NO delivery device with emergency dosing system

Abstract

Title of the Invention: NO Delivery Device with Emergency Dosing System. The invention relates to an NO delivery device (1) for supplying a gas containing NO, comprising an NO injection line (111) with a normally closed valve device (113) and a flow measurement device (112); a backup circuit (200) comprising a backup line (201) connecting to the injection line (111), with a normally open backup solenoid valve (202); and control means (130). In the event of a malfunction of the control means (130), the flow control device (210) supplies the gas at a predetermined backup gas flow rate that was set before said malfunction. A multi-way solenoid valve (205) is arranged downstream of the flow control device (210) and supplies dosing lines (206, 207) with calibrated orifice device (208, 209).Gas supply installation (1, 2) to a patient including such a device (1). Figure from the abstract: Figure 1.

Description

Title of the invention: NO delivery device with emergency dosing system

[0001] The invention relates to a device for delivering gaseous nitric oxide (NO) to a patient comprising an emergency NO dosing system, and intended to be connected to the patient circuit of a mechanical ventilator, i.e. a medical device for administering gas to a patient, which makes it possible to supply the gas at a pre-set flow rate in the event of malfunction, in particular of the control means.

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

[0003] Typically, a small amount of gaseous NO (i.e., a few ppm by volume), diluted in nitrogen (N2), is injected into a gas stream containing oxygen (O2), which is then inhaled by the patient. The NO concentration, which corresponds to a dosage, is determined by the physician or similar professional. Typically, the gas containing O2 is an N2 / O2 mixture or air, such as medical-grade air. In general, the NO concentration in the gas inhaled by the patient is between 1 and 80 ppm by volume (ppmv), depending on the population being treated, i.e., newborns or adults, and therefore on the disease being treated.

[0004] The gas inhaled by the patient can be delivered via a NO delivery device connected to a mechanical ventilator, as described in US-A-5,558,083. The NO delivery device is fluidically connected to one or more gas cylinders containing an N2 / NO mixture with an NO concentration typically ranging from 200 to 1000 ppmv. Generally, the NO delivery system comprises an NO injection module located in the inspiratory limb of a patient circuit fluidly connected, on one side, to the mechanical ventilator and, on the other side, to a respiratory interface delivering the NO-enriched gas to the patient, for example, a breathing mask, a tracheal intubation tube, or similar device.

[0005] The NO delivery system also includes a flow sensor that measures the gas flow rate delivered by the mechanical ventilator (i.e., air or N2 / O2 mixture) in order to determine the quantity of NO to be delivered to comply with the dosage set by the doctor.

[0006] The NO delivery system can ensure NO dosing by means of a proportional solenoid valve delivering a continuous flow of gas containing NO, which is associated with a flow sensor, the two components being arranged in the delivery system, as well as an injection line connected to the NO injection module, as described in US-A-5,558,083.

[0007] Other systems are available where the proportional solenoid valve is replaced by a plurality of "on or off" type solenoid valves, delivering the gas intermittently, i.e. in the form of bursts, 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, known NO delivery systems receive measurements from the flow sensor placed in the inspiratory branch of the patient circuit and adjust in real time the amount of NO to be delivered, according to the desired dosage, by controlling the flow of NO in the injection line.

[0009] Since NO is an effective therapeutic agent, i.e., 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.

[0010] When the patient's condition changes, the NO concentration must be gradually decreased or increased. For example, in a newborn weaning situation where the condition is improving, it is common practice to gradually decrease the dosage, for example in increments of 1 ppm, until a value of zero is reached, at which point the NO delivery system can be stopped.

[0011] A gradual decrease in NO concentration makes it possible to avoid the "rebound" effect which can occur in the event of a rapid change in concentration, for example in the event of abrupt discontinuation of treatment, with the effect of seriously worsening the patient's condition.

[0012] However, NO delivery devices are sophisticated electro-medical systems susceptible to failures or malfunctions that can have a significant impact on ongoing therapy. For example, a major electronic malfunction or defect, particularly in the control systems, can lead to device failure and therefore a complete cessation of NO delivery, with the aforementioned negative consequences.

[0013] In such circumstances, the NO delivery device must warn the user, for example by means of an audible alarm signal, that rapid action is required, typically a switch to a backup pneumatic injection mode, i.e. a so-called "emergency" mode, in order to limit, as much as possible, the adverse effects related to a discontinuation of therapy.

[0014] Such a switch to backup mode is usually done by actuation of a control device, such as a rotary button, commanding for example a continuous delivery of a fixed flow rate of NO, typically of an N2 / NO mixture, for example of the order of 250 mL / min.

[0015] However, an emergency dosing mechanism or system is not without risk, particularly for the following reasons: - Its activation requires the presence of a person with the authority to take this action, for example, a neonatologist. In a hospital setting, several minutes may pass before this person arrives in the treatment room and the rescue dosage is established, which can lead to a temporary interruption of therapy and expose the patient to a rebound effect. - Rescue dosing, such as a pre-set flow rate of N2 / NO mixture, does not guarantee that the desired dosage will always be maintained. In particular, when the rescue dose is significantly lower than the desired dose, the patient may be exposed to an abrupt change in concentration and potentially subject to serious adverse effects, which is undesirable for obvious reasons of patient safety and treatment efficacy. - Rescue dosing is incompatible with certain types of ventilators delivering very low volumes, such as high-frequency oscillating (HFO) ventilators, because it can result in excessively high inhaled nitric oxide (NO) concentrations, sometimes even reaching levels dangerous for the patient. Therefore, if the patient is being treated with an HFO ventilator, there is no way to administer NO to the patient, leading to the aforementioned risks associated with the abrupt cessation of treatment.

[0016] It therefore appears that the current emergency dosing mechanisms do not allow a satisfactory level of safety to be guaranteed and that it would be desirable for the patient, in the event of the implementation of an emergency dosing due to a malfunction of the NO delivery device, to be able to maintain NO therapy, without interrupting the therapy and / or without worrying about the type of ventilator, i.e. HFO ventilator or other, with which the NO delivery device cooperates.

[0017] In other words, one problem is being able to maintain a dosage, i.e. treatment of the patient with inhaled NO, even in the event of failure or malfunction of the NO delivery device, in particular a total cessation of operation of the means of control of the NO delivery device, in particular due to a breakdown, malfunction or lack of power supply.

[0018] One solution according to the invention relates to a device or apparatus for delivering NO to provide a gas containing NO, typically a NO / nitrogen gas mixture, comprising: - a NO injection line to deliver the NO-containing gas, - a valve device arranged on the injection line to control the circulation circulation of NO-containing gas in the injection line, said valve device being configured to be normally in a closed position to prevent any gas circulation in the injection line, - a flow measurement device arranged on the injection line to perform one or more flow measurements of the NO-containing gas circulating in the injection line, - a backup circuit comprising a backup line fluidly connected to the injection line, upstream and downstream of the valve device, said backup line comprising a backup solenoid valve configured to be normally in an open position to allow gas circulation in the backup line, and a flow control device, and - control means, i.e. a control unit, configured to cooperate with the backup solenoid valve, the flow control device, the valve device and the flow measurement device.

[0019] In the event of a malfunction causing a cessation of cooperation with the control means, i.e., in the event of a malfunction of the control means, for example, due to a power supply failure: - The emergency solenoid valve is configured to open to allow gas circulation in the emergency line of the backup circuit. - the valve device is configured to switch to the closed position to stop all gas flow in the injection line, and - the flow control device is configured to supply gas at a predetermined emergency gas flow rate, where said emergency gas flow rate: • is determined by the control means based on at least one gas flow measurement provided by the flow measurement device, during normal operation of the device preceding said malfunction, and • is preset by command of said flow control device by the piloting means, during said normal operation of the device.

[0020] Furthermore: - A multi-way solenoid valve is installed on the backup line, downstream of the flow control device, - said multi-way solenoid valve comprising: • an inlet channel fluidly connected to the backup line downstream of the flow control device, • a first outlet connected fluidly to a first dosing line comprising a first calibrated orifice device, and • a second outlet connected fluidly to a second metering line comprising a second calibrated orifice device, - the first metering line and the second metering line are connected to the backup line, downstream of said first and second calibrated orifice devices, and - the control means are configured to control the multi-way solenoid valve to direct the gas flow to the first dosing line or, alternatively, to the second dosing line.

[0021] Depending on the embodiment considered, the device of the invention may comprise one or more of the following features: - The multi-way solenoid valve includes 3 ports. - the inlet of the multi-way solenoid valve is supplied with gas by the backup line, typically with an N0 / N2 mixture, in case of malfunction of the NO delivery device, in particular of the pilot unit, typically in case of failure of power supply to said pilot unit. - the malfunction causing a cessation of (all) cooperation with the control means includes a defect in said control means or a defect in the electrical supply of said control means. - in case of malfunction of the NO delivery device, the first output channel of the multi-way solenoid valve supplies the first dosing line including the first calibrated orifice device. - alternatively, in the event of a malfunction of the NO delivery device, the second output of the multi-way solenoid valve supplies the second dosing line including the second calibrated orifice device. - The gas inlet of the multi-way solenoid valve includes an upstream port receiving the gas, typically a NO / N2 gas mixture - the first output of the multi-way solenoid valve includes a first downstream port supplying the gas, typically a NO / N2 gas mixture to the first metering line. - the second outlet of the multi-way solenoid valve includes a second downstream port supplying the gas, typically a NO / N2 gas mixture to the second dosing line. The control means are configured to, during normal operation of the device, command the emergency solenoid valve to be in a closed position preventing any gas flow in the emergency line. The control means are configured to, during normal operation of the device, control the valve device to allow gas circulation in the injection line and preferably to allow at least one gas flow measurement by the flow measurement device. The control means are further configured to, during normal operation of the device, control the flow control device to preset the emergency gas flow rate based on at least one gas flow measurement provided by the flow measurement device. In other words, the flow control device is set prior to any malfunction, that is, while the NO supply device is operating normally. During normal operation of the device, the flow measurement device is configured to perform several successive flow measurements; during normal operation of the device, the control means are further configured to determine, for example calculate, the emergency gas flow (i.e. gas flow containing NO, e.g. NO / N2 mixture) from one or more flow measurements performed by the flow measurement device. The backup line connects fluidly to the injection line upstream of the valve device, and upstream or downstream of the flow measurement device, preferably downstream of the flow measurement device. a flow measurement device is arranged on the injection line upstream or downstream of the valve device, preferably downstream of the valve device, the backup line is fluidly 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 backup line is fluidly connected to an upstream portion of the injection line located upstream of the valve device, in particular via its upstream end. The backup line connects fluidly to a downstream portion of the injection line located downstream of the valve device, in particular via its downstream end. It includes memorization techniques to memorize at least part of it successive flow measurements carried out by the flow measurement device, that is to say the successive flow measurements are memorized by memorization means. the storage methods are configured to also store one or more lookup tables. the storage means are configured to also store at least one lookup table giving a relationship between pressure and flow rate of the calibrated orifice device(s). The means of memorization include computer memory, for example RAM, or other. The NO injection line carries a gaseous mixture consisting of NO and nitrogen, preferably a NO / N2 gaseous mixture (i.e. nitric oxide / nitrogen) 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 is configured to be normally open, particularly when not controlled by the control means, typically in the event of a malfunction. The backup solenoid valve is of the on / off type. The control systems include at least one microprocessor. the control means include an electronic card carrying said at least one microprocessor. the injection line is fluidly 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 includes a housing. The NO emergency dosing system is arranged in the housing, in particular the emergency line and the emergency solenoid valve. The backup line connects fluidly to the injection line between the pressure regulating device and the valve device. The valve device includes a solenoid valve, preferably a proportional solenoid valve. The flow control device is configured to form or constitute a proportional pressure and flow generation system. The flow control device includes an actuator means cooperating with a pneumatic pressure regulator. The flow control device includes an actuator means allowing to control the output pressure level of the pneumatic pressure regulator. the flow control device includes an actuator means adjustable by angular displacement. the actuator means includes an electric motor, in particular a stepper motor. the actuator means is powered by the electrical power supply means, i.e. during normal operation. The actuator means comprises an electric motor driving a rotating shaft, which is integral with the pneumatic pressure regulator. The pneumatic pressure regulator includes an inlet port and an outlet port in fluidic communication with the backup line. The control means are configured to control the actuator means to operate a displacement, preferably angular, of the pneumatic pressure regulator between at least: • a fully open position corresponding to a maximum opening level, i.e., corresponding to maximum pressure (and maximum flow rate) of the pneumatic pressure regulator. In the fully open position, all the gas flow supplied by the emergency line enters the pneumatic pressure regulator, i.e., a maximum flow rate, • a fully closed position corresponding to a level of total closure, i.e., corresponding to zero pressure (and zero flow), of the pneumatic pressure regulator. In the fully closed position, no gas flow can pass through the pressure regulator, i.e., a zero flow. • and advantageously at least one intermediate position located between said maximum opening and maximum closing positions, thus corresponding to a pressure level at the outlet of the pneumatic pressure regulator between the maximum pressure value and the zero pressure value (i.e., 0 bar). In the intermediate position, only a portion of the gas flow supplied by the backup line enters the pneumatic pressure regulator, that is to say, one or more reduced or limited flow rates, lower than the maximum flow rate. The control means are configured to control the actuator means to operate an angular displacement of the pneumatic pressure regulator between several angularly distinct positions, angularly offset from each other. The other positions include the fully open position, the fully closed position, and several intermediate positions between the fully open and fully closed positions. These angularly distinct positions each correspond to a specific outlet pressure level and a given gas flow rate, i.e., flow rates between the maximum flow rate, zero flow rate, and intermediate flow rates between these maximum and zero flow rates. The control means are configured to pilot, command, or control the actuator during normal operation of the device, i.e., prior to any malfunction, in order to regulate or adjust the predetermined emergency gas flow rate, i.e., the desired flow rate. the control means are configured to control the actuator means to operate a displacement, preferably angular, of a moving element of said actuator means in a given position corresponding to the preset backup flow rate. the moving element includes a rotating shaft, preferably made of metal or metal alloy. the moving element includes a rotating shaft suitable for being driven in rotation by an electric motor. The control means are configured to determine the opening of the pneumatic pressure regulator and / or the preset emergency flow rate from a stored lookup table. The control means are configured to determine an opening of the pneumatic pressure regulator corresponding to the preset emergency flow rate; the correspondence table is stored by the storage means, like a computer memory. It includes power supply means configured to supply electrical current to components requiring electrical energy to operate, including control means or other components, such as solenoid valves, electric motors.... The means of power supply includes means of connection to the mains (110 / 220V) and / or a battery or similar. The flow control device of the NO emergency dosing system, which forms a proportional system, allows the pre-set emergency gas flow to be (pre)set or adjusted prior to any malfunction of the device preventing any cooperation between the control means and the emergency solenoid valve, the flow control device, the valve device and / or the flow measurement device. the emergency gas flow measured by a NO flow sensor located in the NO injection line corresponds to the last flow measurement operated by the NO flow measurement device that was operated before the malfunction. - the first calibrated orifice of the first calibrated orifice device has a first passage diameter (Dl) and the second calibrated orifice device has a second passage diameter (D2) such that 1.5.D1 < D2 < 4.D1. - the first passage diameter (Dl) and the second passage diameter (D2) are such that 1.8.D1 < D2 < 3.D1, preferably D2 is equal to approximately 2.D1. - the backup solenoid valve is of the on / off type, able to adopt only an open state in which it allows the gas flow to pass and a closed state in which it interrupts the passage of gas flow. - the flow control device comprising an actuator means cooperating with a pneumatic pressure regulator. - the actuator means includes a stepper motor, preferably an electric motor. - The pneumatic regulator is configured to be adjustable over several pressure levels between 0 and 2 bar relative, preferably less than 1.5 bar relative. - the actuator means cooperates with the pneumatic regulator to set a desired output pressure downstream of said pneumatic regulator. - The pneumatic regulator includes an internal spring allowing the desired pressure level to be set. - the actuator means includes a stepper motor configured to adopt several different angular positions, each angular position of the stepper motor corresponding to a given tension of the internal spring of the pneumatic regulator. - The desired output pressure level downstream of the pneumatic regulator is determined by the tension of the internal spring of the pneumatic regulator corresponding to the angular position adopted by the stepper motor. - in normal operation, the control means are configured to control the multi-way solenoid valve to operate fluidic communication between the inlet channel of the multi-way solenoid valve and either of the first and second outlet channels of the multi-way solenoid valve so as to pass the gas flow through the first or second calibrated orifice device.

[0022] The invention also relates to a gas supply installation for a patient, i.e., a human being, comprising: - at least one NO source containing a NO / N2 gaseous mixture, - a NO delivery device according to the invention, supplied with a NO / N2 gas mixture by said at least one NO source, - an inspiratory branch of a patient circuit supplied with a NO / N2 gas mixture by the NO delivery device, and - a medical ventilator, i.e. a respiratory assistance device, in fluidic communication with the inspiratory limb to supply said inspiratory limb with a respiratory gas containing at least 20% oxygen.

[0023] According to the embodiment considered, the gas supply installation of the invention may include one or more of the following features: - the medical ventilator delivers air or an oxygen / nitrogen mixture, i.e. as a breathing gas containing at least 21% vol. of oxygen. - according to one embodiment, the medical ventilator includes a motorized blower (i.e. turbine, compressor or similar) delivering the breathing gas, typically air or an oxygen / nitrogen mixture. - In another embodiment, the medical ventilator includes an internal gas circuit comprising one or more proportional valves for delivering and controlling the gas supply, particularly its flow rate. Such a ventilator is generally supplied with breathing gas via one or more wall outlets supplied with gas from a network of pipes in a hospital or hospital building, typically air or an oxygen / nitrogen mixture. - the medical ventilator includes control means, such as an electronic control board (or boards). - the control means, such as an electronic control board, control or operate the motorized blower or, as the case may be, the proportional valves of the medical ventilator. - the medical ventilator is of the HFO type or includes an HFO function, that is to say it is capable of producing high frequency oscillations. - the NO source contains a NO / N2 gas mixture containing between 100 and 2000 ppmv of NO, the remainder being nitrogen (N2), conditioned at a pressure between 10 and 250 bar abs, typically more than 100 bar abs (before the start of withdrawal). - the NO source contains a NO / N2 gas mixture containing between 100 and 1000 ppmv of NO, the remainder being nitrogen (N2), conditioned at a pressure between 10 and 250 bar abs, typically more than 100 bar abs (before the start of withdrawal). - the source of NO is a (or several) pressurized gas cylinder(s). - the source of NO is a gas cylinder (or cylinders) with a capacity between 0.5 and 50 L (water equivalent). - the gas cylinder comprises a cylindrical body made of steel or aluminum alloy. - the gas bottle is equipped with a simple valve (without regulator) or with 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 includes an inspiratory branch and an expiratory branch. - the patient circuit includes flexible conduits forming the inspiratory and expiratory branches, typically 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. - the inspiratory branch and the expiratory branch include flexible conduits, 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 include a gas humidifier. - The gas humidifier is arranged downstream of the NO injection module so that it can humidify the gas before its administration by inhalation to the patient.

[0024] According to another aspect, the invention also relates to a method for the therapeutic treatment of a person, i.e., a human patient (i.e., adult, child, adolescent, or neonate), suffering from pulmonary hypertension and / or hypoxia, causing pulmonary vasoconstriction or the like, comprising administering by inhalation to the person in need, a gas mixture comprising 1 to 80 ppmv of NO and at least 20 vol.% oxygen, preferably at least 21 vol.% oxygen, by means of a gas supply installation, such as that described above, comprising an NO delivery device equipped with the NO backup dosing system according to the invention, 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 PPHN (persistent pulmonary hypertension of the newborn) or ARDS (acute respiratory distress syndrome) type acute), or caused by cardiac surgery with extracorporeal blood circulation (ECC).

[0025] 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. • The terms “concentration”, “dose” and “content” are considered equivalent. • The terms “piloting”, “command” and “control” are considered equivalent. • The terms "means of / to / for" are considered to be totally equivalent and interchangeable with the terms "device of / to / for" or equivalent terms such as "unit", for example the terms "control means" can be replaced by "control device" or "control unit", the terms "measuring means" can be replaced by "measuring device"... • By “normal operation”: this refers to the usual operation of the NO delivery device for an initial period of time (of non-zero duration), in the absence of any failure, malfunction, defect, or other issue. This initial period typically lasts from one to several minutes, or even hours or days, or longer. • By “malfunction,” we mean a breakdown, anomaly, problem, malfunction, defect, or similar event, whether electrical, mechanical, or otherwise, affecting the normal operation of the NO dispensing device, in particular preventing the operation of the device's control means for a second (non-zero) period of time, for example, due to a failure of the control means and / or a power supply failure. This second period of time varies in duration, for example, from a few seconds to one or more minutes, or tens of minutes, or even longer.

[0026] 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:

[0027] [Fig. 1] schematically illustrates an embodiment of a gas delivery installation comprising a NO delivery device equipped with a dosing system emergency NO according to the present invention.

[0028] [Fig.2] to [Fig.5] schematically illustrate the operation of the calibrated orifice / actuator of the NO emergency dosing system of [Fig. 1].

[0029] [Fig.1] schematically illustrates an embodiment of a gas delivery installation 50 according to the present invention comprising an apparatus or device for delivering NO 1 including an emergency dosing system of NO, associated with a mechanical ventilator 2, i.e. a breathing apparatus delivering a breathing gas.

[0030] This installation 50 is configured to deliver NO in gaseous form to a patient at a desired concentration corresponding to a dosage set by an anesthesiologist or similar physician, typically between 1 and 80 ppmv of NO (i.e. ppm by volume), in particular a flow of NO / N2 mixture.

[0031] The medical ventilator 2 delivers a breathing gas containing at least 20 vol.% of oxygen about, preferably at least 21 vol.% of oxygen about, such as air or an O2 / N2 mixture, into a patient circuit 3, in particular into an inspiratory branch 31 of the patient circuit 3, used to deliver and supply the gas to a patient P and to convey the gases exhaled by the patient via an expiratory branch 32 of the patient circuit 3.

[0032] The medical ventilator 2 is a conventional respiratory assistance device which may include, according to the desired embodiment, either a motorized blower, also called a turbine or compressor, or one or more proportional valves, instead of the motorized blower, which are supplied with gas, for example medical air, by a wall outlet supplied by a hospital network carrying the gas within a hospital establishment.

[0033] In all cases, when the medical ventilator 2 delivers the respiratory gas into the patient circuit 3, its operation is controlled by an electronic control board or similar arranged in the medical ventilator 2. It is electrically powered by means of power supply, such as mains (110 / 220V) and / or an internal battery.

[0034] By way of example, medical ventilator 2 could be the Servo-n Neonatal® from Getinge, which is a proportional valve ventilator including an HFO function. Of course, another medical ventilator 2 could also be suitable.

[0035] As seen on [Fig.1], the inspiratory branch 31 and the expiratory branch 32 are fluidically connected to a junction piece 33, such as a Y-piece or similar, in fluidic communication with a respiratory interface 30 allowing the gas to be delivered to patient P or, conversely, the gases exhaled by patient P to be collected. The respiratory interface 30 can, for example, be a face mask, a tracheal intubation tube or other.

[0036] The inspiratory branches 31 and expiratory branches 32 include ducts, channels fittings, pipes, passages, tubing or the like, for example flexible polymer pipes, suitable for and configured to convey gas flows.

[0037] The respiratory gas flows in the inspiratory branch 31 in the direction from the mechanical ventilator 2 towards patient P, while the exhaled gases enriched in CO2 flow in the expiratory branch 32 towards the mechanical ventilator 2 where they are discharged into the atmosphere.

[0038] A flow sensor 100 and a NO injection module 110 are arranged in the inspiratory branch 31. The flow sensor 100 is generally arranged between the NO injection module 110 and the mechanical ventilator 2 so as to be able to measure the gas flow from the mechanical ventilator 2. The inspiratory branch 31 may also include a humidifier (not shown) to humidify the gas delivered to the patient, which is preferably arranged downstream of the NO injection module 110, i.e. between the NO injection module 110 and the respiratory interface 30, such as a tracheal intubation tube.

[0039] The flow sensor 100 is used to measure the gas flow, e.g. air or O2 / N2 mixture, supplied by the mechanical ventilator 2 and circulating in the inspiratory limb 31. The measurements taken are provided, directly or indirectly, to the control means 130 of the NO delivery device 1 which use them to control or adjust the quantity of NO supplied by the NO delivery device 1, i.e. the NO flow, typically of NO / N2 gas mixture, supplied by the NO delivery device to the NO injection module 110, as explained below.

[0040] One can use, for example, a mass flow sensor, a differential pressure measurement sensor or any other suitable sensor.

[0041] In the embodiment of [Fig. 1], the flow sensor 100 is, for example, of the differential pressure measurement type, that is to say, the flow sensor 100 includes an internal restriction 101 which creates a pressure drop generating a differential or pressure gradient when a gas flow passes through this internal restriction 101. The flow sensor 100 includes upstream chambers 120 and downstream chambers 121 which are separated by a wall 122 through which a gas passage passes so as to form the internal restriction 101.

[0042] Upstream pressure measurement lines 103 and downstream 102 are fluidly connected to the flow sensor 100 at connection sites located upstream and downstream of the internal restriction 101, in particular to the upstream chambers 120 and downstream chambers 121, in order to carry out pressure measurements of the circulating gas flow, before and after pressure loss, i.e. of air or an O2 / N2 mixture.

[0043] 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 pressure lines 102 and downstream pressure lines 103, which form measuring conduits. pressure and provide the differential pressure sensor 104 with pressure measurements of the circulating flow, before and after pressure loss.

[0044] Preferably, the differential pressure sensor 104 is integrated into the housing 10 of the NO delivery device 1, as illustrated in [Fig.1].

[0045] The sensor 104 is also electrically connected to a control unit 130, also called a controller or control means, and / or transmits pressure measurements to it so that they can be processed by computer, in particular to regulate or adjust the start of NO, typically of NO / N2 mixture, supplied by the NO delivery device 1 to the NO injection module 110.

[0046] The NO injection module 110 injects the flow of NO, i.e. NO / N2, into the gas flow circulating in the inspiratory branch 31 to make the desired mixture, i.e. typically a NO / O2 / N2 mixture containing NO at the desired concentration corresponding to the dosage set by a doctor or similar, which is typically between 1 and 80 ppmv, generally between 5 and 40 ppmv of NO, the remainder being oxygen (>20 vol.% approximately) and nitrogen, or even unavoidable impurities (for example argon...) and water vapor, in particular when a humidifier is present downstream of the NO injection module 110.

[0047] Advantageously, a bypass line 105 can be provided which connects to the downstream pressure line 103 in order to convey the pressure information prevailing in said downstream pressure line 103 to a pressure sensor 106, typically of the relative type. This pressure sensor 106 measures the pressure prevailing in the upstream chamber 120 of the flow sensor 100 and can return this value, via an electrical connection, to the control unit 130 for compensation purposes, considering that the actual flow value passing through the flow sensor 100 depends mainly on the differential pressure measurement 104 but is also affected by the relative pressure 106 prevailing upstream of the flow sensor 100.

[0048] The control unit 130 includes a data processing system, in particular for measurements from sensors 100, 104, 106, typically comprising one or more microprocessors arranged on one or more electronic boards and implementing one or more algorithms, i.e., one or more computer programs. Of course, the control unit 130 can also be configured to control other electromechanical elements integrated into the housing 10 of the NO delivery device 1.

[0049] More specifically, the control unit 130 is configured to process and / or utilize the measurements, i.e., the pressure measurement signals or pressure values, transmitted by the differential pressure sensor 104 cooperating with the flow sensor 100, and / or by the pressure sensor 106. Advantageously, the control unit 130 has a pre-recorded, i.e., stored lookup table, which allows a determination of the flow rate of gas circulating in the inspiratory branch 31, i.e. passing through the flow sensor 100, that is to say, to transform a pressure value transmitted by the pressure sensor 104, such here as a differential pressure sensor, into a flow value passing through the flow sensor 100, possibly compensated by the value returned by the pressure sensor 106.

[0050] Generally, determining the flow rate of the gas flow (e.g. air) through the flow sensor 100 then allows the amount of NO (i.e. the NO / N2 flow rate) to be calculated to be injected into the gas flow circulating in the inspiratory branch 31 by the NO injection module 110 in order to deliver NO to the patient at the desired concentration corresponding to the dosage set by an anesthesiologist or similar physician, typically between 1 and 80 ppmv of NO (i.e. ppm by volume).

[0051] In other words, using the pressure measurement returned by the differential pressure sensor 104 and the stored lookup table, the control unit 130 can determine the gas flow rate (e.g. air or N2 / O2 with O2 content > 21% vol.) from the mechanical fan 2 and the amount of NO to be added, via the NO injection module 110, in order to obtain the desired NO concentration.

[0052] As already stated, the final gas mixture obtained at the NO 110 injection module then mainly comprises nitrogen (N2), oxygen (O2) at a content of at least 20 to 21% vol., and NO at a content typically between 1 and 80 ppmv, or even unavoidable impurities and / or water vapor, in particular when a gas humidifier is present.

[0053] More specifically, depending on the gas flow rate (i.e. air or N2 / O2) circulating in the inspiratory limb 31, which has been determined using the flow sensor 100, the control unit 130 determines the quantity of NO, typically of NO / N2 mixture, to be added to the gas having an O2 content > 20% vol. (e.g. air or N2 / O2) circulating in the inspiratory limb 31 in order to obtain the desired final NO concentration.

[0054] The NO 1 delivery device is supplied with gaseous NO, typically a gaseous NO / N2 mixture, from an NO 250 source 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. Typically, the NO 250 source is one or more pressurized gas cylinders containing a NO / N2 mixture with an NO concentration generally between 100 and 30,000 ppmv.

[0055] The NO / N2 mixture is supplied to the injection module 110 by the NO delivery device 1, via an injection line 111, such as a flexible gas line, which is fluidly connected to the high pressure line 116 of the NO delivery device 1, which includes a high pressure inlet 116a fluidly connected to the NO source to be supplied with NO / N2 under pressure, e.g. 10 bar abs.

[0056] The high-pressure line 116, for example a gas passage or conduit, includes a pressure regulator 115 that reduces the pressure of the NO / N2 mixture to a stable value, for example approximately 2 bar abs or any other suitable pressure. The outlet port of the pressure regulator 115 thus provides a stable pressure in the upstream portion of the injection line 111.

[0057] A valve device 113, such as a solenoid valve, advantageously a proportional solenoid valve, for example the miniature VSO series solenoid valve available from Parker, is arranged in the NO delivery device 1 in order to control the flow of gaseous NO within the injection line 111.

[0058] The gas flow circulating in the injection line 111 is measured by a flow measurement device or NO flow sensor 112, arranged on the injection line 111, preferably placed downstream of the valve device 113, as seen in [Fig.1].

[0059] The pressure regulator 115, the valve or solenoid valve device 113, the NO flow sensor 112 and an upstream portion of the injection line 111 are therefore arranged in the housing 10 of the NO delivery device 1.

[0060] The valve device 113 is configured to be normally in a closed position (i.e. a closed state) to prevent any gas circulation in the injection line 111. To switch to the open position, the valve device 113 must be controlled by the pilot means 130, as is the case during normal operation of the NO delivery device 1.

[0061] Furthermore, a backup NO dosing system is provided, i.e. a backup circuit 200, arranged in the housing 10 of the NO delivery device 1, which is configured to operate in the event of a malfunction of the NO delivery device 1, as explained below.

[0062] The emergency circuit 200 includes (at least) an emergency line 201, also called a bypass line, such as a gas passage or conduit, or the like.

[0063] In the embodiment proposed in [Fig.1], the emergency line 201 of the emergency circuit 200 connects fluidly to the injection line 111 at a first connection site 111a, i.e. upstream, located between the pressure regulator 115 and the valve device 113, and at a second connection site 111b, i.e. downstream, located downstream of the valve device 113 and, preferably, downstream of the NO flow sensor 112.

[0064] In other words, the valve device 113 and preferably the NO flow sensor 112 are located between the first and second connection sites 111a, 111b of the backup line 201, that is to say that the backup line 201 bypasses, the valve device 113 and preferably the NO flow sensor 112 arranged on the injection line 111.

[0065] Alternatively, according to another embodiment, the second connection site 111b can be located between the valve device 113 and the NO flow sensor 112.

[0066] In all cases, the gas flows in the backup line 201 in the direction from the first connection site 11la to the second connection site 111b.

[0067] The emergency circuit 200 also includes an emergency solenoid valve 202 and a flow control device 210 which are arranged on the emergency line 201 and which serve to control the gas flow within the emergency circuit 200, typically within the emergency line 201.

[0068] A 3-way solenoid valve 205, i.e. of type 3:2, is arranged on the backup line 201, downstream of the flow control device 210. It is controlled by the pilot means 130.

[0069] The 3-way solenoid valve 205 comprises an upstream port 201a, a first downstream port 205a, and a second downstream port 205b, in fluidic communication. The selection of the fluidic communication between the upstream port 201a and the first downstream port 205a or, alternatively, the second downstream port 205b is operated by the pilot means 130, as described below.

[0070] The 3-way solenoid valve 205 is of the bistable type, that is to say that in the absence of electrical control by the pilot means 130, for example in the event of malfunction, typically in the event of loss of electrical supply, the fluidic communication existing between the upstream port 201a and the first downstream port 205a or the second downstream port 205b is maintained, that is to say it remains in the state in which it was before malfunction.

[0071] As an example, the solenoid valve 205 referenced HDI available from The Lee Company® can be used.

[0072] The first downstream port 205a of the solenoid valve 205 is in fluidic communication with a first dosing line 206, in which is arranged a first calibrated orifice device 208, while the second downstream port 205b of the solenoid valve 205 is in fluidic communication with a second dosing line 207 in which is arranged a second calibrated orifice device 209.

[0073] The first and second calibrated orifice devices 208, 209 have different characteristics in terms of the cross-section of their respective calibrated orifices, e.g., different diameters. Thus, the first calibrated orifice of the first calibrated orifice device 208 may have a first cross-section diameter DI and the second calibrated orifice device 209 has a second cross-section diameter D2, such that DI < D2, preferably 1.5D1 < D2 < 4D1.

[0074] For example, the first calibrated orifice of the first calibrated orifice device 208 may have a first passage diameter DI of the order of 25 pm and the second calibrated orifice of the second calibrated orifice device 209 has a second passage diameter D2 of the order of 50 pm, that is to say that D2 is preferably equal to about 2.D1.

[0075] By way of example, calibrated orifices available from O'Keefe Control® under the references BLP-1-SS and BLP-2-SS can be used. Of course, other calibrated orifices of different diameters and / or shapes can be used.

[0076] Downstream of the first and second calibrated orifice devices 208, 209, the first and second metering lines 206, 207 meet at a connection point 201b, called a node, and are also connected, at this same point 201b, to the downstream part of the backup line 201, which backup line 201 connects fluidly (downstream of point 201b) to the injection line 111 at the second connection point 111b. In other words, the first metering line 206 and the second metering line 207 connect at the node 201b so as to form the downstream part of the backup line 201.

[0077] The emergency solenoid valve 202 is configured to be normally in an open position (i.e. open state) to allow gas circulation in the emergency line 201, that is to say, it allows the gas flow to pass through when it is not or is no longer controlled by the pilot unit 130. During normal operation of the NO delivery device 1, the emergency solenoid valve 202 is therefore controlled by the pilot means 130 to be in a closed position (i.e. closed state) to prevent the NO / N2 flow from using the emergency line 201.

[0078] The backup solenoid valve 202 is preferably an on / off type solenoid valve having two possible states, namely an open state allowing gas flow and a closed state preventing gas flow. It is controlled by the control unit 130. For example, a solenoid valve from the Picosol series of IMI Norgren®, or from the HDI series of The Lee Company®, can be used.

[0079] As already stated, the emergency solenoid valve 202 is normally open, that is to say that in the absence of an electrical command from the control unit 130, the emergency solenoid valve 202 is in the open state, i.e. open position, which then allows the gas from the NO source to use the emergency line 201 from the first connection site 11a towards the second connection site 111b.

[0080] On the other hand, the control unit 130 controls the closing of the emergency solenoid valve 202, that is to say its transition from the open state to the closed state, i.e. in the closed position, any circulation of gas in the emergency line 201 is prevented, in particular when a flow is not desired, typically in normal operation.

[0081] 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 NO delivery device 1, in order to direct the gas flow to the injection line 111 and prevent it from circulating in the emergency line 201, and vice versa in the event of malfunction, as explained below.

[0082] In the embodiment of [Fig.1], the flow control device 210 comprising an actuator means 203, preferably adjustable by angular displacement, typically a stepper motor, cooperating with a pneumatic pressure regulator 204 and thus forming a variable pressure system enabling control of the flow rate and pressure of the gas flow.

[0083] When the emergency solenoid valve 202 is open, i.e., not controlled by the control unit 130, typically in the event of a power failure or malfunction of the control unit 130, the pressure in the upstream portion 201c of the emergency line 201 (i.e., between the first connection point 11a and the pneumatic regulator 204) is equal to the relief pressure of the pressure regulator 115, for example here equal to 2 bar rel. (14 psig). This same pressure is also present at the inlet of the pneumatic regulator 204, which is connected to the emergency line 201.

[0084] The pneumatic regulator 204 can be set to several different pressure levels, typically up to 2 bar relative, for example between approximately 0 and 1.4 bar relative (i.e., 0-20 psi), depending on the tension of its internal spring. A pneumatic regulator available from Beswick Engineering® under the reference PRDB can be used, for example.

[0085] The actuator means 203, namely here a stepper motor, is mechanically coupled to the pneumatic regulator 204 so that a given angular position of the stepper motor influences the tension of the internal spring of the pneumatic regulator 204 and thus fixes an output pressure downstream of said pneumatic regulator 204.

[0086] In other words, the stepper motor can, depending on its angular position, determined by the control means 130, control the pneumatic regulator 204, in particular by acting on the tension of its internal spring, to go from a closed position, i.e. delivering zero pressure at its output, to an open position, delivering maximum pressure at its output, typically less than 2 bar relative, for example on the order of 1.4 bar relative (i.e. approximately 20 psig).

[0087] Of course, depending on the angular position of the stepper motor, i.e. according to its "number of steps", the pneumatic regulator 204 can adopt one (or more) intermediate position, thus delivering a pressure between a minimum, for example 0 bar relative, and a maximum typically less than 2 bar relative, for example 1.4 bar relative.

[0088] Therefore, the resolution in terms of adjustable pressures downstream of the pneumatic regulator 204 depends on the fineness and number of steps defining a given position of the stepper motor, i.e. of the actuator means 203, of its next position.

[0089] Thus, [Fig.2] represents an evolution of the output pressure of the pneumatic regulator 204 as a function of a number of steps (i.e., position of the stepper motor), determined by the control means 130, which shows that the pressure increases linearly as a function of the number of steps. More precisely, we see that the maximum output pressure of the pneumatic regulator 204 is limited to 12 psig (830 mb rel.) but that it could be higher, typically up to 20 psig (1.4 bar rel.), by increasing the number of steps.

[0090] More generally, the pressure at the outlet of the pneumatic regulator 204 is then found at the upstream port 201a of the solenoid valve 205 which is arranged on the backup line 201 downstream of the pneumatic regulator 204.

[0091] In normal operation, the multi-way solenoid valve 205, here with three ways, is also controlled by the pilot means 130 to achieve fluid communication between its inlet channel which is fluidly connected to the backup line 201 downstream of the flow control device 210, and one or the other of its first outlet channel which is fluidly connected to the first dosing line 206, and of its second outlet channel which is fluidly connected to the second dosing line 207, that is to say between its upstream port 201a and one of its downstream ports 205a, 205b.

[0092] The outlet pressure of the pneumatic regulator 204 then propagates in the upstream portion 206a of the first metering line 206 located upstream of the first calibrated orifice 208 or, as the case may be, in the upstream portion 207a of the second metering line 207 located upstream of the second calibrated orifice 209.

[0093] In other words, during the normal operation of the device 1, the control means 130 control the 3-way solenoid valve 205 to operate a fluidic communication between the inlet of said solenoid valve 205 and one or the other of the first and second outlets of the 3-way solenoid valve 205 so as to circulate the gas flow in one or the other of the dosing lines 206, 207, therefore through the first or the second calibrated orifice device 208, 209 which include different passage sections or diameters of their calibrated orifices D1, D2.

[0094] Generally speaking, for any calibrated orifice, there is a relationship between the pressure upstream of the calibrated orifice and the flow rate through it, since the flow rate depends on the dimensions of the orifice in question. Indeed, the flow rate through a calibrated orifice is related to the pressure differential between the pressure upstream and the pressure downstream of that calibrated orifice.

[0095] Thus, [Fig.3] represents the relationship linking the pressure (in psig) upstream of the first orifice of the first calibrated orifice device 208 and the flow rate (in mL / min) through it, i.e. circulating in the downstream portion 206b of the first dosing line 206.

[0096] It can be seen that the flow rate increases as the upstream pressure increases. This increase does not follow a linear law but rather a "square root" type law. square”, as widely documented in the literature.

[0097] Therefore, here, depending on the position of the solenoid valve 205, the flow through the first calibrated orifice of the first calibrated orifice device 208 depends on the difference in pressures prevailing respectively in the upstream 206a and downstream 206b portions of the first dosing line 206, and conversely, the flow through the second calibrated orifice of the second calibrated orifice device 209 depends on the difference in pressures prevailing respectively in the upstream 207a and downstream 207b portions of the second dosing line 207.

[0098] Preferably, the pressure downstream of the first and second calibrated orifices, i.e., downstream of the two calibrated orifice devices 208, 209 (i.e., in the downstream portions 206b, 207b), is otherwise considered negligible. However, additional measuring means, such as an additional pressure measuring device, can be arranged to perform a pressure measurement downstream of the first and second calibrated orifices, for example in the region of node 201b of the backup line 201, and used for pressure compensation purposes to increase the accuracy of the flow control device 210, as detailed below.

[0099] Furthermore, the expression of the flow rate also corresponds to a position of the stepper motor 203, expressed in the form of steps, as shown in [Fig.4], based on the linear relationship linking the position of the motor 203 to the output pressure of the pneumatic regulator 204, as illustrated in [Fig.2].

[0100] Thus, [Fig. 4] shows that a step count of 0 corresponds to a closed position of the pneumatic regulator 204, and each step corresponds to a change in position of the stepper motor 203, slightly opening the pneumatic regulator 204 to allow the gas flow to pass through. For example, 50 steps result in a flow rate of approximately 4 ml / min, while 100 steps result in a flow rate of approximately 5.5 ml / min...

[0101] From there, by filling in a lookup table linking a number of steps (i.e. a position of the stepper motor 203) and a resulting flow rate, the control means 130 can "(pre-)set" the backup dosing system or circuit 200, during the normal operation of the device 1, as explained below, so that it is operational in the event of a malfunction of the control unit 130, typically in the event of a power failure of the control unit 130.

[0102] In other words, during normal operation of the device 1, the control means 130 control the pneumatic regulator 204 to adjust or fix the position of the stepper motor 203 on a determined number of steps corresponding to a desired gas flow rate.

[0103] Similarly, during normal operation of the device 1, when the control means 130 operate the 3-way solenoid valve 205 to perform a fluidic communication between its upstream port 201a and for example its second downstream port 205b, it is possible to establish, as before, a correspondence table linking a number of steps (i.e. a position of the stepper motor 203) and a resulting gas flow, then circulating in the downstream portion 207b of the second dosing line 207, as illustrated in [Fig.5].

[0104] Since the diameter of the second calibrated orifice 209 is larger than that of the first calibrated orifice 208, the resulting flow rate at a similar "step" (i.e., similar position) is greater. For example, for 50 steps, a flow rate of approximately 15 ml / min is obtained (4 ml / min for the first calibrated orifice 208).

[0105] In other words, depending on the configuration of the 3-way solenoid valve 205, the control unit 130 can have a lookup table linking a given control level (i.e. step) to a gas flow through the first or, alternatively, the second calibrated orifice 208, 209 towards the injection line 111 and entering it at the second connection site 111b.

[0106] All of these (pre-)settings are carried out during the proper operation of the device 1, that is to say during its normal operation before any malfunction of the control unit 130, in particular when it is no longer supplied with electrical current, therefore no longer functioning.

[0107] This is then used to ensure the delivery of a backup NO flow (i.e. NO / N2 flow), even in the event of a malfunction of the control unit 130, i.e. when it is no longer supplied with electrical current, therefore no longer functioning, since all the settings have already been made, before the malfunction.

[0108] Thus, in normal operation of the NO delivery device 1, i.e. when the pilot unit 130 is operational and normally supplied with electrical current, the emergency solenoid valve 202 is controlled by the pilot unit 130 to be closed, which prevents any gas circulation in the emergency circuit 200 of [Fig.1], whereas in the event of a malfunction of the device 1 rendering the pilot unit 130 non-operational, such as an electrical fault, the emergency solenoid valve 202 can no longer be controlled by the pilot unit 130 and therefore opens to allow gas to pass into the emergency circuit 200, while the solenoid valve 113 closes, as already explained. The gas flow circulating in the backup circuit 200 is then subjected to the (pre-)settings made before the malfunction, i.e., the position of the stepper motor, sending the flow to the first or second calibrated orifice device 208, 209...

[0109] In general, using a stepper motor as an actuator means 203 is particularly recommended because, unlike solenoid valves 202, 113 which assume a rest position in the event of a power outage, namely an open position for the on / off solenoid valve 202 and a closed position for the solenoid valve proportional 113, the position of the stepper motor does not change, i.e. remains permanent, and fixed according to the last command imposed, and this independently of any power supply.

[0110] In other words, the tension of the internal spring of the pneumatic regulator 204 has a fixed value and is equal to the last control value from the control means 130 and received by the stepper motor, i.e. a given position corresponding to a given number of steps, during the normal operation of the device 1.

[0111] In the event of gas supply to the pneumatic regulator 204, i.e. when the emergency solenoid valve 202 opens due to a lack of control by the pilot means 130, the tension of the internal spring of the pneumatic regulator 204 generates a fixed pressure downstream of the pneumatic regulator 204, which is then found at the upstream port 201a of the solenoid valve 205.

[0112] 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 failure and that can be coupled to a mechanical mechanism enabling the definition or formation of a variable pressure system can be used, such as, for example, a linear motor or other.

[0113] Generally, during its normal operation, the NO 1 delivery device is also electrically powered by an electrical supply, such as the mains (110 / 220V) or an internal battery, in order to allow the proper operation of its components requiring electrical current to function, in particular the actuator 203, such as an electric stepper motor, the control unit 130, the solenoid valves 202, 113, 205 or others.

[0114] In addition, the NO 1 delivery device also includes storage means, such as computer memory, for storing data, information or other data, for example one or more lookup tables, as explained above, gas flow measurements carried out by the flow measurement device 112, or other data.

[0115] Generally, in the event of a major failure in the operation of the NO delivery device 1, such as a power supply failure, for example caused by a break in its power supply cable caused by vibrations during patient transport for example, it must be possible to continue to provide treatment of the patient with inhaled NO despite the malfunction causing a stoppage of operation of the control means 130, typically due to a power supply failure.

[0116] To this end, the device 1 of the invention is configured so that, in the event of such a failure, the emergency solenoid valve 202 moves to the open position to allow gas circulation in the emergency line 201, while, at the same time, the Valve device 113 moves to the closed position to stop any gas circulation in the injection line 111, which allows the gas to be supplied, via the emergency line 201 and the flow control device 210, at a pre-set emergency gas flow rate.

[0117] In fact, during the normal operation of the device 1 prior to the malfunction, said emergency gas flow rate is determined by the control means 130 from one or more gas flow measurements provided by the flow measuring device 112 to the control means 130. The control means 130 can then preset the flow control device 210 and the solenoid valve 205 so that they can deliver the gas at the predetermined emergency gas flow rate.

[0118] In other words, the control means 130 determine the emergency gas flow to be administered in the event of a failure or other malfunction, based on the gas flow measurements provided by the flow measurement device 112 during the normal operation of the device 1, and act on the flow control device 210 and the 3-way solenoid valve 205 to adjust this predetermined emergency gas flow, for example by playing on the pneumatic regulator 204, as explained above.

[0119] More generally, the operation of the gas delivery installation 50 comprising the NO 1 delivery device of the invention is overall as follows.

[0120] As illustrated in [Fig. 1], the NO delivery device 1 cooperates with a mechanical ventilator 2 to provide therapeutic support to patient P. As already explained, the gas flow rate (i.e., air or N2 / O2) from the mechanical ventilator 2 and circulating in the inspiratory limb 31 of the patient circuit 3 is continuously measured by the flow sensor 100 and the control unit 130. The flow measurement(s) performed by the flow sensor 100 allows the control unit 130 to determine, in real time, the NO flow rate to be circulated in the injection line 111 to the NO injection module 110 in order to inject the quantity of NO into the airflow from the ventilator 2 so as to obtain the desired final NO concentration, typically between 5 and 80 ppmv, in the final NO / O2 / N2 gas mixture administered to patient P.

[0121] In normal operation, i.e. without failure or malfunction, in order not to introduce additional flow from the backup line 201 into the injection line 111, the control unit 130 controls the solenoid valve 202, which is preferably of the on / off type, in the closed position and, in parallel, will control the actuator 203, like a stepper motor, in order to pre-set the pneumatic regulator 204 by defining a tension level of its internal spring, preferably according to the position adopted by the stepper motor 203, as explained above.

[0122] This is operated by the pilot unit 130 from one or more flow measurements from the flow measurement device 112.

[0123] More specifically, the pilot unit 130 first performs an average of the flow rate of NO (i.e. of the NO / N2 mixture) having circulated in the injection line 111 for a given time, for example for 1 minute or over a longer period of time (but the flow rate must then be converted to L / min or to ml / min), during the normal operation of device 1.

[0124] The control unit 130 therefore estimates a fixed average NO flow rate value (in L / min or ml / min) allowing it to approach the desired NO concentration.

[0125] Thus, in [Table 1], the fixed average NO flow rate (in ml / min) is given for different selected NO concentrations (in ppmv), i.e. dosages, resulting from different minute ventilations (L / min) measured by the flow sensor 100, which is used by the control means 130 to determine the NO flow rate to be delivered in real time.

[0126] [Table 1] Minute Ventilation (L / min) NO Content (dosage) (in ppmv) 2 4 6 15 5 0.1 0.2 0.3 0.8 10 0.5 1 1.5 3.8 20 1 2 3 7.5 40 2 4 6 15 60 4 8 12 30.1 80 6 12 18.1 45.1

[0127] It is observed that for an average minute ventilation of 2 L / min measured by the flow sensor 100, and for a NO dosage of 5 ppmv, the average NO flow rate is 0.1 ml / min, and increases when the minute ventilation increases and / or the NO dosage increases. The average NO flow rate can therefore vary from 0.1 to 45 ml / min.

[0128] In order to take into account this large flow rate range, as already mentioned, the emergency dosing system 200 is provided with a first and a second calibrated orifice device 208, 209, arranged on the first and second dosing lines 206, 207 arranged downstream of the pneumatic regulator 204.

[0129] As illustrated in [Fig.4], the first calibrated orifice device 208 is configured to generate relatively low flow rates over a wide pressure range, for example flow rates below 10 ml / min, whereas the second calibrated orifice device 209 is configured to generate higher flow rates that can exceed 50 ml / min, as illustrated in [Fig.5].

[0130] However, in the 0-10 ml / min range, it is noted that the relationship between the flow rate and the position of the stepper motor is unfavorable to the calibrated second orifice device 209 because a small variation in the position of the stepper motor 203 causes a significant variation in flow rate, which can impair the accuracy of the generated flow rates.

[0131] Therefore, the system is configured so that the gas flow passes through the first calibrated orifice device 208 when the average NO flow rate is low, i.e. less than or equal to 10 ml / min, and through the second calibrated orifice device 209, for higher average NO flow rates, i.e. greater than 10 ml / min.

[0132] The control unit 130 then operates a specific control of the 3-way solenoid valve 205 according to the average NO flow rate to operate a fluidic communication between its upstream port 201a and its first downstream port 205a (if flow rate <10 ml / min) or, where applicable, its second downstream port 205b (if flow rate > 10 ml / min), in order to direct the emergency NO flow rate towards the first dosing line 206 through the first calibrated orifice device 208 or, where applicable, towards the second dosing line 207 through the second calibrated orifice device 209.

[0133] In normal operation, the control unit 130 averages the NO flow rate and then uses the value thus determined to control the 3-way solenoid valve 205 to select the first or second dosing line 206, 207, therefore the first or second calibrated orifice device 208, 209, intended to take charge of the NO flow, i.e. which will be used to operate the emergency dosing of NO, in case of malfunction of the NO device 1, in particular in case of failure of power supply to the flow sensor 100 or the control unit 130.

[0134] Furthermore, the control unit 130 performs a conversion via a stored lookup table or similar method, taking into account the selected calibrated orifice, i.e., the first or second calibrated orifice device 208, 209, in order to control the actuator 203 of the flow control device 210, such as a stepper motor, and to define a tension level of the internal spring of the pneumatic regulator 204 in order to allow a flow of NO circulating in the backup line 201 of the backup system 200 that is equal to the calculated value of fixed average NO. This calculated value of average NO thus serves as the backup gaseous NO flow in the event of a malfunction of the device 1.

[0135] In normal operation, no gas flows in the backup line 201 because the on / off solenoid valve 202 is closed. The gas flows normally in the injection line 111, via the proportional solenoid valve 113 and the flow metering device 112, before being supplied to the NO injection module 110, which mixes the NO flow with the air or similar flow from the fan 2.

[0136] Therefore, in the event of a major failure of the NO 1 delivery device and / or an interruption of its power supply, with the exception of actuator 203, of The solenoid valve 205 and the pressure regulator 115, which operates purely pneumatically, mean that all electromechanical actuators, particularly the solenoid valves, return to their rest position because the control unit 130 is also de-energized. Furthermore, the various sensors are without power, and therefore unable to communicate and / or control other components.

[0137] Thus, the proportional solenoid valve 113 returns to its rest position, namely its closed position preventing any passage of gas, while the solenoid valve 202 simultaneously returns to its rest position, namely its open position, thus allowing the passage of gas from the NO source into the emergency line 201 of the emergency circuit 200, and its circulation until it reaches the second junction site 111b, then the downstream part of the injection line 111.

[0138] The NO / N2 mixture then flows in the emergency line 201 at the pre-set emergency flow rate which is controlled by the association of the pneumatic regulator 204, in particular by its generated pressure, and the selected calibrated orifice, i.e. the first calibrated orifice device 208 or the second calibrated orifice device 209, knowing that, as already explained, the last valid value of the fixed average NO flow rate was then determined by the control unit 130 during the normal operation of the device 1, prior to its malfunction.

[0139] The NO / N2 relief flow which joins the injection line 111 (at 111b) can then be injected into the inspiratory branch 31 of the patient circuit 3 via the NO injection module 110, as already mentioned.

[0140] Generally, according to the invention, the flow control device 210 is configured to supply the gas, i.e. NO / N2, at a predetermined emergency gas flow rate, where said emergency gas flow rate is determined by the pilot means 130 from one (or more) gas flow measurement provided by the flow measurement device 112, during normal operation of the device 1 prior to the malfunction, for example the last flow value having been measured before the malfunction affecting the proper operation of the device 1.

[0141] The flow value is preset within the flow control device 210, for example by acting on the tension of the internal spring of the pneumatic regulator 204 of the flow control device 210 as explained above, by control, i.e. preset, of the flow control device 210 by the control means 130. The preset takes place, i.e. is operated or carried out, during the normal operation of the device 1.

[0142] Of course, if the backup circuit 200 is used in the event of a malfunction of the NO 1 delivery device, the same accuracy of inhaled NO concentration is not guaranteed as when the NO 1 delivery system is operating in normal operation, i.e. by adjusting the NO flow rate according to the flow rate passing through the flow sensor 100, but this avoids a break in the supply of NO to the patient and, moreover, 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 present, makes it possible to smooth the variations in concentration of NO inhaled by the patient and to get closer to the desired target value, i.e. the NO dosage.

[0143] The emergency dosing system of the invention is therefore particularly interesting to implement because it increases safety for the patient who does not risk being deprived of his NO treatment in the event of a malfunction of the NO delivery device, and receives a dose of NO very close to, or even equal to, the desired dosage.

[0144] In other words, being able to approach the desired target value of NO thanks to the NO 200 backup dosing system integrated into the NO delivery device 1 of the invention considerably improves patient safety compared with a fixed backup NO flow rate usually delivered by the safety system of prior art NO delivery devices.

[0145] Thus, by way of comparison, with a backup system based on a fixed flow rate, such as is classically implemented in prior art NO delivery devices: - for an average NO flow rate of 0.05 L / min required to normally ensure an NO concentration of 10 ppmv (use case in neonatology with HFO type ventilator), the resulting concentration with the fixed flow rate is 50 ppmv, which corresponds to a multiplication by 5 of the desired dosage. - Conversely, for an average NO flow rate of 1 L / min required to ensure 80 ppmv of NO concentration (case of use in adults, for example in case of pulmonary hypertension during cardiac surgery), the resulting concentration drops to 20 ppmv, which corresponds to a 75% reduction in the desired dosage.

[0146] In both cases, significant dosage deviations can lead to unacceptable and dangerous situations for the patient, unlike the NO 200 emergency dosing system integrated into the NO delivery device 1 of the invention, which allows the desired dosage to be respected.

[0147] It follows that the NO 200 emergency dosing system of the invention offers undeniable advantages in enhancing patient safety by: - automatically injecting a backup flow of NO without waiting for the user to realize the situation and intervene by switching to emergency pneumatic dosing. - ensuring that the concentration of NO inhaled by the patient is similar to the concentration desired by the doctor, i.e. the desired dosage.

[0148] Of course, the switch to the NO 200 emergency dosing system of the invention is only temporary, that is to say, it only lasts for the time necessary to replace the faulty equipment or component which triggered the audible and / or visual alarm system in order to alert the care staff.

[0149] To prevent the accidental activation of the NO backup dosing system 200, the control unit 130 is further configured to perform appropriate initialization and shutdown sequences. For example, if the user wishes to stop the NO therapy, the control unit 130 can command the actuator 203 to close the pressure regulator 204. Thus, if the system is intentionally shut down and the solenoid valve 202 is opened, the "closed" configuration of the pressure regulator 204 prevents any flow of NO in the backup line 201 until the NO delivery device 1 has shut down.

[0150] The NO 1 delivery device equipped with the NO 200 backup dosing system of the invention is particularly well suited to supplying gas mixtures comprising 1 to 80 ppmv of NO and at least 20% vol. of oxygen to patients (adults, children, adolescents or newborns), preferably at least 21% vol. of oxygen, suffering from pulmonary hypertension and / or hypoxia, which may cause pulmonary vasoconstrictions or similar conditions, 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 cardiac surgery with extracorporeal blood circulation.

Claims

Demands

1. NO delivery apparatus (1) for supplying a gas containing NO, in particular a NO / N2 gas mixture, comprising: - a NO injection line (111) to convey the NO-containing gas, - a valve device (113) arranged on the injection line (111) to control the circulation of NO-containing gas in the injection line (111), said valve device (113) being configured to be normally in a closed position to prevent any gas circulation in the injection line (111), - a flow measurement device (112) arranged on the injection line (111) to perform one or more flow measurements of the NO-containing gas circulating in the injection line (111), - a backup circuit (200) comprising a backup line (201) fluidly connected to the injection line (111), upstream (11a) and downstream (111b) of the valve device (113), said backup line (201) comprising a backup solenoid valve (202) configured to be normally in an open position to allow gas circulation in the backup line (201), and a flow control device (210), and - control means (130) configured to cooperate with the emergency solenoid valve (202), the flow control device (210), the valve device (113) and the flow measurement device (112), and in which, in the event of a malfunction causing a cessation of cooperation with the control systems (130): - the emergency solenoid valve (202) is configured to switch to the open position to allow gas circulation in the emergency line (201) of the emergency circuit (200), - the valve device (113) is configured to move to the closed position to stop all gas flow in the injection line (111), and - the flow control device (210) is configured for supply the gas at a predetermined emergency gas flow rate, where said emergency gas flow rate: • is determined by the control means (130) from at least one gas flow measurement provided by the flow measurement device (112), during normal operation of the device (1) preceding said malfunction, and • is preset by command of said flow control device (210) by the piloting means (130), during said normal operation of the device (1), characterized in that: - a multi-way solenoid valve (205) is arranged on the backup line (201), downstream of the flow control device (210), - said multi-way solenoid valve (205) comprising: • an inlet channel fluidly connected to the backup line (201) downstream of the flow control device (210), • a first outlet channel fluidly connected to a first dosing line (206) comprising a first calibrated orifice device (208), and • a second outlet channel fluidly connected to a second dosing line (207) comprising a second calibrated orifice device (209), - the first dosing line (206) and the second dosing line (207) are connected (201b) to the backup line (201), downstream of said first and second calibrated orifice devices (208, 209), - and the control means (130) are configured to control the multi-way solenoid valve (205) to direct the gas flow to the first dosing line (206) or, alternatively, to the second dosing line (207).

2. Device according to claim 1, characterized in that the solenoid valve at several lanes (205) includes 3 lanes.

3. Apparatus according to claim 1, characterized in that the first calibrated orifice of the first calibrated orifice device (208) has a first passage diameter (D1) and the second calibrated orifice device (209) has a second passage diameter (D2) such that 1.5.D1 < D2 < 4.D1.

4. Apparatus according to claim 3, characterized in that the first passage diameter (D1) and the second passage diameter (D2) are such that: 1.8.D1 < D2 < 3.D1, preferably D2 is equal to about 2.D1.

5. Device according to claim 1, characterized in that the emergency solenoid valve (202) is of the on / off type capable of adopting only an open state in which it allows the gas flow to pass and a closed state in which it interrupts the passage of gas flow.

6. Device according to claim 1, characterized in that the flow control device (210) includes an actuator means (203) cooperating with a pneumatic pressure regulator (204), preferably the actuator means (203) includes a stepper motor.

7. Device according to claim 6, characterized in that: - the pneumatic regulator (204) is configured to be adjustable over several pressure levels between 0 and 2 bar relative, preferably less than 1.5 bar relative, and - the actuator means (203) cooperates with the pneumatic regulator (204) to fix a desired outlet pressure downstream of said pneumatic regulator (204).

8. Device according to claim 7, characterized in that: - the pneumatic regulator (204) includes an internal spring for adjusting the desired pressure level and - the actuator means (203) includes a stepper motor configured to adopt several different angular positions, each angular position of the stepper motor corresponding to a given tension of the internal spring of the pneumatic regulator (204), so that the desired outlet pressure level downstream of the re- pneumatic regulator (204) is determined by the tension of the internal spring of the pneumatic regulator (204) corresponding to the angular position adopted by the stepper motor.

9. Device according to claim 1, characterized in that in normal operation, the control means (130) are configured to control the multi-way solenoid valve (205) to operate fluidic communication between the inlet channel of the multi-way solenoid valve (205) and either of the first and second outlet channels of the multi-way solenoid valve (205) so as to pass the gas flow through the first or second calibrated orifice device (208, 209).

10. Installation for supplying gas (1, 2) to a patient comprising: - at least one NO source (250) containing a NO / N2 gas mixture, preferably a NO / N2 gas mixture containing between 100 and 2000 ppmv of NO, the remainder being nitrogen (N2), - an NO delivery device (1) according to one of the preceding claims, supplied with NO / N2 gas mixture by said at least one NO source (250), - an inspiratory branch (31) of a patient circuit (3) supplied with NO / N2 gas mixture by the NO delivery device (1), and - a medical ventilator (2) in fluidic communication with the inspiratory branch (31) to supply said inspiratory branch (31) with a breathing gas containing at least 20% oxygen, preferably air or an oxygen / nitrogen mixture.