NO delivery device powered by two gas cylinders

Abstract

Title of the invention: NO delivery apparatus supplied by two gas cylinders. The invention relates to an NO delivery apparatus (1) for supplying a gas containing NO, comprising pilot means (210), a gas circuit (200) comprising circuit sections (201, 202) comprising gas inlets (201.1, 202.1) for fluidly connecting NO containers (10.1, 10.2), as well as pressure measuring means (251, 252) for measuring the pressure and valve means (222.1, 222.2) controlled by the pilot means (210) for controlling the gas flow to the circuit sections (201, 202). The pilot means (210) are configured to control the valve means (222.1, 222.1).2) to allow gas flow within one of the circuit sections (201, 202) and simultaneously prohibit any gas flow within the other circuit sections (201, 202) as long as the pressure (P) measured by the pressure measuring means (251, 252) is greater than or equal to a given threshold pressure, and then switch from one section to the other when the pressure falls below the given threshold pressure. Preferably, a purge step is provided for the section receiving the gas before switching to said section. Installation (100) for supplying a gas mixture containing NO to a patient comprising such an NO delivery device (1). Abstract figure: Figure 2.

Description

Title of the invention: NO delivery device powered by two gas cylinders

[0001] The invention relates to an NO delivery device for supplying a gaseous mixture containing NO, typically an NO / N2 mixture, from one or more NO sources, such as pressurized gas cylinders, and an installation for supplying an NO-based gaseous mixture to a patient comprising such an NO delivery device and a medical ventilator supplying an oxygen-based gas (i.e., approximately >20% vol.), such as air or an O2 / N2 mixture.

[0002] 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.

[0003] To implement inhaled NO therapy, a gas supply system, also called an NO delivery system, is used, comprising an NO delivery device and a medical ventilator, i.e. a respiratory support device, supplying a patient circuit.

[0004] The NO delivery device allows the injection of a gaseous mixture based on NO, typically an NO / nitrogen mixture, into the patient circuit, which is also supplied with a gaseous flow containing oxygen (at least approximately 20% vol.), such as air or an oxygen / nitrogen (O2 / N2) mixture, provided by the medical ventilator. The patient circuit generally comprises one or more flexible conduits fluidically connected to a respiratory interface, such as a tracheal intubation tube or similar device, used to deliver to the patient being treated a therapeutic gaseous mixture containing a given quantity or dose of NO, i.e., a dosage, typically between 5 and 40 ppmv of NO.

[0005] Such a gas supply installation is described, for example, by EP3821929. This type of installation is used in hospitals to administer NO treatment and thus treat patients who need to inhale NO to treat their pulmonary arterial hypertension. Other installations of this type are described by EP4209243, EP4241817, EP4241812, and EP4295882.

[0006] The gaseous NO, typically a gaseous NO / nitrogen mixture, supplying the NO delivery device generally comes from one or more pressurized gas containers, i.e. one or more gas cylinders containing the compressed NO / nitrogen gas mixture, also called "NO cylinders".

[0007] To avoid an interruption in patient treatment when a NO cylinder is empty, i.e., during the time required to replace it with a full NO cylinder, it is recommended to connect the NO delivery device to two NO cylinders. Thus, when an NO cylinder is (nearly) empty, a healthcare professional can operate a switching valve or similar device to shut off the supply from the empty NO cylinder and allow the supply from the full NO cylinder, thereby ensuring a continuous NO fluid supply to the NO delivery device and enabling the replacement of the empty NO cylinder with a full one.

[0008] A problem that arises in practice is that healthcare personnel may either forget to check the pressure displayed by the pressure gauge usually fitted to a NO cylinder and therefore fail to notice that a cylinder is (almost) empty, or be unavailable to perform these checks because they are too busy treating a patient. In both cases, this results in a risk of NO supply disruption, which is unacceptable as it could potentially endanger the patient.

[0009] In other words, one object of the invention is to be able to avoid or minimize this risk of disruption of NO supply caused by a failure to replace a (nearly) empty NO cylinder in order to improve the safety of treatment of a patient treated by administration of gaseous NO.

[0010] One solution of the invention relates to an apparatus or device for delivering, i.e. supplying, NO to provide a gas containing NO comprising: - control systems, preferably microprocessor-based, - a gas circuit comprising a first circuit section including a first gas inlet configured to fluidly connect a first NO container containing NO gas, and a second circuit section including a second gas inlet configured to fluidly connect a second NO container containing NO gas, - a first pressure measuring means, arranged on the first circuit section, configured to measure the pressure within the first circuit section, - a second pressure measurement device, arranged on the second circuit section, configured to measure the pressure within the second circuit section, - a first valve-equipped means, arranged on the first circuit section, controlled by the control means to regulate the gas flow within the first circuit section, i.e., to authorize / allow or, conversely, prohibit / stop any gas circulation within the first circuit section, and - a second valve means, arranged on the second circuit section, controlled by the control means to control the gas flow within the second circuit section, i.e. to authorize / allow or, conversely, prohibit / stop any gas circulation within the second circuit section.

[0011] Furthermore, the control means of the NO delivery device are configured to control the first valve means and / or the second valve means to: i. allow gas circulation within one of the first and second circuit sections and simultaneously prohibit any gas circulation within the other of said first and second circuit sections as long as the pressure (P) measured by the first or second pressure measuring device is greater than or equal to a given threshold pressure (PS), i.e. P > PS, and ii. when the pressure measured (P) by the first or second pressure measuring device becomes lower than the given threshold pressure (PS), i.e.

[0012] P < PS: a. interrupt all gas circulation within said first or second circuit section in which gas circulates, that is to say in one of the two sections, and b. to allow gas circulation within the other of the said first or second circuit section within which gas circulation was prohibited, that is to say in the other of the two sections.

[0013] In other words, in the device of the invention, there is an automatic switchover from one section to the other, as soon as the pressure measured within the section considered becomes less than or equal to the given threshold pressure, which corresponds to an empty or almost empty gas cylinder.

[0014] The gas supply is therefore done in an alternative manner, depending on the pressure prevailing in the first and second sections of the circuit.

[0015] Thus, the control means of the NO delivery device are configured to control the first valve means and / or the second valve means to: - to authorize / permit gas circulation within the first circuit section and simultaneously prohibit any gas circulation within the second circuit section as long as the pressure (P) measured by the first pressure measuring device is greater than or equal to the given threshold pressure (PS), - then, when the pressure measured (P) by the first pressure measuring device becomes lower than the given threshold pressure (PS), to interrupt / stop all gas circulation within the said first circuit section in which gas was circulating until then, and subsequently allow gas circulation within the second circuit section in which gas circulation was prohibited / prevented until then

[0016] And then, reciprocally or alternatively, the control means of the NO delivery device are configured to control the first valve means and / or the second valve means to: - to authorize / allow gas circulation within the second circuit section and simultaneously prohibit any gas circulation within the first circuit section as long as the pressure (P) measured by the second pressure measuring means is greater than or equal to the given threshold pressure (PS), - then, when the pressure (P) measured by the second pressure measuring means becomes less than the given threshold pressure (PS), to interrupt / stop any gas circulation within said second circuit section in which gas was circulating, and then authorize gas circulation within the first circuit section in which gas circulation was prohibited / prevented.

[0017] Put another way, the invention relates to an apparatus or device for delivering, i.e. supplying, NO to provide a gas containing NO comprising: - control systems, and - a gas circuit comprising at least two circuit sections arranged, preferably in parallel, each comprising: • a gas inlet configured to fluidly connect a NO container containing NO-containing gas, and • a pressure measuring device configured to measure the gas pressure within it, and • a valve-operated means controlled by the pilot means to control the gas flow, i.e., to authorize / allow or, conversely, prohibit / stop any gas circulation within the section considered,

[0018] and wherein the control means are configured to control one of the valve means for: - to allow gas circulation within one of the sections and simultaneously prohibit any gas circulation within the other of said sections as long as the pressure (P) measured by the pressure measuring means associated with the section in question is greater than or equal to a given threshold pressure (PS), i.e. P > PS, - and when the measured pressure (P) becomes lower than the given threshold pressure (PS), within the section considered: a. interrupt all gas circulation within the section in question in which gas was circulating, i.e. where a flow had been passing until now, and b. allow gas flow within the other section in which gas flow was prohibited, i.e. in the other section, i.e. the section where the gas flow was interrupted until now.

[0019] Advantageously, before allowing gas to flow within the other section, a purging of said section is carried out.

[0020] Depending on the embodiment considered, the NO delivery (i.e. supply) device, typically of a NO / N2 mixture, of the invention may comprise one or more of the following features: - the first circuit section and the second circuit section connect to each other at a gas circuit connection site located downstream of the first and second valve means. - the first and second valve means include solenoid valves. - the first gas inlet is configured to be fluidly connected to the first NO container via a first gas supply line. - the second gas inlet is configured to be fluidly connected to the second NO container via a second gas supply line. - the first gas supply line and the second gas supply line include flexible pipes or similar. - it also includes a first exhaust line to the atmosphere comprising a first exhaust valve, fluidly connected to the first section of the circuit. - it also includes a second exhaust line to the atmosphere comprising a second exhaust valve, fluidly connected to the second section of the circuit. - the first and second exhaust valves are controlled by the control means. - the first exhaust line to the atmosphere and the second exhaust line to the atmosphere communicate with the atmosphere via one or more exhaust ports. - the exhaust of the gas to the ambient atmosphere is done via a single exhaust port or alternatively via several exhaust ports, for example two exhaust ports. - the control means are further configured to control the second exhaust valve to perform a purge of the second circuit section, before allowing gas to circulate from the second NO container within said second circuit section. Alternatively, the control means are further configured to control the first exhaust valve to purge the first circuit section, before allowing gas to flow from the first NO container into said first circuit section. the control means are further configured to operate a purge of the first or second circuit section and simultaneously of at least part of the first or second gas supply line connected to said first or second circuit section subject to purging, i.e. one or more flexible pipes. the control means are further configured to perform a purge between steps a) and b) above. The control means are also configured to operate a purge for a given purge duration. the purge time is between 10 seconds and 120 seconds, typically at least 30 seconds. the duration of the purge is memorized, for example by means of memorization. The purging of the first and / or second circuit section includes sending or releasing into the atmosphere at least a portion of the pressurized gas (i.e. residual pressure) present in the first or second circuit section and preferably in at least a portion of the first or second gas supply line connected to said first or second circuit section subject to purging. The purging of the first and / or second circuit section includes sending or releasing into the atmosphere at least some of the pressurized gas and at least some of the undesirable species that may be present therein, in particular harmful or toxic species, typically NO2 species. The purge includes a gaseous sweep with the gaseous mixture containing NO, typically the NO / N2 mixture, from the first or second NO container. the purging of the first and / or second circuit section includes a gaseous sweep (at least) of said first and / or second circuit section with the NO / N2 gas mixture, i.e. the NO-based gas from either of the gas containers. The purging includes a gaseous sweep of said first or second circuit section, respectively, and of said first or second gas supply line, respectively, i.e., a gaseous sweep of the first section and the first gas supply line associated with it, or of the second section and the second gas supply line associated with it, with the NO / N2 gas mixture, i.e. the NO-based gas from either of the gas containers, i.e. the first or second gas container, respectively. a sending or release into the atmosphere of at least part of the gaseous atmosphere (i.e. gas containing possible NO2 impurities) present in the first or second circuit section and in the first or second gas supply line, namely purge gas containing the NO / N2 mixture used for gas purging and possibly impurities, such as NO2 species. The given threshold pressure (PS) is memorized by memorization means. the given threshold pressure (PS) is between 2 and 8 bar, preferably between 2.5 and 7 bar, preferably still between 3 and 6 bar. The first NO container and the second NO container contain a NO / N2 mixture containing between 100 and 2000 ppmv of NO, and nitrogen for the rest. when the NO containers are full, the NO / N2 mixture is conditioned there at a pressure of at least 150 bar. the first container of NO and the second container of NO contain a NO / N2 mixture containing between 100 and 1500 ppmv, typically between 200 and 1000 ppmv. It is supplied with a gaseous mixture made up of nitrogen and NO. It includes dose adjustment means configured to allow a user to set or select the NO content setpoint corresponding to the desired final proportion of NO in the combined gas mixture, i.e. a dosage. The means of dose adjustment are part of an HMI (human-machine interface) or GUI (graphical user interface). The dose adjustment means include one or more touch keys, operable by the user, displayed on a digital touchscreen of the HMI, preferably of the color display type. The target NO content is between 1 and 80 ppmv, typically between 5 and 40 ppmv. The means of storage include computer memory, such as flash memory, RAM or similar. The control means include a (micro)controller or similar. - the control means include one (or more) (micro)processor arranged on one (or more) electronic board. - the control means include one (or more) (micro)processor implementing one or more algorithms, including one (or more) algorithm for controlling or managing valves, processing flow or pressure measurements.... - the storage devices are arranged on the electronic board. - it is electrically powered by one or more sources of electric current, typically mains power (110 / 220V) and / or one or more rechargeable batteries.

[0021] The invention also relates to an installation for supplying a gaseous mixture containing NO to a patient comprising: - a NO delivery device according to the invention, supplied with a gas containing NO from two gas containers alternately supplying the gas circuit of the NO delivery device, typically pressurized gas cylinders, - a medical ventilator configured to provide a flow of breathing gas containing O2, and - a breathing circuit including an injection device configured to operate a mixture of NO-containing gas from the NO delivery device with the O2-containing breathing gas flow supplied by the medical ventilator, and obtain a combined gas mixture containing NO and oxygen.

[0022] Furthermore, depending on the embodiment considered, the gas supply installation of the invention may include one or more of the following additional features: - The medical ventilator is configured to provide a flow of breathing gas containing at least 20% vol. approximately of O2, typically a NO / N2 mixture or air. - The NO delivery device and the medical ventilator are fluidly connected to the respiratory circuit. - the flow sensor is arranged in the breathing circuit between the medical ventilator and the injection device. - the injection device includes a first gas inlet supplied with a flow of respiratory gas containing O2, i.e. from the medical ventilator. the injection device further includes a second gas inlet supplied with gas containing NO at the set flow rate, i.e. from the NO delivery device. the injection device further includes a gas outlet supplying the combined gas mixture containing NO and oxygen, obtained by mixing, within the injection device, the gas containing NO (e.g. NO / N2 mixture) with the breathing gas stream containing O2 (e.g. air or O2 / N2 mixture). The medical ventilator delivers air or an oxygen / nitrogen mixture, i.e. as a breathing gas containing at least approximately 20% vol. of oxygen, preferably at least approximately 21% vol. of oxygen. The medical ventilator comprises a motorized blower (i.e., turbine, compressor, or similar) delivering the breathing gas, typically air or an oxygen / nitrogen mixture, or, in another embodiment, an internal gas circuit including one or more proportional valves for routing the gas and controlling its supply, particularly its flow rate. Such a ventilator is generally supplied with breathing gas from one or more wall outlets supplied by a network of pipes in a hospital or hospital building, typically air or an oxygen / nitrogen mixture. The medical ventilator includes control means or a control device, such as an electronic control board (or boards). Preferably, the control means of the medical ventilator operate or control the motorized blower or, as appropriate, the proportional valves of the medical ventilator. The medical ventilator is of the HFO type or includes an HFO function, meaning that it is capable of producing high-frequency oscillations. Each container of NO contains a NO / N2 gas mixture containing between 100 and 2000 ppmv of NO, the remainder being nitrogen (N2), preferably between 100 and 1000 ppmv of NO, conditioned at a pressure between 10 and 250 bar, typically above 100 bar (before the start of withdrawal). Each container of NO is or includes one (or more) gas cylinder(s) with a capacity of between 0.5 and 50 L (water equivalent). Each container of NO is a pressurized gas cylinder. Each NO container comprises a cylindrical body made of steel or aluminum alloy and is equipped with a simple valve (without a regulator) or with an integrated regulator or RDI, preferably an RDI, protected by a protective cover, for example made of metal or polymer. - the breathing circuit of the installation includes an inspiratory branch and an expiratory branch, typically flexible conduits forming the inspiratory and expiratory branches, for example polymer tubing. - the inspiratory branch and the expiratory branch, e.g. flexible conduits, are connected to a junction piece, such as a Y-piece. - the inspiratory limb and / or the expiratory limb are fluidly connected to a patient respiratory interface, preferably via the junction piece. - the patient respiratory interface includes a tracheal intubation tube or respiratory mask, or other. - the inspiratory branch and the expiratory branch are further fluidically connected to, respectively, outlet and inlet ports of the medical ventilator. - the respiratory circuit, in particular the inspiratory branch, may include a gas humidifier. - The gas humidifier is arranged downstream of the injection device, for example a NO injection module, so as to be able to humidify the gas before its administration by inhalation to the patient. - The fan is electrically powered by one or more sources of electrical current, typically mains (110 / 220V) and / or one or more rechargeable batteries.

[0023] According to another aspect, the invention also relates to a method of 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 an administration by inhalation to the person in need, of a gaseous mixture comprising from 1 to 80 ppmv of NO and at least 20% vol. of oxygen about, preferably at least 21% vol.approximately oxygen, by means of a gas supply installation, such as that described above according to the invention, comprising a NO delivery device ensuring delivery of NO at the desired dosage, so as to treat (at least partially) said pulmonary hypertension and / or said hypoxia, which may be caused by one or more pulmonary pathologies or other disorders typically of the type PPHN (persistent pulmonary hypertension of the newborn) or ARDS (acute respiratory distress syndrome), or caused by cardiac surgery with the patient placed under extracorporeal blood circulation (ECC). Definitions

[0024] In general, within the scope of the invention: - "ppmv" means parts per million by volume, - "%vol." means percentage by volume. - "NO" refers to nitrogen monoxide. - “NO2” refers to nitrogen dioxide. - "N2" refers to nitrogen. - "O2" refers to oxygen. - pressures are expressed in absolute bar, abbreviated "bar". - the terms "concentration", "quantity", "proportion", "dose" and " "content" are considered equivalent. - The terms "means of / to / for" are considered to be totally equivalent and interchangeable with 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 terms "memory means" can be replaced by "memory device"... - by "pressure measurement" means a pressure value (e.g. a numerical value) or a signal representative of such a pressure value reflecting or corresponding to the gas pressure measured by a pressure sensor or similar device.

[0025] The invention will now be better understood with reference to the following detailed description, given by way of illustration but not limitation, with reference to the accompanying figures, among which:

[0026] [Fig-1] schematically illustrates an embodiment of a gas administration installation according to the invention.

[0027] [Fig.2] schematically illustrates an embodiment of the internal architecture of the NO delivery device of a gas administration installation according to the invention, in particular a gas administration installation according to [Fig.1].

[0028] [Fig.1] schematically illustrates an embodiment of a gas administration installation 100 according to the invention comprising a NO supply device 1 providing a gas mixture based on nitrogen monoxide (NO), and a medical ventilator 50 providing a gas containing at least 20% vol. of oxygen, such as air or other.

[0029] Installation 100 includes sources of NO 10, namely here two containers or pressurized gas cylinders 10.1, 10.2 each containing a NO / N2 gas mixture, namely here a NO / N2 gas mixture containing between 100 and 1000 ppmv of NO (remaining N2), for example 450 or 800 ppm vol. of NO (remaining N2), or any other suitable concentration, which supply the device or apparatus 1 with the NO / N2 mixture of delivery or supply of NO allowing to monitor and control the supply of the NO / N2 gas mixture.

[0030] The gas cylinders 10.1, 10.2 are each fluidly connected to the NO supply unit 1, via gas supply lines 12, typically a first gas supply line 12.1 and a second gas supply line 12.2, such as flexible hoses 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...

[0031] The gas supply lines 12 are fluidly connected to gas inlets 2, namely a first and a second gas inlet 201.1, 202.1 of the NO delivery device 1 which supply an internal gas circuit 200, as detailed in [Fig.2], used to convey the gas within the NO supply device 1, i.e. in the external casing or housing 1.1 of the device 1.

[0032] In the embodiment of [Fig.2], the internal gas circuit 200 comprises a first circuit section 201, also called the first inlet section, fluidly connected to a first gas inlet 201.1 and a second circuit section 202, also called the second inlet section, fluidly connected to a second gas inlet 202.1 of the apparatus 1. The first and second gas inlets 201.1, 202.1 are also called the first and second NO inlets since they are supplied with a NO / N2 mixture from the gas cylinders 10.1, 10.2.

[0033] The first circuit section 201 includes a first valve means 222.1, typically a first control valve, piloted by the pilot means 210 to control the gas flow within the first circuit section 201, and the second circuit section 202 includes a second valve means 222.2, typically a second control valve, piloted by the pilot means 210 to control the gas flow within the second circuit section 202, typically the first and second valve means 222.1, 222.2 are solenoid valves or the like.

[0034] As illustrated in [Fig.2], the two circuit sections 201, 202 are arranged in parallel with each other but are fluidly connected to each other at a connection site 203 of the gas circuit 200, which connection site 203 is located downstream of the valve means 222.1, 222.2, considering the direction of gas flow in the gas circuit 200, i.e. in the direction going from the first and second gas inlets 201.1, 202.1 towards the control valves 222.1, 222.2.

[0035] The first gas inlet 201.1 is fluidly connected to a first gas supply line 12.1, typically a first flexible hose, while the second gas inlet 201.1 is fluidly connected to a second gas supply line 12.2, typically a second flexible hose. The connections can be made using conventional connectors.

[0036] The valve means 222.1, 222.2, i.e. control valves or the like, control the passage of the NO / N2 flow in the two sections 201, 202 to operate an alternative supply to the downstream part of the gas circuit 200 located in particular downstream of the connection site 203, that is to say that only one or the other of the sections 201, 202 can supply said downstream part of the gas circuit 200 but never both simultaneously, i.e. at the same time.

[0037] In other words, when the first valve means 222.1 is controlled by the pilot means 210 to be in the open position and thus allow gas to pass through, the second valve means 222.2 is (controlled) in the closed position and therefore prevents any gas from passing through, and vice versa. However, it is possible that both valve means 222.1 and 222.2 are both (controlled) in the closed position to block any gas flow into the downstream part of the circuit 200, as explained below.

[0038] Furthermore, it can be seen that the first circuit section 201 and the second circuit section 202 each comprise an atmospheric exhaust line 204.1, 204.2, namely a first 204.1 and a second 204.2 atmospheric exhaust line, typically ducts or the like. The atmospheric exhaust lines 204.1, 204.2 are fluidically connected to the atmosphere via one or more exhaust ports 205, namely here a single exhaust port 205.

[0039] Each atmospheric exhaust line 204.1, 204.2 includes an exhaust valve 206 controlled by the control means 210 so as to control its opening or closing, thus allowing / permitting or preventing / stopping any exhaust of gas from either of the sections 201, 202 to the ambient atmosphere. These atmospheric exhaust lines 204.1, 204.2 are used in particular during the purging phases of the sections 201, 202 and the flexible hoses connected to them, i.e., the first and second gas supply lines 12.1, 12.2, as explained below.

[0040] Furthermore, a first pressure measuring means 251, such as a first pressure sensor, is arranged on the first circuit section 201, in order to measure the pressure of the gas, i.e. NO / N2, within the first circuit section 201 and, similarly, a second pressure measuring means 252, such as a second pressure sensor, is arranged on the second circuit section 202, in order to measure the pressure of the gas, i.e. NO / N2, within the second circuit section 202.

[0041] The first and second pressure measuring means 251, 252 are arranged between the NO inlets 201.1, 202.1 and the two valve means 222.1, 222.2 arranged on the circuit sections 201, 202, as seen in [Fig.2], preferably in close proximity to the NO inlets 201.1, 202.1. These pressure measuring means 251, 252 provide the pressure measurements taken (i.e. signal or value) to the control means 210, which process them as explained below.

[0042] Conventionally, the control means 210 are electrically connected, via electrical or similar links, such as electrical cables, to the pressure measuring means 251, 252, to the exhaust valves 206 and to the valve means 222.1, 222.2, in order to ensure data transfers, typically measurements, and / or control.

[0043] The NO delivery device 1 further includes an oxygen inlet 3 fluidically connected, via an oxygen supply line 11, such as a flexible hose or similar, to an oxygen source (not shown), for example a pressurized oxygen cylinder or a hospital network, i.e., an oxygen supply pipeline installed in a hospital building. This allows the internal gas circuit 200 to be supplied with oxygen when required.

[0044] The medical ventilator 50, i.e. a respiratory assistance device, provides a flow of oxygen-based respiratory gas, i.e. containing at least 20% vol. of oxygen about, preferably at least 21% vol. of oxygen about, such as air or an oxygen / nitrogen (N2 / O2) mixture.

[0045] The medical ventilator 50 and the NO supply device 1 of the installation 100 are in fluidic communication with a breathing circuit 20, also called the patient circuit, in particular with a gas supply line or inspiratory branch 21 of the breathing circuit 20, which serves to convey the gas flow to the breathing interface 40 supplying the therapeutic gas flow to the patient, i.e. a final gas mixture containing the desired NO dosage.

[0046] More specifically, the final gas mixture to be administered to the patient is formed by mixing the oxygen-based flow (e.g. air or O2 / N2 mixture) from the medical ventilator 50 and the flow containing NO, i.e. the NO / N2 gas mixture, delivered by the NO delivery device 1.

[0047] To do this, the NO delivery device 1 supplies or injects the NO / N2 mixture into the breathing circuit 20, typically into the inspiratory branch 21, via a conduit or injection line 23, fluidly connecting the internal gas circuit of the NO supply device 1 to an injection device 24 arranged on the gas supply line 21.

[0048] The injection device 24 is configured to operate a mixture of the NO-containing gas from the NO delivery device 1 with the O2-containing respiratory gas flow from the ventilator 50 and delivered through the inspiratory branch 21 of the respiratory circuit 20, and obtain a combined gas mixture containing NO and oxygen, i.e. the final gas mixture administered to the patient.

[0049] More specifically, the injection device 24 comprises a first gas inlet supplied with a flow of breathing gas containing O2 from the medical ventilator 50, a second gas inlet supplied with gas containing NO, i.e. originating from the NO delivery device 1, 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 breathing gas stream containing O2.

[0050] In other words, the NO / N2 flow brought by the injection line 23 then mixes (thanks to the injection device 24) with the oxygen-based gas flow (> 20% O2), 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. a combined mixture, to be administered to the patient containing essentially NO at the desired dosage, nitrogen (N2) and oxygen (O2), and possibly unavoidable impurities (e.g. argon, CO2, NO2, ....), i.e. a final NO / N2 / O2 gas mixture.

[0051] The inspiratory branch 21 of the circuit 20 further includes a gas humidifier 30 arranged downstream of the injection device 24. It allows the final gas flow, e.g. the combined NO / N2 / O2 gas mixture, to be humidified before it is administered by inhalation to the patient to be treated, by means of a respiratory interface 40, such as a tracheal intubation tube, a respiratory mask or the like.

[0052] A patient exhaled gas recovery line forms an expiratory branch 22 of the patient circuit 20. It is fluidly connected to the inspiratory branch 21 via a connecting piece 25, such as a Y-piece.

[0053] The inspiratory limb 21 is, at its upstream end, fluidically connected to an outlet port 51 of the medical ventilator 50, such as a connector, fitting, or similar device, so as to recover and deliver the oxygen-based gas, typically air or an N2 / O2 mixture supplied by the medical ventilator 50, while the expiratory limb 22, carrying the exhaled gases, is fluidly connected to an inlet port 52 of the medical ventilator 50, such as a connector, fitting, or similar device, so as to return to the medical ventilator 50 all or part of the flow of gases exhaled by the patient. The expiratory limb 22 may include one or more optional components, for example, a CO2 removal device 35, a filter, or the like.

[0054] Furthermore, a flow sensor 25, for example of the hot-wire, differential pressure or mass type, is arranged on the breathing circuit 20, in particular on the inspiratory limb 21, between the ventilator 50 and the injection device 24. The flow sensor 25 is connected to a connection port to the sensor 27, of the NO delivery device 1, via a flow measurement line 26 connecting to said connection port to the sensor 27. It serves to measure the flow rate of gas delivered by the ventilator 50, such as air or N2 / O2, circulating in the inspiratory limb 21, upstream of the injection device.

[0055] These flow measurements taken by the flow sensor 25 allow for more effective control or regulation of the NO (i.e., N2 / O2) flow delivered by the NO delivery device 1, in particular the NO flow rate, since the flow measurements taken by the flow sensor 25 are returned, via the flow measurement line 26 (i.e., electrical cables or the like) and the sensor connection port 27, to the (micro)processor-based control means 210 of the NO delivery device 1, typically a (micro)controller, which processes these flow 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.

[0056] The NO supply device 1 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, used to convey the flow of NO-based gas, i.e. the NO / N2 mixture, from the NO / N2 mixing cylinders 12. The internal gas circuit 200 fluidly connects the gas inlets 201.1, 202.1 of the NO supply device 1 to the injection line 23 so as to convey the flow of NO-based gas between them.

[0057] In the embodiment shown schematically in [Fig. 2], a portion of the internal gas circuit 200 comprises two additional gas sections arranged in parallel, namely a main section 200.1 and a secondary section 200.2, referred to as the backup section. The main section 200.1 and the secondary section 200.2 are fluidly connected to each other and to the rest of the gas circuit 200 at upstream connection points 260 and downstream connection points 261 located, respectively, upstream and downstream of main and secondary flow control means 220, 221.

[0058] In this case, in normal operating mode, the NO / N2 flow passes through the main section 200.1, whereas in case of malfunction, for example if the main flow control means 220, such as a mass flow controller or MFC, are rendered non-operational or malfunctioning, the NO / N2 flow can pass through the backup section 200.2.

[0059] 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, which would be used in normal operating mode and in emergency mode. 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.

[0060] Generally speaking, the main and secondary flow control means 220, 221, such as main and secondary valve means 2200, 2210, schematically represented in [Fig.2], i.e. one (or more) valve(s) 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 there towards the injection line 23, i.e. towards the injection device 24, whether in normal operating mode or in emergency mode.

[0061] 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 solenoid valve(s) 221, preferably actuated in pulsed mode. Preferably, the main and secondary flow control means 220, 221 of the NO supply unit 1 are controlled by the control means 210, i.e., one (or more) control device(s) or (micro)controller, arranged in the housing 1.1 of the NO supply unit 1.

[0062] Generally, the control means 210 of the device 1, such as a controller, include an electronic card comprising one (or more) microprocessor(s) 211 implementing one or more algorithms.

[0063] The control means 210 allow in particular to adjust or control the flow of NO-based gas by controlling all or part of the valve means 2200, 2210, typically opening or closing one or more (electro)valves, to obtain a flow of NO-based gas, typically allowing or stopping the gas flow.

[0064] Of course, the control means 210 also allow calculations to be performed and / or all the electromechanical elements of the device 1 to be controlled or commanded, such as sensors, solenoid valves, displays...

[0065] In particular, in operation, 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, based in particular on the setpoint for NO content adjusted and / or fixed by the user, the composition of the NO / N2 gas mixture, in particular the NO content in this NO / N2 gas mixture, and one (or more) flow measurement(s) operated by the flow sensor 25 arranged on the inspiratory branch 21 and connected by a flow measurement line 26 to the NO supply device 1, in particular to the control means 210, via the connection port to the sensor 27.

[0066] The internal gas circuit 200 of the NO supply device 1 may also include other elements or components, in particular one or more pressure sensors, one or more additional flow sensors or flow meters, 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., the valve means, by For example, an additional flow sensor can 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 conforms to the desired flow rate.

[0067] In [Fig.2], it can be seen that the main section 200.1 includes an additional flow sensor 230 arranged upstream of the flow control means 220, such as valve means 2200, for example a solenoid valve (or 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).

[0068] Furthermore, the secondary section 200.2 includes a calibrated orifice device 240 arranged downstream of secondary flow control means 221, such as secondary valve means 2210, preferably a solenoid valve(s), controlling the flow of gas in the secondary section 200.2.

[0069] Advantageously, the solenoid valve of the secondary flow control means 221 is of the on / off (ON) type, that is to say, able to adopt 2 "stable" positions, namely an open position allowing the gas flow to pass and a closed position preventing any circulation of gas flow.

[0070] Furthermore, the additional flow meter or flow sensor 230 of the MFC can be of the differential pressure, mass or other type, and cooperates with the control means 210 to provide them with flow measurements of the NO / N2 flow.

[0071] Typically, the NO supply device also includes a graphical user interface (GUI) comprising a graphical display 4, preferably a touchscreen, i.e., a touch panel, used to display various information or data, icons, graphs, alarms, etc., as well as virtual selection keys and / or keypads 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 healthcare personnel. Preferably, the display is in color, but it can also be in black and white.

[0072] The power supply for the NO 1 supply unit, in particular for components requiring electrical current to operate, such as the control means 210, the graphic display 4, etc., is conventionally provided by an electrical current source and / or power supply means (not shown), for example, a mains power connection (110 / 220V) of the type power cord and plug, and / or one or more power supply batteries, preferably rechargeable, and / or a current transformer. The power supply for the medical ventilator 50 is provided in a similar manner, in particular by a mains power connection or an internal battery.

[0073] In addition, the installation 100 also includes a gas sampling line 60 which fluidly connects the inspiratory branch 21 to the NO supply device 1. It The gas sampling line 60 is fluidly connected (at 61) to the gas supply line 21, between the humidifier 30 and the junction piece 25, i.e., the Y-piece, typically in the immediate vicinity of the junction piece 25, and also to an inlet port 62 of the NO1 supply device 1, for example, a port 62 carried by a connector, fitting, or similar device, allowing connection of the gas sampling line 60, such as a flexible hose or similar device. The gas sampling line 60 allows gas samples to be taken and conveyed to the NO1 supply device 1 where they are analyzed in an internal gas analyzer (not shown), i.e., 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.In particular, it is necessary to verify that the composition of the final gas conforms to that of the desired NO / N2 / O2 gas mixture to be administered to the patient, specifically to ensure that it does not contain an excessive amount of toxic NO2 species, that its oxygen content is not hypoxic, that it does not contain an excessively high NO2 content, and that its NO content corresponds to the desired dosage, i.e., the dose of NO to be administered by inhalation that is usually chosen by the healthcare staff, i.e., physician or similar. This conformity check is conventionally carried out using dedicated measuring means, typically NO2, NO, and O2 sensors, for example, electrochemical cells or similar devices, which themselves must be calibrated periodically, for example, weekly. The control means 210 of device 1 are further configured to recover and process, i.e.to analyze the signals coming from the different sensors of the gas analyzer, which is arranged in device 1, and to act in response to these signals, in particular to perform a calibration of the sensors.

[0074] The NO setpoint value and / or the NO concentration in the NO / N2 gas mixture supplying device 1 can be entered and / or adjusted and / or modified by the user, for example via the HMI, using dose adjustment means or similar, such as buttons, sliders, or the like. Preferably, the NO setpoint value and / or the NO concentration in the NO / N2 gas mixture supplying device 1 can be stored by the storage means 212 of device 1.

[0075] According to the invention, in order to avoid an interruption in patient treatment when one of the NO cylinders 10.1, 10.2 is empty, due to an oversight or unavailability of healthcare personnel to switch the NO supply device 1 from the empty cylinder to the full cylinder, and thus to improve the safety of treatment for patients receiving gaseous NO, the control means 210 are configured to automatically control the first valve means 222.1 and / or second valve means 222.2 to control the gas flow in the first circuit section 201 and the second circuit section 202 according to a given threshold pressure value (or values).

[0076] More specifically, the control means 210 are programmed to allow gas circulation, i.e. NO / N2, within the first circuit section 201 and simultaneously prohibit any gas circulation within the second circuit section 202 (and vice versa) as long as the gas pressure P measured by the first pressure measuring means 251 is greater than or equal to a given threshold pressure PS, i.e. P > PS, for example a threshold pressure PS between 2 and 6 bar, for example on the order of 4 bar, or any other suitable value.

[0077] The pressure-threshold value PS can be stored by the storage means 212 of the device 1, such as a computer memory, such as a flash memory, RAM or similar.

[0078] In general, when a 10.1, 10.2 gas cylinder is full, the gas pressure inside is generally more than 150 bar, generally at least 180 bar.

[0079] As the gas, i.e. NO / N2, is consumed or used, the first bottle 10.1 empties and the pressure of the gas it supplies to the first section 201 tends to decrease progressively.

[0080] According to the invention, this pressure decrease can be monitored by pressure measurement means 251, 252 which transmit their measurements to the control means 210.

[0081] Thus, when the gas pressure measured P by the first pressure measuring means 251 within the first section 201 becomes less than the given threshold pressure PS, i.e. P < PS, the control means 210 are configured to interrupt any gas circulation within the first circuit section 201 and on the other hand allow gas circulation within the second circuit section 202, which makes it possible to guarantee a continuity of NO supply to the internal circuit 200 of the NO delivery device 1.

[0082] The gas, i.e. NO / N2, is then supplied, in the same way, by the second gas cylinder 10.2, which causes a progressive emptying of this second cylinder 10.2 with, again, a progressive decrease in gas pressure, in particular in the second section 202.

[0083] This is monitored, as explained above, by the piloting means 210 which receive pressure measurements from the second pressure measuring means 252 arranged in the second section 202.

[0084] Here again, when the gas pressure measured P by the second pressure measuring means 252 within the first section 201 becomes lower than the given threshold pressure PS, i.e. P < PS, the control means 210 are configured to interrupt any gas circulation within the second section of circuit 202 and furthermore authorize gas circulation within the first section of circuit 201.

[0085] In other words, thanks to the present invention, there is an automatic switching from one section to the other 201, 202, and this in an alternative manner, depending on the gas pressure which prevails there and the given threshold pressure PS.

[0086] The given threshold pressure value PS can be fixed once and for all and stored or, as appropriate, can be modified, in particular via the HMI of the NO 1 device.

[0087] Advantageously, the given threshold pressure value PS is between 2 and 8 bar, preferably between 2.5 and 7 bar, and even more preferably between 3 and 6 bar. Such a pressure value corresponds to a cylinder that is not yet completely empty but will be shortly. This residual pressure ensures a safe switchover of the gas supply from the (nearly) empty cylinder to a higher pressure cylinder, typically a (nearly) full one, without interruption of the NO supply to the patient during the time required for this switchover, including the purging time.

[0088] Preferably, after interruption of the gas flow, for example in the first section 201 (or alternatively the second section 202) supplied by the (quasi)empty gas cylinder 10.1 but before authorization of the gas flow in the other section, i.e. the second section 202, (or alternatively the first section 201) which is then supplied by the other gas cylinder 10.2, i.e. the full cylinder, a purge is carried out of the second section 202 and preferably of at least a part of the supply line 12.2, such as a flexible conduit, connecting the full gas cylinder 10.2 to the second section 202 in order to rid them of gaseous impurities that may be there, in particular any toxic compound of the NO2 type that may be there resulting from an oxidation of NO molecules by oxygen molecules.

[0089] Of course, the same procedure is used to purge the first section 201 before sending gas into it, when the second gas cylinder 10.2 is almost empty, that is to say when the pressure measured in the second section 202 becomes lower than the threshold pressure PS.

[0090] In all cases, the purging is carried out with a portion of the NO / N2 mixture from the gas containers 10.1, 10.2. To operate the purging of one or the other of the sections 201, 202, and the flexible conduit associated with it, i.e. to which it is fluidly connected, the first 204.1 or the second 204.2 exhaust line to the atmosphere is used depending on the section to be purged, namely the first circuit section 201 or the second circuit section 202, respectively, to vent to the atmosphere, via the exhaust port 205, the gas which is there and at least a portion of the gaseous impurities which may be there, such as toxic NO2 species.

[0091] This purging is done by gaseous scouring with the NO / N2 mixture from the gas containers 10.1, 10.2, which gaseous scouring carries away the gaseous impurities, such as toxic NO2 species, present in the section 201, 202 to be purged and in the associated flexible conduit, and the purge gas flow thus created is evacuated to the outside atmosphere, via the exhaust port 205. This purge flow therefore contains essentially nitrogen, NO and possible impurities such as NO2.

[0092] The control means 210 control the exhaust valve(s) 206 arranged on the first 204.1 and / or the second 204.2 exhaust line connected to the section 201, 202 to be purged so as to control its opening (or closing), to allow (or prohibit) the exhaust of the gas from the section 201, 202 to be purged, and generally from the gas supply line 12.1, 12.2 which is connected to it.

[0093] This increases patient safety by eliminating toxic species that may be present in the unused section and its supply conduit.

[0094] Preferably, the purge is carried out for a given duration, typically between 10 and 120 seconds, typically at least 30 seconds. The purge duration is stored, for example by the storage means of device 1.

[0095] A gas delivery system 100 can be used to administer by inhalation of nitric oxide (NO), i.e. the final mixture obtained NO / O2 / N2, to persons, 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

1. Demands NO delivery apparatus (1) for supplying a gas containing NO comprising: - control systems (210), - a gas circuit (200) comprising: • a first circuit segment (201) comprising a first gas inlet (201.1) configured to fluidly connect a first NO container (10.1) containing the NO-containing gas, and • a second circuit section (202) comprising a second gas inlet (202.1) configured to fluidly connect a second NO container (10.2) containing the NO-containing gas, - a first pressure measurement means (251), arranged on the first circuit section (201), configured to measure the pressure within the first circuit section (201), - a second pressure measurement means (252), arranged on a second circuit section (202), configured to measure the pressure within the second circuit section (202), - a first valve means (222.1), arranged on the first circuit section (201), controlled by the control means (210) to control the gas flow within the first circuit section (201), and - a second valve means (222.2), arranged on the second circuit section (202), controlled by the pilot means (210) to control the gas flow within the second circuit section (202), characterized in that the control means (210) are configured to control the first valve means (222.1) and / or the second valve means (222.2) to: i. allow gas flow within one of the first and second circuit sections (201, 202) and simultaneously prohibit any gas flow within the other of said first and second circuit sections (201, 202) as long as the pressure (P) measured by the first or second means of m ii. when the pressure measurement (251, 252) is greater than or equal to a given threshold pressure (PS), i.e. P > PS, and ii. when the pressure measured (P) by the first or second pressure measurement means (251, 252) becomes less than the given threshold pressure (PS), i.e. P < PS: a. interrupt all gas circulation within said first or second circuit segment (201, 202) within which gas is circulating and b. allow gas circulation within the other of said first or second circuit segment (202) within which gas circulation was prohibited.

2. Device according to claim 1, characterized in that the first circuit section (201) and the second circuit section (202) connect to each other at a connection site (203) of the gas circuit (200) located downstream of the first and second valve means (222.1,222.2).

3. Apparatus according to claim 1, characterized in that the first gas inlet (201.1) is configured to be fluidly connected to the first NO container (10.1) via a first gas supply line (12.1) and the second gas inlet (202.1) is configured to be fluidly connected to the second NO container (10.2) via a second gas supply line (12.2), preferably the first gas supply line (12.1) and the second gas supply line (12.2) comprise flexible hoses.

4. Apparatus according to claim 1, characterized in that: - a first exhaust line to the atmosphere (204.1) comprising a first exhaust valve (206.1), is fluidly connected to the first circuit section (201), and - a second exhaust line to the atmosphere (204.2) comprising a second exhaust valve (206.2), is fluidly connected to the second circuit section (202), and in which said first and second exhaust valves (206.1) are controlled by the control means (210).

5. Apparatus according to claim 4, characterized in that the first exhaust line to the atmosphere (204.1) and the second line exhaust to the atmosphere (204.2) communicate with the atmosphere via a single exhaust orifice (205).

6. Apparatus according to claims 1 and 4, characterized in that the control means (210) are further configured to: - control the second exhaust valve (206.2) to perform a purge of the second circuit section (202), before allowing a gas flow from the second NO container (10.2) within said second circuit section (202) or, - alternatively, control the first exhaust valve (206.1) to perform a purge of the first circuit section (201), before allowing a gas flow from the first NO container (10.1) within said first circuit section (201).

7. Device according to claim 6, characterized in that the piloting means (210) are further configured to operate a purge of the first or second circuit section (201, 202) and simultaneously of at least a part of the first or second gas supply line (12.1, 12.2) connected to said first or second circuit section (201, 202) subject to purging.

8. Device according to claim 1, characterized in that the given threshold pressure (PS) is memorized by memorization means (212) and / or is between 2 and 8 bar, preferably between 3 and 6 bar.

9. Apparatus according to claim 6, characterized in that: - the control means (210) are further configured to perform a purge for a given purge time, by reference a purge time of between 10 seconds and 120 seconds, and / or - the purge comprises a gaseous purge with the gas mixture containing NO, typically the NO / N2 mixture, originating from the first or second NO container (10.1, 10.2).

10. Installation (100) for supplying a gaseous mixture containing NO to a patient comprising: - an NO delivery device (1) according to any one of the preceding claims, supplied with a gas containing NO p returning from two gas containers (10.1, 10.2) alternately supplying the gas circuit (200) of the NO delivery device (1), typically pressurized gas cylinders, a medical ventilator (50) configured to provide a flow of breathing gas containing O2, and a breathing circuit (20; 21) comprising an injection device (24) configured to operate a mixing of the gas containing NO from the NO delivery device (1) with the breathing gas stream containing O2 supplied by the medical ventilator (50), and obtain a combined gas mixture containing NO and oxygen.

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