Therapeutic and diagnostic gas inhalation system and method of use - Patents.com

Abstract

To provide a system for delivering at least one therapeutic gas to a spontaneously breathing patient.SOLUTION: A system configured so as to administer at least one therapeutic gas to a patient includes at least one reservoir tube having a proximal end and a distal end, at least one therapeutic gas injection port, and a patient interface. The patient interface is configured so as to form an airtight seal between the patient and the system.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] Related Applications This application claims priority to U.S. Patent Application No. 62 / 287,652, entitled "SYSTEM FOR NITRIC OXIDE INHALATION," filed January 27, 2016, the entirety of which is incorporated herein by reference for all purposes.

[0002] The present invention relates to a system for delivering at least one therapeutic gas to a spontaneously breathing patient, where the delivery rate of the at least one therapeutic gas exceeds the patient's inspiratory flow rate and where waste of a quantity of the at least one therapeutic gas is minimized or eliminated. [Background technology]

[0003] Inconsistent and inaccurate concentrations of therapeutic gas provided to a patient can reduce the effectiveness of the therapeutic gas administered to the patient. Summary of the Invention

[0004] In one embodiment, the present invention provides a system configured to administer at least one therapeutic gas to a patient, comprising: a. at least one reservoir tube having a proximal end and a distal end, the at least one reservoir tube having a volume greater than a tidal volume of a patient's breath; b. at least one therapeutic gas inlet at a proximal end of the at least one reservoir tube, a delivery tube connected to the at least one therapeutic gas inlet and to the at least one therapeutic gas source; c. a patient interface fluidly connected to a proximal end of the at least one reservoir tube via a check valve; Equipped with the patient interface is configured to form an airtight seal between the patient and the system; the inhalation check valve is configured to close when the patient is exhaling; at least one therapeutic gas is introduced into the at least one reservoir tube at a proximal end through the at least one therapeutic gas inlet at a time-averaged flow rate greater than a time-averaged inhalation flow rate of a patient, the at least one therapeutic gas flowing along the at least one reservoir tube from the proximal end to the distal end while the patient is exhaling; a volume of the at least one therapeutic gas introduced into the at least one reservoir tube while the patient is exhaling is greater than a tidal volume of the patient's inhalation; the inhalation check valve is configured to open when the patient is inhaling; The inhalation check valve provides a system configured to allow at least one therapeutic gas to be administered to a patient.

[0005] In one embodiment, the system further comprises a second check valve, the second check valve configured to close while the patient is inhaling and to open while the patient is exhaling, the system configured such that the second check valve allows gas exhaled by the patient to be exhausted.

[0006] In one embodiment, a system configured to administer at least one therapeutic gas to a patient is configured to minimize the effort required by the patient to inhale, exhale, or inhale and exhale.

[0007] In one embodiment, the at least one reservoir tube is further configured to minimize the effort required by the patient to inhale, exhale, or inhale and exhale.

[0008] In one embodiment, the system configured to administer at least one therapeutic gas to a patient is further configured to monitor a flow of gas through a proximal end of the at least one reservoir tube.

[0009] In one embodiment, the system configured to administer at least one therapeutic gas to a patient is further configured to monitor at least one parameter of a flow of gas through a proximal end of the at least one reservoir tube; The at least one parameter includes a concentration, a flow, a contamination, or any combination thereof.

[0010] In one embodiment, at least one reservoir tube further comprises a flow meter at a distal end.

[0011] In one embodiment, at least one reservoir tube further comprises a flow meter responsive to the flow rate and direction of flow in the reservoir, and may be conveniently located at the distal end of the reservoir.

[0012] In one embodiment, a system is configured to administer at least one therapeutic gas to a patient and is further configured to monitor at least one parameter of the at least one therapeutic gas introduced to the system configured to administer the at least one therapeutic gas to the patient, the at least one parameter including a concentration, a flow rate, a flow volume, a contamination level, or any combination thereof.

[0013] In one embodiment, at least one reservoir tube further comprises a sampling port at a proximal end.

[0014] In one embodiment, the sampling port is configured to deliver gas to a patient, monitor gas delivered to a patient, characterize gas delivered to a patient, or any combination thereof, hi one embodiment, the gas is characterized by content, contaminant level, flow rate, flow volume, concentration, or any combination thereof.

[0015] In one embodiment, the system configured to administer at least one therapeutic gas to a patient is further configured to issue an alert if any one monitored value of the concentration, at least one therapeutic gas, or corresponding flow rate deviates from a threshold value. As used herein, a threshold value can include above, below, or a combination of both above and below a boundary, each of which the monitored value is evaluated to determine if an alert condition exists. As a non-limiting example, upper and lower thresholds of acceptable therapeutic levels of oxygen concentration can be used in the system to alert an operator if either a hyperoxic or hypoxic respiratory mixture is being delivered.

[0016] In one embodiment, the system configured to administer at least one therapeutic gas to a patient is further configured to alter the flow rate and / or concentration of the at least one therapeutic gas if any one monitored value of the characteristic, or flow rate, of the at least one therapeutic gas deviates from at least one threshold value.

[0017] In one embodiment, the at least one therapeutic gas comprises nitric oxide, helium, carbon dioxide, hyperoxic gas, hypoxic gas, tracer gas, or a combination thereof. In one embodiment, the concentration of nitric oxide is 160 ppm in a mixture of oxygen and nitrogen. In one embodiment, the at least one therapeutic gas is nitric oxide. In one embodiment, the nitric oxide is at a concentration of 400 ppm to 0.5 ppm.

[0018] In some embodiments, at least one therapeutic gas is a diagnostic gas.

[0019] In some embodiments, the at least one therapeutic gas is oxygen. [Brief description of the drawings]

[0020] [Figure 1]1 shows a graph depicting a typical volume of air in the lungs during a typical inhalation cycle of a patient in need of the treatment methods described herein. [Figure 2(a)] 1 illustrates operation of a gas delivery system according to some embodiments of the present invention at key points throughout a patient's breathing cycle. [Figure 2(b)] 1 illustrates operation of a gas delivery system according to some embodiments of the present invention at key points throughout a patient's breathing cycle. [Figure 2(c)] 1 illustrates operation of a gas delivery system according to some embodiments of the present invention at key points throughout a patient's breathing cycle. [Figure 2(d)] 1 illustrates operation of a gas delivery system according to some embodiments of the present invention at key points throughout a patient's breathing cycle. [Diagram 3] 1 illustrates a gas delivery system according to some embodiments of the present invention, where a patient breathes into the proximal end of a reservoir through a mouthpiece. [Figure 4] 1 illustrates a gas delivery system according to some embodiments of the present invention, where a patient breathes through a nose mask. [Figure 5(a)] 1 illustrates a gas delivery system according to some embodiments of the present invention, the gas delivery system being configured with both an inlet check valve and an outlet check valve. [Figure 5(b)] 5(a) and 5(b) show a gas delivery system according to some embodiments of the present invention, the gas delivery system being configured with both an inhalation check valve and an exhalation check valve. Alternative patient connections are shown in FIG. [Figure 6] 1 illustrates a gas delivery system according to some embodiments of the present invention, the delivery system being configured with both inhalation and exhalation check valves, as well as an exhalation exhaust tube to direct exhaust air away from the patient. [Figure 7] 1 illustrates a gas delivery system according to some embodiments of the present invention, where the therapeutic gas includes two components that are delivered separately to the proximal end of the reservoir and injected separately into the reservoir. [Figure 8]Some embodiments of the present invention provide a gas delivery system in which a reservoir is formed from two or more tubes and two or more gases are individually delivered to the reservoir. [Figure 9] 1 shows a gas delivery system according to some embodiments of the present invention, where the reservoir is made from multiple small tubes that provide the total volume required. This diagram also introduces both a sample port and a sample line that allows a small amount of gas present at the proximal end of the reservoir to be withdrawn for analysis and monitoring. This sample port is placed just distal to the inhalation valve, effectively isolating it from the patient's exhaled gas. [Figure 10] 1 illustrates a gas delivery system according to some embodiments of the present invention, in which a long reservoir tube is coiled to reduce its physical size. [Figure 11] 11 shows a gas delivery system according to some embodiments of the present invention, where multiple source gases forming the final treatment mixture are mixed prior to injection into the proximal end of the reservoir. FIG. 11 highlights a configuration using a nose mask and one inhalation check valve, where the patient is trained to inhale through the nose and exhale through the mouth. [Figure 12] 1 shows a gas delivery system according to some embodiments of the present invention, where multiple source gases forming the final therapeutic mixture are mixed prior to injection into the proximal end of the reservoir. FIG. 12 shows an embodiment using a face mask in combination with a double check valve "tee", where the tee incorporates inhalation and exhalation check valves that direct inhaled and exhaled gases. [Figure 13] 13 shows a gas delivery system according to some embodiments of the present invention, in which multiple source gases forming the final therapeutic mixture are mixed prior to injection into the proximal end of the reservoir, similar to FIG. 12, but alternatively configured with a nose mask, allowing the patient to optionally exhale through the mouth to reduce exhalation effort. [Figure 14]13 shows a gas delivery system according to some embodiments of the present invention, in which multiple source gases forming a final therapeutic mixture are mixed prior to injection into the proximal end of the reservoir, similar to FIG. 12, but alternatively configured with a mouthpiece to allow the patient to optionally exhale through the nose to reduce exhalation effort. [Figure 15] 1 shows a gas delivery system according to some embodiments of the present invention, in which a variation of a face mask with inhalation and exhalation check valves is fed from a reservoir with an injection port, said injection port being provided with a combined source of a steady flow of oxygen-enriched air and a steady flow of NO. [Figure 16] 1 illustrates a gas delivery system according to some embodiments of the present invention, in which one or more therapeutic gases are mixed with one or more diluent gases, and the mixed gases meet in a mixing region before being injected into a reservoir. [Figure 17] 1 illustrates a gas delivery system according to some embodiments of the present invention, in which multiple input gas streams are mixed to create an overall therapeutic gas mixture injected into a reservoir, with the individual gas streams being generated by a flow metering system comprising a single unit. [Figure 18] 1 illustrates a gas delivery system according to some embodiments of the present invention, in which two incoming steady gas streams are mixed to create an overall therapeutic gas mixture injected into a reservoir, the first steady gas stream being generated by an oxygen-rich air mixer and the second steady stream being generated by an NO flow metering device. [Figure 19] 1 illustrates a gas delivery system according to some embodiments of the present invention, in which multiple incoming steady streams of gas are separately injected into the proximal end of a reservoir. [Figure 20] 5(a) shows a gas delivery system according to some embodiments of the present invention, in which the configuration shown in FIG. 5(a) has been modified by adding a sample port between the inhalation and exhalation check valves that provides a means for sampling gas inhaled and exhaled by the patient. [Figure 21]1 illustrates a gas delivery system according to some embodiments of the present invention, wherein at least one reservoir tube is configured to further include a flow meter at a distal end, said flow meter being responsive to the flow rate and direction of flow in at least one reservoir. [Figure 22] 1 illustrates a gas delivery system according to some embodiments of the present invention, in which a reservoir is configured to function as part of a therapeutic gas delivery system configured to determine an average infusion flow rate requirement, the average infusion flow rate requirement being determined from a gas flow in the reservoir over a time frame of at least one patient breathing period, the average infusion flow rate requirement being used to periodically adjust the average infusion flow rate of at least one therapeutic gas. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] For clarity of disclosure, and not by way of limitation, the detailed description of the invention is divided into the following subsections that describe or illustrate particular features, embodiments or applications of the invention.

[0022] In some embodiments, the present invention provides a system for delivering at least one therapeutic gas to a spontaneously breathing patient, where an average delivery rate of the at least one therapeutic gas meets or exceeds an average inspiratory flow rate of the patient, hi some embodiments, the amount of the at least one therapeutic gas that is wasted is minimized or eliminated.

[0023] In some embodiments, the present invention provides a system configured to administer at least one therapeutic gas to a patient, comprising: a. at least one reservoir tube having a proximal end and a distal end, the at least one reservoir tube having a volume greater than a patient's tidal volume; b. at least one therapeutic gas inlet at a proximal end of the at least one reservoir tube, a delivery tube connected to the at least one therapeutic gas inlet and to the at least one therapeutic gas source; c. a patient interface fluidly connected to a proximal end of the at least one reservoir tube via a check valve; Equipped with the patient interface is configured to form an airtight seal between the patient and the system; the inlet side of the check valve is configured to close when the patient is exhaling; at least one therapeutic gas is introduced through at least one therapeutic gas inlet into at least one reservoir tube at the proximal end at a time averaged flow rate greater than the patient's time averaged inhalation flow rate (patient minute ventilation), and the at least one therapeutic gas flows along the at least one reservoir tube from the proximal end to the distal end while the patient is exhaling; a volume of at least one therapeutic gas introduced into the at least one reservoir tube while the patient is exhaling is greater than the tidal volume of the patient's inhalation; the inhalation check valve is configured to open when the patient is inhaling; The inhalation check valve provides a system configured to allow at least one therapeutic gas to be administered to a patient.

[0024] In some embodiments, the at least one reservoir is configured to allow therapeutic gas to flow between the proximal and distal ends as a steady infusion flow that is alternately higher and lower than the instantaneous patient inhalation flow, hi some embodiments, the at least one reservoir is configured to move the therapeutic gas substantially without mixing in a longitudinal flow direction.

[0025] In some embodiments, the flow channels of the reservoirs can typically have a cross-section having a shape, which can be, but is not limited to, a circle, an oval, an octagon, a square, a rectangle, a hexagon, and the like.

[0026] The following symbols, as defined herein, are shown in the drawings:

number

number

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[0027] FIG. 1 shows a graph depicting a typical volume of air inside the lungs during a typical inhalation cycle of a patient. Tidal volume may vary depending on factors such as the patient's age, the patient's health, the patient's size, etc. As used herein, "tidal volume" refers to the lung volume that represents the normal volume of air moved between normal inspiration and expiration when no extra effort is applied. Thus, tidal volume is the maximum volume taken in by the end of normal gentle inhalation. As a non-limiting example, in a healthy young human adult, the tidal volume is approximately 500 mL per inspiration or 7 mL / kg of body weight. Correspondingly, "minute ventilation" refers to the volume of air that is moved between normal inspiration and expiration when no extra effort is applied. JPEG0007672308000004.jpg1014 indicates the total respiratory volume per minute, which is the number of breaths per minute multiplied by the tidal volume per minute. For example, a patient breathing 20 breaths per minute with a tidal volume of 500 mL will have a tidal volume of 10 LPM (= 20 / min x 500 mL). JPEG0007672308000005.jpg1114 has.

[0028] FIG. 2 illustrates the operation of a device according to some embodiments of the present invention during a typical respiratory cycle of a patient. In panel a) of FIG. 2, the patient is exhaling and the check valve labeled "inhalation check valve" is closed, preventing gas exhaled by the patient from entering the at least one reservoir tube. Instead, gas exhaled by the patient is exhausted from the system via the check valve labeled "exhalation check valve". At least one therapeutic gas enters the system through an inlet port located on the reservoir side of the inhalation check valve at the proximal end of the at least one reservoir tube and flows towards the distal end of the at least one reservoir tube, which is open to a neutral pressure, in this case the surrounding room air.

[0029] In panel b) of FIG. 2, the patient is inhaling, the check valve labeled "inhalation check valve" is open, and at least one therapeutic gas in at least one reservoir tube, and at least one therapeutic gas simultaneously entering the system, is inhaled at a rate JPEG0007672308000006.jpg1110 , allowing ambient air to enter the patient's airway via the inlet port. A check valve labeled "exhaust check valve" closes to prevent the patient from inhaling ambient air. When the patient inhales, ambient air at neutral pressure is inhaled and enters the distal end of the at least one reservoir tube. However, the at least one reservoir tube is configured to prevent the incoming ambient air from unduly mixing with and diluting the at least one therapeutic gas present within the reservoir tube.

[0030] In panel c) of FIG. 2, the patient is near the end of an inhalation cycle, and the check valve labeled "inhalation check valve" is still at least partially open, allowing at least one therapeutic gas in the at least one reservoir tube to enter the system through the inlet port to enter the patient's lungs. The check valve labeled "exhalation check valve" is closed, still preventing the patient from inhaling ambient air. However, there is still a small amount of at least one therapeutic gas remaining in the proximal end of the at least one reservoir tube. At this point in the patient's breathing cycle, the inhalation phase is about to end and the exhalation phase is about to begin.

[0031] In panel d) of FIG. 2, the patient transitions to exhalation and the check valve labeled "inhalation check valve" closes, preventing the gas exhaled from the patient's lungs from entering the at least one reservoir tube. Instead, the gas exhaled by the patient contains the exhaust component of the at least one therapeutic gas and is exhausted from the system via the check valve labeled "exhalation check valve". During exhalation, the at least one therapeutic gas continues to enter the system via the aforementioned inlet port, and the at least one therapeutic gas refills the at least one reservoir tube in preparation for the patient's next breath, the refilling action proceeding from the proximal end of the at least one reservoir tube toward the distal end of the neutral pressure. The incoming fresh at least one therapeutic gas displaces the remaining residual therapeutic gas and the remaining ambient air from the last inhalation cycle toward the distal end of the at least one reservoir tube, causing them to empty from the at least one reservoir tube. In some embodiments, when the inhalation check valve is closed, the at least one reservoir tube is simultaneously refilled.

[0032] In some embodiments, the systems of the present invention are configured to provide a safety mechanism for the patient that allows the patient to breathe ambient air if flow of therapeutic gas to the system is interrupted in accordance with some embodiments of the present invention.

[0033] In some embodiments, the reservoir tube is "open" longitudinally (e.g., at the two ends of a hose) rather than along the perimeter of its cross-sectional shape. In some embodiments, the flow passage is not a "U" shape or other open sided shape that allows air to enter along the side of the reservoir.

[0034] In some embodiments, the at least one therapeutic gas is a mixture of at least two gases, and the mixture of at least two gases is inhaled by the patient using a system according to some embodiments of the present invention.

[0035] Thus, in some embodiments shown in FIGS. 2A-2D, the instantaneous amplitude JPEG0007672308000007.jpg1019 The therapeutic gas inhaled by a patient with JPEG0007672308000008.jpg1010 and a freshly stored therapeutic gas along the entire length of at least one reservoir tube in preparation for inhalation, which includes: JPEG0007672308000009.jpg1120 The instantaneous amplitude of at least one therapeutic gas flow injected JPEG0007672308000010.jpg109 However, since the therapeutic gas stored in the reservoir and the newly supplied therapeutic gas have equal compositions, the two mixtures will have similar compositions. Thus, the therapeutic gas inhaled by the patient will have a consistent composition throughout each inhalation cycle, which is also substantially the same as the composition of the therapeutic gas initially injected.

[0036] In some embodiments, JPEG0007672308000011.jpg98 The at least one reservoir tube is configured to generate a slight net outflow of the at least one therapeutic gas from the distal end of the at least one reservoir tube. In some embodiments, the net outflow acts to expel the "oldest" residual gas charge remaining after a previous inhalation of the at least one therapeutic gas from the at least one reservoir tube, reducing or eliminating potential accumulation of toxic contaminants, such as NO2, in the at least one reservoir tube. Furthermore, the patient breathes a substantially consistent concentration of the at least one therapeutic gas, with the net outflow tending to flush the at least one reservoir tube from one breath to the next. In this situation, the expected total minute ventilation JPEG0007672308000012.jpg912 A small net outflow is introduced by providing some margin, such as 3%-10% of the total minute ventilation (to supply the patient's respiratory needs), to allow for a desired small net outflow surge. In some embodiments, the measured concentrations stabilize within a few percent of the initial start-up setting and are within 5% of the ideal 160 ppm concentration. In some embodiments, the accuracy of the calibration of the flowmeter and gas analyzer used to assess the in-treatment concentrations was about + / - 3% for the concentration values ​​disclosed, so the measurements will vary in concentration relative to themselves over the course of a 30 minute treatment. In some embodiments, the treatment fluctuated by about 3% overall over the course of the 30 minutes.

[0037] Systems according to some embodiments of the present invention are adapted to deliver at least one therapeutic gas to a patient according to the configuration of the patient's airway using a particular patient interface. For example, in some embodiments, the patient inhales through the nose and exhales through the mouth, while in other embodiments, the patient inhales through the mouth and exhales through the nose. Also, for example, the patient can inhale and exhale through either the mouth or the nose alone.

[0038] In some embodiments, the patient is trained to inhale through one airway opening and exhale through a different airway opening, for example, the patient may be trained to inhale through the mouth and exhale through the nose.

[0039] In some embodiments, the patient interface forms an air-tight seal between the patient and the system.

[0040] In some embodiments, the patient interface is a patient interface selected from the group consisting of, but not limited to, a full face mask, a nasal mask, a mouthpiece, and a pillow seal nasal cannula.

[0041] In some embodiments, the systems of the present invention are configured to provide an anti-asphyxiation feature, the anti-asphyxiation feature comprising an open distal end of at least one reservoir tube placed in a neutral pressure breathable atmosphere, in some embodiments, the system is configured to allow the patient to inhale ambient air when at least one therapeutic gas of the system stops entering the system.

[0042] In some embodiments, the systems of the present invention are configured to move at least one therapeutic gas back and forth within a reservoir, for example, "first in, last out," shuttling the gas back and forth within the reservoir tube without significant vertical mixing.

[0043] In some embodiments, the patient interface is held in place by the patient, or in some embodiments, the patient interface is attached to the patient, for example, via an elastic strap placed over the patient's head.

[0044] In some embodiments, at least one reservoir tube has a smooth inner surface. In some embodiments, at least one reservoir tube has a rough inner surface.

[0045] In some embodiments, at least one reservoir tube has a uniform cross-section along its entire length.

[0046] In one example, and with reference to FIG. 3, in some embodiments, the present invention provides a system configured to administer at least one therapeutic gas to a patient, comprising: a. at least one reservoir tube having a proximal end and a distal end, the at least one reservoir tube having a volume greater than a patient's tidal volume; b. at least one therapeutic gas inlet at a proximal end of the at least one reservoir tube, a delivery tube connected to the at least one therapeutic gas inlet and to the at least one therapeutic gas source; c. a patient interface fluidly connected to a proximal end of the at least one reservoir tube via a check valve; Equipped with the patient interface is configured to form an airtight seal between the patient and the system; the patient interface being a mouthpiece configured to form an airtight seal when the patient purses their lips; the inhalation check valve is configured to close when the patient is exhaling; At least one therapeutic gas is introduced through the at least one therapeutic gas inlet into the at least one reservoir tube at the proximal end at a rate greater than the patient's minute ventilation, the at least one therapeutic gas flows along the at least one reservoir tube from the proximal end to the distal end while the patient is exhaling; The check valve is configured to open when the patient is inhaling, providing a system configured to allow at least one therapeutic gas to be administered to the patient.

[0047] 3, the check valve may be removed and the system configured to allow the patient to breathe through the mouth and breathe out through the nose. Thus, in this exemplary embodiment, the patient influences the inhalation check valve function.

[0048] In another example, and with reference to FIG. 4, in one example, in some embodiments, the present invention provides a system configured to administer at least one therapeutic gas to a patient, comprising: a. at least one reservoir tube having a proximal end and a distal end, the at least one reservoir tube having a volume greater than a patient's tidal volume; b. at least one therapeutic gas inlet at a proximal end of the at least one reservoir tube, a delivery tube connected to the at least one therapeutic gas inlet and to the at least one therapeutic gas source; c. a patient interface fluidly connected to a proximal end of the at least one reservoir tube via a check valve; Equipped with the patient interface is configured to form an airtight seal between the patient and the system; the patient interface being a nasal mask configured to form an airtight seal when placed over the patient's nose; the check valve is configured to close when the patient is exhaling; At least one therapeutic gas is introduced through the at least one therapeutic gas inlet into the at least one reservoir tube at the proximal end at a rate greater than the patient's minute ventilation, the at least one therapeutic gas flows along the at least one reservoir tube from the proximal end to the distal end while the patient is exhaling; The check valve is configured to open when the patient is inhaling, providing a system configured to allow at least one therapeutic gas to be administered to the patient.

[0049] In another example, with reference to FIG. 5A, in some embodiments, the present invention provides a system configured to administer at least one therapeutic gas to a patient, comprising: a. at least one reservoir tube having a proximal end and a distal end, the at least one reservoir tube having a volume greater than a patient's tidal volume; b. at least one therapeutic gas inlet at a proximal end of the at least one reservoir tube, a delivery tube connected to the at least one therapeutic gas inlet and to the at least one therapeutic gas source; c. a patient interface fluidly connected to a proximal end of the at least one reservoir tube via a first check valve; Equipped with the patient interface is configured to form an airtight seal between the patient and the system; the patient interface is a face mask configured to cover the patient's mouth and nose and form an airtight seal when placed over the patient's nose and mouth; the first check valve is configured to close when the patient is exhaling; At least one therapeutic gas is introduced through the at least one therapeutic gas inlet into the at least one reservoir tube at the proximal end at a rate greater than the patient's minute ventilation, the at least one therapeutic gas flows along the at least one reservoir tube from the proximal end to the distal end while the patient is exhaling; a volume of at least one therapeutic gas introduced into the at least one reservoir tube while the patient is exhaling is greater than the patient's tidal volume; the first check valve is configured to open when the patient is inhaling to allow the at least one therapeutic gas to be administered to the patient; The patient interface further comprises a second check valve; the second check valve is configured to close when the patient is inhaling and to open when the patient is exhaling; A second check valve provides the system with the ability to allow gas exhaled by the patient to exit the system.

[0050] In some embodiments, the system of the present invention is configured to deliver at least one therapeutic gas or at least one diagnostic gas through a mouthpiece, for example as shown in FIG. 5b.

[0051] In some embodiments, the systems of the present invention are configured to deliver a substantially constant mixture of diagnostic or therapeutic gas in combination with other dilutable breathable gases to a spontaneously breathing patient during the inhalation portion of a breath; The flow of each constituent source gas that is part of the final mixture can be set at a constant rate appropriate to the desired final concentration of the final inhalation mixture; Such source gases may be injected individually or jointly into one or more junctions and ultimately into a proximal end of a reservoir that provides a temporary storage area for inflows not required for patient inhalation, such reservoir having a high order length to cross-sectional aspect ratio that effectively shuttles the gas along its entire length without undue mixing in the longitudinal flow direction; a means for attaching the proximal end of the reservoir to the patient's airway, allowing the patient to inhale freely from the convergence of the proximal end of the reservoir and the injected source gas, but preventing any patient exhaled air from flowing back into the reservoir; The distal end of said conductive reservoir opens into a neutral pressure region in which substantially clean breathable air is present.

[0052] In some embodiments, the sum of the constant individual source rate flows exceeds the time-averaged patient inhalation flow, and therefore a net outflow of gas is present at the distal end of the reservoir. This excess is

number

[0053] In some embodiments, the net outflow or inflow of gas at the distal end of the reservoir is monitored to ensure that ambient air is not typically inhaled by the patient, in which case:

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[0054] In some embodiments, the volume of the reservoir is slightly larger than a typical tidal volume of a patient.

[0055] In some embodiments, the sum of the constant individual source rate flows exceeds the time-averaged patient inhalation flow, and therefore a net outflow of gas is present at the distal end of the reservoir.

[0056] In some embodiments, the sum of the constant individual source rate flows exceeds the time-averaged patient inhalation flow by a small percentage, and therefore the net outflow gas is present at the distal end of the reservoir which should flush the older gas reservoir.

[0057] In some embodiments, the net outflow or inflow of gas at the distal end of the reservoir is monitored by a flow meter.

[0058] In some embodiments, the therapeutic or diagnostic source gas contains a higher concentration of nitric oxide than is required for effective patient delivery, and such gas is diluted with a diluent gas and delivered by the device at a selected constant concentration between 400 ppm and 0.5 ppm, the remainder being air or air enriched with oxygen.

[0059] In some embodiments, two or more types of therapeutic or diagnostic gases are mixed via additional injection points to achieve constant concentrations of two or more target gases during inhalation by the same patient.

[0060] In some embodiments, means for preventing backflow of exhaled patient breath into at least one reservoir tube is provided by a directional flow check valve disposed between the patient's airway, the coupled proximal outlet of the reservoir tube, and the source gas injection point.

[0061] In some embodiments, the means for preventing the patient's exhaled breath from flowing back into the reservoir involves the patient training a breathing pattern in which they alternate between breathing through only the mouth and nose, but not the other, and then alternate between breathing through only the mouth and nose, but not the other.

[0062] In some embodiments, the reservoir is formed from a single long flow passageway with a volume sufficient to equal or exceed the patient's tidal volume, while at the same time having a cross-section sufficient to provide low effort of breathing.

[0063] In some embodiments, the reservoir has a sufficient infusion flow rate such that the gas stored in the at least one reservoir tube is not exhausted before the end of the patient's inhalation. JPEG0007672308000015.jpg810 However, during the patient's inhalation, JPEG0007672308000016.jpg818 The flow rate may be smaller than the patient's tidal volume, but only if sufficient flow is provided to supply

[0064] In some embodiments, the reservoir is formed from multiple parallel flow channels, each individually exhibiting a high order length vs. cross-sectional extent aspect, with each individual flow channel circulating any gases through the channel in a manner that inhibits longitudinal mixing of the gases, but such that the parallel ensemble provides a total volume sufficient to equal or exceed the patient's tidal volume.

[0065] In some embodiments, the present invention is a delivery device configured to provide a breathable mixture of gases including a therapeutic or diagnostic gas and a diluent gas, where a constant ratio of components is desired during inhalation by a spontaneously breathing patient, comprising: a source of one or more steady flows of the therapeutic or diagnostic source gas and the diluent gas injecting into one or more adjacent gas ports located at a proximal end of a reservoir; The reservoir is formed from one or more parallel channels that are long compared to their cross-sectional extent, a distal end of the reservoir is open to a source of breathable gas at ambient pressure; The net volume of the reservoir is equal to or greater than the patient's inhaled tidal volume, the sum of all injected flows of therapeutic gas and diluent gas is equal to or greater than the patient minute flow rate; The proximal end of the reservoir and the insufflation port are connected to a conduit that connects to the patient's airway with an airtight seal.

[0066] In some embodiments, the patient's airway is separated from the proximal end of the reservoir and the gas injection point by a directional check valve.

[0067] In some embodiments, any insufflated flow that exceeds the patient's minute ventilation is exhausted from the distal end of the reservoir without restriction.

[0068] In some embodiments, one of the injected constant gas streams carries a fixed ratio of nitric oxide, said nitric oxide in the injected stream being at a higher concentration than required for patient treatment, and the final mixed nitric oxide for patient treatment is adjustable in the range of 400 ppm to 0.5 ppm, delivered with a dilution balance of air or oxygen-enriched air.

[0069] In some embodiments, the diagnostic gas comprises a tracer gas, including but not limited to helium, hydrogen, sulfur hexafluoride, carbon monoxide, or combinations thereof.

[0070] In some embodiments, the device includes a flow port with an outward flow check valve to exhaust the patient's exhaled breath.

[0071] In some embodiments, the distal end of the reservoir is equipped with a flow monitor capable of assessing the net flow of gas into and out of the distal end of the reservoir, hi some embodiments, the distal flow assessment can be performed automatically, manually, or any combination thereof.

[0072] In some embodiments, the device of the present invention further comprises at least one alarm, at least one monitor, or any combination thereof, such as, but not limited to, those related to constituent gas flow rates, gas concentrations, total flow rates, total volumes, contamination levels, humidity, temperature, time, or any combination thereof.

[0073] In some embodiments, the at least one monitor is configured to notify at least one entity (e.g., without limitation, a caregiver (e.g., without limitation, a doctor, nurse, parent, etc.), a medical provider, a knowledgeable patient) if at least one of the following conditions is met: the sum of the individual constant source rate flows does not exceed the time averaged patient inhalation flow; if the net outflow or inflow of gas at the distal end of the reservoir allows the patient to inhale ambient air; if the volume of the reservoir is depleted during the course of a typical inhalation by the patient; if the sum of the individual constant source rate flows does not exceed the time averaged patient inhalation flow by a small percentage; if the fixed concentration is not within a predetermined range established as part of the intended treatment; if reflux of the patient's breath is detected; if the total duration of the treatment is shorter or longer than the prescribed time by a predetermined time; or any combination thereof. In some embodiments, the at least one alarm is configured to alert at least one entity (e.g., a caregiver, a medical provider, etc.) if the at least one monitor identifies at least one of the conditions described herein.

[0074] In some embodiments, the devices of the present invention can be used to treat a single subject or can be reused sequentially for multiple subjects. In some embodiments, treatment can be utilized within a hospital environment or outside of a hospital environment (e.g., but not limited to, at home, airports, malls, public health clinics, quarantine facilities, etc.).

[0075] In some embodiments, an exhaust manifold may be required to transport the exhaled gases to an analysis, exhaust, disposal or decontamination area, as shown in FIG.

[0076] In some embodiments, the composition of the exhaled gas can be analyzed to assess the patient's uptake of components of the therapeutic or diagnostic tracer gas, or residual components of the therapeutic gas. In some embodiments, the exhaled gas may contain contaminants that require treatment before entering the environment. For example, exhaled residual components and contaminants may include gases such as unabsorbed NO, NO2 produced as a by-product of NO, infectious particulates, or radioactive materials.

[0077] At least one reservoir tube Typical tidal volumes for human patients range from 3 ml / kg (e.g., but not limited to, pediatric) to 5 ml / kg (e.g., but not limited to, adult) body weight. In some embodiments, typical tidal volumes for human patients range from 50 mL (e.g., but not limited to, pediatric) to 750 mL (e.g., but not limited to, adult).

[0078] In some embodiments, the at least one reservoir tube is configured to hold a sufficient amount of at least one therapeutic gas to support flow during patient inhalation. In some embodiments, the sufficient volume of the at least one therapeutic gas is equal to the patient's tidal volume. In some embodiments, the sufficient volume is equal to 100%+x% of the patient's tidal volume, where x% is a portion of the tidal volume (e.g., not limited to 10%), such that the reservoir is sized to store 110% of the patient's tidal volume. In some embodiments, the length, and therefore the volume, of the at least one reservoir tube is intended to be tailored to suit the characteristics of a particular patient. In some embodiments, the infused flow is intended to be tailored to suit the characteristics of a particular patient. In some embodiments, the at least one reservoir tube volume and the infused flow rate are intended to be tailored to suit the characteristics of a particular patient. JPEG0007672308000017.jpg1010 Both are intended to be tailored to suit the characteristics of a particular patient.

[0079] In some embodiments, at least one reservoir tube comprises a tube having a smooth inner wall surface and a high length to cross-sectional extent ratio. In some embodiments, at least one reservoir tube has a sufficiently rounded aspect and a uniform inner diameter, the uniform diameter being a small fraction of the length of the reservoir (e.g., but not limited to, 0.5% to 5% of the length of the reservoir).

[0080] Thus, by way of example, for a 100 kg patient with a tidal volume of 500 mL, using at least one reservoir tube with an inner diameter of 19 mm, the length of the at least one reservoir tube to hold 550 mL (e.g., a reservoir volume with a margin of 10% above the tidal volume) can be calculated as follows: [Table 1]

number

[0081] So a 1.76 metre reservoir tube with an internal diameter of 19mm will give an internal reservoir volume of 500mL. To create a 10% margin volume, the length needs to be increased to 1.94 metres (thus increasing the reservoir to 550mL).

[0082] In some embodiments, multiple tubes operating in parallel can form a reservoir, which may have a shorter overall length while still holding a sufficient volume of at least one therapeutic gas. These parallel tube arrays can include two parallel tubes, or can extend to multiple parallel tubes of smaller diameter. Examples of these embodiments are shown in Figures 7-9. In these examples, each tube to the right of itself exhibits a high order length to cross-sectional extent ratio, and the assembly will generally be shorter.

[0083] So, as an example, if we have a tidal volume of 500 ml and a total reservoir volume V R For a 100 kg patient using at least one reservoir tube with an inner diameter of 19 mm configured with a tidal volume of 510 mL (e.g., this represents a 2% margin for the tidal volume), if multiple reservoir tubes can be used, the reservoir configuration can be determined as follows:

[0084] The length of the tubing is a function of the number of tubes used and the inner diameter of each tube. For example, for a desired reservoir volume V of 510 mL, R Let the number of similar round tubes, N, be 30, each with an inner diameter D of 6 mm. tube After selecting, the length of each small tube is:

number

number

[0085] In this manner, a "straw bundle" configuration can be constructed as shown in FIG.

[0086] In some embodiments, the rate at which the sufficient amount of the at least one therapeutic gas is introduced into the at least one reservoir tube is configured to introduce a sufficient amount during an exhalation phase of the patient's breathing cycle. In some embodiments, the rate at which the sufficient amount of the at least one therapeutic gas is introduced into the at least one reservoir tube is configured to introduce a sufficient amount for about 2 seconds when the patient breathes 30 times per minute.

[0087] In some embodiments, the reservoir volume should equal or slightly exceed (e.g., up to 10%) the patient's exhaled tidal volume. In some embodiments, the total incoming therapeutic gas flow should equal or slightly exceed the patient's volume. In an exemplary embodiment, the patient's breathing pattern is used to guide the system of the present invention, where the patient has a tidal volume of 500 mL, the patient breathes 30 times per minute, and the reservoir volume is 510 mL. Thus, the patient's minute ventilation is JPEG0007672308000022.jpg915 is equal to (500 mL / breath x 30 breaths / minute), or 15 liters per minute (LPM). Therefore, JPEG0007672308000023.jpg99 should be set at a slightly increased level (510 mL x 30 breaths / min) or 15.3 LPM.

[0088] The introduction of the at least one therapeutic gas into the at least one reservoir tube should be at a rate that does not induce turbulent flow, but induces bulk flow of the gas along the entire length of the reservoir. In some embodiments, the introduction of the gas is at a rate that causes the flow of the at least one therapeutic gas to be laminar. Thus, in some embodiments, the interior cross-sectional extent of the at least one reservoir tube and / or the interior surface texture of the at least one reservoir tube are selected to cause the flow of the at least one therapeutic gas to remain laminar along the entire length of the reservoir.

[0089] For example, the Reynolds number is a measure of the laminar or turbulent nature of a gas flow. Reynolds numbers below 2,300 are considered to be laminar. For flow in pipes or tubes, the Reynolds number, Re, is commonly defined as:

number

[0090] Thus, in this exemplary embodiment, a 19mm reservoir tube and an assumed flow rate of 16 LPM in the reservoir tube (previous JPEG0007672308000026.jpg88 (rounded up from ) will result in the following during reservoir filling:

number

[0091] Thus, in this example, having a reservoir fill rate of 16 LPM results in a Re value in laminar flow conditions. In some embodiments, the flow of at least one therapeutic gas in at least one reservoir tube during the inhalation phase is still laminar. As an example, assuming a patient breathes according to a calculation similar to that of the previous example, with a peak inhalation flow rate of about 40 LPM (taking in 500 mL in about 0.75 seconds, see the cyclic flow pattern in FIG. 1), the demand on the reservoir during inhalation will be about 24 LPM (i.e., 40 LPM minus 16 LPM of the inhalation flow is directly supplied by the inhalation flow of therapeutic gas). Thus, the induced reservoir flow rate is associated with a Reynolds number of about 1730, which is still within the range considered to be laminar flow.

[0092] In some embodiments, at least one reservoir tube is coiled. The flow inside a coiled tube tends to remain in the viscous region at higher flow rates for comparable Re than in a straight tube. Curvature-induced helical vortices (Dean vortices) tend to suppress the onset of turbulence and delay the transition from laminar flow. The critical Reynolds number, Re, that marks the transition from laminar to turbulent flow is cr teeth,

number

[0093] An example embodiment of a system of the present invention having at least one coiled reservoir tube is shown in FIG.

[0094] In some embodiments, the flow rate and flow direction of at least one reservoir tube can be monitored to assess the operation of the reservoir.

[0095] In some embodiments, at least one reservoir tube further comprises a flow meter at its distal end, as shown, for example, in FIG.

[0096] In some embodiments, the system configured to administer at least one therapeutic gas to a patient is further configured to monitor the flow of gas through the proximal end of the at least one reservoir tube by repositioning the flow meter of FIG.

[0097] In some embodiments, the system configured to administer at least one therapeutic gas to a patient is further configured to monitor the at least one therapeutic gas introduced to the system configured to administer at least one therapeutic gas to a patient, for example, as shown in Figures 10 and 20 via sampling ports and lines.

[0098] In some embodiments, at least one reservoir tube further comprises a sampling port at a proximal end.

[0099] In some embodiments, the system configured to administer at least one therapeutic gas to a patient is further configured to issue an alert if any one monitored value of the concentration or flow rate of the at least one therapeutic gas deviates from a threshold value.

[0100] In some embodiments, the system configured to administer at least one therapeutic gas to a patient is further configured to alter the flow rate and / or concentration of the at least one therapeutic gas if the monitored value of any one of the concentrations or flow rates of the constituent gases of the at least one therapeutic gas deviates beyond a threshold value.

[0101] In some embodiments, the proximal end of at least one reservoir tube has two or more inlet ports. In some embodiments, the therapeutic gas can be introduced into the system through one inlet port and the diluent gas can be introduced into the system through a second inlet port. In some embodiments, the therapeutic gas and the diluent gas can be mixed prior to being introduced into the system. FIGS. 11-17 show embodiments in which the therapeutic gas and the diluent gas are mixed prior to being introduced into the system. FIGS. 18-20 show embodiments in which the therapeutic gas and the diluent gas are mixed prior to being introduced into the system. FIG. 21 shows an embodiment in which at least one reservoir tube is further configured with a flow meter at its distal end.

[0102] FIG. 22 illustrates a reservoir device as described in some embodiments of the present invention, the reservoir comprising: Periodically determining the average injected flow requirement; wherein said periodic determination is based on a flow measurement signal obtained from a flow meter responsive to an average flow and a flow direction in the reservoir; the flow requirement determination is performed over a time frame greater than 1 breath but less than 30 breaths; the total flow rate of injected therapeutic gas is periodically adjusted based on the pattern of average injected flow rate requirements just determined, which adjustments are performed simultaneously to maintain the individual constituent gas flow rates at predetermined fixed ratios such that the net outflow of the reservoir is maintained, on average, generally in the outflow direction, so that the reservoir is periodically flushed with fresh therapeutic gas; The system is configured to function as part of a therapeutic gas delivery system capable of adjusting the flow rate of the infused therapeutic gas by monitoring the outflow of the reservoir and responding to natural changes in the patient's breathing pattern. In some embodiments, some embodiments of the inventive system respond to longer term variations in the patient's breathing rhythm without the need to interrupt or adjust the flow during individual breathing cycles. In some embodiments, the flow adjustments are performed by a system operator (such as, but not limited to, an automated device that implements this function via analog, digital or computational means as known in the art). In some embodiments, the system is configured to adjust the total flow rate of infused therapeutic gas by monitoring the outflow of the reservoir and responding to natural changes in the patient's breathing pattern.

[0103] In some embodiments, the at least one reservoir tube is further configured to minimize the effort required by the patient to inhale, exhale, or both inhale and exhale. In some embodiments, the diameter of the at least one reservoir tube is configured to minimize the effort required by the patient to inhale, exhale, or both inhale and exhale.

[0104] In some embodiments, the at least one reservoir tube is further configured to minimize the effort required by the patient to inhale. In some embodiments, the diameter of the exhaust port and the diameter of the reservoir tube are configured to minimize the effort required by the patient to exhale.

[0105] At least one therapeutic gas In some embodiments, the at least one therapeutic gas is selected from the group consisting of oxygen, nitric oxide, carbon monoxide, and nitrous oxide. In some embodiments, the at least one therapeutic gas comprises aerosolized particles, microparticles, nanoparticles, or any combination thereof, and the aerosolized particles, microparticles, nanoparticles, or any combination thereof are stable in aerosol suspension for a period of time consistent with therapeutic needs, typically, and without limitation, at least one day.

[0106] In some embodiments, the systems of the present invention do not include a scrubbing element (e.g., a mechanism configured to remove a portion of the therapeutic gas, including, but not limited to, helium gas, NO, and oxygen).

[0107] In some embodiments, the systems of the present invention include a scrubbing element (eg, a mechanism configured to remove a portion of the therapeutic gas, including, but not limited to, a diagnostic gas, such as a tracer gas).

[0108] In some embodiments, the systems of the present invention do not include mechanisms used to regulate, inhibit, control, or any combination thereof, the flow of therapeutic gas to the patient after the initial flow rate has been established.

[0109] In some embodiments, the systems of the present invention include mechanisms used to regulate, inhibit, control, or any combination thereof, the flow of therapeutic gas to the patient after an initial flow rate has been established.

[0110] In some embodiments, the at least one therapeutic gas is diluted prior to being introduced into the system of the present invention, however, in some embodiments, the at least one therapeutic gas is diluted upon being introduced into the system of the present invention.

[0111] In some embodiments, the gas used to dilute the at least one therapeutic gas includes oxygen. In some embodiments, the gas used to dilute the at least one therapeutic gas includes oxygen and an inert gas, such as nitrogen. In some embodiments, the gas used to dilute the at least one therapeutic gas is compressed air.

[0112] In some embodiments, at least one therapeutic gas is administered along with supplemental oxygen.

[0113] In some embodiments, the at least one therapeutic gas and the gas used to dilute the at least one therapeutic gas are stored in compressed gas cylinders. In some embodiments, the gas is dispensed using gas flow control devices known in the art, such as, but not limited to, rotameters, mass flow meters, and positive displacement pumps.

[0114] In some embodiments, the therapeutic gas is a mixture of gases, and the therapeutic gas is mixed with breathable air.

[0115] In some embodiments, the systems of the present invention are further configured to reduce "dead volume" in the patient's connection between the patient's airway and the inhalation check valve, thereby reducing the potential for NO2 formation.

[0116] In some embodiments, the nitric oxide is stored in and dispensed from cylinders containing medical grade medicinal gases.

[0117] In some embodiments, the patient is treated with the system of the present invention via the methods disclosed in U.S. Patent Application Publication No. 2015 / 0044305. In some embodiments, the treatment method further includes monitoring one or more of on-site and off-site parameters, such as vital signs, methemoglobin levels, pulmonary function parameters, blood chemistry and hematology parameters, blood coagulation parameters, inflammatory marker levels, liver and kidney function parameters, and vascular endothelial activation parameters.

[0118] In some embodiments, patients are treated with the systems of the present invention via the methods disclosed in WO 2013 / 132497.

[0119] In some embodiments, at least one reservoir tube further comprises a flow meter at a distal end.

[0120] In some embodiments, at least one reservoir tube further comprises a sampling port at a proximal end.

[0121] In some embodiments, the present invention provides a system configured to administer at least one therapeutic gas to a patient, comprising: a. at least one reservoir tube having a proximal end and a distal end, the at least one reservoir tube having a volume within ±20% of the patient's tidal volume; b. at least one therapeutic gas inlet at a proximal end of at least one reservoir tube, a delivery tube connected to the at least one therapeutic gas inlet and to the at least one therapeutic gas source, and a distal end of the reservoir open to a source of breathable gas at ambient pressure; c. a patient interface fluidly connected to a proximal end of the at least one reservoir tube via a check valve; Equipped with the patient interface is configured to form an airtight seal between the patient and the system; The inlet side of the check valve is configured to close when the patient is exhaling; at least one therapeutic gas is introduced into the at least one reservoir tube at the proximal end via the at least one therapeutic gas inlet at a flow rate sufficient to prevent the exhaustion of all of the at least one therapeutic gas stored in the at least one reservoir tube during a typical single inhalation by a patient; at least one therapeutic gas flows along the at least one reservoir tube from a proximal end to a distal end while the patient is exhaling; The inlet side of the check valve is configured to be open when the patient is inhaling; The intake side of the check valve is a system configured to allow at least one therapeutic gas to be administered to a patient.

[0122] The present invention is further illustrated by the following non-limiting examples. EXAMPLES

[0123] Example 1: Effect of the coil radius of at least one reservoir tube on laminar flow and nitric oxide concentration in at least one reservoir tube Experiments were conducted with 160 ppm nitric oxide introduced into a coiled reservoir tube with the coil radii shown in the table below. After the gas was shuttled back and forth in the reservoir tube simulating a breathing cycle, the nitric oxide concentration in the reservoir tube was compared to the ideal 160 ppm value. [Table 4]

[0124] No significant change in NO concentration was observed. It was confirmed that a coil radius of approximately 145 mm could be utilized without the reservoir tube being significantly twisted or deformed in cross section. Assuming a coil radius of 145 mm is utilized, the critical Reynolds number Re cr The nominal Re is about 2100. cr Given a value of , laminar flow should be maintained throughout the respiratory cycle.

[0125] Publications cited in this document in their entirety are incorporated herein by reference in their entirety.

Claims

1. 1. An apparatus configured to administer at least one therapeutic gas to a patient, comprising: a. at least one reservoir tube having a proximal end and a distal end, the distal end being open to ambient air, the at least one reservoir tube including a sampling port and having a volume greater than a tidal volume of the patient's breath; b. at least one therapeutic gas inlet at the proximal end of the at least one reservoir tube, a delivery tube connected to the at least one therapeutic gas inlet and to at least one therapeutic gas source; c. a patient interface fluidly connected to the proximal end of the at least one reservoir tube via an intake check valve, the sampling port being distal to the intake check valve, the patient interface configured to form an airtight seal between the patient and the device; An apparatus comprising:

2. The apparatus of claim 1 further comprising a discharge check valve.

3. 10. The device of claim 1, wherein the patient interface is selected from a full face mask, a nasal mask, a mouthpiece, and a pillow seal nasal cannula.

4. The device of claim 1 , wherein the at least one reservoir tube is further configured to minimize the effort required for the patient to inhale.

5. 10. The device of claim 1, further comprising an exhaust port, the diameter of the exhaust port configured to minimize the effort required by the patient to exhale.

6. The apparatus of claim 1 , configured to monitor flow of the at least one therapeutic gas through the proximal end of the at least one reservoir tube.

7. configured to monitor at least one parameter of the flow of the at least one therapeutic gas through the proximal end of the at least one reservoir tube; The apparatus of claim 1 , wherein the at least one parameter comprises a concentration, a flow, a contamination, or any combination thereof.

8. The device of claim 1 , wherein the at least one reservoir tube further comprises a flow meter at the distal end.

9. The device of claim 1 , wherein the sampling port is at the proximal end of the at least one reservoir tube.

10. 10. The apparatus of claim 9, wherein the sampling port is configured to monitor and / or characterize the at least one therapeutic gas delivered to the patient.

11. The apparatus of claim 1 , wherein the at least one therapeutic gas is characterized by content, contamination, flow, concentration, or any combination thereof.

12. The device of claim 1, further configured to generate an alarm if the concentration or flow rate of at least one of the therapeutic gases deviates from a threshold value.

13. The apparatus of claim 1, further comprising: a flow rate and / or concentration of said at least one therapeutic gas being altered if the concentration or flow rate of said at least one therapeutic gas deviates beyond a threshold value.

14. 10. The apparatus of claim 1, wherein the at least one therapeutic gas comprises nitric oxide, helium, carbon dioxide, a hypoxic gas, a diagnostic gas, or any combination thereof.

15. 15. The apparatus of claim 14, wherein the at least one therapeutic gas is nitric oxide.

16. 16. The apparatus of claim 15, wherein the concentration of nitric oxide is 160 ppm in the mixture of oxygen and nitrogen.

17. 16. The device of claim 15, wherein the nitric oxide is at a concentration of 400 ppm to 0.5 ppm.

18. The apparatus of claim 1 , wherein the at least one therapeutic gas is a tracer gas.

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