1 ppm for 30 min with close observation of body and central pressure, and then discontinued. The withdrawal should be repeated at least every 12 hours when the patient's condition is stable at a low dose of nitric oxide. Too violent withdrawal carries the risk of a re-increase in pulmonary artery pressure followed by circulatory instability.Method of administration. For intratracheal delivery. Nitric oxide is administered by mechanical ventilation after dilution with a mixture of oxygen and air, using the inhalation kit for nitric oxide. The inhalation kit must provide a constant concentration of the inhaled drug, regardless of the ventilator. When using a constant-flow neonatal respirator, this can be achieved by introducing low-flow nitric oxide into the inspiratory arm of the ventilator's circulatory system. Intravenous ventilation used in newborns may be associated with rapid jumps in the concentration of nitric oxide. The inhalation kit for nitric oxide used for ventilation with intermittent flow should be constructed in such a way as not to allow rapid jumps in the concentration of nitric oxide. The concentration of the inhaled drug must be continuously measured in the inspiratory arm of the circular system close to the patient. The NO concentration must be measured at the same location₂ and FiO₂. For reasons of patient safety, the alarm system should be set to the appropriate parameters for nitric oxide (+/- 2 ppm of the recommended dose), NO₂ (1 ppm) and FiO₂ (+/-0,05). Monitoring methemoglobin formation (MetHb). Measurement of MetHb concentration should be performed within 1 hour of starting nitric oxide therapy (in neonates and infants using an analyzer that can distinguish MetHb from fetal hemoglobin). The dose of nitric oxide should be reduced and the use of reducing preparations (eg methylene blue) should be considered if the concentration of MetHb in newborns and infants is> 2.5%, and in adults if MetHb concentration rises to a level that has a potentially adverse effect on oxygen supply. In newborns and infants, it is recommended to measure MetHb concentration once a day or every 2 days.Monitoring of the production of nitrogen dioxide (NO₂). Immediately before the application, it is required to use the appropriate procedure for emptying the installation with NO₂ NO concentration₂ should be kept as low as possible and always <0.5 ppm. If the concentration of NO₂ is> 0.5 ppm, check that the installation is working properly, recalibrate the NO analyzer₂ and reduce the dose of nitric oxide and / or FiO as much as possible₂.