Gas supply system with a medical ventilator and a NO delivery device with an emergency dosing system

Description

[0001] The invention relates to a gas supply installation comprising a medical ventilator, i.e. a medical gas delivery apparatus, and a nitric oxide (NO) gas delivery device or apparatus for supplying a NO-containing gas to a patient, via a main NO delivery system, which installation further comprises an emergency NO dosing system for supplying the NO-containing gas at a given emergency flow rate in the event of a malfunction of the main NO delivery system, in particular in the event of loss of the signal from the flow sensor arranged on the patient circuit supplied by the medical ventilator.

[0002] NO is a gas that, when inhaled, dilates the pulmonary vessels and increases oxygenation by improving gas exchange. The properties of NO are used to treat various medical conditions, such as pulmonary arterial hypertension of the newborn or PPHN (for Persistent Pulmonary Hypertension of the Newborn ) , Acute Respiratory Distress Syndrome or ARDS observed mainly in adults or pulmonary hypertension in cardiac surgery, as taught in particular by EP-A-560928, EP-A-1516639 or US-A-10,201,564.

[0003] Usually, a small amount of gaseous NO (i.e. a few ppm vol.), diluted in nitrogen (N 2 ) is injected into a gas stream containing at least 21% vol. of oxygen (O 2 ) which is then inhaled by the patient. The concentration of NO, which corresponds to a dosage, is determined by the physician or similar. Typically, the gas containing the O 2 is typically an N 2 / O 2 mixture or air, such as medical grade air. In general, the concentration or dosage of NO in the gas inhaled by the patient, i.e. after mixing the NO / N 2 mixture with air or an O 2 / N 2 mixture, is between 1 and 80 ppm by volume (ppmv), depending on the population treated, i.e. newborns or adults, and therefore the disease to be treated.

[0004] The gas inhaled by the patient can be delivered by means of a NO delivery device associated with a mechanical ventilator, as described by US-A-5,558,083. The NO delivery device is fluidically connected to one or more gas cylinders containing a mixture of N 2 / NO whose NO concentration typically lies between 200 and 800 ppmv. Generally, the NO delivery system comprises a NO injection module placed in the inspiratory branch of a patient circuit fluidly connected, on the one hand, to the mechanical ventilator and, on the other hand, to a respiratory interface delivering the NO-enriched gas to the patient, for example a respiratory mask, a tracheal intubation tube or the like.

[0005] An NO delivery system also includes a flow sensor which measures the gas flow delivered by the mechanical ventilator (i.e. air or N 2 / O 2 mixture) in the patient circuit in order to determine the quantity of NO to be delivered to comply with the dosage set by the doctor. It should be noted that this so-called "flow" sensor can be of the type measuring and providing flow signals or measurements themselves, but also of the type measuring and providing pressure signals or measurements which are then converted into flow by control means, in particular within a microprocessor.

[0006] The NO dosage can be ensured by means of a proportional solenoid valve delivering a continuous flow of gas containing the NO, which is associated with a flow sensor, called a NO flow sensor, these two components being arranged in the NO delivery device, as well as by an injection line connecting the NO delivery device to the NO injection module arranged on the patient circuit, as described in US-A-5,558,083.

[0007] Other NO delivery devices exist, in which the proportional solenoid valve is replaced by a plurality of "all or nothing" type solenoid valves, delivering the gas intermittently, i.e. in the form of pulses, generally at high frequency, the amplitude and duration of which make it possible to guarantee the correct quantity of gas circulating in the injection line connected to the NO injection module.

[0008] In all cases, the known NO delivery installations receive the measurements or signals from the flow sensor placed in the inspiratory branch of the patient circuit and adjust in real time the quantity of NO to be delivered, according to the desired dosage, by controlling the flow of NO in the injection line. The combination of the flow sensor placed in the inspiratory branch of the patient circuit and the proportional or "on / off" type solenoid valve(s) and the NO flow sensor, if present, as well as the control means as described below which are arranged in the NO delivery device, form a main NO delivery system.

[0009] Since NO is an effective therapeutic agent, meaning that very low concentrations (i.e., a few ppmv) produce a therapeutic effect, its correct dosage is of critical importance and medical teams must constantly adapt the dosage according to the patient's condition. Therefore, as the patient's condition changes, the NO concentration must be gradually decreased or, conversely, increased to take into account the patient's condition. For example, in a weaning situation for a newborn whose condition improves, it is usual to gradually decrease the dosage, for example in 1 ppm steps, until a zero value is reached, allowing NO delivery to be stopped. A gradual decrease in the NO concentration helps avoid the "rebound effect" that can occur in the event of a rapid variation in the concentration, typically in the event of abrupt discontinuation of treatment, which could have the effect of seriously worsening the patient's condition.

[0010] However, NO delivery systems are sophisticated electro-medical systems that are susceptible to failures, i.e. malfunctions, which can have a significant impact on the ongoing therapy. For example, an electronic malfunction or defect, in particular of the control means and / or the main NO delivery system, can lead to a breakdown of the device and therefore a complete cessation of NO delivery, with the aforementioned negative consequences.

[0011] There are many possible failures, such as: a loss of signal from the flow sensor measuring the gas flow delivered by the mechanical ventilator, which flow sensor is arranged in the patient circuit of the ventilator and subject to multiple constraints from users; a loss of electrical connection between the solenoid valve(s) or the NO flow sensor and the control means, following repeated vibrations occurring for example during the transport of a patient; or a sudden loss of the control means in the event of a major failure, resulting for example from an electronic malfunction or fault.

[0012] In such circumstances, the NO delivery device must warn the user by means of an audible and / or visual alarm signal that rapid action is required, for example to switch to a backup pneumatic injection mode in order to limit as much as possible the adverse effects linked to a discontinuation of therapy caused by the failure.

[0013] Such a switch to emergency mode is usually carried out by manually actuating a rotary button or the like controlling the switch from the normal NO administration mode to an emergency mode, in which, for example, a continuous delivery of a fixed flow rate of N 2 / NO mixture is carried out, i.e. of the order of 250 mL / min. However, such an emergency dosing mechanism or system is not without risk, in particular for the following reasons: its activation requires the presence of a person with authority to undertake this action, for example a neonatology doctor. It may therefore take several minutes for this person to arrive and therefore for the emergency dosage to be established, which leads to a discontinuation of the therapy and exposes the patient to a rebound effect; the emergency dosage, i.e. a single flow of N 2 / NO mixture, does not guarantee that the desired dosage is respected.In particular, when the rescue dosage is much lower than the desired dosage, the patient may be exposed to an abrupt change in concentration and potentially subject to significant adverse effects; and / or the rescue dosage is incompatible with certain types of ventilators delivering very low volumes, such as high-frequency oscillation (HFO) ventilators, because this may result in an inhaled NO concentration that is too high and may reach levels that are dangerous for the patient. Therefore, if the patient is treated with such a ventilator (i.e. HFO), there is no means of administering NO to the patient, which leads to the aforementioned risks related to the abrupt cessation of treatment.

[0014] It therefore appears that the current emergency dosing mechanisms do not guarantee a satisfactory level of safety and that it would be desirable for the patient, in the event of emergency dosing being implemented due to a malfunction of the NO delivery system, to be able to maintain NO therapy, without interrupting the therapy, and without worrying about the type of ventilator, i.e. HFO or other, with which the NO delivery system of the NO delivery system cooperates.

[0015] In an attempt to remedy this, EP-A-3410927 proposes a dosage in response to the loss of the signal, i.e. data, from the flow sensor measuring the gas flow delivered by the mechanical ventilator, which flow sensor is arranged in the patient circuit of the ventilator and subject to multiple constraints from users. The proposed solution is based on controlling the proportional solenoid valve of the NO delivery device so as to deliver a constant NO flow based on stored historical data previously measured by the flow sensor measuring the gas flow delivered by the ventilator and stored in a memory of the device.

[0016] However, this solution is imperfect because it does not ensure the delivery of an average NO flow in the event of another failure, such as a loss of electrical connection with the solenoid valve(s), or between the NO flow sensor and the control means, or even a sudden loss of the control means themselves.

[0017] WO2016096056A1 proposes a backup system with a constant dosage value predefined in the control unit. In other words, a problem is to be able to maintain a dosage, i.e. a treatment of the patient with inhaled NO at the desired concentration, in the event of failure or malfunction of the flow sensor which is typically located in the patient circuit and to which the medical ventilator and the NO delivery device are connected but also other failures as mentioned above.

[0018] A solution according to the invention relates to an installation for supplying gas to a patient comprising: a NO delivery device or apparatus (i.e. NO supply) configured to supply a NO / N 2 gas mixture comprising: ▪ a NO injection line for conveying the NO / N 2 gas mixture, ▪ a valve device arranged on the injection line to control the circulation of the NO / N 2 gas mixture in the injection line, ▪ a backup line fluidically connected to the injection line upstream and downstream of the valve device, said backup line comprising a backup solenoid valve and a flow control device, and ▪ control means, also called a control unit, configured to cooperate with the backup solenoid valve, the flow control device and the valve device, a medical ventilator configured to supply a respiratory gas containing oxygen, typically at least about 21% oxygen, such as air or an N 2 / O 2 mixture,a patient circuit to which the NO delivery device and the medical ventilator are fluidically connected to supply said patient circuit with said NO / N 2 gas mixture and with said respiratory gas containing oxygen, typically approximately at least 21% oxygen, and a flow sensor configured to determine (i.e. measure) and provide the means for controlling the NO delivery device with at least one measurement signal representative of the gas flow rate within the patient circuit, namely one (or more) signal(s) or one (or more) flow rate or pressure measurement.

[0019] Furthermore, according to the invention, in the event of interruption of reception, i.e. in the event of loss of signal, by the control means of the NO delivery device or apparatus, of the measurement signal supplied by the flow sensor: the emergency solenoid valve switches, i.e. is configured to switch, to the open position to allow circulation of the NO / N 2 gas mixture in the emergency line, the valve device switches, i.e. is configured to switch, to the closed position to stop any circulation of gas in the injection line, and the flow control device is configured to supply the NO / N 2 gas mixture at a pre-set emergency gas flow rate, i.e. preset, where said emergency gas flow rate is determined by the control means from at least one measurement signal supplied by the flow sensor, before said interruption of reception of said signal, and preset by control of the flow control device by said control means, before said interruption of reception of said signal.

[0020] In the context of the invention: "ppmv" means parts per million by volume, "%vol." means percentage by volume. "NO" means nitric oxide. "N2" means nitrogen. "O2" means oxygen. "Normal operation": means normal operation, in the absence of any breakdown, malfunction, defect or other. "Malfunction" means a breakdown, defect, disconnection or similar, reversible or permanent, of electrical, mechanical or other origin, affecting normal operation by preventing any reception by the control means of the measured signal(s) (i.e. measurements made) and transmitted by the flow sensor. "Flow sensor" means a sensor of the type measuring and providing one or more flow rate signals or measurements themselves or of the type measuring and providing one or more pressure signals or measurements which are then converted into flow rate by the control means.

[0021] Depending on the embodiment considered, the NO delivery device or apparatus and / or the installation of the invention may comprise one or more of the following characteristics: the valve device of the NO delivery device is configured to be normally in a closed position (i.e., rest state) to prevent, i.e., stop or oppose, any circulation of gas in the injection line, i.e., the closed position corresponds to its rest state. the emergency solenoid valve of the NO delivery device is configured to be normally in an open position (i.e., rest state) to allow, i.e., authorize, a circulation of gas in the emergency line, i.e., the open position corresponds to its rest state. in their rest state, the valve device and the emergency solenoid valve of the NO delivery device are no longer or not controlled by the control means. in the event of signal loss, the control means are configured to stop controlling (i.e.,no longer control) the valve device and the emergency solenoid valve of the NO delivery device which then automatically switch to their rest state. in the event of signal loss, the control means are configured to stop controlling (i.e. no longer control) the valve device and the emergency solenoid valve of the NO delivery device so that: ∘ said valve device switches from an open position allowing the passage of gas in the injection line to the closed position and ∘ said emergency solenoid valve switches from a closed position preventing the passage of gas in the emergency line to the open position. a flow measurement device is arranged on the injection line of the NO delivery device to carry out one or more flow measurements of the gas containing NO circulating in the injection line. the emergency line is fluidically connected to the injection line upstream or downstream of the flow control device.the control means (i.e. control device) are further configured to calculate the emergency gas flow rate (i.e. emergency NO / N 2 mixture flow rate) from the last gas flow rate measured by the flow sensor measuring the gas flow rate from the ventilator, before said interruption of reception of said signal. the control means are further configured to determine, i.e. calculate, the emergency flow rate from one or more respiratory gas flow rates, preferably several gas flow rates, supplied by the ventilator having been measured by the flow sensor, before said interruption of reception of said signal, and a desired dosage, i.e. a final NO concentration to be obtained after mixing the NO / nitrogen mixture from the NO delivery device and the respiratory gas flow containing at least 21% O 2 from the ventilator, typically air or an oxygen / nitrogen mixture.the flow control device is configured to supply the NO / N 2 gas mixture at a pre-set emergency gas flow rate, determined by the control means from several measurement signals supplied by the flow sensor for a given duration, before said interruption of reception of said signal, for example for several seconds or tens of seconds, said measurement signals being used to calculate an average flow rate over said given duration. the emergency gas flow rate is determined by the control means from an average gas flow rate calculated from several gas flow rates measured by the flow sensor for a given duration, before said interruption of reception of said signal, preferably the given duration is between several seconds and several tens of seconds. the control means are configured to determine, iecalculate the emergency flow rate from one or preferably more respiratory gas flow rates supplied by the ventilator having been measured by the flow sensor, before said interruption of reception of said signal, and a desired dosage where the NO content in the mixture administered to the patient is between 1 and 80 ppmv. the control means of the NO delivery device are further configured to, during normal operation (i.e. before any malfunction), control the emergency solenoid valve so that it is in a closed position (i.e. active state) preventing any circulation of gas in the emergency line. the control means of the NO delivery device are further configured to, during normal operation, control the valve device to authorize (i.e. active state) a circulation of gas in the injection line and at least one measurement of gas flow rate by the flow measurement device.the control means are further configured to control, before any malfunction with loss of signal from the flow sensor (i.e. during normal operation), the flow control device of the emergency line to pre-set the emergency gas flow to be delivered in the event of interruption of signal reception from the flow sensor, i.e. in the event of loss of signal from the flow sensor. during normal operation, the flow sensor is configured to carry out several flow or pressure measurements (i.e. of the respiratory gas supplied by the ventilator) and transmit said flow or pressure measurement(s) to the control means, preferably via a differential pressure sensor. during normal operation, the control means are further configured to determine, i.e.calculate an average gas flow rate over a given duration from several flow or pressure signals or measurements made by the flow sensor (i.e. of the respiratory gas supplied by the ventilator), i.e. the flow rate of respiratory gas supplied by the ventilator averaged over the given duration, for example over several seconds or tens of seconds. the average flow rate is calculated by the control means over a given duration of several seconds to several tens of seconds, typically between 5 and 60 seconds, or another duration. the control means are further configured to store at least one gas flow rate (i.e. of the respiratory gas supplied by the ventilator), in particular the average flow rate, determined from the signal(s) or flow rate or pressure measurements coming from the flow sensor (i.e. of the respiratory gas supplied by the ventilator).the oxygen-containing respiratory gas supplied by the ventilator is air or a nitrogen / oxygen mixture containing approximately at least 21% vol. of oxygen, or even pure oxygen (i.e. approximately 100% vol.). it comprises storage means. the flow values ​​obtained via the flow sensor are stored in the storage means of the NO delivery device. the storage means comprise a computer memory, for example a random access memory. the patient circuit comprises a NO injection module supplied with NO / N 2 mixture by the NO delivery device, preferably via the injection line, such as a flexible gas pipe. the flow sensor is arranged on the patient circuit, preferably on an inspiratory branch of said patient circuit, and is electrically connected to the control means, via one or more electrical connections (e.g. cables or the like). the flow sensor (i.e.used to measure the flow rate of the respiratory gas supplied by the ventilator) is arranged on the patient circuit between the medical ventilator and the NO injection module. According to one embodiment, the flow sensor is of the mass flow sensor type or the like. In this case, the flow sensor is electrically connected to the control means, via one or more electrical connections, such as cables or the like. According to another embodiment, the flow sensor is of the differential pressure measurement type, i.e. a pressure sensor. In this case, the flow sensor is arranged on the patient circuit and cooperates with a differential pressure sensor arranged in the NO delivery device.the differential pressure sensor is arranged on an electronic card in the NO delivery device and cooperates with the control means of the NO delivery device, preferably the same electronic card carries said differential pressure sensor and at least one microprocessor of said control means. the flow sensor comprises a pressure measurement module arranged on the patient circuit, in particular in the inspiratory branch, comprising pressure measurement sockets. the measurement module is crossed by the gas flow circulating in the patient circuit, in particular in the inspiratory branch. the pressure measurement sockets of the measurement module of the flow sensor located on the patient circuit are pneumatically connected to the differential pressure sensor by an upstream line and the downstream pressure measurement line in order to supply gas pressures to said differential pressure sensor.Preferably, the upstream line and the downstream line are gas conduits, pipes or the like. The interruption of the reception, by the control means of the NO delivery device, of said at least one measurement signal supplied by the flow sensor results from, i.e. is consecutive to, an untimely disconnection of at least one of the upstream and downstream pressure measurement lines. The pressure measurement module of the flow sensor comprises an internal gas passage comprising an internal restriction creating a pressure drop, i.e. generating a pressure differential or gradient, when a gas flow circulates in the internal passage and passes through said internal restriction. The pressure measurement module of the flow sensor comprises upstream and downstream chambers, within the internal passage of the flow sensor, separated by a wall through which a gas passage orifice passes so as to form the internal restriction.the upstream and downstream pressure measurement lines fluidly connect the pressure measurement module of the flow sensor to the differential pressure sensor so as to enable the pressure to be measured before and after pressure loss, i.e. upstream and downstream of the internal restriction. the upstream and downstream pressure measurement lines are fluidically connected to the upstream and downstream chambers of the pressure measurement module of the flow sensor in order to carry out pressure measurements of the circulating flow therein, i.e. before and after pressure loss. the upstream and downstream pressure measurement lines comprise pressure measurement conduits or the like configured to supply the differential pressure sensor with the pressures measured before and after pressure loss. the differential pressure sensor is arranged in the NO delivery device.the differential pressure sensor is electrically connected to the control means or is configured to transmit the pressure measurements from the flow sensor to the control means. the control means are configured to process the pressure measurements, i.e. pressure differential, by computer and to deduce therefrom at least one gas flow rate. the control means are configured to determine at least one flow rate of respiratory gas coming from the ventilator and circulating in the inspiratory branch from the pressure values ​​and at least one pre-recorded correspondence table making it possible to transform one or more pressure values, in particular transmitted by the differential pressure sensor, into a flow rate value. the pre-recorded correspondence table(s) is recorded in the storage means.the differential pressure sensor is arranged in the NO delivery device and cooperates with the control means to provide them with the pressure values ​​measured by the measurement module of the flow sensor. the backup line of the NO delivery device is fluidically connected to the injection line by an upstream end, upstream of the valve device, and by a downstream end, downstream of the valve device so as to bypass said valve device. the NO delivery device comprises a backup NO dosing system comprising the backup line. the flow measurement device of the NO delivery device is arranged on the injection line upstream or downstream of the valve device, preferably downstream of the valve device.the NO delivery line of the NO delivery device carries a gas mixture formed of NO and nitrogen, preferably a NO / N 2 gas mixture containing between 100 and 2000 ppmv of NO, typically less than 1000 ppmv of NO, the remainder being nitrogen (and possibly unavoidable impurities) the emergency solenoid valve of the NO delivery device is configured and / or controlled to be normally open. the emergency solenoid valve of the NO delivery device is of the on / off type. the control means of the NO delivery device comprise at least one microprocessor. the control means of the NO delivery device comprise an electronic card carrying said at least one microprocessor.the injection line of the NO delivery device is fluidically connected to a high pressure line via a pressure regulating device, the high pressure line and the pressure regulating device being arranged in the NO delivery device. the NO delivery device comprises a housing. the NO backup dosing system is arranged in the housing of the NO delivery device, in particular the backup line and the backup solenoid valve. the valve device of the NO delivery device comprises a solenoid valve, preferably a proportional solenoid valve. the flow control device of the NO delivery device is configured to form, constitute or comprise a proportional type calibrated orifice, i.e. to form a proportional calibrated orifice system.the flow control device comprises a proportional calibrated orifice system controlled by the control means to adjust the pre-set emergency gas flow rate. the control means of the NO delivery device are further configured to, prior to any interruption in the reception or loss of the signal(s) from the flow sensor, act on the proportional calibrated orifice system of the flow control device of the emergency line to preset (i.e. adjust or adjust before any loss of signal) the desired emergency gas flow rate, i.e. emergency NO / N 2 flow rate, which is determined from the respiratory gas flow rate having been measured by the flow sensor, before the interruption in the reception of said signal, i.e. loss of signal, and the desired NO dosage.the flow control device of the NO delivery device comprises an actuator means cooperating with a movable element comprising a through-recess, said movable element being able to be angularly displaced by the actuator means. the actuator means comprises an electric motor driving a rotary shaft, the movable element being integral with said rotary shaft. the electric motor is a stepper motor. the movable element is arranged movable in an internal housing comprising an inlet port and an outlet port in fluid communication with the emergency line. the movable element is a sphere, that is to say spherical, for example a ball or the like. the internal housing has a spherical shape complementary to that of the spherical movable element.the control means are configured to control the actuator means to operate an angular movement of the movable element between at least: ∘ a total opening position corresponding to a total opening level of the calibrated orifice of the flow control device, ∘ a total closing position corresponding to a total closing (i.e. blocking) level of the calibrated orifice of the flow control device, and ∘ at least one intermediate position located between said total opening position and total closing position corresponding to a partial opening level of the calibrated orifice of the flow control device.the control means of the NO delivery device are configured to control the actuator means to operate an angular movement of the mobile element between at least: ∘ a fully open position in which all the gas flow supplied by the emergency line enters the through-hole of the mobile element, i.e. a maximum flow rate, ∘ a fully closed position in which no gas flow can pass through the through-hole of the mobile element, i.e. a zero flow rate, and ∘ at least one intermediate position located between said fully open position and fully closed position, in which only part of the gas flow supplied by the emergency line enters the through-hole of the mobile element, i.e. one or more reduced flow rates.the control means of the NO delivery device are configured to control the actuator means to operate an angular displacement of the movable element between several intermediate positions, angularly offset from each other, each corresponding to a calibrated orifice opening level and / or to a given gas flow rate, i.e. reduced flow rates between the maximum flow rate and the zero flow rate. the control means of the NO delivery device are configured to control the actuator means to set or adjust the emergency gas flow rate, before any loss of signal from the flow sensor. the control means of the NO delivery device are configured to determine a given calibrated orifice opening corresponding to the emergency flow rate. the control means of the NO delivery device are configured to determine the given calibrated orifice opening and / or the emergency flow rate from a correspondence table.the NO delivery device comprises electrical power supply means supplying electrical current to the components requiring electrical energy to operate, in particular the control means. the electrical power supply means comprises means for connection to the mains (110 / 220V) and / or a battery or the like. the emergency gas flow rate is determined by the control means from the last flow rate measurement(s) of the respiratory gas flow (i.e. air or N 2 / O 2 ) circulating in the inspiratory branch, having been carried out by the flow sensor, before the malfunction (i.e. loss of signal), and transmitted to the control means of the NO delivery device. The control means further use the desired NO dosage in the final gas mixture, typically between 1 and 80 ppmv to determine the emergency gas flow rate.

[0022] In addition, the installation for supplying gas to a patient further includes:at least one source of NO containing a NO / N 2 gas mixture and supplying said NO / N 2 gas mixture to the NO delivery device. a patient circuit comprising an inspiratory branch supplied with NO / N 2 gas mixture by the NO delivery device, and with a respiratory gas containing oxygen, typically approximately at least 21% oxygen, such as air or an O 2 / N 2 mixture, by the medical ventilator, ie a respiratory assistance device. the medical ventilator delivers air or an oxygen / nitrogen mixture (ie O 2 / N 2 ). the medical ventilator comprises a motorized blower (ie also called a turbine, compressor or the like) delivering the respiratory gas, typically air or an oxygen / nitrogen mixture. the medical ventilator comprises a motorized blower controlled by control means, such as an electronic control card, arranged in the casing of the medical ventilator.the medical ventilator is of the HFO (High Frequency Oscillations) type, i.e. high frequency oscillation, or of the conventional type, such as a critical care ventilator. the NO source contains a NO / N 2 gas mixture containing between 100 and 2000 ppmv of NO, the remainder being nitrogen (N 2 ), conditioned at a pressure between 10 and 250 bar abs, typically at more than 100 bar abs (before the start of withdrawal). the NO source contains a NO / N 2 gas mixture containing between 100 and 1000 ppmv of NO, the remainder being nitrogen (N 2 ), conditioned at a pressure between 10 and 250 bar abs, typically at more than 100 bar abs (before the start of withdrawal). the NO source is one (or more) pressurized gas cylinders. The source of NO is one or more gas cylinders with a capacity of between 0.5 and 50 L (water equivalent). The gas cylinder comprises a cylindrical body made of steel or aluminum alloy.The gas cylinder is equipped with a simple valve (without regulator) or with an integrated regulator or RDI. The gas cylinder is equipped with an RDI protected by a protective cover, for example made of metal or polymer. The patient circuit comprises an inspiratory branch and an expiratory branch. The patient circuit comprises flexible pipes forming the inspiratory branch and / or the expiratory branch, typically 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 comprises a tracheal intubation tube or respiratory mask. The inspiratory branch and the expiratory branch comprise flexible pipes, for example made of polymer.the inspiratory branch and the expiratory branch are further fluidically connected to, respectively, outlet and inlet ports of the medical ventilator. the inspiratory branch of the patient circuit may comprise a gas humidifier. the gas humidifier is arranged downstream of the NO injection module so as to be able to humidify the gas before its administration by inhalation to the patient. the concentration or dosage of NO in the final gas mixture, i.e. the gas which is inhaled by the patient, after mixing the NO / N 2 mixture with the respiratory gas containing approximately at least 21% vol. of oxygen coming from the ventilator, such as air or an O 2 / N 2 mixture, is between 1 and 80 ppm by volume (ppmv), depending on the population treated, i.e. newborns or adults, the condition of the patient and / or the disease to be treated.

[0023] The invention also relates to a use of a gas supply installation and / or the NO delivery device according to the invention equipped with the NO emergency dosing system of the invention are particularly well suited for use in the context of a therapeutic treatment method with supply of a gas mixture comprising from 1 to 80 ppmv of NO (dosage) and approximately at least 21% vol. of oxygen and generally nitrogen to a patient (i.e.an adult, child, adolescent or newborn), in need thereof, which patient suffers from pulmonary hypertension and / or hypoxia, causing pulmonary vasoconstrictions or similar, typically resulting from or caused by one or more pulmonary pathologies or disorders such as PPHN (persistent pulmonary hypertension of the newborn) or ARDS (acute respiratory distress syndrome), or resulting from or caused by cardiac surgery with the patient being placed on extracorporeal circulation (ECC).

[0024] 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 diagrams a gas delivery installation equipped with an emergency NO dosing system according to the present invention; Fig. 2 schematizes the association between calibrated orifice and actuator of the emergency NO dosing system of Fig. 1 ; And Fig. 3 à Fig. 5 schematize the operation of the calibrated orifice / actuator association of Fig. 2 .

[0025] Fig. 1 schematizes an embodiment of a gas delivery installation 1, 2 according to the present invention comprising a NO delivery device 1 comprising an emergency NO dosing mechanism, associated with a mechanical ventilator 2, i.e. a respiratory assistance device delivering a respiratory gas, making it possible to deliver NO in gaseous form to a patient at a desired concentration corresponding to a dosage set by an anesthesiologist or the like, typically between 1 and 80 ppmv of NO (i.e. ppm by volume).

[0026] The medical ventilator 2 delivers a respiratory gas containing at least 21% oxygen, such as air or an NO / N 2 mixture, into a patient circuit 3, in particular into an inspiratory branch 31 of said patient circuit 3, used to convey and supply the respiratory gas to a patient P during his inspiratory phases, that is to say to provide respiratory assistance to the patient P, and to convey the gases exhaled by the patient during his expiratory phases.

[0027] The medical ventilator 2 is a conventional device comprising, for example, a motorized blower, also called a turbine or compressor, delivering the respiratory gas into the patient circuit 3 and whose operation is controlled by one or more electronic control cards or the like. It is electrically powered by electrical supply means, such as the mains (110 / 220V) and / or an internal battery.

[0028] As seen on Fig. 1 , the patient circuit 3 here comprises an inspiratory branch 31 and an expiratory branch 32 fluidly connected to a Y part 33 or similar, in fluid communication with a respiratory interface 30 making it possible to deliver the gas to the patient P or to collect the gases exhaled by said patient P. The respiratory interface 30 can for example be a face mask or an intubation probe.

[0029] The inspiratory 31 and expiratory 32 branches comprise conduits, pipes, hoses, passages, tubing or the like, for example flexible polymer pipes, capable of and configured to convey the gas flows.

[0030] The respiratory gas circulating in the inspiratory branch 31 of the patient circuit 3, i.e. going from the mechanical ventilator 2 to the patient P, is inhaled by the patient P while the gases exhaled by said patient P, i.e. gases enriched in CO 2 , pass through the expiratory branch 32 of the patient circuit 3 towards the mechanical ventilator 2 to be discharged into the atmosphere by the mechanical ventilator 2.

[0031] Furthermore, a flow sensor 100 and an NO injection module 110 are arranged in the inspiratory branch 31 of the patient circuit 3. The flow sensor 100 is preferably arranged in the inspiratory branch 31 between the NO injection module 110 and the mechanical ventilator 2.

[0032] The inspiratory branch 31 may also comprise a humidifier (not shown) in order to humidify the gas delivered to the patient P. Preferably, the humidifier is placed downstream of the NO injection module 110, that is to say between said NO injection module 110 and the respiratory interface 30 supplying the gas to the patient P.

[0033] The flow sensor 100 is used to measure the gas flow, i.e. a flow rate, delivered by the mechanical ventilator 2 and circulating in the inspiratory branch 31. The flow sensor 100 may be a sensor of the type measuring and providing flow rate signals or measurements proper, for example a mass flow rate sensor, or of the type measuring and providing pressure signals or measurements which are then converted into flow rate by the control means, for example a differential pressure measurement sensor, also called a differential pressure sensor.

[0034] In the embodiment of Fig. 1 , the flow sensor 100 is of the differential pressure measurement type, that is to say that the flow sensor 100 comprises a measurement module 100-1 comprising an internal restriction 101 which creates a pressure loss generating a pressure differential or gradient when a gas flow passes through this internal restriction 101.

[0035] As seen in Fig. 1 , the measurement module 100-1 of the flow sensor 100 comprises upstream 120 and downstream 121 chambers which are separated by a wall 122 through which a gas passage passes so as to form the internal restriction 101. An upstream line 103 and a downstream line 102 for measuring pressure, i.e. pneumatic lines, such as gas conduits, are fluidically connected to the measurement module 100-1 of the flow sensor 100 at connection sites located upstream and downstream of the internal restriction 101, in particular to the upstream 120 and downstream 121 chambers in order to carry out the pressure measurements of the circulating flow there, before and after pressure loss.

[0036] The pressure difference created by the internal restriction 101 is determined by a differential pressure sensor 104 connected to the flow sensor 100 via the upstream 102 and downstream 103 lines which form pressure measurement conduits and provide the differential pressure sensor 104 with the pressure measurements of the circulating flow, before and after pressure loss. Preferably, the differential pressure sensor 104 is integrated into the housing 10 of the NO 1 delivery device. The sensor 104 can either be electrically connected to a control unit 130, also called control means 130, or can transmit the pressure measurements to it so that they can be processed electronically.

[0037] The control unit 130, i.e. the control means 130, comprises a data processing system, i.e. measurements, comprising for example one (or more) microprocessor(s) arranged on one (or more) electronic card and implementing one (or more) algorithm(s), i.e. one (or more) computer program.

[0038] In other words, the control unit 130 is configured to process and / or exploit the pressure measurement signals or the pressure values ​​transmitted by the differential pressure sensor 104 cooperating with the flow sensor 100.

[0039] For example, the control unit 130 has a pre-recorded correspondence table which allows the determination of the gas flow rate circulating in the inspiratory branch 31 and the measurement module 100-1 of the flow sensor 100, that is to say to transform a pressure value transmitted by the differential pressure sensor 104 into a flow rate value passing through the measurement module 100-1 of the flow sensor 100.

[0040] Such a determination of the flow rate passing through the flow sensor 100 then makes it possible to calculate the quantity of NO to be added to the gas circulating in the inspiratory branch 31 before reaching the patient P.

[0041] In other words, by using the pressure measurement returned by the differential pressure sensor 104 and the correspondence table, the control unit 130 can determine the gas flow rate from the mechanical ventilator 2 and the quantity of NO to be added, via the NO injection module 110, in order to obtain the desired NO concentration, i.e. the dosage defined by the doctor, to be inhaled by the patient P.

[0042] Of course, the control unit 130 can also be configured to control other electromechanical elements integrated into the housing 10 or external casing of the NO 1 delivery device.

[0043] According to another embodiment (not shown), the flow sensor 100 could also be a mass flow sensor or the like which would be connected directly to the control means 130, via one (or more) electrical connections, such as one or more cables or the like, to provide them with a signal, such as a voltage, or a measurement of the flow rate passing through the sensor 100. In this case, the differential pressure sensor 104 is removed.

[0044] Generally speaking, the final gas mixture, i.e. the NO-based respiratory gas which is then administered by inhalation to the patient, obtained at the NO injection module 110 arranged on the inspiratory branch 31 then mainly comprises nitrogen (N 2 ), oxygen (O 2 ), typically in a content of approximately at least 21% vol., and NO at a content typically between 1 and 80 ppmv, for example of the order of 10 to 20 ppmv.

[0045] More precisely, during normal operation, depending on the gas flow rate (i.e. air or N 2 / O 2 ) circulating in the inspiratory branch 31 having been determined using the flow sensor 100, the control unit 130 determines the quantity of NO, typically a mixture of NO and N 2 , to be added to the gas circulating in the inspiratory branch 31 by the NO injection module 110, in order to obtain the desired concentration or dosage, i.e. set by the doctor or the like, during normal operation of the gas supply installation 1, 2.

[0046] Typically, the concentration or dosage of NO in the gas inhaled by the patient, after mixing the NO / N 2 mixture with air or an O 2 / N 2 mixture, is between 1 and 80 ppm by volume (ppmv), for example in the order of 10 to 20 ppmv, depending on the population treated, i.e. newborns or adults, and therefore the disease to be treated.

[0047] The NO 1 delivery device is supplied with gaseous NO, typically in a gaseous NO / N 2 mixture, coming from a source of NO 250 fluidly connected to the NO 1 delivery device, in particular to a high pressure line 116 of said NO 1 delivery device, by a supply line 251, such as a flexible conduit or the like.

[0048] Typically, the source of NO 250 is one (or more) pressurized gas cylinders containing a mixture of NO / N 2 containing an NO concentration generally between 100 and 2000 ppmv, preferably between 200 and 1000 ppmv, for example of the order of 800 ppmv, and conditioned at a pressure (when completely full) which can reach 200 to 250 bar abs, or even more.

[0049] The NO / N 2 mixture is supplied to the injection module 110 by the NO 1 delivery device via an injection line 111, such as a flexible gas pipe.

[0050] The injection line 111 located in the housing 10 of the NO 1 delivery device is fluidically connected to a high pressure line 116 of the NO 1 delivery device, which high pressure line 116 has a high pressure inlet fluidically connected to the NO source to be supplied with NO / N 2 under pressure, i.e. at a pressure of up to 200 bar abs.

[0051] The high pressure line 116, for example a gas passage or conduit, is also arranged in the housing 10 of the NO 1 delivery device and comprises a pressure regulator 115 which reduces the pressure of the NO / N 2 mixture to a stable value, for example 4 bar abs. The outlet port of the pressure regulator 115 provides a stable pressure in the upstream portion of the injection line 111.

[0052] A valve device 113, such as a solenoid valve, preferably a proportional solenoid valve, such as the Parker miniature VSO series for example, is arranged in the device 1 in order to control the flow rate of gaseous NO within the injection line 111. The gas flow rate circulating in the injection line 111 is measured by a flow rate measuring device 112, also called a NO flow rate sensor, arranged on the injection line 111, preferably placed downstream of the solenoid valve 113, as seen in Fig. 1 .

[0053] The pressure regulator 115, the valve or solenoid valve device 113, the NO flow sensor 112 and a portion of the injection line 111 are arranged in the housing 10 of the NO 1 delivery device.

[0054] The valve device 113 is configured to be normally in a closed position (i.e., a rest state) to prevent any circulation of gas in the injection line 111.

[0055] Advantageously, in the rest state, the valve device 113 is not controlled by the control means 130. In other words, when the control means 130 stop / cease controlling the valve device 113, it automatically (re)enters the rest state, i.e. the closed position.

[0056] Conversely, to move to the open position, the valve device 113 must be controlled by the control means 130, as is the case during normal operation of the gas supply installation 1, 2.

[0057] Furthermore, according to the invention, a backup NO dosing system 200 is provided, arranged in the housing 10 of the NO 1 delivery device and used in the event of failure, as detailed below.

[0058] The emergency NO dosing system 200 comprises a backup line 201, also called a bypass line, such as a gas passage, a gas conduit or the like. The backup line 201 is fluidically connected to the injection line 111 at a first connection site 111a located upstream of the valve device 113, such as a proportional solenoid valve, and here downstream of the pressure regulator 115, and at a second connection site 111b located downstream of the valve device 113 and, preferably, downstream of the NO flow sensor 112.

[0059] In other words, a valve device 113, such as a proportional solenoid valve, and preferably the NO flow sensor 112 are located between the first and second connection sites 111a, 111b of the emergency line 201, that is to say that the emergency line 201 bypasses, the valve device 113 and preferably the NO flow sensor 112 located on the injection line 111. According to another embodiment, the second connection site 111b could be located downstream of the valve device 113 and upstream of the NO flow sensor 112, that is to say between these two elements.

[0060] The emergency line 201 comprises an emergency solenoid valve 202 and a flow control device 210 forming part of the emergency dosing system 200 of the invention. This emergency solenoid valve 202 is configured to be normally in an open position (i.e. open state) to allow gas to circulate in the emergency line 201.

[0061] The flow control device 210 in fact forms a proportional type calibrated orifice system 204 making it possible to adjust or regulate the flow of emergency gas, i.e. NO / N 2 mixture, circulating in the emergency line 201. It can take different forms, i.e. arrangements, in particular that illustrated in Fig. 2 à Fig. 5 and detailed below.

[0062] The emergency solenoid valve 202 is preferably an “all or nothing” type solenoid valve having two possible states, namely an open state and a closed state, for example a solenoid valve from the Picosol series from IMI Norgren. The emergency solenoid valve 202 is normally open, that is to say that in the absence of an electrical command coming from the control unit 130, the emergency solenoid valve 202 is in its rest state, that is to say in the open position, which then allows the gas from the NO source to take the emergency line 201 from the first connection site 111a towards the second connection site 111b.

[0063] In other words, as previously for the valve device 113, in its rest state, the emergency solenoid valve 202 is not controlled by the control means 130. In other words, when the control means 130 stop / cease controlling the emergency solenoid valve 202, it also automatically (re)enters the open position which corresponds to its rest state.

[0064] Here again, it is the control means or control unit 130 which ensure the closing of the emergency solenoid valve 202, i.e. its transition from the rest state (i.e. open position) to its active state, i.e. in the closed position, as is the case during normal operation of the gas supply installation 1, 2.

[0065] In other words, the control means 130, i.e. the control unit, are configured to cooperate with the emergency solenoid valve 202, the flow control device 210, the valve device 113 and the flow measurement device 112, during normal operation of the device 1 and the gas supply installation 1, 2.

[0066] In the embodiment shown on Fig. 2 à Fig. 5 , the flow control device 210 comprising or forming a proportional calibrated orifice system, that is to say constituting, including or forming a proportional type calibrated orifice 204, comprises an actuator means 203 cooperating with a mobile element 2042 arranged in a compartment 2041, said mobile element 2042 comprising a through recess 2043.

[0067] However, the flow control device 210 constituting the calibrated orifice 204 of the proportional type may take another form, for example a needle valve type device or even an assembly comprising a pressure regulator arranged upstream of a fixed orifice, said pressure regulator being able to be set to different outlet pressures, thus generating different flow rates passing through said fixed orifice.

[0068] So, Fig. 2 is a sectional diagram of an embodiment of the flow control device 210, i.e. of the calibrated orifice 204, which is formed here by the actuator means 203 and the movable element 2041 associated with the through-hole 2043, of the emergency NO dosing system equipping the NO delivery device 1 of the invention.

[0069] The actuator means 203, more simply called actuator, of Fig. 2 is preferably a 2030 stepper type motor, for example like that marketed by the Portescap company, extended by an axis 2031 mechanically coupled at 2031a to the mobile element 2042.

[0070] Furthermore, the movable element 2042 is here a sphere. The sphere forming the movable element 2042 may be metallic, for example made of stainless steel, and has a through-hole 2043, i.e. it is diametrically crossed by a bore or internal passage allowing the passage of gas. The movable element 2042, i.e. the sphere, is housed in an internal compartment or housing 2041 forming a sphere chamber which is here of generally spherical shape. The housing 2041 is arranged in a part forming a body 2040. The external diameter of the sphere 2042 is substantially equal to the internal diameter of the internal housing 2041.

[0071] The body part 2040 may also be metallic, for example a steel ball or the like. It includes an inlet port 201a and an outlet port 201b in fluid communication with the internal housing 2041.

[0072] On Fig. 2 , it is seen that the through-recess 2043 of the sphere 2042 is aligned with the inlet 201a and outlet 201b ports of the body 2040, which are in fluid communication with the emergency line 201, that is to say they are in fluid continuity, so that the gas can flow from the inlet port 201a to the outlet port 201b via the through-recess 2043 of the sphere 2042.

[0073] As indicated, the actuator means 203 is here a stepper motor 2030 driving the axis 2031 and therefore the sphere 2042 in rotation. In response to a command from the control unit 130, the stepper motor 2030 will adopt a different position and cause the axis 2031 to rotate, which will then also drive the sphere 2042 in rotation.

[0074] Considering that the control unit 130 is capable of varying the control value proportionally, it follows that the axis 2031 can undergo more or less significant rotational movements proportionally, for example between 0 and 90°. In other words, the rotational movement undergone by the axis 2031 is therefore transmitted to the sphere 2042 which pivots in response, within its housing 2041, as illustrated in Fig. 3 à Fig. 5 , which allows the desired gas flow rate to be set or adjusted, during normal operation of the device 1.

[0075] So, Fig. 3 is a top diagram of the calibrated orifice 204 of Fig. 2 showing, as already explained, the axis 2031 which requires the sphere 2042 to present its recess 2043 in continuity with the inlet ports 201a and outlet ports 201b of the body 2040 so as to create a fluid connection between said inlet ports 201a, 201b and thus allow the passage of gas through the ports 201a, 201b and the recess 2043. The calibrated orifice 204 is then at its maximum opening, that is to say in the fully open position. In this position, the axis AA of the through-hole 2043 of the sphere 2042 is (quasi)coaxial with the axis BB passing through the inlet (201a) and outlet (201b) ports so that the opening is maximum, therefore the maximum flow in the emergency line 201, including through the through-hole 2043 of the sphere 2042.

[0076] In Fig. 4 , the control unit 130 has controlled the stepper motor 2030 to cause the axis 2031 to undergo a rotation here of the order of 90° and consequently also the sphere 2042 which also undergoes the same rotation of 90°. After rotation, the inlet ports 201a and outlet ports 201b of the body 2040 of the calibrated orifice 204 no longer face the recess 2043 of the sphere 2042 but a non-hollowed out, i.e. solid, portion 2044 of the sphere 2042 and are then completely blocked by the non-hollowed out portion 2044 of the sphere 2042. The fluid connection is then broken and no gas can circulate between the inlet ports 201a and outlet ports 201b of the body 2040 of the calibrated orifice 204. The calibrated orifice 204 is then completely closed.

[0077] In this so-called closed position, the axis AA of the through-hole 2043 of the sphere 2042 is (quasi) perpendicular to the axis BB passing through the inlet (201a) and outlet (201b) ports so that no gas passes through the through-hole 2043, therefore in the emergency line 201.

[0078] Between Fig. 3 et Fig. 4 , the control unit 130 imposed extreme control values ​​on the actuator 203, i.e. between 0° and 90° of rotation, making it possible to obtain either complete communication (cf. Fig. 3 ), or complete insulation (cf. Fig. 4 ) of the inlet ports 201a and outlet ports 201b of the body 2040 of the calibrated orifice 204.

[0079] However, the control unit 130 is also configured to be able to assign, proportionally, commands causing a rotation of the axis 2031 and the sphere 2042 between these two extreme angular positions, i.e. 0° and 90° of rotation, i.e. an angle that is not zero but less than 90°.

[0080] So, Fig. 5 gives the example of an intermediate angular position where the sphere 2042 has undergone a rotational movement of the order of 45°. In this case, the inlet port 201a of the body 2040 of the calibrated orifice 204 is partially obstructed, that is to say exposed to non-hollowed out 2044 and hollowed out 2043 parts of the sphere 2042. The gas passage section of the hollowed out part 2043 of the sphere 2042 in fluidic relation with the inlet port 201a is then defined by an opening level (or size) O. This gas passage section is always less than the maximum fluidic connection section as shown in Fig. 3 . By means of axial rotation, the same opening level O appears between the outlet port 201b and the hollowed-out portion 2043 of the sphere 2042 of the body 2040 of the calibrated orifice 204.

[0081] In the so-called intermediate positions, the axis AA of the through-hole 2043 of the sphere 2042 and the axis BB passing through the inlet (201a) and outlet (201b) ports form between them a variable angle strictly comprised here between 0 and 90° so that the passage of gas through the through-hole 2043, therefore in the emergency line 201, is limited / reduced but not zero, nor maximum, that is to say according to the desired opening O of the calibrated orifice 204.

[0082] Thus, depending on the command imposed on the actuator 203 by the control unit 130, the opening level O defined by the intersection of the inlet ports 201a, outlet ports 201b and the hollowed-out part 2043 of the sphere 2042, varies from a zero value ( Fig. 3 ) to a maximum value ( Fig. 4 ), that is to say can take the intermediate values ​​located between these two extreme values, i.e. between 0 and 90°, which makes it possible to regulate or adjust the gas flow circulating in the emergency line 201.

[0083] Indeed, it is easily understood that each level or opening value O corresponds to an equivalent calibrated orifice whose gas passage diameter is a function of the positioning of the sphere 2042 and consequently of the command sent by the control unit 130, i.e. the control means, to the actuator 203.

[0084] As already said, this assembly therefore forms a proportional calibrated orifice since its caliber or opening level O varies according to the angular position taken by the sphere 2042 within the body 2040 of the calibrated orifice 204.

[0085] However, the pressure prevailing in the upstream portion of the emergency line 201, that is to say upstream of the calibrated orifice 204, is stable and known since it corresponds to the pressure relief of the pressure regulator 115 set for example at 4 bar abs. The gas flow rate circulating in the downstream portion of the emergency line 201, that is to say downstream of the calibrated orifice 204, is therefore a function of the opening level O.

[0086] Thus, the control unit 130 can have a correspondence table linking a given control level to an opening level and to a gas flow rate passing through the calibrated orifice 201 in the direction of the injection line 111 and entering it at the second connection site 111b.

[0087] For reasons of simplification, it is assumed that the pressure level prevailing in the inspiratory branch 31 of the patient circuit 3, and therefore in the NO injection module 110 and the injection line 111 is negligible with respect to the pressure relief pressure of the pressure regulator 115 and therefore has no impact on the accuracy of the flow rate measurements circulating in the emergency line 201 carried out by the control unit 130.

[0088] Of course, according to a particular embodiment, additional measuring means, such as an additional pressure measuring device arranged to carry out a pressure measurement downstream of the calibrated orifice 204 of the emergency line 201 can be implemented, i.e. used, for compensation purposes, without changing in any way the subject of the present invention.

[0089] Finally, it should be noted that the choice of a stepper motor is particularly recommended because, unlike the solenoid valves 202, 113 which will take a rest position, in the event of a power cut, namely an open position for the on / off solenoid valve 202 and a closed position for the proportional solenoid valve 113, the position of the stepper motor remains permanent and fixed according to the last command imposed. In other words, the calibrated orifice 204 has a fixed opening level corresponding to the last command value received by the stepper motor, i.e. the last command coming from the control means 130.

[0090] Of course, the present invention is not limited to a stepper motor type actuator. Indeed, any other actuator that maintains its position in the event of a power supply failure and can be coupled to a mechanical mechanism for defining a calibrated orifice of variable size can be used, such as a linear motor or other.

[0091] Furthermore, the NO 1 delivery device is electrically powered by a power supply, such as the mains (110 / 220V) or an internal battery, in order to allow the proper functioning of its components requiring electric current to operate, in particular the actuator 203, such as a stepper electric motor, the control unit 130, the solenoid valves 202, 113, or others.

[0092] In addition, the NO 1 delivery device also comprises storage means, such as a computer memory, for storing data, information or other, for example one or more correspondence tables, the gas flow rate measurements carried out by the flow rate measuring device 112 or coming from the flow rate sensor 100 and / or processed by the control means 130, or other.

[0093] According to the invention, in the event of a failure in the operation of the installation 1, 2 resulting from a loss of the signal, i.e. measurements, coming from the flow sensor 100, for example in the event of disconnection of the upstream lines 103 and / or downstream line 102 for pressure measurement, which can be mechanically coupled, it must be possible to continue to provide treatment of the patient with inhaled NO, despite the malfunction.

[0094] To do this, in the event of loss of signal by the control means 130 of the signal(s) coming from the flow sensor 100, the emergency solenoid valve 202 ceases to be controlled by the control means 130, as it is during normal operation of the installation 1, 2, so as to automatically move to the open position, i.e. to its rest state, to allow circulation of an emergency gas flow (i.e. NO / N 2 mixture) in the emergency line 201 and, at the same time, the valve device 113 also ceases to be controlled by the control means 130, to move to the closed position, i.e. to its rest state, in order to stop any circulation of gas (i.e. NO / N 2 mixture) in the injection line 111, which makes it possible to supply the gas (i.e. NO / N 2 mixture) at an emergency gas flow rate, via the emergency line 201 and the flow control device 210, even in the event of signal loss.

[0095] In this case, the emergency gas flow corresponds to a gas flow preset at the flow control device 210 forming a proportional calibrated orifice system, during normal operation of the installation, i.e. before the loss of signal from the flow sensor 100.

[0096] More precisely, the emergency gas flow rate corresponds to the “last” flow rate having been calculated by the control means 130 from the last measurement signal(s) corresponding to the flow rate(s) of respiratory gas (e.g. air or N 2 / O 2 ) in the inspiratory branch, having been supplied by the flow sensor 100 of the patient circuit 3 to the control means 130, before said interruption of reception of said signal, and moreover from the desired NO dosage, which is typically between 1 and 80 ppmv. The desired NO dosage or concentration in the final mixture is set by the healthcare personnel, e.g. a doctor or the like, and can be stored in the NO delivery device 1.

[0097] Preferably, the emergency gas flow rate is calculated from several flow rate values ​​having been measured by the flow rate sensor 100 within the inspiratory branch of the patient circuit 3, during normal operation of the installation 1, 2. Said flow rate values ​​are averaged by the control means, that is to say that the control means 130 calculate an average gas flow rate or “average flow rate” over a given period of time, during which the values ​​have been operated, for example for several seconds or tens of seconds. The emergency gas flow rate is then preset at the flow rate control device 210 forming the proportional calibrated orifice system, also during normal operation of the installation 1, 2.

[0098] In other words, during normal operation of the installation 1, 2 preceding the malfunction, the emergency gas flow rate is determined by the control means 130 from the last gas flow rate measurement(s) provided by the flow sensor 100, in particular an average flow rate, as explained above, and possibly stored, and of course, the desired dosage, i.e. NO content in the final mixture. The control means 130 can then act immediately, i.e. before any possible future signal loss, on the flow rate control device 210 of the NO supply device 1 to adjust the calibrated orifice located there so that it is capable of immediately delivering an emergency gas flow (i.e.NO / N 2 mixture) at the desired emergency gas flow rate via the emergency line 201, as soon as a loss of signal is detected and the control means 130 cease or stop their control of the emergency solenoid valve 202 and the valve device 113 which then pass into their respective rest states, namely in the open position for the emergency solenoid valve 202 and in the closed position for the valve device 113 so as to ensure circulation of the NO / N 2 gas mixture in the emergency line 201 but to prevent or stop any circulation of gas in the injection line 111.

[0099] The control means 130 therefore determine the emergency gas flow rate, before any loss of signal, from the desired NO dosage and the last gas flow rate measurement(s) provided by the flow rate measuring device 100, during normal operation, i.e. before signal interruption, and act on the flow rate control device 210 to preset this emergency gas flow rate, for example by adjusting the caliber or opening level O acting on the angular position taken by the sphere 2042 within the body 2040 of the calibrated orifice 204, as explained above. Preferably, the last flow rate measurements are used by the control means 130 to calculate an average flow rate over a given duration of a few seconds or tens of seconds preceding the malfunction and it is this average flow rate which is used to determine the emergency gas flow rate making it possible to obtain the desired dosage.

[0100] More specifically, the operation of the emergency NO dosing system 200 of the NO delivery device 1 of the invention is generally as follows.

[0101] As illustrated in Fig. 1 , the NO 1 delivery device cooperates with a mechanical ventilator 2 in order to provide therapeutic assistance to the patient P. As already explained, the flow rate of the flow of respiratory gas containing oxygen, typically approximately at least 21% vol. of O 2 , (eg air or N 2 / O 2 , or even pure O 2) coming from the mechanical ventilator 2 and circulating in the inspiratory branch 31 of the patient circuit 3 is continuously measured by the flow sensor 100 and transmitted to the control unit 130, as detailed above depending on whether the flow sensor 100 is a flow sensor itself or a differential pressure sensor.

[0102] These flow rate measurements allow the control unit 130 to determine, in real time, the NO flow rate, i.e. emergency flow rate, to be injected into the injection line 111 and the NO injection module 110 in order to satisfy the desired NO concentration or dosage in the gas supplied to the patient, namely between 1 and 80 ppmv, typically between 5 and 80 ppmv, for example of the order of 10 to 20 ppmv.

[0103] In normal operation, the control unit 130 controls the valve device 113, preferably a proportional solenoid valve, in the open position (i.e. active state) to allow circulation of the NO / nitrogen mixture in the injection line 111. Conversely, in order not to introduce additional flow from the emergency line 201 into the injection line 111, the control unit 130 controls the solenoid valve 202, which is preferably of the all-or-nothing type, in the closed position (i.e. active state) and, in parallel, will control the actuator 203, i.e. stepper motor, in order to pre-adjust the calibrated orifice 204 by defining a given opening level O, therefore an emergency flow.

[0104] This is carried out in the following manner by the control unit 130, from one or preferably several measurements of the flow rate of respiratory gas (e.g. air or N 2 / O 2 , or even O 2 ) coming from the ventilator 2, which circulates in the inspiratory branch 31 of the patient circuit 3 at a flow rate(s) determined by the flow sensor 100, which is transmitted to the control means 130.

[0105] The control unit 130 uses the respiratory gas flow rate measurements to preferentially calculate an average flow rate over a given duration, for example a few seconds, and then evaluate the NO flow rate value (in L / min) making it possible to obtain or approach the desired NO concentration or dosage, e.g. between 1 and 80 ppmv, for example of the order of 10 to 20 ppmv, after mixing the NO / nitrogen mixture flow supplied by the injection line 111 with the respiratory gas circulating in the inspiratory branch 31 of the patient circuit 3. In other words, the calculation of the NO flow rate value takes into account, during normal operation of the installation, the respiratory gas flow rate measured in the patient circuit 3 by the flow sensor 100, in particular an average flow rate calculated by the control means 130.

[0106] More precisely, when the emergency flow rate value has been determined, the control unit 130 performs a conversion by means of a stored correspondence table so as to control the actuator 203 of the flow control device 210 and consequently define an opening level of the calibrated orifice 204 in order to set a flow rate of NO that can circulate in the emergency line 201 equal to the calculated value of fixed average NO, that is to say corresponding to the pre-set emergency flow rate. It should be emphasized that this activity has no physical effect, i.e. no gas flow rate circulates in the emergency line 201 because the on / off solenoid valve 202 is closed, during normal operation of the installation 1, 2, that is to say before any loss of signal from the flow sensor 100.

[0107] On the other hand, in the event of an interruption in the signal from the flow sensor 100, the valve device 113, typically a proportional solenoid valve, returns to its rest state, namely it goes into its closed position preventing any passage of gas, while the emergency solenoid valve 202 simultaneously returns to its rest state, namely its open position, allowing the passage of gas from the NO source into the emergency line 201 and its circulation until it reaches the second junction site 111b, then the downstream part of the injection line 111. The control unit 130 then ceases to control the valve device 113 and the emergency solenoid valve 202 which then automatically return to their rest state.

[0108] In other words, the passages of the valve device 113, typically a proportional solenoid valve, and / or of the solenoid valve 202 into their rest state occur naturally, that is to say independently of any command by the control means 130. These rest states are in fact “default” states of the valve device 113 and of the solenoid valve 202.

[0109] The NO / N 2 mixture can then circulate in the emergency line 201 at an emergency flow rate calculated as explained above and detailed below, which is controlled by the calibrated orifice of the flow control device 210. The flow of NO / N 2 at the emergency flow rate joins the injection line 111 (at 111b) and can then be injected into the inspiratory branch 31 of the patient circuit 3 via the NO injection module 110, as already explained, to obtain the final mixture to be administered to the patient which is at the desired dosage of NO, that is to say usually between 1 and 80 ppm of NO, for example of the order of 10 to 20 ppmv.

[0110] It is therefore understood that, according to the invention, the flow control device 210 is configured, i.e. preset during normal operation of the installation 1, 2, to supply, in the event of a malfunction with loss of signal from the flow sensor 100, the gas, i.e. NO / N 2 , at an emergency gas flow rate which has been determined by the control means 130 from one (or more) gas flow rate measurements provided by the flow sensor 100, for example via the upstream and downstream lines 103, 102, and the differential pressure sensor 104, before the malfunction, preferably the last flow rate value of the respiratory gas coming from the ventilator 2 and having been measured before the malfunction, caused for example by an untimely or accidental disconnection of the upstream and downstream lines 103, 102, or even a sudden failure of the flow sensor 100.

[0111] The flow rate value of NO is therefore pre-set within the flow rate control device 210 by the control means 130, for example by acting on the angular position taken by the sphere 2042 within the body 2040 of the calibrated orifice 204 of the flow rate control device 210 in order to vary the caliber or opening level O, as explained above, by controlling said flow rate control device 210 by the control means 130, said pre-setting taking place, that is to say being operated or carried out, during said normal operation of the device 1.

[0112] Of course, injecting a continuous flow of NO into the inspiratory branch 31 of the patient circuit 3 does not guarantee the same precision of concentration of inhaled NO as when the NO delivery system 1 operates in normal operation, that is to say by adjusting the flow of NO according to the flow passing through the flow sensor 100, but the buffer volume generated by the portion of the inspiratory branch 31 located downstream of the NO injection module, which is possibly increased by the volume of the humidification chamber when it is present, makes it possible to smooth out the variations in concentration of NO inhaled by the patient and to get closer to the desired target value, that is to say the NO dosage.

[0113] In any case, being able to approach the desired target NO value thanks to the backup NO dosing system 200 integrated into the NO delivery device 1 of the invention considerably improves safety for the patient in comparison with a fixed backup NO flow rate (for example 250 mL / min) usually delivered by the safety system of the NO delivery devices of the prior art.

[0114] Thus, for comparison, while the backup NO dosing system 200 integrated into the NO delivery device 1 of the invention makes it possible to guarantee an NO concentration substantially equal to the desired dosage, with a backup system based on a fixed flow rate of 250 mL / min, as conventionally implemented in the NO delivery devices of the prior art: for an average NO flow rate of 0.05 L / min required to normally ensure an NO concentration of 10 ppmv (case of use in neonatology with HFO type ventilator), the resulting concentration with the fixed flow rate of 250 mL / min is 50 ppmv, which corresponds to a fivefold increase in the desired dosage. conversely, for an average NO flow rate of 1 L / min required to ensure an 80 ppmv NO concentration (case of use in adults, for example in the case of pulmonary hypertension during cardiac surgery), the resulting concentration drops to 20 ppmv, which corresponds to a 75% decrease in the desired dosage.

[0115] In both cases, significant dosage deviations can lead to unacceptable and dangerous situations for the patient, unlike the NO backup dosage system 200 integrated into the NO delivery device 1 of the invention, which allows the desired dosage to be respected.

[0116] In other words, the inventive NO emergency dosing system 200 has undeniable advantages in enhancing patient safety by: automatically injecting an emergency flow of NO without waiting for the user to become aware of the situation and intervene by switching to the emergency pneumatic dosage. ensuring that the concentration of NO inhaled by the patient is similar to the concentration desired by the doctor, i.e. the desired dosage.

[0117] Of course, the switch to the emergency NO dosing system 200 of the invention is only temporary, that is to say it only lasts the time necessary to replace the faulty equipment or component which triggered the audible and / or visual alarm system in order to alert the nursing staff.

[0118] In order to avoid the improper activation of the emergency NO dosing system 200, the control unit 130 is further configured to carry out appropriate initialization and shutdown sequences. For example, in the event of the user intentionally stopping the NO therapy, the control unit 130 can control the actuator 203 in order to close the calibrated orifice 204. Thus, in the event of voluntary shutdown and therefore opening of the solenoid valve 202, the “closed” configuration of the calibrated orifice 204 then prohibits any circulation of NO flow in the emergency line 201, while the NO delivery device 1 is stopped.

[0119] Generally speaking, according to the invention, in the event of failure of the flow sensor 100 measuring the gas flow rate from the mechanical fan 2 accompanied by a loss of the measurement signal, for example in the event of disconnection of the upstream 103 and / or downstream 102 pressure measurement lines connected to the flow measurement module 100-1 of the flow sensor 100, the control unit 130 retains its ability to control the actuators of the NO 1 delivery device.

[0120] In this case, the control unit 130 can detect the loss of signal from the flow sensor 100 and then immediately “activate” the emergency dosing system 200 by stopping the control of both the proportional solenoid valve 113 and the solenoid valve 202 so that the proportional solenoid valve 113 moves to the rest position, i.e. to the closed position, and the solenoid valve 202 of the emergency line 201 simultaneously moves to its rest position, i.e. an open position allowing circulation of the gas coming from the NO source in the emergency line 201 and through the flow control device 210 which then delivers the NO / N 2 flow at the preset flow rate, as explained above.

[0121] The NO / N 2 mixture flow can then take the emergency line 201 at the flow rate pre-set by the flow control device, for example a calibrated orifice or the like, before any loss of signal due to a malfunction, namely the emergency flow rate determined by the control unit 130 from the last measurement of the flow rate of the respiratory gas obtained before the malfunction and the desired dosage, i.e. the desired NO content after mixing the NO / N 2 flow with the respiratory gas coming from the ventilator 2, such as air or an N 2 / O 2 mixture, said mixing taking place in the inspiratory branch 31 at the NO injection module 110, so as to obtain the final mixture to be administered to the patient containing the desired NO dosage, typically between 1 and 80 ppmv, for example of the order of 10 to 20 ppmv.

[0122] In other words, the flow of NO / N 2 coming from the emergency line 201 will then join the injection line 111 (at 111b) to be injected into the inspiratory branch 31 of the patient circuit 3 via the NO injection module 110, and mix there with the flow of respiratory gas, such as air or a nitrogen / oxygen mixture, containing oxygen, typically approximately at least 21% vol. of oxygen, coming from the ventilator 2, as already explained.

[0123] Of course, such a situation in which the control unit 130 detects a loss of signal from the flow sensor 100, can be resolved and then return to normal, for example when the user reconnects the upstream lines 103 and / or downstream line 102 for measuring the pressure of said flow sensor 100, if it / they have been disconnected involuntarily so as to cause the malfunction and the loss of signal.

[0124] Then, when the control unit 130 determines that the signal from the flow sensor 100 is valid again, i.e. restoration of the reception of the signal, it can return to a normal operating state of the NO 1 delivery device, i.e. by controlling the solenoid valve 202 again in a closed position to isolate the backup dosing system 200 from the injection line 111, and furthermore by controlling the proportional solenoid valve 113 again in order to deliver the flow of NO to be injected into the injection line 111 and the NO injection module 110 in order to satisfy the desired concentration of NO in the gas supplied to the patient.

[0125] Similarly, although this occurrence is rarer, the control unit 130 can also determine that an internal failure of the NO flow sensor 112 has occurred, such as a break in its power cable, caused by vibrations during patient transport for example.

[0126] In this case, the control unit 130 is configured to operate in an identical manner to the previous case resulting from a loss of signal from the flow sensor 100 due to an accidental disconnection of the upstream lines 103 and / or downstream line 102, in order to activate the emergency dosing system 200. However, such an internal failure of the sensor 112 is generally permanent and irreversible, and therefore requires technical intervention to replace the damaged, i.e. malfunctioning, elements.

[0127] The NO 1 delivery device equipped with the emergency NO dosing system 200 of the invention is particularly well suited to the supply of a gas mixture comprising from 1 to 80 ppmv of NO (dosage) and at least 21% vol. of oxygen to patients (adults, children, adolescents or newborns), suffering from pulmonary hypertension and / or hypoxia, which can cause pulmonary vasoconstrictions or the like, for example caused by pulmonary pathologies or disorders such as PPHN (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.

Claims

1. Installation (1, 2) for supplying gas to a patient, comprising: - an NO delivery device (1) configured to supply an NO / N2 gas mixture, comprising: ■ an NO injection line (111) for conveying the NO / N2 gas mixture, ■ a valve device (113) arranged on the injection line (111) in order to control the circulation of the NO / N2 gas mixture in the injection line (111), ■ a backup line (201) that connects fluidly to the injection line (111) upstream and downstream of the valve device (113), said backup line (201) comprising a backup solenoid valve (202) and a flow rate control device (210), and ■ operating means (130) configured to interact with the backup solenoid valve (202), the flow rate control device (210) and the valve device (113), - a medical ventilator (2) configured to supply a respiratory gas containing oxygen, - a patient circuit (3) to which the NO delivery device (1) and the medical ventilator (2) are fluidly connected in order to supply said patient circuit (3) with said NO / N2 gas mixture and with said respiratory gas containing oxygen, and - a flow rate sensor (100) configured to supply to the operating means (130) of the NO delivery device (1) at least one measurement signal representing at least one gas flow rate within the patient circuit (3), and in which in the event of the interruption of reception, by the operating means (130) of the delivery device (1), of said at least one measurement signal supplied by the flow rate sensor (100): - the backup solenoid valve (202) is configured to switch to an open position in order to allow the circulation of the NO / N2 gas mixture in the backup line (201), - the valve device (113) is configured to switch to a closed position in order to stop any circulation of gas in the injection line (111), and - the flow rate control device (210) is configured to supply the NO / N2 gas mixture at a pre-set backup gas flow rate, where said backup gas flow rate has been determined by the operating means (130) on the basis of at least one measurement signal supplied by the flow rate sensor (100), before said interruption of reception of said signal, and pre-regulated by a command to the flow rate control device (210) from said operating means (130), before said interruption of reception of said signal.

2. Installation according to Claim 1, characterized in that the flow rate sensor (100) is arranged on the patient circuit (3).

3. Installation according to one of the preceding claims, characterized in that the flow rate sensor (100) is a mass flow sensor or a differential pressure measurement sensor.

4. Installation according to one of the preceding claims, characterized in that the flow rate sensor (100) is of the type that measures differential pressure, comprising a measurement module (100-1) traversed by an internal gas passage comprising an internal restriction (101), an upstream line (103) and a downstream line (102) for measuring pressure being fluidly connected to the measurement module (100-1) of the flow rate sensor (100) so as to make it possible to measure the pressure upstream and downstream of the internal restriction (101).

5. Installation according to Claim 4, characterized in that a differential pressure sensor (104) is connected to the flow rate sensor (100) via the upstream (103) and downstream (102) pressure measurement lines, said differential pressure sensor (104) being arranged in the delivery device (1) and interacting with the operating means (130) in order to supply them with the pressure values measured by the flow rate sensor (100).

6. Installation according to one of the preceding claims, characterized in that the operating means (130) are configured to determine the backup gas flow rate on the basis of at least one measurement signal supplied by the flow rate sensor (100), before said interruption of reception of said signal, and on the basis of a desired final concentration.

7. Installation according to Claims 1 and 6, characterized in that the backup gas flow rate is determined on the basis of an average gas flow rate calculated on the basis of a plurality of gas flow rates measured by the flow rate sensor (100) in a given duration, before said interruption of reception of said signal; the given duration is preferably between several seconds and several tens of seconds.

8. Installation according to one of the preceding claims, characterized in that the valve device (113) comprises a proportional solenoid valve.

9. Installation according to Claim 1 or 6, characterized in that the operating means (130) are configured to determine a backup flow rate on the basis of at least one respiratory gas flow rate measured by the flow rate sensor (100), before the interruption of reception of said signal, and on the basis of a final NO concentration to be obtained after mixing of the NO / nitrogen mixture coming from the NO delivery device (1) and the flow of respiratory gas containing O2 coming from the ventilator (2), typically air or an oxygen / nitrogen mixture.

10. Installation according to Claim 1, characterized in that the flow rate control device (210) comprises a proportional calibrated orifice system commanded by the operating means (130) to regulate the pre-set backup gas flow rate.

11. Installation according to Claim 1, characterized in that the operating means (130) of the NO delivery device (1) comprise at least one microprocessor.

12. Installation according to Claim 1, characterized in that the valve device (113) of the NO delivery device (1) is configured so that it is normally in a closed position corresponding to an idle state, preventing any circulation of gas in the injection line (111).

13. Installation according to Claim 1, characterized in that the backup solenoid valve (202) of the NO delivery device (1) is configured so that it is normally in an open position corresponding to an idle state, allowing the circulation of gas in the backup line (201).

14. Installation according to Claims 1, 12 and 13, characterized in that in the event of a loss of signal, the operating means (130) are configured to stop operating the valve device (113) and the backup solenoid valve (202) of the NO delivery device (1), which then automatically switch to their idle state.

15. Installation according to Claim 1, characterized in that the operating means (130) of the NO delivery device (1) are further configured to, prior to any interruption of the reception or loss of the signal coming from the flow rate sensor (100), act on a proportional calibrated orifice system () of the flow rate control device (210) of the backup line (201) in order to pre-regulate the desired backup gas flow rate.