FR3160894A1 - NO supply device with automatic setting of alarm thresholds - Google Patents

Abstract

Title of the invention Apparatus for supplying NO with automatic setting of alarm thresholds The invention relates to an apparatus (1) for supplying a gas containing NO comprising an internal gas circuit (200) for conveying a flow of gas containing NO, comprising flow control means (220, 221); NO dose adjustment means for setting a NO dose (DNO) of between 1 and 80 ppmv; and microprocessor (211) control means (210) for controlling the flow control means (220, 221). The control means (210) can automatically calculate, from the set NO dose (DNO), a high NO alarm threshold corresponding to a maximum NO content (Tmax) and a low NO alarm threshold corresponding to a minimum NO content. Abstract figure: Figure 2

Description

NO supply device with automatic setting of alarm thresholds

The invention relates to an NO delivery apparatus and an installation for supplying a NO-based gas mixture to a patient, typically an NO/nitrogen (N ₂ ) mixture, comprising such an NO delivery apparatus and a medical ventilator delivering an oxygen-based respiratory gas (≥ 20% approx.).

Inhaled nitric oxide (NO or NOi) is a gaseous drug commonly used to treat patients with acute pulmonary arterial hypertension, particularly pulmonary vasoconstrictions in adults or children, including newborns (PPHN), as described for example by EP-A-560928 or EP-A-1516639.

To implement inhaled NO therapy, a gas supply system, also called an NO administration system, is used, comprising an NO delivery device and a medical ventilator, i.e. a respiratory assistance device, supplying a patient circuit which generally comprises one or more flexible conduits fluidically connected to a respiratory interface, such as a tracheal intubation tube or the like, used to deliver to the patient to be treated, a final gas mixture containing the NO.

Such a gas supply installation is described for example by EP3821929. This type of installation is used in a hospital environment to administer NO treatment and thus treat patients who need to inhale NO to treat their pulmonary arterial hypertension. Installations of this type are also described by EP3233171, EP3410927, EP3410927, EP4209243, EP4241817, EP4241812 and EP4295882.

In such an installation, the NO delivery device makes it possible to inject a gaseous flow based on NO, typically an NO/nitrogen gas mixture, into the patient circuit also supplied with a flow of respiratory gas containing oxygen (at least approximately 20% vol.), such as air or an oxygen/nitrogen mixture (O ₂ /N ₂ ), supplied by the medical ventilator, so as to obtain a combined flow, also called "final gaseous mixture", comprising NO at the desired dosage, typically less than 50 ppmv of NO, at least approximately 20% vol. of oxygen and nitrogen (N ₂ ), or even unavoidable impurities.

Flow control means of the device make it possible to control or adjust the flow rate of gas containing NO, e.g. NO/N ₂ mixture, in order to obtain the desired combined gas mixture, e.g. the final mixture containing NO at the desired dosage.

In fact, the flow rate of NO-based gas depends in particular on the flow rate of oxygen-based respiratory gas, i.e. air or N ₂ /O ₂ mixture, coming from the medical ventilator. It is therefore necessary to continuously measure the flow rate of the oxygen-based respiratory gas using a flow sensor arranged in the patient circuit, upstream of the injection site of the NO-based mixture and to use these measurements to calculate the flow rate of NO-based gas to be supplied.

However, in practice, we observe more or less significant fluctuations in the NO content of the combined gas mixture, which result from variations in the flow rate of oxygen-based respiratory gas supplied by the medical ventilator.

It is understood that such variations can be critical for the patient if they are significant and lead to an NO content (very) far from the desired dosage, i.e. if the NO content is excessive or insufficient.

In order to ensure increased safety for the patient, the user, such as a healthcare professional, can generally set on the NO delivery device maximum and minimum values (i.e. high and low thresholds) of acceptable NO content in the combined gas mixture.

By ensuring monitoring, i.e. continuous monitoring, of the composition of the combined gas mixture obtained, it is possible to ensure that the proportion of NO present does not deviate too much from the desired dosage.

Indeed, in the event that the measured NO content exceeds one of the high or low thresholds, an audible alarm and/or a visual alarm can be triggered by the NO delivery device in order to warn the nursing staff and allow them to take corrective measures.

However, setting the high and low NO alarm thresholds corresponding to the maximum and minimum acceptable NO levels (thresholds) is not easy because these thresholds depend closely on the chosen dose.

Therefore, the nursing staff can make mistakes when calculating them and/or then entering them into the NO delivery device, and it is easy to understand that any error can endanger the patient.

In addition, poorly chosen alarm thresholds lead to false alarm triggers, which must be avoided.

A problem is therefore to improve patient safety, in particular to be able to avoid or at least minimize the aforementioned risks and/or false alarm triggers, by proposing an improved NO delivery device, i.e. one that is safer in terms of determining NO alarm thresholds.

• des moyens de réglage de dose de NO configurés pour permettre à un utilisateur de régler, c'est-à-dire choisir, fixer ou sélectionner, une dose de NO (D_NO) comprise entre 1 et 80 ppmv, et
• des moyens de pilotage à microprocesseur.

A solution relates to a device for delivering, i.e. supplying, a gas containing NO, such as a NO/N gas mixture₂, including:

• NO dose adjustment means configured to allow a user to adjust, i.e. choose, set or select, a NO dose (D _NO ) between 1 and 80 ppmv, and
• microprocessor control means.

• un seuil d’alarme NO haut correspondant à une teneur maximale de NO (T_max), telle que : 1,1 . D_NO≤ T_max≤ 1,3 . D_NO, c'est-à-dire que la teneur maximale de NO (T_max) est supérieure de 10% à 30% à la valeur de dose de NO (D_NO) réglée,
• et un seuil d’alarme NO bas correspondant à une teneur minimale de NO (T_min), telle que : 0,7 . D_NO≤ T_min≤ 0,9 . D_NO, c'est-à-dire que la teneur minimale de NO (T_min) est inférieure de 10% à 30% à la valeur de dose de NO (D_NO) réglée.

Furthermore, according to the invention, the control means are configured to automatically calculate, from the NO dose (D _NO ) set:

• a high NO alarm threshold corresponding to a maximum NO content (T _max ), such that: 1.1 . D _NO ≤ T _max ≤ 1.3 . D _NO , i.e. the maximum NO content (T _max ) is 10% to 30% higher than the set NO dose value (D _NO ),
• and a low NO alarm threshold corresponding to a minimum NO content (T _min ), such that: 0.7 . D _NO ≤ T _min ≤ 0.9 . D _NO , i.e. the minimum NO content (T _min ) is 10% to 30% lower than the set NO dose value (D _NO ).

In other words, according to the invention, the control means of the device automatically calculate the values of the high and low NO alarm thresholds from the NO dose value (D _NO ) set by adding or, conversely, subtracting 10% to 30% from the NO dose value (D _NO ), preferably of the order of 20%.

The fact that the NO alarm thresholds are calculated automatically by the NO delivery device as soon as the user has set the desired NO dose (D _NO ), i.e. the desired dosage, is a great advantage in terms of safety because there are no more errors in calculating or entering values into the device and, moreover, due to compliance with the therapeutic window, i.e. administration of NO within a tolerance range acceptable to the patient. Patient safety is therefore considerably improved.

• il comprend en outre un circuit de gaz interne pour acheminer un flux de gaz contenant du NO, comprenant des moyens de contrôle de débit configurés pour contrôler le flux de gaz contenant du NO au sein dudit circuit de gaz.
• les moyens de pilotage sont configurés pour piloter les moyens de contrôle de débit pour autoriser, interdire ou ajuster le débit gazeux, notamment au sein dudit circuit de gaz.
• les moyens de pilotage coopèrent avec les moyens de réglage de dose de NO, en particulier la dose réglée via les moyens de réglage de dose de NO est fournie aux moyens de pilotage afin de calculer les seuils d’alarme NO haut et bas.
• les moyens de pilotage sont configurés pour calculer, à partir de la dose de NO (D_NO) réglée, un seuil d’alarme NO haut correspondant à une teneur maximale de NO (T_max), telle que : T_max≤ 1,25 . D_NO
• de préférence, les moyens de pilotage sont configurés pour calculer, à partir de la dose de NO (D_NO) réglée, un seuil d’alarme NO haut correspondant à une teneur maximale de NO (T_max), telle que : T_max≤ 1,20 . D_NO
• de préférence encore, les moyens de pilotage sont configurés pour calculer, à partir de la dose de NO (D_NO) réglée, un seuil d’alarme NO haut correspondant à une teneur maximale de NO (T_max), telle que : T_max= 1,20 . D_NO
• les moyens de pilotage sont configurés pour calculer, à partir de la dose de NO (D_NO) réglée, un seuil d’alarme NO bas correspondant à une teneur minimale de NO (T_min), telle que : 0,75 . D_NO≤ T_min
• de préférence, les moyens de pilotage sont configurés pour calculer, à partir de la dose de NO (D_NO) réglée, un seuil d’alarme NO bas correspondant à une teneur minimale de NO (T_min), telle que : 0,80 . D_NO≤ T_min
• de préférence encore, les moyens de pilotage sont configurés pour calculer, à partir de la dose de NO (D_NO) réglée, un seuil d’alarme NO bas correspondant à une teneur minimale de NO (T_min), telle que : 0,80 . D_NO= T_min
• les moyens de pilotage sont configurés pour calculer une teneur maximale de NO (T_max) telle que : T_max- D_NO≥ 2 ppmv , c'est-à-dire que l’écart entre la dose de NO (D_NO) réglée et la teneur maximale de NO (T_max) doit être au minimum de 2 ppmv. Par exemple, pour une dose de NO (D_NO) de 10 ppmv, la teneur maximale de NO (T_max) doit être fixée à au moins 12 ppmv.
• les moyens de pilotage sont configurés pour calculer une teneur minimale de NO (T_min) telles que : D_{NO -}T_min≥ 2 ppmv , c'est-à-dire que, là aussi, l’écart entre la dose de NO (D_NO) réglée et la teneur minimale de NO (T_min) doit être au minimum de 2 ppmv. Par exemple, pour une dose de NO (D_NO) de 10 ppmv, la teneur minimale de NO (T_min) doit être fixée à au plus 8 ppmv.
• il comprend un afficheur graphique ou tout autre dispositif d’affichage, tel un écran tactile.
• les moyens de pilotage sont configurés pour commander un affichage sur l’afficheur graphique de la teneur maximale de NO (T_max) correspondant au seuil d’alarme NO haut.
• les moyens de pilotage sont configurés pour commander un affichage sur l’afficheur graphique de la teneur minimale de NO (T_min) correspondant au seuil d’alarme NO bas.
• le circuit de gaz interne de l’appareil véhiculant le gaz contenant le NO, tel un mélange NO/N₂, est raccordé fluidiquement à un circuit respiratoire véhiculant un gaz respiratoire contenant de l’oxygène, tel de l’air ou un mélange gazeux O₂/N₂(>20% O₂), pour y injecter le gaz contenant le NO et obtenir un mélange gazeux combiné contenant du NO et de l’oxygène, c'est-à-dire le mélange final à administrer au patient.
• il comprend des moyens de mesure de concentration de NO pour déterminer la teneur en NO dans le mélange gazeux combiné contenant du NO et de l’oxygène, tel un capteur de NO, par exemple à cellule électrochimique.
• il comprend des moyens d’alarme, typiquement une alarme sonore et/ou visuelle.
• les moyens de pilotage sont configurés pour agir sur des moyens d’alarme pour déclencher une alarme, en particulier une alarme sonore et/ou visuelle.
• les moyens d’alarme peuvent comprendre un dispositif de type buzzer, et/ou un haut-parleur, ou tout autre dispositif permettant d’émettre un signal sonore audible par l’oreille humaine, i.e. par le personnel soignant.
• les moyens d’alarme peuvent comprendre un dispositif lumineux, par exemple comprenant une ou des diodes (LED) ou analogue.
• les moyens d’alarme peuvent comprendre un affichage d’un message d’alerte ou analogue sur l’afficheur graphique.
• les moyens de pilotage sont configurés pour déclencher une alarme, i.e. pour activer des moyens d’alarme, lorsque lesdits moyens de pilotage déterminent que la teneur en NO dans le mélange gazeux combiné déterminée par les moyens de mesure de concentration de NO, est supérieure ou égale à la teneur maximale de NO (T_max) ou inférieure ou égale à la teneur minimale de NO (T_min).
• les moyens de pilotage sont configurés pour commander un affichage sur l’afficheur graphique de la teneur en NO dans le mélange gazeux combiné ayant été déterminée par les moyens de mesure de concentration de NO.
• il comprend des moyens de mémorisation configurés pour mémoriser la teneur maximale de NO (T_max) correspondant au seuil d’alarme NO haut et la teneur minimale de NO (T_min) correspondant au seuil d’alarme NO bas.
• les moyens de réglage de dose sont configurés pour permettre à l’utilisateur de modifier la dose de NO (D_NO) et/ou les seuils d’alarme NO haut et bas.

• il est alimenté en un gaz contenant du NO en une proportion initiale donnée, typiquement un mélange NO/N₂.
• il est alimenté en un gaz contenant une proportion initiale de NO comprise entre 100 et 1500 ppmv, typiquement entre 200 et 1000 ppmv.
• il est alimenté en un mélange gazeux formé d’azote et de NO.
• les moyens de réglage de dose de NO sont configurés pour permettre à l’utilisateur de régler une dose de NO, i.e. consigne de teneur en NO, correspondant à la proportion de NO souhaitée dans le mélange gazeux combiné, c'est-à-dire après mélange du mélange NO/N₂avec le flux de gaz respiratoire à base d’oxygène, i.e. une posologie en NO.
• les moyens de réglage de dose de NO font partie d’une IHM (interface homme-machine) ou IGU (interface graphique utilisateur).
• l’IHM comprend l’afficheur graphique.
• les moyens de réglage de dose de NO comprennent une ou des touches virtuelles tactiles, actionnables par l’utilisateur, s’affichant sur l’afficheur graphique de type écran digital à dalle tactile.
• les moyens de réglage de dose de NO comprennent une touche « + » permettant d’incrémenter une valeur de dose de NO et/ou une touche « - » permettant de décrémenter une valeur de dose de NO. Typiquement, l’incrémentation ou la décrémentation se fait de +/- 1 ppmv.
• les moyens de réglage de dose de NO comprennent en outre une touche de validation pour valider/confirmer une valeur de dose de NO ayant été fixée, de préférence une touche de validation virtuelle affichée par l’écran d’affichage.
• alternativement, les moyens de réglage de dose de NO comprennent un organe de sélection mécanique, tel un (des) boutons ou touches à actionnement digital, tel un bouton-poussoir ou analogue, ou un bouton rotatif ou analogue
• l’afficheur graphique est du type à affichage en couleurs.
• les moyens de réglage de dose de NO sont configurés pour permettre à l’utilisateur de régler une dose de NO, i.e. une consigne de teneur en NO, comprise entre 1 et 50 ppmv, typiquement entre 5 et 40 ppmv.
• les moyens de mémorisation comprennent une mémoire informatique, telle une mémoire flash, une RAM ou analogue.
• les moyens de contrôle de débit sont agencés sur le circuit de gaz interne.
• les moyens de contrôle de débit comprennent des moyens à vannes, telles des électrovannes ou analogues.
• les moyens de pilotage sont configurés pour contrôler les moyens de contrôle de débit pour autoriser ou empêcher le passage du flux de NO/N₂dans le circuit de gaz interne.
• les moyens de contrôle de débit comprennent une (ou des) électrovanne proportionnelle et/ou une (ou des) électrovanne tout ou rien.
• les moyens de contrôle de débit principaux comprennent un contrôleur de débit massique (Mass Flow Controler).
• le contrôleur de débit massique (Mass Flow Controler) ou MFC comprend au moins une électrovanne proportionnelle pilotée par les moyens de pilotage et un capteur de débit principal.
• les moyens de pilotage à microprocesseur comprennent un (micro)contrôleur ou analogue.
• les moyens de pilotage à microprocesseur comprennent un (ou des) (micro)processeur agencé sur une (ou des) carte électronique.
• les moyens de pilotage comprennent un (ou des) (micro)processeur mettant en œuvre un ou des algorithmes, notamment un (ou des) algorithme de pilotage des moyens de contrôle de débit, un (ou des) algorithme de traitement des mesures de débit de gaz respiratoire ou de mesures de concentration en NO, NO₂et/ou en O₂….
• les moyens de mémorisation sont agencés sur la carte électronique.

Depending on the embodiment considered, the delivery apparatus of the invention may comprise one or more of the following features:

• it further comprises an internal gas circuit for conveying a flow of gas containing NO, comprising flow control means configured to control the flow of gas containing NO within said gas circuit.
• the control means are configured to control the flow control means to authorize, prohibit or adjust the gas flow, in particular within said gas circuit.
• the control means cooperate with the NO dose adjustment means, in particular the dose adjusted via the NO dose adjustment means is supplied to the control means in order to calculate the high and low NO alarm thresholds.
• the control means are configured to calculate, from the NO dose (D _NO ) set, a high NO alarm threshold corresponding to a maximum NO content (T _max ), such that: T _max ≤ 1.25 . D _NO
• preferably, the control means are configured to calculate, from the NO dose (D _NO ) set, a high NO alarm threshold corresponding to a maximum NO content (T _max ), such that: T _max ≤ 1.20 . D _NO
• more preferably, the control means are configured to calculate, from the NO dose (D _NO ) set, a high NO alarm threshold corresponding to a maximum NO content (T _max ), such that: T _max = 1.20 . D _NO
• the control means are configured to calculate, from the NO dose (D _NO ) set, a low NO alarm threshold corresponding to a minimum NO content (T _min ), such that: 0.75 . D _NO ≤ T _min
• preferably, the control means are configured to calculate, from the NO dose (D _NO ) set, a low NO alarm threshold corresponding to a minimum NO content (T _min ), such that: 0.80 . D _NO ≤ T _min
• more preferably, the control means are configured to calculate, from the NO dose (D _NO ) set, a low NO alarm threshold corresponding to a minimum NO content (T _min ), such that: 0.80. D _NO = T _min
• the control means are configured to calculate a maximum NO content (T _max ) such that: T _max - D _NO ≥ 2 ppmv , i.e. the difference between the set NO dose (D _NO ) and the maximum NO content (T _max ) must be at least 2 ppmv. For example, for a NO dose (D _NO ) of 10 ppmv, the maximum NO content (T _max ) must be set at least 12 ppmv.
• the control means are configured to calculate a minimum NO content (T _min ) such that: D _{NO -} T _min ≥ 2 ppmv , that is to say that, here too, the difference between the NO dose (D _NO ) set and the minimum NO content (T _min ) must be at least 2 ppmv. For example, for a NO dose (D _NO ) of 10 ppmv, the minimum NO content (T _min ) must be set at most 8 ppmv.
• It includes a graphic display or other display device, such as a touch screen.
• the control means are configured to control a display on the graphic display of the maximum NO content (T _max ) corresponding to the high NO alarm threshold.
• the control means are configured to control a display on the graphic display of the minimum NO content (T _min ) corresponding to the low NO alarm threshold.
• the internal gas circuit of the device carrying the gas containing NO, such as a NO/N ₂ mixture, is fluidically connected to a respiratory circuit carrying a respiratory gas containing oxygen, such as air or a gas mixture O ₂ /N ₂ (>20% O ₂ ), to inject the gas containing NO and obtain a combined gas mixture containing NO and oxygen, i.e. the final mixture to be administered to the patient.
• it comprises NO concentration measuring means for determining the NO content in the combined gas mixture containing NO and oxygen, such as an NO sensor, for example an electrochemical cell.
• it includes alarm means, typically an audible and/or visual alarm.
• the control means are configured to act on alarm means to trigger an alarm, in particular an audible and/or visual alarm.
• the alarm means may include a buzzer-type device, and/or a loudspeaker, or any other device making it possible to emit an audible sound signal to the human ear, i.e. to the healthcare staff.
• the alarm means may comprise a light device, for example comprising one or more diodes (LEDs) or the like.
• the alarm means may include a display of an alert message or the like on the graphic display.
• the control means are configured to trigger an alarm, i.e. to activate alarm means, when said control means determine that the NO content in the combined gas mixture determined by the NO concentration measuring means is greater than or equal to the maximum NO content (T _max ) or less than or equal to the minimum NO content (T _min ).
• the control means are configured to control a display on the graphic display of the NO content in the combined gas mixture having been determined by the NO concentration measuring means.
• it comprises storage means configured to store the maximum NO content (T _max ) corresponding to the high NO alarm threshold and the minimum NO content (T _min ) corresponding to the low NO alarm threshold.
• the dose adjustment means are configured to allow the user to modify the NO dose (D _NO ) and/or the high and low NO alarm thresholds.

• it is supplied with a gas containing NO in a given initial proportion, typically a NO/N ₂ mixture.
• it is supplied with a gas containing an initial proportion of NO of between 100 and 1500 ppmv, typically between 200 and 1000 ppmv.
• It is supplied with a gaseous mixture of nitrogen and NO.
• the NO dose adjustment means are configured to allow the user to adjust a NO dose, i.e. NO content setpoint, corresponding to the desired proportion of NO in the combined gas mixture, i.e. after mixing the NO/N ₂ mixture with the oxygen-based respiratory gas flow, i.e. a NO dosage.
• The NO dose adjustment means are part of an HMI (human-machine interface) or GUI (graphical user interface).
• The HMI includes the graphic display.
• the NO dose adjustment means comprise one or more virtual touch keys, operable by the user, displayed on the graphic display of the digital touch screen type.
• the NO dose adjustment means comprise a “+” key for incrementing a NO dose value and/or a “-” key for decrementing a NO dose value. Typically, the increment or decrement is +/- 1 ppmv.
• the NO dose setting means further comprise a validation key for validating/confirming a NO dose value having been set, preferably a virtual validation key displayed by the display screen.
• alternatively, the NO dose adjustment means comprise a mechanical selection member, such as one or more digitally actuated buttons or keys, such as a push button or the like, or a rotary knob or the like
• the graphic display is of the color display type.
• the NO dose adjustment means are configured to allow the user to adjust a NO dose, i.e. an NO content setpoint, between 1 and 50 ppmv, typically between 5 and 40 ppmv.
• the storage means include computer memory, such as flash memory, RAM or the like.
• the flow control means are arranged on the internal gas circuit.
• the flow control means include valve means, such as solenoid valves or the like.
• the control means are configured to control the flow control means to allow or prevent the passage of the NO/N ₂ flow in the internal gas circuit.
• the flow control means comprise one or more proportional solenoid valves and/or one or more on-off solenoid valves.
• The main flow control means include a mass flow controller.
• The mass flow controller (MFC) comprises at least one proportional solenoid valve controlled by the control means and a main flow sensor.
• the microprocessor control means comprise a (micro)controller or the like.
• the microprocessor control means comprise one (or more) (micro)processors arranged on one (or more) electronic card.
• the control means comprise one (or more) (micro)processors implementing one or more algorithms, in particular one (or more) algorithms for controlling the flow control means, one (or more) algorithms for processing respiratory gas flow measurements or NO, NO ₂ and/or O ₂ concentration measurements, etc.
• the storage means are arranged on the electronic card.

The invention also relates to an installation for supplying a gas containing NO comprising the NO delivery apparatus according to the invention supplied with a NO/N ₂ gas mixture by a source of NO/N ₂ mixture, and a medical ventilator configured to supply a flow of respiratory gas containing O ₂ to said respiratory circuit.

• le ventilateur médical est configuré pour fournir un flux de gaz respiratoire contenant au moins 20%vol. environ d’O₂, typiquement un mélange NO/N₂ou de l’air.
• l’appareil de délivrance de NO et le ventilateur médical sont raccordés fluidiquement au circuit respiratoire.
• un capteur de débit est agencé dans le circuit respiratoire entre le ventilateur médical et le dispositif d’injection.
• un dispositif d’injection est agencé dans le circuit respiratoire, en aval du capteur de débit.
• le dispositif d’injection est configuré pour permettre d’injecter le gaz contenant du NO provenant de l’appareil de délivrance de NO dans le flux de gaz respiratoire contenant de l’O₂provenant du ventilateur médical pour obtenir le mélange gazeux combiné à fournir au patient en ayant besoin.
• le dispositif d’injection est configuré pour opérer un mélange du gaz contenant du NO provenant de l’appareil de délivrance de NO avec le flux de gaz respiratoire contenant de l’O₂acheminé par le circuit respiratoire, et obtenir un mélange gazeux combiné contenant du NO et de l’oxygène, voire d’autres composés comme de l’azote ou des impuretés inévitables.
• le dispositif d’injection comprend une première entrée de gaz alimentée en flux de gaz respiratoire contenant de l’O₂, i.e. provenant du ventilateur médical.
• le dispositif d’injection comprend en outre une seconde entrée de gaz alimentée en gaz contenant du NO provenant de l’appareil de délivrance de NO.
• le dispositif d’injection comprend en outre une sortie de gaz fournissant le mélange gazeux combiné contenant du NO et de l’oxygène, obtenu par mélange, au sein du dispositif d’injection, du gaz contenant du NO (e.g. mélange NO/N₂) avec le flux de gaz respiratoire contenant de l’O₂(e.g. air ou mélange O₂/N₂).
• le ventilateur médical délivre de l’air ou un mélange oxygène/azote, i.e. en tant que gaz respiratoire contenant au moins 20% vol. environ d’oxygène, de préférence au moins 21% vol. environ d’oxygène.
• le ventilateur médical comprend une soufflante motorisée (i.e. turbine, compresseur ou analogue) délivrant le gaz respiratoire, typiquement de l’air ou un mélange oxygène/azote ou, selon un autre mode de réalisation, un circuit de gaz interne comprenant une ou des vannes proportionnelles pour acheminer le gaz et contrôler sa fourniture, notamment son débit. Un tel ventilateur est généralement alimenté en gaz respiratoire par une (ou des) prise murale alimentée en gaz par un réseau de canalisations d’un établissement ou bâtiment hospitalier, typiquement de l’air ou un mélange oxygène/azote.
• le ventilateur médical comprend des moyens ou un dispositif de commande, telle une (ou des) carte de commande électronique. De préférence, les moyens de commande du ventilateur médical pilotent ou commandent la soufflante motorisée ou, selon le cas, les valves proportionnelles du ventilateur médical.
• le ventilateur médical est de type HFO ou comprend une fonction de HFO, c'est-à-dire qu’il est apte à produire des oscillations à haute fréquence.
• la (les) source de NO alimentant l’appareil de délivrance de NO contient un mélange gazeux NO/N₂contenant entre 100 et 2000 ppmv de NO, le reste étant de l’azote (N₂), de préférence entre 100 et 1000 ppmv de NO, conditionné à une pression comprise entre 10 et 250 bar abs, typiquement à plus de 100 bar abs (avant début de soutirage).
• la source de NO est ou comprend une (ou des) bouteille de gaz ayant une contenance comprise entre 0,5 et 50 L (équivalent en eau).
• la (les) bouteille de gaz comprend un corps cylindrique en acier ou en alliage d’aluminium et est équipée d’un robinet simple (sans détendeur) ou à détendeur intégré ou RDI, de préférence un RDI, protégé par un capotage de protection, par exemple en métal ou polymère.
• le circuit respiratoire (i.e. circuit patient) comprend une branche inspiratoire et une branche expiratoire, typiquement des conduites flexibles formant la branche inspiratoire et la branche expiratoire, par exemple des tuyaux en polymère.
• la branche inspiratoire et la branche expiratoire, e.g. des conduites flexibles, sont raccordées à une pièce de jonction, telle une pièce en Y.
• la branche inspiratoire et/ou la branche expiratoire sont reliées fluidiquement à une interface respiratoire patient, de préférence via la pièce de jonction.
• l'interface respiratoire patient comprend une sonde d’intubation trachéale ou masque respiratoire, ou autre.
• le circuit respiratoire, en particulier la branche inspiratoire, peut comprendre un humidificateur de gaz.
• l’humidificateur de gaz est agencé en aval du dispositif d’injection, par exemple un module d’injection de NO, de manière à pouvoir humidifier le gaz avant son administration par inhalation au patient.
• le ventilateur et l’appareil de délivrance de NO sont alimentés électriquement par une ou des sources de courant électrique, typiquement le secteur (110/220V) et/ou une ou des batteries rechargeables.

According to the embodiment considered, the installation for supplying a gas containing NO of the invention may comprise one or more of the following characteristics:

• the medical ventilator is configured to provide a flow of breathing gas containing at least about 20% vol. O ₂ , typically a NO/N ₂ mixture or air.
• The NO delivery device and the medical ventilator are fluidically connected to the breathing circuit.
• A flow sensor is arranged in the breathing circuit between the medical ventilator and the injection device.
• an injection device is arranged in the respiratory circuit, downstream of the flow sensor.
• the injection device is configured to inject the NO-containing gas from the NO delivery apparatus into the _O2- containing breathing gas stream from the medical ventilator to obtain the combined gas mixture to be delivered to the patient in need thereof.
• the injection device is configured to operate a mixture of the gas containing NO coming from the NO delivery device with the flow of respiratory gas containing O ₂ conveyed by the respiratory circuit, and to obtain a combined gas mixture containing NO and oxygen, or even other compounds such as nitrogen or unavoidable impurities.
• the injection device comprises a first gas inlet supplied with a flow of respiratory gas containing O ₂ , i.e. coming from the medical ventilator.
• the injection device further comprises a second gas inlet supplied with gas containing NO from the NO delivery apparatus.
• the injection device further comprises a gas outlet providing the combined gas mixture containing NO and oxygen, obtained by mixing, within the injection device, the gas containing NO (eg NO/N ₂ mixture) with the flow of respiratory gas containing O ₂ (eg air or O ₂ /N ₂ mixture).
• the medical ventilator delivers air or an oxygen/nitrogen mixture, i.e. as a breathing gas containing at least approximately 20% vol. oxygen, preferably at least approximately 21% vol. oxygen.
• the medical ventilator comprises a motorized blower (i.e. turbine, compressor or the like) delivering the respiratory gas, typically air or an oxygen/nitrogen mixture or, according to another embodiment, an internal gas circuit comprising one or more proportional valves for conveying the gas and controlling its supply, in particular its flow rate. Such a ventilator is generally supplied with respiratory gas by one or more wall outlets supplied with gas by a network of pipes in a hospital establishment or building, typically air or an oxygen/nitrogen mixture.
• the medical ventilator comprises control means or a device, such as an electronic control card(s). Preferably, the control means of the medical ventilator drive or control the motorized blower or, as the case may be, the proportional valves of the medical ventilator.
• the medical ventilator is of the HFO type or includes an HFO function, that is, it is capable of producing high-frequency oscillations.
• the NO source(s) supplying the NO delivery apparatus contains a NO/N ₂ gas mixture containing between 100 and 2000 ppmv of NO, the remainder being nitrogen (N ₂ ), preferably between 100 and 1000 ppmv of NO, conditioned at a pressure of between 10 and 250 bar abs, typically at more than 100 bar abs (before the start of withdrawal).
• the source of NO is or includes one (or more) gas cylinders with a capacity of between 0.5 and 50 L (water equivalent).
• the gas cylinder(s) comprises a cylindrical body made of steel or aluminium alloy and is equipped with a simple valve (without regulator) or with an integrated regulator or RDI, preferably an RDI, protected by a protective cover, for example made of metal or polymer.
• the respiratory circuit (i.e. patient circuit) comprises an inspiratory branch and an expiratory branch, typically flexible pipes forming the inspiratory branch and the expiratory branch, for example polymer pipes.
• the inspiratory branch and the expiratory branch, e.g. flexible pipes, are connected to a junction piece, such as a Y piece.
• the inspiratory branch and/or the expiratory branch are fluidically connected to a patient respiratory interface, preferably via the junction piece.
• the patient respiratory interface includes a tracheal intubation tube or breathing mask, or other.
• the breathing circuit, particularly the inspiratory branch, may include a gas humidifier.
• the gas humidifier is arranged downstream of the injection device, for example an NO injection module, so as to be able to humidify the gas before its administration by inhalation to the patient.
• the ventilator and the NO delivery device are electrically powered by one or more electrical power sources, typically the mains (110/220V) and/or one or more rechargeable batteries.

According to another aspect, the invention also relates to a method for the therapeutic treatment of a person, i.e. a human patient (i.e. adult, child, adolescent or newborn), suffering from pulmonary hypertension and/or hypoxia, causing pulmonary vasoconstrictions or the like, comprising administration by inhalation to the person in need thereof, of a gas mixture comprising from 1 to 80 ppmv of NO, typically less than 40 ppmv, and at least approximately 20% vol. of oxygen, preferably at least 21% vol. of oxygen approximately, by means of a gas supply installation, such as that described above according to the invention, comprising an NO delivery apparatus according to the invention ensuring delivery of NO, so as to treat (at least partially) said pulmonary hypertension and/or said hypoxia, which may be caused by one (or more) pathology or other pulmonary disorders typically of the PPHN type (persistent pulmonary hypertension of the newborn) or ARDS (acute respiratory distress syndrome), or caused by a cardiac surgery operation with the patient being placed under extracorporeal blood circulation (ECC).

Definitions

• « ppmv » signifie partie par million en volume,
• « %vol. » » signifie pourcentage en volume.
• « NO » désigne le monoxyde d’azote.
• « NO₂» désigne le dioxyde d’azote.
• « N₂» désigne l’azote.
• « O₂» désigne l’oxygène.
• les termes « concentration », « quantité », « proportion », « dose » et « teneur » sont considérés comme équivalents.
• les termes « moyen de/à/pour » sont considérés comme totalement équivalents et substituables par les termes « dispositif de/à/pour », par exemple les termes « moyens de pilotage » peuvent être remplacés par « dispositif de pilotage », les termes « moyens à vannes » peuvent être remplacés par « dispositif à vannes », les « moyens de mémorisation» peuvent être remplacés par « dispositif de mémorisation» ...
• par « mesure de débit », on entend une valeur de débit (e.g. une valeur numérique) ou un signal représentatif d’une telle valeur de débit reflétant ou correspondant à un débit gazeux mesuré par un capteur de débit, tel un capteur de débit massique.
• par « mesure de pression », on entend une valeur de pression (e.g. une valeur numérique) ou un signal représentatif d’une telle valeur de pression reflétant ou correspondant à la pression gazeuse mesurée par un capteur de pression.
• par « mesure de concentration », on entend une valeur de teneur en un composé gazeux donné, comme le NO, le NO₂ou l’O₂, c'est-à-dire une valeur numérique ou un signal représentatif d’une telle valeur de teneur reflétant ou correspondant à la proportion (i.e. quantité) du composé gazeux considéré dans un mélange gazeux donné, mesurée par des moyens de mesure de concentration, telles des capteurs à cellules électrochimiques.

Generally speaking, within the framework of the invention:

• “ppmv” means parts per million by volume,
• “%vol.” means percentage by volume.
• "NO" stands for nitric oxide.
• “ _NO2 ” stands for nitrogen dioxide.
• “ _N2 ” stands for nitrogen.
• “ _O2 ” stands for oxygen.
• the terms “concentration”, “quantity”, “proportion”, “dose” and “content” are considered equivalent.
• the terms "means of/to/for" are considered to be completely equivalent and substitutable by the terms "device of/to/for", for example the terms "control means" can be replaced by "control device", the terms "valve means" can be replaced by "valve device", the "memorization means" can be replaced by "memorization device" ...
• by "flow measurement" is meant a flow value (e.g. a digital value) or a signal representative of such a flow value reflecting or corresponding to a gas flow rate measured by a flow sensor, such as a mass flow sensor.
• by "pressure measurement" is meant a pressure value (e.g. a digital value) or a signal representative of such a pressure value reflecting or corresponding to the gas pressure measured by a pressure sensor.
• by "concentration measurement" is meant a value of content of a given gaseous compound, such as NO, NO ₂ or O ₂ , that is to say a numerical value or a signal representative of such a content value reflecting or corresponding to the proportion (i.e. quantity) of the gaseous compound considered in a given gaseous mixture, measured by concentration measuring means, such as electrochemical cell sensors.

The invention will now be better understood thanks to the following detailed description, given for illustrative but non-limiting purposes, with reference to the appended figures among which:

FIG. 1 schematizes an embodiment of a gas administration installation comprising an NO delivery apparatus according to the invention.

FIG. 2 schematizes an embodiment of the internal architecture of the NO delivery device according to the invention, such as that of the installation of FIG. 1 .

FIG. 3 schematizes an embodiment of the display of different information on the display of an NO delivery device according to the invention, such as that of FIG. 2 .

FIG. 1 schematizes an embodiment of a gas administration installation 100 according to the invention comprising an NO 1 delivery apparatus according to the invention making it possible to provide a gas mixture based on nitrogen monoxide (NO), typically a NO/N ₂ gas mixture, and a medical ventilator 50 providing a gas containing at least 20% vol. of oxygen, typically air, an O ₂ /N ₂ gas mixture or other.

The installation 100 here comprises two pressurized gas cylinders 10 each containing a gas mixture based on NO, namely a NO/N ₂ gas mixture here containing between 100 and 1000 ppmv of NO (N ₂ remainder), for example 450 or 800 ppm vol. of NO (N ₂ remainder), or any other suitable concentration, which supply the NO/N ₂ mixture to the device or apparatus 1 for delivering or supplying NO, making it possible to monitor and control the supply of the NO/N ₂ gas mixture.

The gas cylinders 10 are fluidically connected to the NO supply apparatus 1, via gas supply lines 12, such as flexible pipes or conduits or the like, which may be equipped with gas pressure regulating and/or monitoring devices, such as a gas regulator 13, pressure gauges, etc. The gas supply lines 12 are connected to one or more gas inlets 2 of the NO supply apparatus 1 which supply an internal gas circuit 200, as shown diagrammatically in FIG. 2 , used to convey the gas within the NO 1 supply device, i.e. into the external housing or casing 1.1 of the NO delivery device 1 according to the invention.

In the embodiment of FIG. 2 , the internal gas circuit 200 is connected to two gas inlets 2 arranged in parallel and each supplying a dedicated inlet section 200.3 of the internal gas circuit 200. Control valves 222 or the like control the passage of the NO/N ₂ flow in these inlet sections 200.3.

The NO 1 delivery apparatus further comprises an oxygen inlet 3 fluidically connected, via an oxygen supply line 11, such as a flexible hose or the like, to an oxygen source (not shown), for example a pressurized oxygen cylinder or a hospital network, i.e. an oxygen supply pipe arranged in a hospital building. This makes it possible to supply the internal gas circuit 200 with oxygen when necessary.

The medical ventilator 50, i.e. a respiratory assistance device, provides a flow of oxygen-based respiratory gas, i.e. containing at least approximately 20% vol. of oxygen, preferably at least approximately 21% vol. of oxygen, such as air or an oxygen/nitrogen mixture (N ₂ /O ₂ ).

The medical ventilator 50 and the NO 1 supply apparatus of the installation 100 are in fluid communication with a respiratory circuit 20, also called a patient circuit, in particular with a gas supply line or inspiratory branch 21 of the respiratory circuit 20, which is used to convey the gas flow to the respiratory interface 40 supplying the therapeutic gas flow to the patient, i.e. a combined gas mixture, i.e. the final mixture, containing the desired NO dosage. This combined gas mixture is obtained by mixing the oxygen-based flow (e.g. air or O ₂ /N ₂ mixture) from the medical ventilator 50 and the flow containing NO, i.e. the NO/N ₂ gas mixture, delivered by the NO 1 delivery apparatus.

To do this, the NO 1 delivery device supplies or injects the NO/N ₂ mixture into the breathing circuit 20 carrying the oxygen-based flow, via a conduit or an injection line 23, fluidically connecting the internal gas circuit 200 of the NO 1 delivery device to an injection device 24 arranged on the gas supply line 21.

The injection device 24 is configured to operate a mixture of the gas containing NO coming from the NO 1 delivery apparatus with the flow of respiratory gas containing O ₂ coming from the ventilator 50 and conveyed by the inspiratory branch 21 of the respiratory circuit 20, and to obtain a combined gas mixture containing NO and oxygen, that is to say the final gas mixture administered to the patient.

More specifically, the injection device 24 comprises a first gas inlet supplied with a flow of respiratory gas containing O ₂ coming from the medical ventilator 50, a second gas inlet supplied with gas containing NO, i.e. coming from the NO 1 delivery apparatus, and a gas outlet providing the combined gas mixture containing NO and oxygen, obtained by mixing, within the injection device 24, the gas containing NO with the flow of respiratory gas containing O ₂ .

In other words, the flow of NO/N ₂ supplied by the injection line 23 then mixes (thanks to the injection device 24) with the flow of oxygen-based gas (> 20% O ₂ ), e.g. air or an oxygen/nitrogen mixture, delivered by the medical ventilator 50 and conveyed by the inspiratory branch 21 of the patient circuit 20 so as to obtain a final mixture, i.e. the combined mixture, to be administered to the patient containing essentially NO at the desired dosage, nitrogen (N ₂ ) and oxygen (O ₂ ), and possibly unavoidable impurities (e.g. argon, CO ₂ , NO ₂ , etc.), i.e. a final gas mixture NO/N ₂ /O ₂ .

The inspiratory branch 21 of the circuit 20 further comprises a gas humidifier 30 arranged downstream of the injection device 24. It makes it possible to humidify the final gas flow, e.g. the combined gas mixture NO/N ₂ /O ₂ , before it is administered by inhalation to the patient to be treated, by means of a respiratory interface 40, such as a tracheal intubation probe, a respiratory mask or the like.

A line for recovering gases exhaled by the patient forms an expiratory branch 22 of the patient circuit 20. It is fluidically connected to the inspiratory branch 21 via a connecting piece 25, such as a Y-shaped piece.

The inspiratory branch 21 is, at its upstream end, fluidically connected to an outlet port 51 of the medical ventilator 50, such as a connector, fitting or the like, so as to recover and convey the oxygen-based gas, typically air or N ₂ /O ₂ mixture provided by the medical ventilator 50, while the expiratory branch 22 conveying the exhaled gases is fluidically connected to an inlet port 52 of the medical ventilator 50, such as a connector, fitting or the like, so as to return to the medical ventilator 50 all or part of the flow of gases exhaled by the patient. The expiratory branch 22 may comprise one or more optional components, for example a CO ₂ removal device 35, ie a CO ₂ trap, such as a hot tank or the like, making it possible to remove the CO ₂ present in the gases exhaled by the patient, a filter or the like.

Furthermore, a flow sensor 25, for example of the hot wire or pressure differential type, is arranged on the respiratory circuit 20, in particular on the inspiratory branch 21, between the ventilator 50 and the injection device 24. The flow sensor 25 is connected to a sensor connection port 27, of the NO 1 delivery device, via one or more flow measurement lines 26 connecting to said sensor connection port 27. It is used to measure the flow rate of gas delivered by the ventilator 50, such as air or N ₂ /O ₂ , circulating in the inspiratory branch 21, upstream of the injection device.

These flow rate measurements made by the flow sensor 25 make it possible to more effectively control or regulate the delivery of the NO flow (i.e. N ₂ /O ₂ ) by the NO 1 delivery device, in particular the NO flow rate, since the flow rate measurements made by the flow sensor 25 are returned, via the flow rate measurement line 26 (i.e. electrical cables or the like) and the sensor connection port 27, to (micro)processor control means 210 of the NO 1 delivery device, typically a controller, which process these flow rate measurements as explained below and illustrated in FIG. 2 The sensor connection port 27 is electrically connected to the control means 210 via one or more electrical connections, for example electrical cables or the like.

The NO 1 supply apparatus comprises a rigid casing 1.1, for example made of polymer, comprising the internal gas circuit 200 on FIG. 2 , typically gas lines, passages or conduits or the like, which fluidically connects the gas inlet(s) 21 of the NO 1 supply apparatus to the injection line 23 so as to convey the NO-based gas flow therebetween.

In the embodiment shown schematically in FIG. 2 , a portion of the internal gas circuit 200 comprises two gas sections arranged in parallel, namely a main section 200.1 and a secondary section 200.2, called the emergency section. The main section 200.1 and the secondary section 200.2 are fluidically connected to each other and to the rest of the gas circuit 200 at upstream 260 and downstream 261 connection sites located, respectively, upstream and downstream of the main and secondary flow control means 220, 221.

In normal operation of the device 1, the flow of NO/N ₂ passes through the main section 200.1, whereas in the event of a malfunction rendering the main flow control means 220 non-operational, the flow of NO/N ₂ is diverted and then passes through the emergency section 200.2.

Of course, according to another embodiment (not shown), the internal gas circuit 200 could be configured differently, for example comprising a single gas line instead of the two sections 200.1, 200.2. However, in this embodiment, a malfunction of the main flow control means 220 could not be taken into account and the device 1 would then become non-functional.

Generally speaking, the main and secondary flow control means 220, 221, such as main and secondary valve means 2200, 2210, shown diagrammatically in FIG. 2 , i.e. one (or more) valve device(s), for example one (or more) proportional solenoid valve(s) controlled by the control means 210, are arranged on the internal gas circuit 200, in particular on the main 200.1 and secondary 200.2 sections, and serve to control or adjust the gas flow which circulates therein towards the injection line 23, i.e. towards the injection device 24, whether in normal operating mode or in emergency mode.

Preferably, the main section 200.1 comprises a proportional solenoid valve 220 and an additional flow sensor 230, typically a mass flow controller or MFC, while the secondary section 200.2 comprises one (or more) on-off (ON) solenoid valves 221, preferably controlled in pulsed mode.

Preferably, the main and secondary flow control means 220, 221 of the NO 1 supply device are controlled, i.e. monitored, by the piloting means 210, i.e. one (or more) piloting devices or (micro)controllers, arranged in the housing 1.1 of the NO 1 supply device.

Typically, the control means 210 comprise one or more electronic cards comprising one or more microprocessors 211 implementing one or more algorithms. The control means 210 make it possible in particular to adjust or control the flow rate of NO-based gas by controlling all or part of the valve means 2200, 2210, typically to open or close one or more (electro)valves, to obtain a flow rate of NO-based gas, typically to authorize or stop the gas flow.

Of course, the control means 210 also make it possible to carry out calculations and/or to control or command all the electromechanical elements of the device 1, such as the sensors, the displays, etc.

As explained below, the control means 210 can determine the flow rate of NO to be supplied to obtain the desired NO content in the combined mixture, i.e. the desired NO dosage, in particular from a set NO content setpoint adjusted and/or set by the user, i.e. a dose of NO (D _NO ) adjusted by the user, the composition of the NO/N ₂ gas mixture, in particular the NO content in this NO/N ₂ gas mixture which can be stored by the device 1, and one or more flow rate measurements carried out by the flow sensor 25 arranged on the inspiratory branch 21 and connected by a flow rate measurement line 26 to the NO 1 supply device, in particular to the control means 210, via the sensor connection port 27.

The internal gas circuit 200 of the NO 1 supply apparatus may also comprise other elements or components, in particular one (or more) pressure sensor 250, one (or more) additional flow sensor or flow meter and/or calibrated orifice devices 240 or others. These other elements may be arranged upstream and/or downstream of the flow control means 220, 221, i.e. valve means, for example an additional flow sensor may be used to determine the flow rate of NO-based gas circulating in all or part of the internal gas circuit 200, in particular to ensure that it complies with the desired flow rate.

In FIG. 2 , we see that the main section 200.1 comprises an additional flow sensor 230 arranged upstream of the flow control means 220, such as valve means 2200, for example one or more solenoid valves, preferably a proportional solenoid valve, controlling the passage of gas in the main section 200.1. This assembly forms a mass flow controller (MFC).

Furthermore, the secondary section 200.2 comprises a calibrated orifice device 240 arranged downstream of secondary flow control means 221, such as secondary valve means 2210, preferably one or more solenoid valves, controlling the flow rate of gas passing through the secondary section 200.2.

Advantageously, the solenoid valve of the secondary flow control means 221 is of the all-or-nothing (TOR) type, i.e. capable of adopting two “stable” positions, namely an open position allowing the gas flow to pass and a closed position preventing any circulation of gas flow.

Furthermore, the additional flow meter or flow sensor 230 of the MFC may be of the pressure differential, mass or other type, and cooperates with the control means 210 to provide them with flow rate measurements of the NO/N ₂ flow.

Usually, the NO 1 supply device also includes a graphical user interface or GUI comprising a graphical display 4, preferably a touch screen, i.e. a touch panel, used to display various information or data, icons, curves, alarms, etc., as well as virtual selection keys and/or blocks or windows, used in particular to make choices, selections or to enter information, such as desired values (e.g. flow rate, NO dosage, etc.), or any other information or data useful to the healthcare staff. Preferably, the display is in color but it can also be in black and white.

However, according to another embodiment, the device 1 may also comprise one or more mechanical selection members, i.e. non-virtual, such as one or more selection buttons or keys actuated by digital pressure from the user, one or more rotary selection buttons or other. The selections or choices made via this or these mechanical selection members may be displayed on the graphic display 4 of the IGU.

The electrical power supply of the NO 1 supply apparatus, in particular of the components requiring electrical current to operate, such as the control means 210, the graphic display 4, etc., is conventionally provided by a source of electrical current and/or electrical power supply means (not shown), for example a connection to the mains current (110/220V) of the electrical cord and connection plug type, and/or one (or more) electrical power supply batteries, preferably rechargeable, and/or a current transformer. The electrical power supply of the medical ventilator 50 is provided in a similar manner, in particular by a connection to the mains current or an internal battery.

In addition, the installation 100 also comprises a gas sampling line 60 which fluidically connects the inspiratory branch 21 to the NO 1 supply device.

The gas sampling line 60 makes it possible to monitor, i.e. to follow up, the composition of the combined gas mixture containing NO, _O2 , etc., in order to ensure that the contents of NO, _O2 and also of toxic _NO2 species that may be formed are compliant, in particular that the proportion of NO is indeed between fixed high and low NO alarm thresholds, i.e. between maximum and minimum acceptable NO contents. Otherwise, the control means of the device 1 trigger an audible alarm and/or a visual alarm in order to alert the nursing staff.

The gas sampling line 60, also called the monitoring line, is fluidically connected to a connection site 61 on FIG. 1 , to the gas supply line 21, between the humidifier 30 and the junction piece 25, i.e. Y-shaped piece, typically in the immediate vicinity of the junction piece 25, and furthermore to an inlet port 62 of the NO 1 supply device, for example a port 62 carried by a connector, fitting or the like, allowing the connection of the gas sampling line 60, such as a flexible pipe or the like.

The gas sampling line 60 makes it possible to take gas samples and convey them to the NO 1 supply device where they are analyzed in an internal gas analyzer (not shown), that is to say within a calibration line comprising at least one sensor, in particular one or more electrochemical cells, electrically connected to the control means, in order to verify their conformity.

As already stated, it is appropriate to check that the composition of the final gas, i.e. the combined gas mixture, is consistent with that of the desired NO/N ₂ /O ₂ gas mixture to be administered to the patient, in particular to ensure that it does not contain an excessive quantity of toxic NO ₂ species, that its oxygen content is not hypoxic, and that its NO content corresponds to the desired dosage (neither too high nor too low), i.e. the dose of NO to be administered by inhalation which is chosen by the healthcare personnel, i.e. doctor or similar.

This compliance check is typically carried out using dedicated NO, _NO2 and _O2 concentration measuring means, typically _NO2 , NO and _O2 sensors, for example electrochemical cells or the like, which must be calibrated periodically, for example every week.

The control means 210 of the device 1 are further configured to recover and process, i.e. analyze, the signals coming from the various means for measuring the concentration of NO, NO ₂ and O ₂ , such as sensors, of the gas analyzer, which is arranged in the device 1, and to act in response to these signals, in particular to carry out a calibration of the sensors, trigger audible and/or visual alarms, etc.

Generally speaking, the control means 210 with (micro)processor 211, such as a controller, determine the set flow rate of gas containing NO to be supplied to the injection device 24 and control the flow control means 220, 221, such as proportional solenoid valves 220 and/or TOR 221, to supply the gas containing NO at the set flow rate. The determination of the NO set flow rate is carried out from a measurement of the respiratory gas flow rate, i.e. the flow rate value or signal, operated and supplied by the flow sensor 25 to the control means 210, from a NO content set point corresponding to the final proportion of NO desired in the combined gas mixture, typically set by the user, i.e. the healthcare staff, and from the initial proportion of NO in the gas containing NO supplying the NO 1 delivery apparatus, i.e. the quantity of NO present in the NO/N ₂ mixture coming from the gas cylinders 10, typically between 200 and 1000 ppmv, for example 450 or 800 ppmv.

Preferably, the dose of NO (D _NO ) and/or the NO content in the NO/N ₂ gas mixture supplying the device 1 are stored by the storage means 212 of the device 1.

The desired NO dose (D _NO ), which is typically between 1 and 80 ppmv, i.e. the NO setpoint, can be entered and/or adjusted and/or modified by the user, for example via the HMI, using dose adjustment means or the like, such as one or more keys, rotary knobs, sliders or the like.

Advantageously, the NO dose adjustment means comprise one or more virtual keys displayed on the display screen 4. For example, they comprise a “+” key for incrementing a NO dose value and a “-” key for decrementing a NO dose value. Typically, the increment or decrement is +/- 1 ppmv.

A validation key can also be provided to validate/confirm a NO dose value that has been set, preferably a virtual validation key displayed on the display screen.

Furthermore, the NO content in the NO/N ₂ gas mixture supplying the device 1 may be adjustable or not, i.e. memorized once and for all or adjustable by the user, within a dedicated or similar menu of the device 1, for example by using, again, adjustment means, such as one or more keys, rotary knobs, sliders or others.

As already explained, in order to be able to detect and warn the user, i.e. the nursing staff, in the event of excessive or, conversely, insufficient NO concentration in the combined gas mixture supplied to the patient, it is essential to set the high and low NO alarm thresholds, i.e. (at least) a high threshold and a low threshold, corresponding to the maximum and minimum acceptable NO levels taking into account the fluctuations in NO concentration that may exist due to possible variations in particular in the flow rate of oxygen-based respiratory gas coming from the medical ventilator 50.

Thanks to the invention, this setting of the high and low NO alarm thresholds is greatly facilitated and is done automatically, via the control means 210, as soon as the NO dose (D _NO ) desired by the user is set, which avoids calculation errors and also errors linked to the entry of these NO alarm thresholds into the NO delivery device.

Patient safety is also greatly improved.

To do this, according to the invention, once the desired dose of NO (D _NO ), i.e. the desired dosage, typically between 1 and 80 ppmv, preferably less than or equal to 40 ppmv, more preferably less than or equal to 30 ppmv, advantageously less than or equal to 20 ppmv, has been set by the user using the NO dose setting means, the chosen value, i.e. the set dose of NO (D _NO ), is used by the control means 210 to automatically calculate said high and low NO alarm thresholds.

• le seuil d’alarme NO haut correspondant à une teneur maximale de NO (T_max), telle que : 1,1 . D_NO≤ T_max≤ 1,3 . D_NO, de préférence T_max≤ 1,25. D_NO, de préférence encore T_max≤ 1,2.D_NO, par exemple T_max= 1,2.D_NO, et
• un seuil d’alarme NO bas correspondant à une teneur minimale de NO (T_min), telle que : 0,7 . D_NO≤ T_min≤ 0,9 . D_NO, de préférence 0,75 . D_NO≤ T_min, de préférence encore 0,80 . D_NO≤ T_min, par exemple T_min= 0,8.D_NO.

The calculation is made from the NO dose value (D _NO ) set, namely that:

• the high NO alarm threshold corresponding to a maximum NO content (T _max ), such that: 1.1 . D _NO ≤ T _max ≤ 1.3 . D _NO , preferably T _max ≤ 1.25. D _NO , more preferably T _max ≤ 1.2.D _NO , for example T _max = 1.2.D _NO , and
• a low NO alarm threshold corresponding to a minimum NO content (T _min ), such that: 0.7 . D _NO ≤ T _min ≤ 0.9 . D _NO , preferably 0.75 . D _NO ≤ T _min , more preferably 0.80 . D _NO ≤ T _min , for example T _min = 0.8.D _NO .

In other words, according to the invention, the control means 210 of the device 1 automatically calculate the values of the high and low NO alarm thresholds by adding or, conversely, subtracting from 10% to 30%, preferably approximately 20%, to the NO dose value (D _NO ) set, depending on the tolerance value (%) that can be accepted, that is to say the fluctuations in NO contents in the combined gas mixture that can be tolerated within the framework of the patient's treatment.

The tolerance value (%), for example 20%, may be non-modifiable, for example set at the factory and stored in the device, or, according to another embodiment, may be modifiable by the user, for example within a configuration menu of the device 1. The percentage (%) of tolerance may depend on different factors, for example for a particular treatment protocol.

The tolerance value (%) and/or the calculation formulas including this tolerance value (%) are stored within the device 1, for example within the storage means 212.

Once determined, the maximum NO content (T _max ) corresponding to the high NO alarm threshold and the minimum NO content (T _min ) corresponding to the low NO alarm threshold are preferably memorized, i.e. recorded, by the storage means 212. For example, for a dose of NO (D _NO ) set at 20 ppm, the delivery apparatus of the invention, typically its control means, automatically calculates high and low NO alarm thresholds of between 14 and 18 ppmv for the minimum NO content (T _min ) and between 22 and 26 ppmv for the maximum NO content (T _max ).

• T_max= 1,20.D_NO, pour le seuil d’alarme NO haut, soit 20% de plus que la dose de NO (D_NO) réglée, et
• T_min= 80.D_NOpour le seuil d’alarme NO bas, soit 20% de moins que la dose de NO (D_NO) réglée.

If the percentage (%) of tolerance has been set at 20% due to adjustments made for example in the factory, and stored in device 1, the calculation formulas above then become:

• T _max = 1.20.D _NO , for the high NO alarm threshold, i.e. 20% more than the NO dose (D _NO ) set, and
• T _min = 80.D _NO for the low NO alarm threshold, i.e. 20% less than the set NO dose (D _NO ).

Therefore, for the NO dose (D _NO ) set at 20 ppmv, the device 1 can then automatically calculate high and low NO alarm thresholds equal to 16 ppmv for the minimum NO content (T _min ) and between 24 ppmv for the maximum NO content (T _max ), i.e. thresholds equal to 20 ppmv +/- 20% (i.e. +/- 4 ppmv).

Similarly, for a dose of 15 ppmv for example, the high and low NO alarm thresholds would then be equal to 12 ppmv and 18 ppmv, i.e. 15 ppmv +/- 20% (i.e. +/- 3 ppmv).

In all, in particular for the set NO doses (D _NO ) which are less than 10 ppmv, the control means (210) are configured to calculate and/or set maximum and minimum NO contents (T _max , T _min ) preferably deviating by at least 2 ppmv from the set NO dose (D _NO ), i.e.: T _max - D _NO ≥ 2 ppmv and D _{NO -} T _min ≥ 2 ppmv.

Thus, for example, for a set NO dose (D _NO ) of 5 ppmv and a tolerance of 20%, the control means (210) are configured to calculate and/or set maximum and minimum NO contents (T _max , T _min ) of 3 ppmv for the minimum NO content (T _min ) and 7 ppmv for the maximum NO content (T _max ), whereas in theory, they should be 4 ppmv and 6 ppmv, respectively.

Such a deviation of at least 2 ppmv from the set NO dose (D _NO ) makes it possible to avoid too frequent alarm triggers while ensuring good safety for the patient.

Once the high and low NO alarm thresholds have been determined, they are preferably displayed by the graphic display 4, as illustrated in FIG. 3 , which schematizes a display in a first dedicated window 41, of the maximum NO content (T _max ) corresponding to the high NO alarm threshold, namely here 24 ppmv, and of the minimum NO content (T _min ) corresponding to the low NO alarm threshold, namely here 16 ppmv.

It can be seen that the instantaneous NO content value (NO _inst ) is also displayed in the first window 41, namely 0.8 ppmv here, which is measured by the NO concentration measuring means, such as an NO sensor. In this case, since the treatment has not yet started (displayed information: WAITING - Patient Not Treated), the NO value in the flow sent to the patient is almost zero (0.8 ppmv) because the flow of respiratory gas coming from the medical ventilator 50 has not yet been mixed with the NO/N ₂ mixture flow coming from the device 1. Therefore, the NO concentration measuring means only determine a negligible quantity in the air flow, i.e. in the form of traces or unavoidable impurities.

FIG. 3 therefore illustrates the display 4 after setting the dose of NO (D _NO ) by the user and calculating the alarm thresholds (T _max , T _min ) but just before the start of the patient's treatment, which can then begin after the user presses the virtual start button 45 displayed on the graphic display 4. Moreover, we also see that the dose of NO (D _NO ) set, i.e. the dosage, is also displayed within a second window 42, namely here 20 ppmv.

The NO concentration measuring means provide the NO measurements (i.e. value or signal) to the control means 210 which process them to possibly trigger alarms and/or control their display on the display 4, in order to ensure effective monitoring of the operation of the device 1 and/or the installation 100.

In addition, the display 4 also displays the NO ₂ and O ₂ concentrations measured by the NO ₂ and O ₂ concentration measuring means, typically NO ₂ and O ₂ sensors, for example electrochemical cells or the like, and processed by the control means 210, which also control their display on the display 4, namely here in third and fourth windows 43, 44.

We see that the NO ₂ content measured and displayed in the third window 43 is equal here to 0 ppmv, which is normal since the treatment has not yet started, so no oxidation of the NO molecules to form the toxic NO ₂ species could have taken place.

On the other hand, it is noted that the supply of the flow of respiratory gas containing oxygen, such as air or a gas mixture formed of 21% O ₂ and remainder N ₂ for example, coming from the ventilator 50 has started since the O ₂ concentration measuring means have detected an oxygen content of approximately 21% vol. in the gas flow present in the respiratory circuit 20. This oxygen content is displayed in the fourth window 44.

During operation of the apparatus 1, when the control means 210 detect a concentration of NO greater than the maximum NO content (T _max ), i.e. exceeding the high threshold, or, conversely, less than the minimum NO content (T _min ), i.e. exceeding the low threshold, they act on alarm means of the apparatus 1 to trigger an alarm, which may be audible, for example a sound coming from a buzzer or the like, and/or visual, for example an alert message displayed on the graphic display 4, in order to warn the nursing staff that the NO content of the combined gas mixture is too high or, conversely, too low.

Of course, other alarms can be triggered by the control means 210 in the event of detection of an excessively high NO ₂ content, for example exceeding approximately 1 to 3 ppmv or an excessively low oxygen content, for example less than approximately 19 to 20% vol. These alarms can be set in the factory and/or optionally, can be modified by the user.

A gas administration installation 100 including an NO 1 delivery apparatus according to the invention can be used to administer nitric oxide (NO) by inhalation, i.e. the final mixture obtained NO/O ₂ /N ₂ , to people, i.e. patients, suffering from acute pulmonary arterial hypertension, in particular to operate a dilation of their pulmonary vessels and an increase in their oxygenation by improving pulmonary gas exchange, in particular to treat Pulmonary Arterial Hypertension of the Newborn or PPHN, Acute Respiratory Distress Syndrome or ARDS observed mainly in adults, or pulmonary hypertension (PH) in cardiac surgery in adults or children.

Claims (10)

Apparatus for delivering (1) a gas containing NO comprising:

• NO dose adjustment means configured to allow a user to adjust a NO dose (D _NO ) between 1 and 80 ppmv,
• and control means (210) with microprocessor (211),

characterized in that the control means (210) are configured to automatically calculate, from the dose of NO (D_NO) set:

• a high NO alarm threshold corresponding to a maximum NO content (T _max ), such that: 1.1 . D _NO ≤ T _max ≤ 1.3 . D _NO
• and a low NO alarm threshold corresponding to a minimum NO content (T _min ), such that: 0.7 . D _NO ≤ T _min ≤ 0.9 . D _NO

Apparatus according to claim 1, characterized in that the control means (210) are configured to calculate, from the dose of NO (D_NO) set:

• a high NO alarm threshold corresponding to a maximum NO content (T _max ), such that: T _max ≤ 1.25 . D _NO and/or
• a low NO alarm threshold corresponding to a minimum NO content (T _min ), such as: 0.75 . D _NO ≤ T _min

Apparatus according to one of the preceding claims, characterized in that the control means (210) are configured to calculate, from the dose of NO (D_NO) set:

• a high NO alarm threshold corresponding to a maximum NO content (T _max ), such that: T _max ≤ 1.20 . D _NO and/or
• a low NO alarm threshold corresponding to a minimum NO content (T _min ), such as: 0.80 . D _NO ≤ T _min

Apparatus according to one of the preceding claims, characterized in that the control means (210) are configured to calculate, from the dose of NO (D_NO) set:

• a high NO alarm threshold corresponding to a maximum NO content (T _max ), such that: T _max = 1.20 . D _NO and/or
• a low NO alarm threshold corresponding to a minimum NO content (T _min ), such that: T _min = 0.80 . D _NO

Apparatus according to one of the preceding claims, characterized in that the control means (210) are configured to calculate the maximum and minimum NO contents (T _max , T _min ) such that: T _max - D _NO ≥ 2 ppmv and/or
D _{NO -} T _min ≥ 2 ppmv. Apparatus according to one of the preceding claims, characterized in that it comprises a graphic display (4) and the control means (210) are configured to control a display on the graphic display (4) of the maximum NO content (T _max ) corresponding to the high NO alarm threshold and of the minimum NO content (T _min ) corresponding to the low NO alarm threshold. Apparatus according to one of the preceding claims, characterized in that it comprises an internal gas circuit (200) conveying the gas containing NO fluidically connected to a respiratory circuit (20; 21) conveying a respiratory gas containing oxygen to inject the gas containing NO and obtain a combined gas mixture containing NO and oxygen,
- it comprises NO concentration measuring means for determining the NO content in the combined gas mixture containing NO and oxygen, and
- the control means (210) are configured to trigger an alarm, when said control means (210) determine that the NO content in the combined gas mixture determined by the NO concentration measuring means, is greater than or equal to the maximum NO content (T _max ) or less than or equal to the minimum NO content (T _min ). Apparatus according to claims 6 and 7, characterized in that the control means (210) are configured to control a display (41) on the graphic display (4) of the NO content (NO _inst ) in the combined gas mixture having been determined by the NO concentration measuring means. Apparatus according to claims 1 and 6, characterized in that the NO dose adjustment means comprise one or more virtual touch keys, operable by the user, displayed on the graphic display (4) of the digital screen type with touch panel. Installation for supplying a gas containing NO (100) comprising the NO delivery apparatus (1) according to one of the preceding claims supplied with a NO/N ₂ gas mixture by a source of NO/N ₂ mixture, and a medical ventilator (50) configured to supply a flow of respiratory gas containing O ₂ to said respiratory circuit (20; 21).