seen therein is an installation for dispensing no that can be used to administer a gaseous mixture of no and nitrogen at high concentration , that is to say 1200 ppm or more , preferably between 1500 and 4500 ppm , to a patient p with hypoxemic respiratory distress with an fio 2 of around 100 %, for example an adult suffering from ards or a newborn suffering from persistent pulmonary hypertension . this installation comprises a ventilator 1 comprising a respiratory circuit or patient circuit 2 with two branches , that is to say with an inhalation branch 3 and an exhalation branch 4 . the inhalation branch 3 is designed to convey respiratory gas from the ventilator 1 to the patient p , whereas the exhalation branch 4 is designed to convey the gas exhaled by the patient p to the ventilator 1 . at the patient p , the gas is administered by means of a patient interface 11 , for example a respiratory mask or a tracheal cannula or catheter . the ventilator 1 is supplied , via a first delivery line 10 , with air ( o 2 content of 21 % by volume ) originating from an air source 7 and via a second delivery line 10 ′ with oxygen resulting from an oxygen source 7 ′, such as an oxygen cylinder or a duct transporting oxygen originating from an oxygen production unit , such as a pressure swing ( psa ) unit , or from an oxygen storage unit , such as a buffer or storage tank . the oxygen - rich gas is delivered by the ventilator 1 into the inhalation branch 3 of the patient circuit 2 . furthermore , a device 5 for dispensing no is fluidically connected to said inhalation branch 3 of the patient circuit 2 in order to deliver therein , via a feed line 12 , an no / n 2 mixture containing a high concentration of no , that is to say at least 1200 ppm by volume , according to the present invention . the device 5 for dispensing no is itself supplied with an no / n 2 mixture , via a gas feed line 9 , by a source of no 6 such as a gas cylinder equipped with a valve or integrated valve regulator 8 , preferably protected by a cap for protection against impacts . the device 5 for dispensing no makes it possible in particular to control the amount of no / n 2 released into the inhalation branch 3 , and also the method of releasing this mixture , that is to say continuously or in a pulsed manner , for example only during the inhalation phases of the patient p . therefore , in the inhalation branch 3 , a dilution of the no / n 2 mixture with the oxygen - rich gas dispensed by the ventilator 1 takes place . the dilution depends on the content of the initial no / n 2 mixture but also on the concentration of gas to be administered to the patient . the no / n 2 gas mixture according to the invention is therefore an inhalable medicament that can be used in combination with an assisted ventilation 1 for the treatment in particular of newborns having a gestational age of at least 34 weeks exhibiting hypoxemic respiratory distress combined with clinical or echocardiographic signs of pulmonary arterial hypertension , with the purpose of improving oxygenation and avoiding recourse to extracorporeal oxygenation . it may also be used for treating adults or children suffering from ards . the examples below give examples of mixtures that can be used in patients suffering from ards or pphn . seen in tables 1 and 2 is the advantage of using high concentrations of no in the initial mixture , all the more so when the target dosages of no are high ( e . g . non - responsive patient requiring dosages of greater than 20 ppmv ) and when the required fio 2 values are also high , that is to say of the order of 90 % to 100 %. indeed , such high fio 2 values cannot be maintained for excessively low initial concentrations , that is to say of less than 1000 ppmv approximately , and in this case , the positive effects of the no are offset by the deleterious effects of the dilution on the fio 2 . generally , the invention also relates to a therapeutic treatment method , wherein a gaseous medicament comprising a mixture of nitrogen monoxide ( no ) and nitrogen ( n 2 ) is administered by inhalation to a patient suffering from hypoxemic respiratory distress linked to pulmonary vasoconstriction , such as ards , or pphn , said gas mixture containing at least 1200 ppm by volume ( ppmv ) of nitrogen monoxide ( no ), and said patient being an adult , a child or a newborn . prior to being administered to the patient , the mixture of nitrogen monoxide ( no ) and nitrogen ( n 2 ) is diluted with an oxygen - containing gas , preferably this dilution is carried out in the ventilation circuit of a medical ventilator or the like . generally , table 1 below shows the volumes ( in ml ) of no / n 2 administered in the inhalation branch 3 of the patient circuit 2 of the ventilator 1 for a volume per minute of 10 l / min of the ventilator ( i . e . air / o 2 ), in order to obtain no concentrations between 5 and 40 ppmv , as a function of the no concentration in the cylinder containing the no / n 2 mixture , i . e . ranging from 100 to 3500 ppmv . as can be seen in table 1 , the volumes of no administered in order to obtain doses of 5 ppmv are respectively 556 ml for a concentration of 100 ppmv of no and 14 ml for a concentration of 3500 ppmv . likewise , for doses of 40 ppmv , the volumes are 4444 ml for a concentration of 100 ppmv of no and 114 ml for an no concentration of 3500 ppmv . this clearly demonstrates the advantage that there is in using high no concentrations , that is to say of at least 1200 ppmv , in order to reduce the impact of the volume of no administered and of the associated dilution on the ventilator parameters ( see table 2 ) since the higher the concentration , the lower the volume of no required . furthermore , table 2 illustrates the dilution percentages (%) obtained for no concentrations from 100 to 3500 ppmv in order to obtain doses ranging from 5 to 40 ppmv , under the same administration conditions as those from table 1 ( i . e . ventilation of 10 l / min ). as can be seen , for a same treatment set point , the dilution becomes negligible for high no concentrations , that is to say of at least 1200 ppmv , and hence no longer influences the ventilator parameters and set points . indeed , the lower the volume of no , the less it will change the ventilation set points and counteract the beneficial effects of the treatment , in particular the fio 2 . according to the invention , the use of a gas mixture containing at least 1200 ppm by volume ( ppmv ) of nitrogen monoxide ( no ), typically containing from 1200 to 4500 ppmv , is therefore recommended . lastly , tables 3 to 5 below show the impact of the dilutions on the desired fio 2 values for initial no concentrations in the cylinder of 225 , 450 and 2000 ppmv . the fio 2 is a very important parameter within the context of the illnesses treated by no ( neonatal refractory hypoxemia , ards , etc .) given that for these illnesses fio 2 values of the order of 100 % may be necessary . this implies that the dilution must be as low as possible in order to retain an fio 2 value as high as possible and therefore the beneficial effect of the treatment by inhaled no . as can be seen in tables 3 and 4 relating to low initial contents of no , namely 225 and 450 ppmv of no ( remainder nitrogen ), the decreases of fio 2 caused by the dilution may represent around 20 % to 30 % of the desired fio 2 ( i . e . the set point fio 2 ), which becomes prejudicial to the treatment by no since a low fio 2 value cancels out the positive effects of the no . conversely , as shown in table 5 , using a high concentration of no ( here 2000 ppm of no in nitrogen ) does not modify or else negligibly modifies ( i . e . around & lt ; 1 %) the fio 2 set points thus making it possible to treat patients with o 2 contents of almost 100 % over short periods , in order to get through certain extreme situations . although an increase in the concentration of no in the cylinders may appear simple at first glance , it does entail problems linked to the potential toxicity of high contents of no (& gt ; 800 ppmv ), since any excessive dose , due to a poor dilution for example , may result in a toxic dose being administered to the patient and since , furthermore , the higher the concentration of no , the greater the risk of forming toxic compounds , such as toxic no 2 that is formed by oxidation of no in the presence of oxygen . in other words , the solution proposed by the invention goes against certain prejudices that exist in the field in question , which consider that the use of no at high doses , that is to say greater than 1200 ppmv , is dangerous and not recommended . it will be understood that many additional changes in the details , materials , steps and arrangement of parts , which have been described herein in order to explain the nature of the invention , may be made by those skilled in the art within the principle and scope of the invention as expressed in the appended claims . thus , the present invention is not intended to be limited to the specific embodiments in the examples given above .
the invention concerns a gaseous medicine comprising a mixture of nitrogen monoxide and nitrogen for use by inhalation for the treatment of hypoxemic respiratory failure linked to pulmonary vasoconstriction in humans , said gaseous mixture containing between 1200 and 4500 ppm by volume of nitrogen monoxide and said hypoxemic respiratory failure being chosen from acute respiratory distress syndrome or persistent pulmonary hypertension of the newborn infant .