Apparatus for monitoring nitric oxide delivery

Description

TECHNICAL FIELD

[0001] Embodiments of the present invention generally relate to the field of nitric oxide delivery apparatus.

BACKGROUND

[0002] Nitric oxide (NO) is a gas which, when inhaled, dilates the blood vessels of the lungs, improving blood oxygenation and reducing pulmonary hypertension. Therefore, nitric oxide is supplied in the respiratory gases for patients with pulmonary hypertension.

[0003] Often, apparatuses used for the delivery of a nitric oxide drug make it possible to directly set the dose in ppm in the inspiratory gas inhaled by the patient in order to provide a constant concentration over the period of breathing. As the respiratory gas flow rate increases and decreases during the inspiratory and expiratory phases, it is difficult to deliver a proportional relative dose of NO gas delivered as a function of the inspiratory flow.

[0004] The closed loop proportional flow control methods that are used to titrate the desired dose have limitations in terms of the dynamic range and pulsatile step response to changes in respiratory gas flow. It is known that the major limitation is at the extremes of the NO flow control range, i.e., less than 1% or greater than 100% of the NO flow control range. Common flow control technologies involving a solenoid valve in conjunction with a flow sensor and microprocessor-driven PID (proportional, integral, differential) control are used for turbulent mixing of gas streams. At the lower 1% of the control range, the integral error is minimal, allowing the proportional control valve to be amplified sufficiently. An over-damped system coupled with a poor step response of the flow control valve can result in an under-delivery of the desired NO gas over a large part of the breathing period. At the other extreme, when peak inspiratory flow exceeds 100% of the NO flow control range for a significant part of the breathing period, there is also underdelivery of the set dose. Additionally, fine-tuned proportional control, a fast-response control system coupled with high hysteresis, or a poorly performing proportional control valve can lead to an overdose when operating below 1% of the control range.

[0005] Indeed, some delivery apparatuses automatically turn off when the determined calculated relative amount of NO flow in the inspiratory gas flow is more than 2 times or less than half of the desired set dose in ppm. When nitric oxide supply is suddenly interrupted, patients may experience side effects such as deterioration of arterial oxygen partial pressure (PaO2) and increase in pulmonary artery pressure (PAP).

[0006] A variation or irregularity in the unknown inspiratory flow profile from a booster such as a respiratory gas delivery system can result in these flow conditions, and in combination with an insufficient dynamic proportional control range, can lead to a shutdown of the NO inhalation system or other NO delivery device. Additionally, current inhaled NO delivery systems have an insufficient dynamic range of delivery and cannot be used along with gentle ventilation as gentle ventilation often requires less flows than normal ventilation. This can again lead to shutdown of the delivery apparatus and, consequently, rebound overpressure and oxygen desaturation, which can lead to serious adverse events such as death.

[0007] Additionally, the design of the nitric oxide delivery system ensures that the NO gas delivery is completely independent from the measurement of the gas concentration in the inspiratory limb of the patient circuit. Traditionally gas concentration measurements are displayed in ppm on the main screen of the device with the NO delivery inhibition proportional control characteristic. As a result of this independence, and in the event that the set dose does not equal the given concentration measurement result, it is difficult for the user to judge which part of the system monitoring or delivery is malfunctioning.

[0008] There is therefore a need to monitor and display the flow (s) from a patient support device to ensure safe delivery of nitric oxide as well as to provide the user with a method to determine the constraints of the mixing characteristics of dynamic relative NO gas delivery.

SUMMARY OF THE INVENTION

[0009] A first aspect of the invention relates to an apparatus for delivering a therapeutic gas to a patient. According to one or more embodiments, the apparatus includes a first inlet to be placed in fluid communication with a nitrogen oxide-containing therapeutic gas supply, a second inlet for being in fluid communication with a respiratory gas supply system that supplies the patient with breathing gas. a therapy gas injector module to be placed in fluid communication with the first inlet and the second inlet to provide a combined flow of respiratory gas and therapy gas; an outlet in fluid communication with the therapy injector module to provide the patient with a combined flow of respiratory gas and therapy gas; and a control circuit comprising a first flow sensor for measuring respiratory gas flow from the respiratory gas supply system and a second flow sensor for measuring therapy gas flow. wherein the control circuit determines the calculated nitric oxide dose from the measured respiratory gas flow and the measured therapy gas flow or the known therapy gas flow, and a display in conjunction with the control circuit that provides a visual and / or numerical indication of the calculated nitric oxide dose as a percentage of the calculated concentration delivered nitric oxide compared to the desired delivered concentration of nitric oxide delivered to the patient, wherein the desired concentration delivered is set by the user.

[0010] In one or more embodiments of this aspect, the control circuit includes a CPU and a flow controller, the CPU transmitting and receiving signals to the flow sensor and the flow controller, such that the control circuit provides a proportional flow of therapy gas to provide the desired nitric oxide concentration. to the patient. In some embodiments, the control circuit further includes software to support clinical decisions. In a particular embodiment, the clinical decision support software includes instructions for clearing the upper and lower limits of the maximum and minimum calculated dose to avoid shutdown of the apparatus.

[0011] In one or more embodiments, the visual and / or numerical indication of the calculated dose of nitric oxide is given in parts per million (ppm) and / or as a percentage of the desired concentration delivered. In some embodiments, the calculated dose of nitric oxide is one or more of average calculated dose, current calculated dose, maximum calculated dose, and minimum calculated dose.

[0012] In certain embodiments, the apparatus further comprises an indicator that provides an alarm when the calculated nitric oxide dose rises above or falls below a predetermined level. According to one or more aspects, the alarm comprises one or more of an audible alarm, a visual alarm, and a text alarm. In some embodiments, the indicator is an icon or graphic on the display that provides a visual and / or numerical indication of the calculated dose.

[0013] One or more embodiments of this aspect provide that the display also provides a visual and / or numerical indication of measured respiratory gas flow. In certain embodiments, the visual and / or numerical indication of a measured respiratory gas flow includes one or more of a volumetric flow rate, tidal volume, and minute ventilation.

[0014] According to one or more embodiments, the respiratory gas delivery system comprises an apparatus for ventilation.

Another aspect relates to a method of monitoring the delivery of therapeutic gas to a patient, comprising providing a respiratory gas flow, providing a therapeutic gas flow containing nitric oxide, measuring a respiratory gas flow to obtain a measured respiratory gas flow, measuring a therapeutic gas flow containing nitric oxide to obtain a measured flow. therapy gas flow or a known flow of therapy gas is obtained, delivering respiratory gas and therapy gas to the patient, determining the calculated nitric oxide dose from the measured respiratory gas flow and the measured therapy gas flow or the known therapy gas flow, and displaying the calculated nitric oxide dose and / or measured respiratory gas flow on the display module.

[0016] According to one or more examples, the method further comprises comparing the calculated dose of nitric oxide to a predetermined limit value and providing an alarm if the calculated dose of nitric oxide is above or below the limit value. In certain embodiments, the alarm comprises one or more of an audible alarm, a visual alarm, and a text alarm.

[0017] In some embodiments, the predetermined limit includes a delivery error greater than or equal to about 25%. Other predefined limits include, but are not limited to, delivery errors greater than or equal to the following values: +/- 1%, +/- 2%, +/- 5%, +/- 10%, +/- 15%, +/- 20%, +/- 25%, +/- 30%, +/- 35%, +/- 40%, +/- 45%, +/- 50%, +/- 55%, + / - 60%, +/- 65%, +/- 70%, +/- 75%, +/- 80%, +/- 85%, +/- 90%, +/- 95% or +/- 100% .

[0018] According to one or more embodiments, the calculated dose of nitric oxide is displayed in parts per million (ppm) and / or as a percentage of the desired concentration delivered. In some embodiments, the calculated dose of nitric oxide is one or more of average calculated dose, current calculated dose, maximum calculated dose, and minimum calculated dose.

[0019] In certain examples, the method further comprises adjusting the flow of respiratory gas delivered to the patient and / or the desired target NO concentration in response to an alarm. For example, the respiratory gas flow can be adjusted by changing the setting on the ventilator by the clinician.

[0020] In some examples, the method further comprises displaying measured respiratory gas flow. In one or more embodiments, displaying the measured respiratory gas flow includes displaying one or more of volumetric flow rate, tidal volume, and minute ventilation. Some embodiments provide that the measured respiratory gas flow is one or more of averaged flow rate, peak flow rate, and minimum measured flow rate.

[0021] More generally, some of the features and technical advantages of the present invention are set out above. It will be appreciated by those skilled in the art that the specific embodiments disclosed can readily be used as a basis for modifying or designing other structures or processes falling within the scope of the present invention. It will also be appreciated by those skilled in the art that such equivalent structures do not depart from the scope of the invention as set forth in the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to understand the above features of the present invention in detail, the more detailed description of the invention, briefly summarized above, may be made of embodiments, some of which are illustrated in the accompanying drawings. It should be noted, however, that the accompanying drawings only illustrate typical embodiments of this invention and therefore should not be taken as limiting its scope as the invention may embrace other equally effective forms.

FIG. 1 shows an apparatus for monitoring the flow of a gas inspired by a patient containing therapeutic gas in a patient according to one or more embodiments of the invention;

FIG. 2 depicts a system for delivering a therapeutic gas to a patient in accordance with one or more embodiments of the invention;

FIG. 3 is a block diagram of a method of monitoring the delivery of a therapeutic gas to a patient according to one or more examples;

FIG. 4 is a block diagram of another method of monitoring therapeutic gas delivery with feedback for selecting a dose or correcting flow in a patient in accordance with one or more embodiments of the invention;

FIG. 5 is a screen displaying the respiratory flow and the calculated NO dose delivered as compared to the dose set in a reported respiratory gas flow rate measurement time period in accordance with one or more aspects of the invention;

FIG. 6 shows the maximum deliverable NO concentration as a function of the breathing gas flow rate for a nitric oxide delivery device at the maximum NO flow rate and

FIG. 7 is a screen displaying the calculated dose in ppm from the known therapy gas flow rate and the measured respiratory gas flow rate.

DETAILED DESCRIPTION

[0023] Before describing the series of exemplary embodiments of the invention, it is to be understood that the invention is not limited to the details of the construction steps set forth in the description below. The invention is capable of other forms and of being practiced or carried out in various ways.

[0024] Some aspects of the invention essentially provide an apparatus for delivering nitric oxide therapeutic gas to a patient. The therapy gas contains nitric oxide in a carrier gas such as nitrogen. Suitable therapeutic gases may have varying nitric oxide concentrations, and exemplary nitric oxide concentrations in the therapeutic gas include, but are not limited to, 100 ppm to 10,000 ppm. In a specific embodiment, the nitric oxide concentration is about 800 ppm.

[0025] The apparatus includes a control circuit and display that measures the flow of therapy gas and breathing gas to determine and display the calculated dose of nitric oxide. Other examples relate to a method of monitoring the delivery of a nitric oxide therapeutic gas to a patient.

[0026] In one aspect, apparatuses are provided which include: a first inlet for receiving a nitrogen oxide therapy gas supply; a second inlet for receiving breathing gas; a therapy gas injector module in fluid communication with the first inlet and the second inlet to provide a combined flow of therapy gas and respiratory gas; an outlet in fluid communication with the therapy gas injector module for delivering respiratory gas and therapy gas to the patient; and a control circuit for determining the calculated dose of nitric oxide from the measured respiratory gas flow and the measured therapy gas flow or a known therapy gas flow.

[0027] One or more embodiments relates to an apparatus comprising: a first inlet to be placed in fluid communication with a supply of nitric oxide containing therapeutic gas, a second inlet to be placed in fluid communication with a respiratory gas delivery system that supplies the patient with breathing gas, a therapy gas injector module in fluid communication with the first inlet and second inlet to deliver a combined flow of therapy gas and breathing gas, an outlet in fluid communication with the therapy gas injector module and configured to deliver respiratory gas and therapy gas to the patient; a control circuit comprising a first flow sensor for measuring respiratory gas flow from a respiratory gas delivery system and a second flow sensor for measuring therapy gas flow, the control circuit determining the calculated dose of nitric oxide from the measured respiratory gas flow and the measured therapy gas flow, and the display in combination with a control circuit that provides a visual and / or numerical indication of the calculated dose of nitric oxide. Alternatively, instead of determining a calculated dose of nitric oxide from a measured therapeutic gas flow, the calculated dose may be based on a known or assumed therapeutic gas flow. This known therapy gas flow can be a constant therapy gas flow, such as when the nitric oxide delivery apparatus is in a hold mode.

[0028] FIG. 1 fig one embodiment of a therapy gas delivery monitoring apparatus according to this aspect. The first inlet 101 is configured to be placed in fluid communication with the nitric oxide therapy gas. The second inlet 102 is configured to be placed in fluid communication with the respiratory gas delivery system that supplies respiratory gas to the patient. The therapy injector module 103 is in fluid communication with the first inlet 101 and the second inlet 102 and the outlet 104. A side view of the therapy injector module 103 is shown. Outlet 104 is in fluid communication with the first inlet 101 and the second inlet 102 and is configured to supply respiratory gas and therapy gas to the patient. The first flow sensor 106 is in fluid communication and downstream of the second inlet 102 and monitors respiratory gas flow through the therapy injector module 103. The control circuit 105 is connected to the therapy injector module 103 and connects the flow sensor 106 to the CPU 108 and the indicator 107. The control circuit 105 may also be coupled with a second flow sensor 115 that measures therapy gas flow to the therapy injector module 103. If the flow rate measured by the flow sensor 106 is greater than or less than a predetermined level, the central processing unit (CPU) 108 may send a signal to the indicator 107. The CPU 108 may also determine the calculated dose of nitric oxide from the measured therapy gas flow rate from the flow sensor 115, the measured respiratory gas flow rate from the flow sensor 106, and the concentration of nitric oxide in the therapy gas. Alternatively, the CPU 108 may use the known therapy gas flow rate to determine the calculated dose. The indicator 107 may inform the user of the apparatus that flow is not within the specified range. The indicator 107 can be part of the display, such as an icon or graphic symbol on the display screen.

[0029] The flow sensors 106 and 115 may be any suitable flow measurement device. This includes, but is not limited to, a pneumotachometer, a thermoanemometer, a thermal resistance anemometer, a thermal flow sensor, a rotating rotor with a variable orifice, thermal time of flight, and the like. Flow transducers that measure pressure, such as pressure drop through an orifice, to determine flow are also suitable. According to one embodiment, the flow sensor 106 is part of the therapy injector module 103. In one such embodiment, flow sensor 106 includes a hot thin film sensor and a thermistor. A thermistor measures the temperature of the breathing gas flowing through the injector module 103. A constant temperature hot thin film sensor measures the flow of breathing gas, which is proportional to the energy required to maintain a constant temperature of the platinum thin film. In other embodiments, flow sensor 106 is upstream of the therapy injector module 103.

[0030] In some embodiments, the flow sensor 115 is part of a therapeutic injector module. In other embodiments, the flow sensor 115 is located upstream of the therapy injector module 103, such as in the control module of the nitric oxide delivery device.

[0031] The term "control circuit" is intended to cover a variety of methods that may be used to perform various signal processing functions to operate a therapy gas delivery apparatus. In a particular embodiment, the control circuit includes a CPU 108 and a flow controller. The CPU 108 can send and receive signals from the flow sensor 103 and flow controller (not shown) such that the control circuit maintains a set dose of NO therapy gas to the patient. In a particular embodiment, the CPU obtains information from the flow sensor and the input device that allows the user to select the desired dose of nitric oxide.

[0032] In a particular form of the control circuit, a flow sensor 103 is in conjunction with a CPU 108 that monitors the flow of each of the gases to the patient, as described herein. If a specific dose of nitric oxide is to be administered, the CPU 108 can calculate the necessary therapy gas flow from the measured respiratory gas flow and the concentration of nitric oxide in the therapy gas. This calculation can be done using the following equation:

Therapeutic ^— [Yset / (Therapeutic "Yset)] * QBreathing where QBreathing is the breathing gas flow rate, Yset is the desired concentration of nitric oxide, Ytherapeutic is the concentration of nitric oxide in the therapeutic gas supply, and Qtera_P.eutic means the flow of a therapeutic gas required to deliver the desired concentration of nitric oxide in a gas mixture.

[0033] The central processing unit may be one of any form of computer processor that can be used in an industrial or medical setting in devices or subprocessors for controlling the flow of various medical gases. The CPU may be coupled to memory (not shown) and may be one or more readily available memories such as random access memory (RAM), read only memory (ROM), flash memory, compact disc, floppy disk, hard disk or any other form of local or remote digital storage device. Auxiliary circuits (not shown) may be coupled to the CPU to support the CPU in the usual manner. These circuits include cache, power supplies, clock circuits, input / output circuits, subsystems, and the like.

[0034] The control circuit may additionally include software to support clinical decisions. Such software can provide instructions for a variety of tasks, such as delivering alarms when a calculated NO dose and / or measured respiratory gas flow increases above or below a predetermined level. The preset level can be the level at which the camera turns off. Alternatively, the predetermined level may be the level that is reached before the apparatus is turned off. Thus, in the case of an apparatus that turns off when the delivered dose of NO is below a minimum threshold, the predetermined level may be above this minimum threshold.

[0035] The predetermined level may be embedded in clinical decision support software or may be provided by the user through an input device. In one embodiment, the clinical decision support software includes instructions for clearing the upper and lower limits of the maximum and minimum concentrations, errors, or data flows at which the shutdown is triggered. According to certain messengers, clinical decision support software includes instructions to deliver an alarm when these limits are reached and to avoid a potential shutdown of the apparatus, which could lead to a missed drug delivery. Alternatively, the device may include clinical decision support software that provides instructions so that the device can automatically adjust these limits without requiring user intervention.

[0036] The clinical decision support software may also include instructions to change the temporal sensitivity of the apparatus to changes in respiratory gas flow and / or calculated dose. As a result, the apparatus may vary the period of time necessary to maintain low-flow or under-delivery conditions before the apparatus is turned off. For example, the apparatus may extend the pre-shutdown time from about 1 to 2 seconds to a few seconds so that shutdown only occurs if low flow and / or under delivery continues for an extended period of time.

[0037] The apparatus may also include an indicator to inform the user of the apparatus when the calculated dose and / or respiratory gas flow increases above or falls below a predetermined level. In one or more embodiments, the indicator provides an alarm when the calculated dose and / or respiratory gas flow rises above or falls below a predetermined level. In certain embodiments, the alarm comprises one or more of an audible alarm, a visual alarm, and a text alarm. Such alarms may be delivered at the location of the apparatus itself or may be provided at a remote location, such as, for example, directly to a medical staff station or nursing station. When the alarm is delivered at a remote location, the signal can be transferred from the camera to the remote location using any wired or wireless connection. Examples of alarms include text messages, sirens, sounds, alarms, flashing images, display color changes, or any other means of attracting the user's attention.

[0038] In certain embodiments, more than one alarm may be provided. For example, a low priority alarm may be provided when respiratory gas flow drops below a first predetermined level, and a high priority alarm may be provided when respiratory gas flow drops below a second, lower predetermined level. Such a graduated alarm system can alert medical personnel to a relatively small variation in flow rate, but can also provide a more severe alarm when hazardous conditions are present that require immediate attention. Alternatively, a high priority alarm may be provided when the flow rate has remained below a predetermined level for a predetermined period of time, thus indicating a persistent low flow condition.

[0039] The apparatus may also include a display that provides visual and / or numerical indications of the volumetric breathing gas flow and / or the calculated dose. This visual and / or numerical indication may include any way of displaying the respiratory gas flow and / or the calculated dose, including numbers, graphics, images, or the like. The display may be any type of suitable display device, including a dial, scale, or other analog device, or any electronic display device, including LED, LCD, CRT, etc. Such device does not need to be connected to the camera and may be used in a remote mode. In certain embodiments, the visual and / or numerical indication of respiratory gas flow includes one or more of a volumetric flow rate, tidal volume, and minute ventilation. The displayed flow rate may include one or more of: average flow rate, current flow rate, peak flow rate, minimum measured flow rate, or other measurements related to breathing gas flow.

[0040] In FIG. 5 shows an example of a screen displaying the flow of breathing gas. The screen in FIG. 5 includes an indicator in the lower left corner showing the average and peak breathing gas flow rate. In FIG. 5 gauge ranges from 0.0 to 120 standard liters per minute. The black region of 2.0 to 60 liters per minute is the target range for breathing gas with 60 liters per minute being the upper limit and 2.0 liters per minute being the lower limit. White regions above 60 liters per minute and below 2.0 liters per minute may be regions where delivery accuracy may not be as expected, with dose set above 40ppm, or where an alarm or other notification is sent to the user so that the user is informed to make appropriate adjustments to the ventilator or iNO delivery system. The flow rate and the upper limit of flow may be adjusted depending on the sensitivity of the flow sensor and / or the injector module or depending on the patient being treated. As seen in FIG. 5, other information may also be displayed on the screen, such as the concentrations of O2, NO2 and NO that are administered to the patient. Additionally, in the screen shown in FIG. 5 Other parameters related to breathing gas flow and nitric oxide delivery can also be displayed, such as current breathing gas flow rate, minimum measured breathing gas flow rate, average nitric oxide dose amount, current nitric oxide dose amount, minimum and maximum nitric oxide dose amount, average nitrogen oxide flow rate, current nitrogen oxide flow rate, minimum and maximum nitrogen oxide flow rates, target delivered nitric oxide concentration, cylinder nitric oxide concentration, etc.

[0041] The CPU may also calculate the delivered concentration based on the measured flow rate of nitric oxide and the measured flow rate through the breathing circuit. The calculated delivered concentration can be compared to the delivered concentration set by the user to provide the calculated delivery as a percentage, with 100% being the ideal delivery. In some embodiments, the calculated delivery percentage and / or the calculated delivered concentration may be displayed on the screen as the calculated nitric oxide dose. For example, the percentage of calculated delivery may also be displayed on the screen as shown in FIG. 5 or the calculated delivery may be displayed as the NO concentration in ppm as shown in FIG. 7.

[0042] In FIG. 5 the calculated delivery indicator has a black target delivery region, a white over delivery region, and a white under delivery region. The delivery target region may include some accuracy tolerance for nitric oxide delivery, such as +/- 1%, +/- 2%, +/- 5%, +/- 10%, +/- 15%, +/- 20%, + / 25%, +/- 30%, +/- 35%, +/- 40%, +/- 45%, +/- 50%, +/- 55%, +/- 60%, +/- 65%, +/- 70%, +/- 75%, +/- 80%, +/- 85%, +/- 90%, +/- 95% or +/- 100%. If the calculated delivery is in the white overdelivery region or the white undelivering region, an alarm may sound or another user notification may be delivered. As with the displayed breathing gas flow, the calculated delivery can be displayed as present value, average value, minimum value and / or maximum value.

[0043] By providing a graphical inspiratory flow in conjunction with the graphical% delivery error, the user can set proportional NO flow control limits on the device. With this information in hand, the user can adjust the respiratory gas flow rate and / or the desired ppm dose to ensure that the nitric oxide delivery system is not operating outside of its delivery range. Thanks to the independent monitoring of the NO gas concentration, you can additionally compare the measured deviation with the set one. The under delivery of NO can then be compensated by the user up or down from the desired set dose.

[0044] Some current nitric oxide delivery systems have a maximum NO flow that can be delivered. For example, the nitric oxide delivery device may have a maximum NO flow of 6.35 l / min. This means that the maximum possible NO concentration delivered will vary depending on the ventilator flow rate and the concentration of nitric oxide in the therapy gas supply. For 800 ppm NO cylinders, the maximum possible NO concentration delivered will range from about 80 ppm at a constant flow of 60 l / min to about 40 ppm at a constant flow of 120 l / min. In FIG. 6 shows a NO delivered dose limitation for such a delivery system based on expected inspiratory flow rates from the ventilator. For example, when inspiratory flows are kept at greater than 120 l / min with a dose set above 60 ppm, under-delivery conditions may exist, as the maximum NO flow rate cannot deliver the required amount of NO to achieve a dose of 60 ppm. .

[0045] In FIG. 7 shows an example graphic display of the calculated dose of nitric oxide in the form of concentration in ppm. As can be seen, the calculated dose in ppm may be displayed as a graph indicating the concentration, but other means of displaying the calculated dose may be to display the calculated dose in ppm as an actual number, i.e. 26 ppm. Displaying the calculated dose as a concentration in ppm can be particularly useful when the nitric oxide delivery apparatus is in a hold mode in which the device does not provide proportional or relative nitric oxide delivery. For example, in some situations it may be necessary to provide a constant therapy gas flow that is independent of the respiratory gas flow rate, such as a therapy gas flow rate of 250 mL / min. In this maintenance mode, the device can calculate the nitric oxide dose based on the constant therapy gas flow rate and the measured respiratory gas flow rate. The device can assume that the constant therapy gas flow rate is a specific flow rate (ie, 250 ml / min) or that the constant flow rate of therapy gas can actually be measured. Since the therapy gas flow is constant and no longer dependent on the respiratory gas flow rate, the nitric oxide concentration delivered to the patient will vary with the respiratory gas flow rate (i.e., the sustaining therapy gas delivery is not proportional to the measured respiratory gas flow rate). Accordingly, it may be advantageous to provide an estimated maintenance dose based on a known therapeutic gas flow rate (which may be the assumed flow rate) and the measured respiratory gas flow rate.

[0046] In the constant therapy gas flow maintenance mode, it may be useful to display a graph or other graphical representation on the display to help the clinician predict what nitric oxide concentration will be appropriate for the particular respiratory gas flow rates. An example of such a plot is shown in the lower right corner of FIG. 7. Using this information, the clinician can set a specific flow rate or control the pressure on the ventilator to achieve the desired concentration of nitric oxide for delivery in maintain mode.

[0047] In some embodiments, the respiratory gas flow rate and / or the calculated nitric oxide dose is displayed on the main screen used with the therapy. However, in one or more other forms, the flow rate and / or the calculated dose do not appear directly on the main screen, but the user may access a screen that displays information such as respiratory flow rate history or current respiratory gas flow rate. The history of the respiratory flow rate can include peak and / or average flow rates for a specified period of time, such as a prior 5, 10, 15, 20, 30, or 45 seconds, a prior 1, 2, 5, 10, 15, 20, 30, 45 , 60 minutes or from the time of starting the administration of the current therapy. In some embodiments, the respiratory flow rate history is provided for a previous few seconds, such as about 10 seconds. The apparatus may include suitable components for calculating and storing respiratory flow history information, such as a CPU and memory. Likewise, the displayed calculated dose may be an actual, average, maximum and / or minimum value. Calculated dose history may include peak and / or average flow rates for a specific time period, such as prior 5, 10, 15, 20, 30, or 45 seconds, prior 1, 2, 5, 10, 15, 20, 30, 45, 60 minutes or from the time of starting the administration of the current therapy. In some embodiments, the calculated dose history is provided for a previous few seconds, such as about 10 seconds.

[0048] The apparatus may include an input device that receives input from a user. Such user inputs may include performance characteristics parameters such as desired nitric oxide concentration and flow limits. In one embodiment, the input device and the display device may be incorporated into a single unit, such as a touch screen device.

[0049] The respiratory gas supply system may include any system capable of supplying a respiratory gas supply to a patient. The respiratory gas may be supplied by a ventilation device, mechanically assisted ventilation or self-ventilation. Examples of suitable respirators include, but are not limited to, conventional respirators, nozzle ventilators, high frequency oscillating respirators, and continuous positive airway pressure (CPAP) devices. Non-invasive approaches to deliver breathing gas may also be used, including bubble CPAP, Synchronized Positive Inspiratory Airway Pressure (SiPAP), nasal tube, and high-flow heated nasal tube.

[0050] The therapy injector module combines the flow of respiratory gas and the flow of therapy gas. The Injector Module guarantees the correct delivery of inhaled nitric oxide in a fixed dose based on changes in the breathing gas flow thanks to the connection to the CPU.

[0051] In some embodiments, a nitric oxide delivery device is suitable for use with gentle ventilation strategies. Gentle ventilation can be a ventilator strategy that reduces shear stress and alveolar pressures while maintaining adequate oxygenation and ventilation to reduce lung damage and reduce long-term pulmonary complications. Gentle ventilation includes, but is not limited to: (1) maintaining adequate ventilation and oxygenation of the newborn; (2) limitation of pressure peaks during mechanical ventilation; (3) adjusting the pressure (s) in the ventilator necessary to maintain an adequate volume of the lungs without damaging them.

[0052] In some examples, gentle ventilation comprises reducing the inspiratory pressure sufficient to allow some permissive hypercapnia. Gentle ventilation may include, but is not limited to, the use of non-invasive ventilation (NIV) methods of breathing support to limit lung damage as the device and equipment deliver gas flow at lower pressures, thus eliminating high PIP (peak airway pressures) breathing into breathing, which increases the frequency of lung damage caused by shear and distension of the alveoli. Gentle ventilation may include bubble CPAP, SiPAP, HHHFNC (heated, humidified, high flow nasal cannula), and mechanical ventilation methods, with the intubated infant receiving PIP less than or equal to 20 cm H2O and oxygen saturation is 88-92%. For infants using HFOV or HJV, pressures are maintained to reduce lung damage. Equipment to maintain a gentle ventilation approach includes, but is not limited to, a nasal cannula, nasal whiskers, and NIV assist adaptive masks. Examples of suitable equipment for gentle ventilation are Neopuff® and High Flow Bubble CPAP available from Fisher & Paykel Healthcare, Inc. and products available in

Vapotherm, Inc ..

[0053] Another aspect of the invention relates to a system for delivering a therapeutic gas to a patient. The system includes: supplying nitrogen oxide therapy gas; a breathing gas supply system that supplies a patient with breathing gas and a therapy gas delivery device, the therapy gas delivery device comprising: a first inlet configured to be in fluid communication with a therapeutic gas supply, a second inlet configured to be in fluid communication with a respiratory gas delivery system, a therapy gas injector module to be placed in communication with the first inlet and a second inlet to provide a combined flow of respiratory gas; and therapeutic gas, an outlet in fluid communication with the injector module and configured to deliver respiratory gas and therapy gas to the patient; a control circuit in conjunction with a first flow sensor that measures respiratory gas flow from the respiratory gas supply system and a second sensor that measures therapy gas flow to determine a calculated nitric oxide dose from the therapy gas and respiratory gas flow rates; and a display for providing a visual and / or numerical indication of the calculated dose of nitric oxide.

[0054] FIG. 2 illustrates one embodiment of a system for delivering a therapeutic gas to a patient according to this aspect. The therapy injector module 203 is in fluid communication with the first inlet 201 and the second inlet 202. The first inlet 201 is in fluid communication with the therapy gas injector tube 210 which is in fluid communication with a supply of nitric oxide therapy gas. The second inlet 202 is in fluid communication with the respiratory gas supply system 211, which is illustrated as a respirator. The arrows in FIG. 2 indicate the flow direction of breathing gas and the combined gas, therapy gas and breathing gas mixture. The flow sensor 206 is a communication link to flow into and downstream of the second inlet 202 and monitors respiratory gas flow through the therapy injector module 203. A top view of the therapy injector module 203 is shown. Therapy gas and respiratory gas mix in the therapy injector module 203 to deliver the gas mixture. The line 205 of the injector module connects the therapy injector module 203 to the control module 209. A flow sensor 206 in the control module 209 measures the flow of therapy gas flowing through the therapy gas injector tube 210 to the therapy injector module 203. The control module 209 also includes a display 208 that can display real-time respiratory gas flow and / or a calculated nitric oxide dose and / or provide alarms when the respiratory gas flow rises above or falls below a predetermined level. The inspiratory breathing tube 212 is in fluid communication with the outlet 204 and nasal cannula 214. An inspiratory breathing tube supplies a gas mixture, respiratory gas, and therapy gas to the nasal cannula 214, which supplies the gas mixture to the patient. The gas sampling line 213 to the patient redirects a portion of the gas mixture flow from the inspiratory breathing tube 212 and leads it to the sampling block 219.

[0055] The sampling block 219, also known as the sampling pump, takes a portion of the gas mixture flow through the sampling line 213. As shown in FIG. 2, a sampling block 219 may be embedded in the control module 209. The sampling block analyzes the concentrations of nitric oxide, oxygen and nitrogen dioxide in the gas mixture. Typically the sampling block takes about 250 ml / min of the gas mixture. However, when the respiratory gas flow rate is close to 250 ml / min, withdrawing 250 ml / min of the gas mixture would leave little or no gas for delivery to the patient. Therefore, in one or more embodiments, the sampling block is modified to draw or aspirate volumes of combined therapy gas and respiratory gas such that the sampled gas per minute is less than or equal to 100 ml / min. In certain embodiments, the gas sampled sample is less than or equal to 50 ml / min. In further embodiments, the gas sample taken is less than or equal to 20 ml / min. The sampling block may have smaller pumps or more sensitive sensors to take samples with lower flow rates.

[0056] The concentration of nitric oxide, oxygen and nitrogen dioxide measured in the sampling block 219 may be displayed on the display 208. As a result of sampling a smaller amount of gas mixture, perhaps the refresh rate of the monitored values ​​will need to be faster with respect to the displayed values.

[0057] The therapy gas delivery apparatus in a therapeutic gas delivery system may include any or all of the previously described forms of the therapeutic gas delivery apparatus.

[0058] The respiratory gas supply system of the therapeutic gas delivery system may include any system capable of providing a respiratory gas supply to a patient. The respiratory gas may be supplied by any form of assisted ventilation device or by mechanically assisted ventilation or self-ventilation. Examples of suitable ventilation apparatuses include, but are not limited to, conventional respirators, jet ventilation respirators, high frequency oscillating ventilation respirators, and CPAP apparatuses. Non-invasive approaches, including CPAP bubble, SiPAP, nasal cannula, and high-flow heated nasal cannula, may also be used for breathing gas supply.

[0059] According to another aspect, there is provided a method of monitoring the delivery of therapeutic gas to a patient, the method comprising: providing a flow of respiratory gas; providing a nitrogen oxide therapy gas flow; breathing gas flow measurement; therapy gas flow measurement; supplying the patient with breathing gas and therapeutic gas; determining a calculated nitric oxide dose from the measured respiratory gas flow and the measured therapy gas flow or the known therapy gas flow, and displaying the calculated nitric oxide dose on the display module.

[0060] FIG. 3 shows a block diagram of one example of a method 300 for monitoring therapy gas delivery to a patient. Respiratory gas flow is delivered 301 to a delivery apparatus, such as a therapy injector module. Respiratory gas flow may be delivered from the ventilator to the injector module as described above. The flow of nitric oxide therapy gas is also supplied 302 to the delivery apparatus. The respiratory gas flow is measured 303 and this measured respiratory gas flow can be displayed 304 on the display module. Therapy gas flow is also measured 310. The measured flow rates of respiratory gas and therapy gases are then used to determine the calculated nitric oxide dose 311, then the calculated nitric oxide dose can be displayed 312. Instead of using a measured therapy gas flow rate, a known therapeutic gas flow rate may be used. The measured respiratory gas flow and / or the calculated nitric oxide dose can be compared 305 with a predetermined limit value. In FIG. 3 the predetermined limit is the lower limit. If the measured respiratory gas flow and / or the calculated dose is less than 306 the predetermined limit, an alarm is provided 307. Then, breathing gas and therapy gas are delivered to the patient. For example, the injector module may combine the flow of respiratory gas from the ventilator with the flow of therapy gas from the nitric oxide delivery device and deliver this combined flow to the patient. If the measured respiratory gas flow and / or the calculated dose are not less than 306 a predetermined limit, then the breathing gas and therapy gas are delivered 308 to the patient without delivering 307 an alarm. Each of the steps provided above is optional and the scope of any particular method is not limited by the particular combination shown in FIG. 3.

[0061] FIG. 4 shows a block diagram of other examples of a method 400 for monitoring therapy gas delivery to a patient. A flow of respiratory gas is provided 401 to the delivery apparatus and a flow of nitric oxide therapy gas is also provided 402. The respiratory gas flow is measured 403 and the measured respiratory gas flow may be displayed 404 on the display module. Therapy gas flow is also measured 410. The measured flow rates of the respiratory gas and the therapy gases are then used to determine the calculated NO dose 411, then the calculated NO dose can be displayed 412. The measured breathing gas flow and / or the calculated NO dose may be compared 405 with the defined limit value. which in FIG. 4 is the lower limit value. As in FIG. 3, if the measured respiratory gas flow and / or the calculated dose are less 406 than the predetermined limit, an alarm is provided 407. In response to the delivered alarm 407, the respiratory gas flow rate and / or the desired nitric oxide concentration can be adjusted 409. The breathing gas and nitric oxide therapy gas are then delivered 408 to the patient. If the measured respiratory gas flow and / or the calculated dose are not less than 406 the predetermined limit, then proceed directly to delivering 408 respiratory gas and NO therapy gas. Again, each of the above-provided steps is optional and the scope of each particular method is not limited by the particular combination shown in FIG. 4.

[0062] References in this specification to "one form", "specific forms", "one or more forms" or "forms" mean that the particular feature, structure, material, or characteristic described in conjunction with the form is included in the specification. at least one embodiment of the invention. Thus, the appearance of phrases such as "in one or more forms", "in certain forms", "in one form" or "as" in various places throughout this specification does not necessarily mean reference to the same embodiment of the invention. Additionally, specific features, structures, materials, or characteristics may be combined in any suitable manner in one or more forms. The order in which the method described above is described should not be considered a limitation and methods may use the steps described in a different order or with omissions or additions.

[0063] It is to be understood that the foregoing description is illustrative and not limiting. Many other embodiments will be apparent to those of ordinary skill in the art from the foregoing description. Accordingly, the scope of the invention should be determined with reference to the appended claims, along with the full range of equivalents to which such claims are entitled.