WO2006090260A1

WO2006090260A1 - Means and method for supplying therapeutic gas to a spontaneously breathing patient

Info

Publication number: WO2006090260A1
Application number: PCT/IB2006/000404
Authority: WO
Inventors: Curtis Figley
Original assignee: Pulmonox Technologies Corporation
Priority date: 2005-02-28
Filing date: 2006-02-28
Publication date: 2006-08-31

Abstract

A system supplies therapeutic gas, such as Nitric Oxide, to a spontaneously breathing patient in easily adjustable ratios with respect to ambient air and oxygen gas. The system includes a plurality of fluid conduits connected in parallel with each other to a fluid manifold which, in turn, is fluidically connected to a gas delivery device, such as a mask or the like. The fluid conduits all have essentially identical flow characteristics and are all under a common pressure differential. Accordingly, flow through each conduit is essentially identical to flow through any other conduit. Therefore, altering the concentration of one gas with respect to other gases is achieved by adding fluid conduits to the flow system for the particular gas.

Description

MEANS AND METHOD FOR SUPPLYING THERAPEUTIC GAS TO A SPONTANEOUSLY BREATHING PATIENT

Technical Field

The present invention relates to the general art of surgery, and to the particular field of respiratory methods and devices for supplying respiratory gas in response to breathing of a patient.

Background Art

There are a number of airway and lung diseases and conditions suffered both by humans and by other animals in which the various parts of the usual breathing airways and lungs may become irritated, infected, or otherwise impaired through the various actions and mechanisms of the specific diseases or conditions. The severity of these effects can vary from simple irritation through to the extreme of life threatening illness. This can be extremely serious in some cases, for it is in the lung spaces that oxygen in the inhaled air diffuses through the lung tissue into the blood capillaries running therethrough to bind to the haemoglobin in the blood, while carbon dioxide released by the blood diffuses out and is exhaled; obviously, if the movement of air, oxygen and carbon dioxide is significantly reduced by the effects, the situation may become life threatening.

There are additionally a number of lung conditions in which the lung's small peripheral arteries— the pulmonary arteries-also constrict, typically those deep in the lungs where the oxygen tension falls as in an asthmatic attack, pneumonia, or chronic lung diseases like bronchitis and emphysema (and it should also be noted that such constriction often occurs without the causative mechanism being fully explained; this is the so-called primary pulmonary hypertension). Whatever the reason, the result is that the flow of blood to the capillaries is impaired, and the ensuing increase in the resistance to blood flow~the raised pulmonary vascular resistance—may be so severe as to cause the right ventricle of the heart to fail, and death to ensue.

A well-known and effective dilating agent for treating both lung problems of the blood-vessel-constriction type and of the asthma airway type is the gas Nitric Oxide (NO). Nitric oxide has also recently been shown to have a cidal effect on many types of bacterial infections and has been shown to have beneficial antiviral effects. These characteristics have been shown to occur "post infection" and when used as a "prophylactic", indicating that nitric oxide therapy may be used beneficially in both curative and preventative modes.

Nitric oxide is one of several gaseous oxides of nitrogen commonly found in nature; two others are nitrous oxide (N₂-O), known as "laughing gas", and at one time used as a general anaesthetic, and nitrogen dioxide (NO₂). The latter, to which nitric oxide is converted by a reaction with free oxygen at a rate. which is dependent on the nitric oxide concentration, is a highly reactive and rather dangerous gas that dissolves in water to form nitric acid (HNO₃) and nitric oxide, and is one of the main constituents of so-called "acid rain".

Nitric oxide is quite normally generated in animal (particularly human) life, starting from available organic nitrogenous materials or even from inorganic nitrogen derivatives (such as nitrates). For example, in the human system there is an enzyme called Nitric oxide Synthase (NOS) that does this, starting from the amino acid L-arginine, either continuously or upon induction by some other factor (the enzyme thus exists in both "constitutive" and "inducible" isoforms). Nitric oxide is rapidly absorbed by the lung tissue and then into the blood stream, but it is not carried along therein because it reacts very rapidly with the haemoglobin, the oxygen-carrying pigment' in red blood cells to form the stable product methaemoglobin (and nitrite and nitrate), by which route the nitric oxide is effectively inactivated. NO is an environmental pollutant produced as a byproduct of combustion. At high concentrations (generally at or above 1000 ppm), NO is toxic. NO also is a naturally occurring gas that is produced by the endothelium tissue of the respiratory system. In the 1980's, it was discovered by researchers that the endothelium tissue of the human body produced NO, and that NO is an endogenous vasodilator, namely, an agent that widens the internal diameter of blood vessels.

The obvious way to deliver nitric oxide to the sites in the airways and lungs where it is needed is by inhalation. While NO has shown promising preliminary results with respect to the treatment and prevention of the diseases mentioned above, delivery methods and devices must cope with certain problems inherent with gaseous NO delivery. First, exposure to high concentrations of NO is toxic especially over 1000 ppm. Even lower levels of NO can be harmful if the time exposure is relatively high. For example, the Occupational Safety and Health Administration (OSHA) has set exposure limits for NO in the workplace at 25 ppm time-weighted average for eight (8) hours. Traditionally, NO has been administrated to patients in the concentration range of about 1 ppm to about 100 ppm, but recent work has indicated that doses as high as 200 ppm may produce beneficial effects in terms of disease and infection control, as long as the duration of the therapy is limited.

Another problem with the delivery of NO is that NO rapidly oxidizes in the presence of oxygen to form NO₂, which is highly toxic, even at low levels. For example, OSHA has set exposure limits for NO₂ at 5 ppm. In any NO delivery device it is thus desirous to reduce, to the largest extent possible, the conversion of No to NO₂. The rate of oxidation of NO to NO₂ is dependent on numerous factors, including the concentration of NO, the concentration of O₂, and the time available for reaction. One problem with the inhalation of NO is that when NO is therapeutically inhaled, it is often mixed with high concentrations of O₂. Consequently, this increases the conversion rate of NO to NO₂. It is thus preferable to minimize the contact time between NO and O₂ when the NO is combined with a source of oxygen gas. As can be understood, the concentration of nitric oxide thus delivered must be high enough to have the required cidal, antiviral, vasodilatory or bronchodilatory effect and yet low enough to minimize its rapid conversion to the harmful nitrogen dioxide (for which even as much as 5 ppm is considered a dangerous and toxic quantity). As a result, the nitric oxide concentration in the inhaled mixture with air (and sometimes with oxygen-enriched air, with its greater ability to oxidize the nitric oxide to the dangerous nitrogen dioxide) has to be very carefully controlled; this is more difficult than it might seem.

For most lung diseases and conditions to be treated using nitric oxide, the ideal way to administer the required mixture of gases is, with the Patient fully conscious, via a simple face mask, the mask being fed either with the mixture itself or with the two components in controlled quantities.

It is extremely desirable to keep a watchful eye on the actual amount of nitric oxide being received deep within the lungs, and to check that the nitrogen dioxide level is below the maximum permitted value. Accordingly, each method is inevitably carried out with the assistance of sampling and analyzing equipment to detect the nitric oxide and nitrogen dioxide concentrations and to take some remedial action if appropriate.

This requirement inhibits, if not prevents, widespread use of NO as a therapeutic gas. Therefore, there is a need for a means and a method for administering therapeutic gas, such as NO, to a spontaneously breathing patient in a manner that is simple enough for minimally trained personnel to safely and accurately practice.

The above-discussed requirement has also caused systems embodying the prior art to be complex, complicated and expensive. This has also inhibited the widespread use of NO as a therapeutic gas.

Therefore there is a need for a means and a method for administering therapeutic gas, such as NO, to a spontaneously breathing patient in a manner that is simple and inexpensive and does not require complex and complicated machinery and systems.

Methods and devices for delivering NO to a patient have been developed to minimize the conversion of NO to NO₂. For example, with respect to the delivery of NO to patients connected to a mechanical ventilator, the NO/NO₂ stream has been introduced directly into the respiratory limb of a patient breathing circuit. These arrangements have the advantage over other designs that combine and mix NO/NO₂ and Air/0₂ prior to their input to the ventilator since the contact time between NO and O₂ is reduced.

Generally, NO is administered to patients that are either spontaneously breathing or connected to a mechanical ventilator. In spontaneously breathing patients, a patient typically wears a tight fitting mask, transtracheal O₂ catheter, nasal cannula, or other tubing passing directly into the airway of a patient. NO is typically mixed with O₂ and air prior to introduction into the patient airway. These spontaneous systems, however, suffer from the limitation that the NO concentration can fluctuate within a relatively wide range. The dose of NO varies with the patient's ventilatory pattern due to the fact that the patient's inspiration profile changes on a breath-by-breath basis. The delivered dose of NO is thus approximated from assumptions regarding the patient's ventilatory pattern.

There are several different methods of delivering NO to a mechanically-ventilated patient. In one method, the NO/N₂ stream is premixed with Air/O₂ prior to entering the ventilator. While such pre-mixing may better permit the inspired concentration of NO to be controlled, the production of NO₂ is significantly higher given the longer contact time between NO and O₂. This is particularly true for ventilators with large internal volumes. In another method of delivery, NO is continuously injected into the inspiratory limb of the ventilator circuit. This method, however, has difficulty maintaining a stable NO concentration throughout the entire inspiration flow. Moreover, when continuously injected NO is used with adult ventilators that have phasic flow patterns (flow only during inspiration), the inspiratory circuit fills with NO during expiration, and a large bolus of NO is delivered to the patient in the next breath. This method may result in an inspired NO concentration that may be more than double the calculated or estimated dose. In addition, the concentration of delivered NO varies with the length of the patient's expiration. For example, when the expiratory time is short, the delivered NO concentration is lower due to less time for filling the inspiratory limb with NO.

Yet another method of delivering NO involves intermittent injections of an NO-containing gas into the patient's inspiratory limb, in this regard, NO is delivered into the inspiratory limb only during the inspiratory phase. For this method to be acceptable, however, the flow from the ventilator must be continuously and precisely measured, and the injected dose of NO must be precisely titrated such that the delivered NO and inspiratory flow waveform are not affected.

It is thus desirous to have a device and method of delivery of NO to a patient that can control the delivery of an NO-containing gas as well as an oxygen-containing gas to a patient via a single mechanism. The device preferably provides constant concentration of NO to the patient during inspiration. In addition, the device preferably does not suffer from the limitation of other delivery systems, where NO may remain in the system between breaths. Namely, the device and method preferably eliminates any bolus or residue of NO-containing gas that might build-up between breaths.

NO, usually diluted with N2, is generally supplied in gas cylinders and is subsequently mixed with a respiratory gas, usually a mixture of air and oxygen (O₂), before the final mixture is delivered to the patient. As suggested above, the biggest problem with NO is that it is a highly reactive gas and forms, with O₂, nitrogen dioxide (NO₂) -a highly toxic gas even in small concentrations. Since respiratory gas often contains an elevated concentration of O₂, typically 50-80% O₂, special measures may be necessary to minimize the amount of NO₂ delivered to the patient.

One approach to minimize the opportunity for NO₂, to form is to supply the gas containing NO closely as possible to the patient, even inside the patient. This has the disadvantage, however, that the NO and respiratory gases may not have time to mix thoroughly, and a heterogeneous gas mixture could be carried into the lungs.

Another option is to mix the two gases continuously as they flaw at a constant rate past an inspiratory line, so that the patient then draws a fresh mixture into her/his lungs at every breath. Implementing this option is difficult, however, when the patient is incapable of spontaneous breathing with an adequate volume. Moreover, large amounts of gas would be consumed, and gas containing NO would have to be evacuated to prevent a rise in the level of NO₂ in the room.

Another possibility is to mix the gases in the customary fashion and to install an NO₂ absorber or an NO₂ filter before the patient. A disadvantage here is the difficulty in determining the supplied concentration of NO. An absorber must be monitored to keep it from becoming saturated, thereby losing its ability to absorb NO₂, and a filter must be arranged to keep NO₂ from escaping into the room.

Therefore, there is a need for a means and a method for administering therapeutic gas, such as NO, to a patient, but in a manner that is safe and effective.

Still further, there is to be a wide spread use of this therapeutic gas. Technicians, as well as other such clinical health care workers should be capable of administering the treatment to a patient. In some cases, it is even beneficial if the patient can administer the treatment himself without supervision. The systems for administering therapeutic gas, in particular NO, that are known to the inventor are generally complicated, complex and difficult to operate. As such, these systems are not amenable to such wide use. With the advent of highly communicable diseases, such as SARS, influenza and the like, it would be beneficial if treatment using therapeutic gas, such as NO, could be widely and readily available. This would be especially helpful if a patient could travel to a nearby site, such as a drug store, and receive treatment with therapeutic gas. In influenza situations or even in simple common cold situations, this would be extremely beneficial. However, with the complexity of presently available systems, this is not practical.

Therefore, there is a need for a means and a method for administering therapeutic gas to a patient in a widely available manner.

Still further, during certain periods of the year, such as during Winter months, certain ailments, such as influenza, are widespread. In some cases, the ailment may reach epidemic proportions for some time periods. During such outbreaks, it would be extremely beneficial if treatment is widely and rapidly available. During such outbreaks, time may be of the essence and if effective treatment is available on a widespread scale, the outbreak can be better controlled. However, due to the complexity of presently-available therapeutic gas administration systems, wide and rapid deployment of such systems to the most severely affected areas may be difficult and expensive. In some cases, due to the extreme complexity of the systems, rapid deployment may be impossible. In fact, due to the complexity of many of the systems, it may not even be possible to manufacture and deliver such systems with the speed required to adequately and effectively treat such outbreaks. Additionally, it may be desirous to administer NO prophylacticly to prevent certain individuals (for example health care workers that may or may possibly come in contact with highly infectious agents) from becoming infected in the normal course of their work. This would dramatically increase the need for simple and cost effective delivery means and methods.

Therefore, there is a need for a means and a method for administering therapeutic gas, such as NO, to a wide range of patients using a system that is rapidly manufactured and rapidly deployable to a wide range of locations.

Disclosure of Invention

It is a main objective of the present invention to provide a means and a method for effectively and accurately providing therapeutic gas to a spontaneously breathing patient.

It is another objective of the present invention to provide a means and a method for effectively and accurately providing nitric oxide gas to a spontaneously breathing patient.

It is another objective of the present invention to provide a means and a method for effectively and accurately providing therapeutic gas to a spontaneously breathing patient which is easy and intuitive to operate and maintain, and which can be operated by patients themselves or by clinical support personnel.

It is another objective of the present invention to provide a means and a method for effectively and accurately providing therapeutic gas to a spontaneously breathing patient which is easy and inexpensive to manufacture and which is amenable to changes as needed.

It is another objective of the present invention to provide a means and a method for effectively and accurately providing therapeutic gas to a spontaneously breathing patient, which is easy and inexpensive to manufacture and which is amenable to rapid and efficient distribution. It is another objective of the present invention to provide a means and a method for effectively and accurately providing therapeutic gas to a spontaneously breathing patient which is easy to operate using a minimum number of controls while still producing accurate operation.

For compressible flow through a conduit, flow rate is a function of temperature, specific gravity, upstream pressure, pressure differential, internal conduit diameter and surface conditions, and an expansion factor for the particular conduit. When all of these factors are constant for each of a plurality of conduits, flow through each of the conduits will be identical to flow through the other conduits. In a parallel arrangement, the pressure differential across each of the conduits is identical and thus the total flow in the parallel system will be a simple arithmetic addition of the flows through each conduit. That is, for N conduits, each conduit will have a flow of 1/N of the total flow in such an arrangement.

For parallel flow configurations, if one conduit path is divided into a path containing several conduits, so that the overall flow system has N paths and one path is made up of S conduits, the total flow for that path will be equal to S/N of the total flow in the system. Thus, for the overall system, flow can be expressed as: ((S-i/N) + (S₂/N) +....+ (SN/N)) where S is a number of 1 or greater and each factor represents a particular path from the inlet of the system to the outlet of the system. For example, if there are three systems, and one of the systems has three conduits, then the total flow of the system will be [(1/5) + (1/5) + (3/5)]F, were F represents the total flow of the system.

Using this, a mixture can be established for several systems in which the ratio, or concentration, of any particular element can be selected.

The system embodying the present invention uses this concept of parallel flow by having a plurality of flow conduits that are in parallel with each other between a common upstream pressure and a common downstream pressure to thus establish a single pressure differential imposed on all flow paths and having all flow conduits used between the input and the output of the system having, if not exactly identical fluid flow characteristics, then fluid flow characteristics that are so close to each other as to be identical for all purposes that are practical for the purposes of this invention. This situation will be referred to as "substantially" identical which means in the context of the present disclosure: "characteristics, such as conduit internal flow area, conduit internal surface conditions, expansion factors, of one fluid flow conduit are identical to the same characteristics of another or other fluid flow conduits for all purposes that are practical for the purposes of this invention." Those skilled in the fluid flow art will understand what ranges the fluid flow characteristics can be to stay within the meaning of "substantially similar."

The inlet, or upstream, pressure for the gas delivery system embodying the present invention will be ambient and the outlet pressure will be established at a fluid manifold to which a gas delivery device, such as a mask, will be fluidically connected to be supplied with the gas from the system of the present invention. The fluid manifold is large enough with respect to the fluid conduits so that fluid pressure fluctuations during operation of the system will be non-existent for purposes of the operation of the system.

The fluid manifold is fluidically connected to a patient gas delivery device, such as a mask or the like, and fluid pressure at the mask is established by inhalation of the patient to which the gas delivery is attached, and is considered as being downstream pressure with respect to fluid flow from the fluid manifold to the patient. Therefore, with respect to the fluid manifold and the patient, fluid manifold pressure is upstream pressure and fluid pressure at the patient is downstream pressure, with a pressure gradient being established between the fluid manifold and the gas delivery device during patient inhalation that causes fluid to flow from the fluid manifold to the gas delivery device. With respect to gas being supplied to the fluid manifold, fluid manifold pressure is downstream pressure with respect to the conduits of the gas delivery system and ambient pressure is upstream pressure, with a pressure gradient being established between the inlets of the fluid conduits and the fluid manifold during patient inhalation that causes gas to flow into the fluid manifold from the parallel fluid conduits.

Because the fluid flow conditions through any conduit is equal to the fluid flow conditions in any other conduit and the system embodying the present invention utilizes a parallel flow circuit between the gases supplied to the fluid manifold and the fluid manifold, mixing ratios are simple to set by simply adding the desired number of fluid flow conduits to the system.

The system is easy to set up and operate, accurate and stable. Thus, a person having minimal skills can safely and accurately operate the system embodying the present invention to deliver therapeutic gas, such as NO, to a patient. Thus, a system for delivering NO to a patient can be readily available to a wide range of people for a wide range of uses. The system is simple to manufacture and assemble and thus can be quickly manufactured and sent to and set up at various locations on a rapid basis.

Brief Description of Drawings

Figure 1 is a schematic illustrating the principles of parallel flow which are utilized in the system embodying the present invention.

Figure 2 is a schematic illustrating the application of the principles of parallel flow to a gas flow system.

Figure 3 is a schematic illustrating the operation of the system embodying the present invention.

Figure 4A is a schematic illustrating one form of the system embodying the present invention. Figure 4B is a schematic illustrating another form of the system embodying the present invention.

Figure 5 is a schematic illustrating another form of the system embodying the present invention.

Figure 6 is a schematic illustrating another form of the system embodying the present invention.

Figure 7 is a schematic illustrating another form of the system embodying the present invention.

Figure 8 is a schematic illustrating another form of the system embodying the present invention.

Figure 9 shows an element used in one form of the system embodying the present invention.

Figure 10 is an element used in one form of the system embodying the present invention

Figure 11 shows a check valve arrangement used on one form of the system embodying the present invention.

Best Mode for Carrying Out the Invention

Other objects, features and advantages of the invention will become apparent from a consideration of the following detailed description and the accompanying drawings.

The system embodying the present invention utilizes the principle of parallel flow to permit controlling the amounts of various gases, such as therapeutic gas, including NO, with respect to other gases, such as ambient air and/or oxygen, or the like by simple manipulation of easily assembled elements.

The principle of parallel flow is illustrated in Figure 1. As is well understood from basic linear electronic circuits, when a resistive element is placed between two poles each of which is at a different potential, current will flow. A parallel circuit is formed when two or more resistive elements are placed between the same two terminals so that the same potential difference is applied to all of the resistive elements. The current flow through each resistive element is a function of the resistance of the element and total current flow between the two terminals is an arithmetic sum of the current flow through the resistive elements.

This same principle is applied to parallel fluid conduits in a parallel fluid circuit such as shown in Figure 1. Referring to Figure 1 , it can be understood that if Pi is greater than P₀, then a pressure gradient equal to (Pi - P₀) is established. If a plurality of fluid conduits are fluidically connected between P| and P₀, flow will occur in the directions indicated in Figure 1 as U, f₂, . . .fn- As those skilled in the art will understand, compressible fluid flow through a conduit is affected by conduit characteristics, such as geometry, conduit size, conduit interior surface conditions as well as the properties of the fluid itself. If the conduit characteristics of each fluid conduit are essentially identical to the conduit characteristics of every other fluid conduit in the flow circuit, then flow through each of the conduits should be nearly identical to flow through each, of the other conduits in the flow circuit. Thus, total flow between Pi and P₀ will be a simple arithmetic sum of fi+f2+...+fN-

It should be noted, that as long as the condition of "essentially identical" flow characteristics are maintained, there is in principal no limitation of the system in terms of the actual form of the flow character. That is, the individual restrictor elements do not need to have a particular flow behavior. In practice, however, the flow restrictors must not introduce too high a pressure drop, else the patient will need to exert excessive breathing effort. Also, in practice, it is beneficial in many cases to select restrictors with approximately linear flow versus pressure drop characteristics (that is, restrictors that have relatively long channels compared to the cross section dimensions), to mitigate the small variations introduced by pressure drops on the manifolds, interference of the restrictor inlet and outlet ports, and other non-ideal behaviors.

This principle is applied in system 10 embodying the present invention to control the concentration of a particular gas reaching a patient. Thus, referring to Figure 2, it will be understood that if all of the conduits Ci, C₂, C₃ have essentially identical characteristics, and if P₀ is lower than atmospheric pressure, then the gases shown as Gas-i, Gas₂ and Atm, all of which are at atmospheric, or ambient, pressure, will flow into fluid manifold F at essentially the same flow rates. Thus, mixing the gases is a simple operation, which will include simply adding conduits to one of the sources. This is indicated in Figure 3 where three conduits C₃, C₄, and C₅ are associated with one flow entrance port A and one conduit C₂ and Ci is associated with each of the other two flow entrance ports B and C for fluid manifold F. If the entrance end of each conduit is maintained at or near atmospheric pressure, and the exit end of each conduit is maintained at the fluid pressure in manifold F, then three times as much fluid will flow into port

A as into either ports B or C. Total flow into manifold F will thus be (3A + B + C) and the amount of fluid flowing into port A is 3/5 of the total fluid flowing into manifold F. This ratio is easily and quickly adjusted by adding more fluid conduits to one of the ports, or removing one or more of the conduits from port A.

As those skilled in the art will understand, this principle can be applied to adjust the concentration of a gas, such as a therapeutic gas such as NO, being applied to a patient via a gas delivery device, such as mask M. For example, referring to Figure 4B, if NO is mixed with oxygen gas and ambient air, then the concentration of NO represented as <NO>therapy = [QNO/ (QNO⁺

Qair+Qθ2)] <NO>_Source, Which reduces to <NO>therapy [(Ni)/(Ni+N₂+N3)]<NO>_SOurce, with <NO>thera_Py representing the concentration of a gas in the mixture. For the set up shown in Figure 3, if the gases include ambient air, oxygen and NO, then air can be supplied at port A, while Oxygen is supplied at port B and NO is supplied at port C, whereby the NO will be diluted to 1/5 the total fluid flowing into manifold F. If the NO is supplied from a source which has a concentration of 800 ppm, then the dose of NO supplied to the patient will be 160 ppm, which is a recommended concentration of this gas for several of the intended applications. The oxygen applied to the patient can also be adjusted since atmospheric air contains about 21 % oxygen and thus the patient will have a mixture of gas that contains approximately 33% oxygen applied via the fluid manifold.

It is noted that while NO and oxygen are disclosed, those skilled in the art will understand that other gases can be used without departing from the scope of the present disclosure.

Each of the fluid flow conduits has an inlet end (inlet ends Cn.₅₁, in system 10 shown in Figure 3), and the inlet ends are maintained at an inlet pressure essentially equal to atmospheric pressure P_ATM (also referred to as ambient pressure), with ambient pressure being higher than the pressure inside fluid manifold F. This is represented as ΔP = (P_atm -P_F) where PF is the pressure in the fluid manifold and PATM is ambient, or atmospheric, pressure adjacent to the system. The fluid pressure inside fluid manifold F is established when a patient inhales and this inhalation pressure is applied to the fluid manifold F via mask M and conduit P_M, so that Pi = P_F during patient inhalation. By definition, the inhalation pressure Pi (=PF) will be below ambient pressure PATM SO a pressure difference ΔP will be established across each fluid conduit Ci_-5 that is essentially equal and the pressure gradient associated with the pressure difference is in a direction to cause fluid to flow toward the fluid manifold.

While five fluid conduits are shown, it will be understood that any number of fluid conduits can be used, and such other forms of the system are intended to be covered as well since they will be within the teaching of this disclosure. For example, referring to Figure 5, four fluid conduits are associated with a container of air enriched with Oxygen gas and one fluid conduit is associated with a container of NO. The overall mixture will thus contain 1/5 NO and 4/5 of the enriched air. If the NO is supplied at 800 ppm, it will be applied to the patient at 160 ppm because it will be diluted to 1/5 by the mixing process of the system embodying the present invention. Similar results can be obtained if twenty fluid conduits are associated with the enriched air supply and five fluid conduits are associated with the NO supply.

The system embodying the present invention can assume a multitude of forms, just so the overall concept of parallel fluid flow between a single ΔP is used. Thus, some of the systems can include reservoirs Reservoir_o for oxygen gas and reservoirs Reservoir_No for NO gas. These reservoirs are generally highly flexible bags that will remain at or near ambient pressure while the gas is being stored. The reservoirs can also include vent valves to limit the fill pressure of the reservoir bags, such as vent valve 20 shown in Figure 5 on reservoir ReservoirNo- This valve may be implemented in many ways, extending from a simple flap cut into the bag to a low resistance check valve and to other methods known to the art. Alternately, the relative fill level of the reservoir could be controlled or maintained by an automatic valve in either the supply conduit or vent port, such a valve being actuated by a pressure sensor sensing the reservoir or by other mechanisms known to the art for detecting the fill state of the reservoir. A reservoir Reservoir_Ai_R for oxygen enriched air can also be used if desired, and this reservoir is preferably held open to the ambient environment so reservoir Reservoir_AiR will also be maintained at ambient pressure.

If flexible reservoirs such as described above are used, then it is desirable to replenish the gas stored in the reservoir. As used herein, the term "flexible reservoir" means a reservoir that has walls that will transmit ambient pressure directly and essentially undiminished to the interior of the reservoir. Ultra-flexible material such as a plastic film type material can be used for this purpose. This is achieved using supply systems O₂ and NO₂ shown in Figures 4A and 4B with flow switches or regulators S₀ and SN_O associated therewith so the reservoirs remain "about" full (that is, at some fill level acceptably above empty but below a point where the flexible reservoir 5. becomes excessively extended) while also remaining at or near ambient pressure. As shown in Figure 7, indicators 30 and controls 40 can also be included as required to further control and monitor the system. The indicators can be used to warn of system inconsistencies or misbehaviors and can also be used to monitor fill levels for reservoirs and the like. The o flow conduits can also include quasi-linear restrictors, such as restrictor 41 , to mitigate non-ideal behaviors elsewhere in the system.

As shown in Figure 8, the above-disclosed fluid conduits can be replaced by mesh screens, such as screen 40 and screen 42. The mesh for the screens is selected to have sufficient fluid passages to account for the 5 above-discussed mixing ratios. That is, if the flow area for screen 40 is A₄₀ and that of screen 42 is A₄₂, then <NO>therapy = [(A₄₂V(A₄₀ + A₄₂)]<NO>_SOurce- For example, screen 40 may have twice as many fluid passages as screen 42 with screen 40 being associated with oxygen and/or ambient air and screen 42 being associated with therapeutic gas. The mesh openings must 0 be arranged and selected so that flow from one opening does not overly- influence flow through adjacent openings so the above-discussed parallel flow conditions can be established and maintained. However, those skilled in the art will be able to design such mesh elements to achieve this objective based on the teaching of the present disclosure.

5 As shown in Figure 9, the mesh screens shown in Figure 8 can be replaced by plates 50 having a plurality of spaced-apart holes, such as holes 52 and 54. The holes in plates 50 can be spaced and sized according to the same principles as discussed above for the flow passages associated with the mesh screens. As shown in Figure 10, a check valve 60 can be located in fluid conduit C_M SO the patient performs one-half of the flow directing function. The check valve controls inhalation flow so it flows into the mask, or mouth piece or cannula or the like in direction I when the patient inhales, but cannot flow in the reverse direction on exhalation (i.e., toward the fluid manifold) due to the check valve. The patient would exhale through their nose, or mouth (which ever is not connected to the delivery device), before the next inhalation. This reduces the effort required for breathing since there is little resistance on exhalation and also keeps exhaled breath from mixing into the fluid contained in the fluid manifold. Another check valve system 70 is shown in Figure 11 and includes a rocker plate 72 which is moved by fluid pressure associated with filling the manifold or with exhalation of the patient as indicated by arrows 76 and 78 respectively. This implementation allows a reactive gas to remain effectively isolated from the others between inhalations, to prevent the problems associated with mixing the reactive gas with air.

The present invention can also be constructed to include a bias flow to further reduce the production of NO2. The bias flow would be induced by a fan or pump mechanism as indicated in Figure 7 by system 80 and will be in direction 82, wherein there would be a minimum flow drawn through the common supply manifold. This flow could be smaller than, equal to, or could exceed the peak flow demanded by the patient. In this fashion, gas can not stagnate between breaths and therefore the reaction products will not collect in the conduits.

Operation and use of the system embodying the present invention can be understood from the foregoing, and thus will not be presented in detail. Use of the system is begun by placing a mask or a tube into fluidic connection with a patient. The patient begins to breath normally and this produces a low pressure in the fluid manifold downstream of the fluid conduits. The -P across the fluid conduits is approximately the same for each fluid conduit since they are all connected to a common point at their outlets but also because they are all supplied at about ambient pressure on their inlet ends. Since the relative flows are fixed, so is the concentration of each component gas stream. Oxygen gas flow is adjusted in a gas reservoir to be mildly enriched (compared to air), to for example, 25% O₂. Flow of NO is begun and adjusted until the NO reservoir is about 70% full at the start of a breath to a minimum of about 20% full at the end of a breath. The proper concentration or mix is established by selecting the number of fluid conduits as discussed above. The patient can be monitored and the therapeutic gas shut off when treatment is completed. The flow control systems can be used to monitor gas flow to the patient. In some systems, the flow control systems can include automatic controls as well. The NO reservoir can be emptied (such as allowing the flexible bag to fully deflate) and the patient is removed from the system.

It is understood that while certain forms of the present invention have been illustrated and described herein, it is not to be limited to the specific forms or arrangements of parts described and shown.

Claims

1. A system for delivering therapeutic gas to a spontaneously breathing patient comprising:

A) a gas delivery device associated with a patient to deliver

5 therapeutic gas to the patient when the patient inhales with inhalation of the patient producing an inhalation pressure;

B) a fluid manifold fluidically connected to said gas delivery device and having a fluid manifold inhalation pressure which is a function of patient inhalation pressure; o C) an ambient air delivery system fluidically connected to said fluid manifold and having at least one fluid conduit having an inlet end fluidically connected to ambient air and an outlet end fluidically connected to said fluid manifold, the fluid conduit of said ambient air system having specified fluid flow characteristics and having a pressure differential defined between the 5 inlet end and the outlet end with ambient air fluid pressure at the inlet end of the fluid conduit being greater than fluid pressure at the outlet end of the fluid conduit in said fluid manifold when said fluid manifold is at patient inhalation pressure so that ambient air flows to said fluid manifold through said ambient air delivery system for patient inhalation; 0 D) a therapeutic gas delivery system fluidically connected to said fluid manifold and having at least one fluid conduit having an inlet end fluidically connected to a source of therapeutic gas and an outlet end fluidically connected to said fluid manifold, the fluid conduit of said therapeutic gas system having fluid flow characteristics which are essentially similar to the 5 fluid flow characteristics of the fluid conduit of said ambient air delivery system, the fluid conduit of said therapeutic gas delivery system being in parallel with the fluid conduit of said ambient air delivery system and having an inlet pressure that is essentially equal to the pressure of ambient air at the inlet of said ambient air delivery system and having a pressure o differential defined between the inlet end and the outlet end of the fluid conduit of said therapeutic gas delivery system that is equal to the pressure differential across the fluid conduit of said ambient air delivery system; and E) an oxygen gas delivery system fluidically connected to said fluid manifold and having at least one fluid conduit having an inlet end fluidically connected to a source of oxygen gas and an outlet end fluidically connected to said fluid manifold, the fluid conduit of said oxygen gas system having fluid flow characteristics which are essentially similar to the fluid flow characteristics of the fluid conduit of said ambient air delivery system, the fluid conduit of said oxygen gas delivery system being in parallel with the fluid conduit of said ambient air delivery system and having a inlet pressure that is essentially equal to the pressure of ambient air at the inlet of said ambient air delivery system and having a pressure differential defined between the inlet end and the outlet end of the fluid conduit of said oxygen gas delivery system that is equal to the pressure differential across the fluid conduit of said ambient air delivery system.

2. A system for delivering therapeutic gas to a spontaneously breathing patient comprising:

A) a gas delivery device associated with a patient to deliver therapeutic gas to the patient when the patient inhales with inhalation of the patient producing an inhalation pressure; B) a fluid manifold fluidically connected to said gas delivery device and having a fluid manifold inhalation pressure which is a function of patient inhalation pressure;

C) an ambient air delivery system fluidically connected to said fluid manifold and having at least one fluid conduit having an inlet and an outlet and a pressure differential between the inlet of the fluid conduit of said ambient air delivery system and the outlet of the fluid conduit of said ambient air delivery system, the fluid conduit of said ambient air delivery system having specified fluid flow characteristics;

D) a therapeutic gas delivery system fluidically connected to said fluid manifold and having at least one fluid conduit having an inlet and an outlet and a pressure differential between the inlet of the fluid conduit of said therapeutic gas delivery system and the outlet of the fluid conduit of said therapeutic gas delivery system, the pressure differential of the fluid conduit of said therapeutic gas delivery system being essentially equal to the pressure differential of the fluid conduit of said ambient air delivery system, the fluid conduit of said therapeutic gas delivery system having fluid flow characteristics which are essentially equal to the fluid flow characteristics of the fluid conduit of said ambient air delivery system;

E) an oxygen gas delivery system fluidically connected to said fluid manifold and having at least one fluid conduit having an inlet and an outlet and a pressure differential between the inlet of the fluid conduit of said oxygen gas delivery system and the outlet of the fluid conduit of said oxygen gas delivery system, the pressure differential of the fluid conduit of said oxygen gas delivery system being essentially equal to the pressure differential of the fluid conduit of said ambient air delivery system, the fluid conduit of said oxygen gas delivery system having fluid flow characteristics which are essentially equal to the fluid flow characteristics of the fluid conduit of said ambient air delivery system; and

F) the fluid conduits of the ambient air delivery system and the therapeutic gas delivery system and the oxygen gas delivery system all being in parallel with each other and all having essentially the same fluid flow characteristics and all having essentially the same pressure differential thereacross.

3. The system defined in Claim 2 wherein said ambient air delivery system includes a plurality of fluid flow conduits, each conduit having an inlet fluidically connected to ambient air and an outlet fluidically connected to said fluid manifold and each fluid flow conduit of said ambient air delivery system being connected in parallel with the fluid flow conduits of said therapeutic gas delivery system and said oxygen gas delivery system.

4. The system defined in Claim 2 wherein said therapeutic gas delivery system includes a source of therapeutic gas which has a gas pressure that is essentially equal to the pressure of ambient air at the inlet of the fluid conduit of said ambient air delivery system.

5. The system defined in Claim 2 wherein said oxygen gas delivery system includes a source of oxygen gas which has a gas pressure that is essentially equal to the pressure of ambient air at the inlet of the fluid conduit of said ambient air delivery system.

6. A system for delivering therapeutic gas to a spontaneously breathing patient comprising:

A) a fluid manifold having a manifold pressure; B) a gas delivery device adapted to be associated with a spontaneously breathing patient and which is fluidically connected to said fluid manifold and which delivers gas from said fluid manifold to the patient when the patient inhales;

C) a gas delivery system having an outlet fluidically connected to said fluid manifold and an inlet having an inlet pressure and a pressure differential between the outlet end and the inlet end, said gas delivery system including

(1 ) an ambient air conduit,

(2) a therapeutic gas conduit, and (3) a mixing gas conduit;

D) the ambient air conduit, and the therapeutic gas conduit, and the mixing gas conduit all having essentially the same fluid flow characteristics and all being fluidically connected in parallel with each other to said fluid manifold.

7. The system defined in Claim 6 further including a plurality of ambient air conduits all of which have fluid flow characteristics that are essentially similar to each other and to the fluid flow characteristics of the therapeutic gas conduit and the mixing gas conduit and all being connected in parallel with each other and with the therapeutic gas conduit and the mixing gas conduit.

8. A system for delivering therapeutic gas to a spontaneously breathing patient comprising:

A) a fluid manifold having a manifold pressure;

B) a gas delivery device adapted to be associated with a

5 spontaneously breathing patient and which is fluidically connected to said fluid manifold and which delivers gas from said fluid manifold to the patient when the patient inhales;

C) a gas delivery system having an outlet fluidically connected to said fluid manifold and an inlet having an inlet pressure and a pressure o differential between the outlet end and the inlet end, said gas delivery system including a plurality of fluid flow conduits connected in parallel with each other to said fluid manifold and all having essentially the same fluid flow characteristics so that the total number of fluid conduits in said gas delivery system is N and the fluid flow through any fluid conduit of said gas 5 delivery system is 1/N times the total fluid flow to said fluid manifold.

9. The system defined in Claim 8 wherein said gas delivery system includes an ambient air delivery system, a therapeutic gas delivery system and an oxygen gas delivery system.

10. The system defined in Claim 9 wherein said ambient air delivery o system includes a plurality of fluid conduits.

11. The system defined in Claim 8 wherein the inlet pressure of said gas delivery system is ambient pressure.

12. The system defined in Claim 9 wherein said therapeutic gas delivery system includes a therapeutic gas reservoir that operates at a 5 pressure effectively the same as the ambient pressure.

13. The system defined in Claim 9 wherein said oxygen gas delivery system includes an oxygen gas reservoir that operates at a pressure effectively the same as the ambient pressure.

14. The system defined in Claim 12 wherein the therapeutic gas reservoir includes a pressure regulator.

15. The system defined in Claim 13 wherein the oxygen gas reservoir includes a pressure regulator.

16. A system for delivering therapeutic gas to a spontaneously breathing patient comprising:

A) a fluid manifold having a manifold pressure;

B) a gas delivery device adapted to be associated with a spontaneously breathing patient and which is fluidically connected to said fluid manifold and which delivers gas from said fluid manifold to the patient when the patient inhales;

C) a gas delivery system having an inlet at an inlet pressure and an outlet fluidically connected to said fluid manifold and at fluid manifold pressure and including a plurality of essentially identical flow conduits connected in fluid parallel with each other between the inlet and the outlet of said gas delivery system so that if the total number of fluid conduits is N, the fluid flow through any one conduit is 1/N times the total fluid flow to the fluid manifold through said gas delivery system.

17. The system defined in Claim 16 wherein said gas delivery system includes an ambient air delivery system and a therapeutic gas delivery system, and the ambient air delivery system includes a plurality of flow conduits.

18. A method for delivering therapeutic gas to a spontaneously breathing patient comprising: A) placing a breathing device on a patient;

B) fluidically connecting the breathing device to a fluid manifold;

C) supplying ambient air to the fluid manifold via at least one fluid conduit;

D) supplying therapeutic gas to the fluid manifold via at least one fluid conduit;

E) supplying oxygen gas to the fluid manifold via at least one fluid conduit;

F) connecting the fluid conduits to the fluid manifold in a manner that places the fluid conduits in fluid parallel relationship with each other;

G) mixing the ambient air and the therapeutic gas and the oxygen gas in the fluid manifold; and

H) adjusting the ratio of ambient air to therapeutic gas by adjusting the number of fluid conduits carrying ambient air to the fluid manifold with respect to the number of fluid conduits carrying therapeutic gas to the fluid manifold.

19. The method defined in Claim 18 in which the step of mixing includes maintaining the fluid conduits in identical fluid'flow characteristics with each other.

20. A method for producing a fixed concentration of a therapeutic gas diluted in air or oxygen-enriched air which comprises:

providing a set of matched flow paths that are in parallel relationship with each other between two locations;

fluidically connecting at least one flow path to a source of therapeutic gas;

fluidically connecting at least one flow path to a source of diluting gas;

mixing the diluting gas with the therapeutic gas;

adjusting the ratio of therapeutic gas to diluting gas by adding flow paths to the flow path associated with the diluting gas; using a patient's breathing effort to produce a pressure differential across the flow paths;

flowing gas through the flow paths under the influence of the pressure differential; and

flowing the mixture of gases to the patient.

21. The method defined in Claim 20 further including maintaining the sources of therapeutic gas and diluting gas at atmospheric pressure.

22. The method defined in Claim 20 further including preventing patient exhaled breath from mixing with the mixed therapeutic and diluting gases.

23. The method defined in Claim 20 further including providing a reservoir for therapeutic gas and a reservoir for diluting gas and further including a step of preventing further incoming flow into the reservoirs when the reservoirs are full.

24. The method defined in Claim 20 further including disposing of the flow paths after use.

25. A system for delivering therapeutic gas to a spontaneously breathing patient comprising: A) a gas delivery device associated with a patient to deliver therapeutic gas to the patient when the patient inhales with inhalation of the patient producing an inhalation pressure;

B) a fluid manifold fluidically connected to said gas delivery device and having a fluid manifold inhalation pressure which is a function of patient inhalation pressure;

C) an ambient air delivery system fluidically connected to said fluid manifold and having at least one fluid conduit having an inlet end fluidically connected to ambient air and an outlet end fluidically connected to said fluid manifold, the fluid conduit of said ambient air system having specified fluid flow characteristics and having a pressure differential defined between the inlet end and the outlet end with ambient air fluid pressure at the inlet end of the fluid conduit being greater than fluid pressure at the outlet end of the fluid conduit in said fluid manifold when said fluid manifold is at patient inhalation pressure so that ambient air flows to said fluid manifold through said ambient air delivery system for patient inhalation; D) a therapeutic gas delivery system fluidically connected to said fluid manifold and having at least one fluid conduit having an inlet end fluidically connected to a source of therapeutic gas and an outlet end fluidically connected to said fluid manifold, the fluid conduit of said therapeutic gas system having fluid flow characteristics which are essentially similar to the fluid flow characteristics of the fluid conduit of said ambient air delivery system, the fluid conduit of said therapeutic gas delivery system being in parallel with the fluid conduit of said ambient air delivery system and having a inlet pressure that is essentially equal to the pressure of ambient air at the inlet of said ambient air delivery system and having a pressure differential defined between the inlet end and the outlet end of the fluid conduit of said therapeutic gas delivery system that is equal to the pressure differential across the fluid conduit of said ambient air delivery system; and

E) an mixing gas delivery system fluidically connected to said fluid manifold and having at least one fluid conduit having an inlet end fluidically connected to a source of mixing gas and an outlet end fluidically connected to said fluid manifold, the fluid conduit of said mixing gas system having fluid flow characteristics which are essentially similar to the fluid flow characteristics of the fluid conduit of said ambient air delivery system, the fluid conduit of said mixing gas delivery system being in parallel with the fluid conduit of said ambient air delivery system and having a inlet pressure that is essentially equal to the pressure of ambient air at the inlet of said ambient air delivery system and having a pressure differential defined between the inlet end and the outlet end of the fluid conduit of said mixing gas delivery system that is equal to the pressure differential across the fluid conduit of said ambient air delivery system.

26. The system defined in Claim 14 further including a quasi-linear restrictor in fluid communication with the therapeutic pressure regulator to mitigate non-ideal behaviors in flow.

27. The system defined in Claim 14 further including a quasi-linear restrictor in fluid communication with the oxygen gas pressure regulator to mitigate non-ideal behaviors in flow.

28. The system defined in Claim 8 wherein said gas delivery system includes a control system.

29. The system defined in Claim 9 wherein said gas delivery system includes a control system associated with said therapeutic gas delivery system.

30. The system defined in Claim 9 wherein said gas delivery system includes a control system associated with said oxygen gas delivery system.

31. The system defined in Claim 8 wherein said gas delivery system includes a NO gas delivery system.

32. The system defined in Claim 1 wherein said therapeutic gas includes NO.

33. The system defined in Claim 25 wherein said therapeutic gas includes NO.

34. The system defined in Claim 2 wherein said therapeutic gas includes NO.

35. The system defined in Claim 6 wherein the mixing gas is oxygen.

36. The system defined in Claim 35 wherein the therapeutic gas is NO.

37. The system defined in Claim I further including a bias flow system.

38. The system defined in Claim 8 further including a bias flow system.