Device for ventilating a patient and method for operating a device for ventilating a patient

Abstract

The present invention pertains to a device (1) for ventilating a patient, including an invasive mechanical ventilator (2) for periodically providing a breathing gas to an invasive patient interface (20), wherein a gas injector (4) for injecting nitric oxide supplied by a source of nitric oxide (3) into the breathing gas supplied by the invasive mechanical ventilator (2) is provided.

Claims

1. Nitric oxide for the use in preventing ventilator associated pneumonia in an invasive mechanical ventilator.

2. Nitric oxide according to claim 1, characterized in that the nitric oxide is present in the breathing gas supplied to the patient by means of the invasive mechanical ventilator in a concentration of between 0.1 ppm and 200 ppm, preferably between 1 ppm and 160 ppm, more preferred between 1 ppm and 80 ppm, more preferred between 10 ppm and 40 ppm, more preferred between 15 ppm and 20 ppm.

3. Nitric oxide according to claim 1 or 2, characterized in that the nitric oxide is supplied to the patient continuously together with the breathing gas supplied by the invasive mechanical ventilator.

4. Nitric oxide according to claim 1 or 2, characterized in that the nitric oxide is supplied in a constant concentration to the breathing gas throughout an inhalation cycle, in at least a pulse throughout an inhalation cycle, during every second breathing cycle or during every other natural number of breathing cycles except one.

5. Nitric oxide according to any of claims 1 to 4, characterized in that the nitric oxide is supplied to the breathing gas during an interval of between 1 minute to 60 minutes, preferably between 1 minute and 30 minutes, more preferably between 5 minutes and 20 minutes with an intermission between two subsequent intervals of between 1 minute to 1 day, preferably of between 1 hour and 8 hours, more preferably between 2 hours and 6 hours, most preferred between 3 hours and 5 hours.

6. Device (1) for ventilating a patient, including an invasive mechanical ventilator (2) for periodically providing a breathing gas to an invasive patient interface (20), characterized in that a gas injector (4) for injecting nitric oxide supplied by a source of nitric oxide (3) into the breathing gas supplied by the invasive mechanical ventilator (2) is provided.

7. The device (1) according to claim 6, characterized by a controller (6) programmed for controlling the gas injector (4) for adjusting the injection of nitric oxide into the breathing gas to a predetermined concentration of nitric oxide.

8. The device (1) according to claim 7, characterized in that the controller (6) is programmed to control the gas injector (4) to inject the nitric oxide such that a concentration of nitric oxide in the breathing gas of between 0.1 ppm and 200 ppm, preferably between 1 ppm and 160 ppm, more preferred between 1 ppm and 80 ppm, more preferred between 10 ppm and 40 ppm, more preferred between 15 ppm and 20 ppm is achieved.

9. The device (1) according to claim 6 or 7, characterized in that the controller (6) is programmed to control the gas injector (4) to inject the nitric oxide in a constant concentration to the breathing gas throughout the inhalation cycle, in at least a pulse throughout an inhalation cycle, during every second breathing cycle or during every other natural number of breathing cycles except one.

10. The device (1) according to any of claims 6 to 9, characterized in that the controller (6) is programmed to control the gas injector (4) to inject the nitric oxide during an interval of between 1 minute to 60 minutes, preferably between 1 minute and 30 minutes, more preferably between 5 minutes and 20 minutes with an intermission between two subsequent intervals of between 1 minute to 1 day, preferably of between 1 hour and 8 hours, more preferably between 2 hours and 6 hours, most preferred between 3 hours and 5 hours.

11. The device (1) according to any of claims 6 to 10, characterized in that it comprises a gas sensor (5) for sensing the gas concentration of nitric oxide in the breathing gas administered to the patient interface (20) wherein the gas sensor (5) is in communication with the controller (6).

12. Method for operating a device for ventilating a patient, preferably a device (1) according to any of claims 6 to 11, including an invasive mechanical ventilator (2) for periodically providing a breathing gas to an invasive patient interface (20), characterized in that nitric oxide is injected into the breathing gas provided to the invasive patient interface (20).

13. The method of claim 12, characterized in that nitric oxide is injected to achieve a concentration of between 0.1 ppm and 200 ppm, preferably between 1 ppm and 160 ppm, more preferred between 1 ppm and 80 ppm, more preferred between 10 ppm and 40 ppm, more preferred between 15 ppm and 20 ppm in the breathing gas provided to the invasive patient interface (20).

14. The method according to claim 12 or 13, characterized in that nitric oxide is injected in a constant concentration to the breathing gas throughout an inhalation cycle or in at least a pulse throughout an inhalation cycle.

15. The method according to any of claims 12 to 14, characterized in that the nitric oxide is injected during every second breathing cycle or every other natural number of breathing cycles except one.

16. The method according to any of claims 12 to 15, characterized in that the nitric oxide is injected to the breathing gas during an interval of between 1 minute to 60 minutes, preferably between 1 minute and 30 minutes, more preferably between 5 minutes and 20 minutes with an intermission between two subsequent intervals of between 1 minute to 1 day, preferably of between 1 hour and 8 hours, more preferably between 2 hours and 6 hours, most preferred between 3 hours and 5 hours.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0055] The present disclosure will be more readily appreciated by reference to the following detailed description when being considered in connection with the accompanying drawings in which:

[0056] FIG. 1 is a schematic view of a device for ventilating a patient in an intensive care unit;

[0057] FIG. 2 is a schematic view of another device for ventilating a patient;

[0058] FIG. 3 is a schematic diagram showing the breathing cycle in the device; and

[0059] FIG. 4 is a schematic diagram showing the relation between concentration and duration of treatment.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

[0060] In the following, the invention will be explained in more detail with reference to the accompanying Figures. In the Figures, like elements are denoted by identical reference numerals and repeated description thereof may be omitted in order to avoid redundancies.

[0061] In FIG. 1 a device 1 for ventilating a patient, in particular an invasive mechanical ventilator, is shown. Mechanical ventilators (or simply ventilators in this context) are machines designed to mechanically move breathable air into and out of the lungs of a patient to provide the mechanism of breathing for a patient who is physically either unable to breathe, or is breathing insufficiently.

[0062] In its simplest form, a modern invasive mechanical ventilator consists of a compressible air reservoir or turbine, air and oxygen supplies, a set of valves and tubes, and a disposable or reusable “patient circuit”. The air reservoir is pneumatically compressed several times a minute to deliver room-air or in most cases an air/oxygen mixture to the patient. When overpressure is released, the patient will exhale passively due to the lungs' elasticity, the exhaled air being released usually through a one-way valve within the patient circuit called the patient manifold. The oxygen content of the inspired gas can be set from 21 percent (ambient air) to 100 percent (pure oxygen). Pressure and flow characteristics can be set mechanically or electronically.

[0063] The patient circuit usually consists of a set of three durable, yet lightweight plastic tubes, separated by function (e.g. inhaled air, patient pressure, exhaled air) wherein the patient-end of the circuit is invasive for the current description of the embodiment. The invasive method requires intubation, which for long-term ventilator dependence will normally be a tracheotomy cannula, as this is much more comfortable and practical for long-term care than is larynx or nasal intubation.

[0064] Ventilator-associated pneumonia (VAP) is a concomitant inflammation and infection of the respiratory system which leads to pneumonia. Ventilator-associated pneumonia (VAP) is a life-threatening condition and the second leading cause of infection and death in hospital-acquired infections. 22.8 Percent of the patients receiving mechanical ventilation acquire VAP, which accounts for 86 percent of the patients acquiring hospital associated pneumonia. Not only does this increase the burden and morbidity of a patient, the required hospitalization of six days on average, costs of e.g. diagnostics, medical treatment and professional care together form severe health economics side effects of invasive mechanical ventilation.

[0065] The device 1 includes an invasive mechanical ventilator 2 for providing a breathing gas under positive pressure and positive airflow to a patient who is physically unable to breath or is breathing insufficiently. Inhalation is provided periodically by means of the provision of the positive pressure and positive airflow to the patient. Exhalation can be provided by means of simply releasing the positive pressure provided and using the elastic properties of the lungs of the patients. Exhalation can also be assisted by applying a moderate negative pressure.

[0066] In the present example, the invasive mechanical ventilator 2 is shown as an intensive-care ventilator. The breathing gas is delivered via a hose 26 to an invasive patient interface 20 which is shown exemplary as an endotracheal tube. Generally, an intubation apparatus providing a direct access to the upper airways of the patient to be treated is used as the invasive patient interface 20.

[0067] In other embodiments, the invasive patient interface 20 may have any form which is suitable to supply a patient with a direct access to the upper airways, in particular when undergoing treatment in an intensive care unit. Accordingly, the patient interface 20 may be an endotracheal tube, a tracheostomy tube, a tracheal button, a catheter-based apparatus or any other known device to supply a direct access and a positive airflow to the upper airways of a patient.

[0068] The invasive mechanical ventilator 2 could also be provided in a different setup such as a transport ventilator, a neonatal ventilator or any other device which provides a positive airflow pressure to a patient in a ventilation setup in which the patient is incapable or insufficiently capable to breathe spontaneously.

[0069] The invasive mechanical ventilator 2 provides to the patient a breathing gas in the form of either ambient air, medical air or any other breathable gas mixture provided by a source of breathing gas 22 under positive pressure. The principle of the provision of a breathing gas to a patient under positive pressure in order to achieve in the patient a positive airflow is generally known.

[0070] The invasive mechanical ventilator 2 blows breathing gas at a prescribed positive pressure through the hose 26 to the invasive patient interface 20. In the gas path between the invasive mechanical ventilator 2 and the invasive patient interface 20 a positive pressure is build up and maintained. In the invasive patient interface 20, a pressure relief valve 24 is present which is provided in the form of a one-way valve, which is used for exhalation.

[0071] To prevent or reduce the occurrence of ventilator associated pneumonia (VAP), the following setup for injecting nitric oxide into the breathing air of the patient is provided: A source of gaseous nitric oxide 3 is provided which is intended to enrich the breathing gas which is to be supplied to the patient with nitric oxide in order to prevent the occurrence of VAP.

[0072] To this end, the source of gaseous nitric oxide 3 is connected to a gas injector 4 which is arranged for injecting nitric oxide provided by the source of gaseous nitric oxide 3 to the breathing gas. In the embodiment shown, the gas injector 4 injects the nitric oxide to the breathing gas upstream of the invasive mechanical ventilator 2. In a different embodiment, the gas injector 4 is arranged downstream of the invasive mechanical ventilator 2 or is integrated into the invasive mechanical ventilator 2.

[0073] In other words, the gas injector 4 can be situated between the source of breathing gas 22 and the invasive mechanical ventilator 2 or at the hose 26 close to the invasive mechanical ventilator 2 or close to the patient interface 20.

[0074] Additional means may be applied to perfuse nitric oxide enriched breathing air through proximal air canalization parts e.g. during the inhalation phase. In such an embodiment it is preferred that the gas injector 4 is situated close to the invasive patient interface 20 in order to be in a position to control the injection of the nitric oxide precisely.

[0075] A gas sensor 5 is present which can be situated in the invasive mechanical ventilator 2 or at any other position along the breathing gas path. The gas sensor 5 senses the gas concentrations of the breathing gas provided by invasive mechanical ventilator 2 and provides a feedback means for adjusting the injection of nitric oxide by the gas injector 4.

[0076] The gas sensor 5 may also be situated in a position different from the position shown in the Figures. In particular, said gas sensor 5 may be situated in the invasive patient interface 20.

[0077] When the patient exhales by means of the elasticity of the lungs, a pressure relief valve 24 or any other suitable exhaust opening situated in the invasive patient interface 20, releases the exhaled breathing gas of the patient to the outside. Accordingly, when the patient exhales, the invasive mechanical ventilator 2 does not provide a positive air flow of breathing gas towards the patient interface. The pressure relief valve 24 or any other suitable exhaust opening may be controlled by the invasive mechanical ventilator 2. The gas sensor 5 may be in communication with the invasive mechanical ventilator, such that the gas injector 4 is not controlled during an exhaling phase.

[0078] Accordingly, as schematically shown in FIG. 3, the invasive mechanical ventilator 2 provides an air pressure between a lower threshold L and an upper threshold U periodically, depending on the setting of the control system of the invasive mechanical ventilator 2. The treatment plan of the patient may require a variation of the ventilation pattern such that the different breathing cycles might have a different shape. The invasive mechanical ventilator 2 may also take into account some reflexes of the patient when the patient attempts to breath spontaneously and may also take into account the exhalation pattern when determining the inhalation pattern. These applications and control methods are generally known.

[0079] However, in the simplest form of a treatment protocol, a breathing cycle is provided and the invasive mechanical ventilator 2 provides the breathing gas to the patient up to a pre-set upper pressure threshold U and starts again providing the breathing gas to the patient as soon as—after exhalation—a lower threshold L is reached. This is schematically shown during the inhalation phases I and III in FIG. 3.

[0080] Upon reaching an air pressure above an upper threshold U, the invasive mechanical ventilator 2 no longer provides a positive gas flow from the invasive mechanical ventilator 2 towards the patient interface 20 and allows a passive exhalation in phases II and IV to take place. Again upon reaching an air pressure at a lower threshold L, the invasive mechanical ventilator 2 actively induces an inhaling phase III, continued by another exhaling phase IV as described above and this process is continuously performed.

[0081] A controller 6 is provided which is connected to the gas sensor 5 to receive the signal of the gas concentrations measured by gas sensor 5. The controller 6 is programmed for controlling the injection of the nitric oxide into the breathing gas by means of triggering the gas injector 4. The controller 6 may be in communication with the invasive mechanical ventilator 2. If the invasive mechanical ventilator 2 initiates an inhaling phase, the continuous injection of nitric oxide is triggered by the controller 6.

[0082] Accordingly, nitric oxide is only injected by the gas injector 4 into the breathing gas provided under positive airflow if the patient inhales. By this means nitric oxide consumption can be reduced. Furthermore, as nitric oxide is rapidly oxidized to nitrogen dioxide, the nitric oxide is preferably injected as late as possible into the airflow.

[0083] The nitric oxide is provided to the breathing gas by means of the gas injector 4 either continuously or intermittently. If the nitric oxide is provided continuously, the concentration of nitric oxide which is administered to the patient is constant during the breathing cycle. Accordingly, all regions of the lungs which are ventilated are exposed to nitric oxide in order to prevent, reduce or suppress the development of ventilator-associated pneumonia (VAP) and/or the concomitant inflammation and infection of the respiratory system leading to pneumonia.

[0084] However, nitric oxide can also be added to the breathing gas of the patient in a different pattern, for example every second breathing cycle only (or after any suitable number of breathing cycles). In order to treat different areas or regions within the lung of the patient, a single or a number of subsequent pulses P of nitric oxide can be injected into the positive flow of breathing gas detected by the flow rate sensor 5. By triggering the different spikes of the injection of nitric oxide, the depth within the lungs that can be reached by the nitric oxide can be varied. The different pulses may have differing widths, depending on the respective prescription.

[0085] In an alternative, the nitric oxide is injected into the breathing gas as a constant flow or varying flow of gas.

[0086] The controller 6 is programmed and arranged to control the gas injector 4 such that the concentration of the nitric oxide in the breathing gas can be controlled, preferably to a concentration of between 0.1 ppm and 200 ppm, preferably between 1 ppm and 160 ppm, more preferred between 1 ppm and 80 ppm, more preferred between 10 ppm and 40 ppm, more preferred between 15 ppm and 20 ppm.

[0087] Preferably, the controller 6 is further programmed for controlling the injection of the nitrous oxide via the gas injector 4 with a feedback loop provided by the gas sensor 5. If measured gas concentrations by gas sensor 5 do not match the predefined values, gas concentrations can be adjusted as such.

[0088] The concentration of the nitric oxide is chosen such that a reduction, suppression or prevention of multiplication and/or replication of bacteria, viruses, protozoae, fungi and/or microbes is achieved. Preferably, low concentrations are applied to reduce detrimental effects on host tissue, however, higher concentrations may be chosen if other effects such as e.g. vasodilatation, mucolytic properties and/or bactericidal effects are favorable for the patient and these concentrations can be applied continuously without reaching toxic in vivo levels.

[0089] The source of gaseous nitric oxide 3 preferably provides a carrier gas, for example N.sub.2, such that the nitric oxide is provided in a concentration of about 100 ppm to 10000 ppm, preferably 1000 ppm to 10000 ppm. The higher the concentration of the nitric oxide in the source of gaseous nitric oxide 3, the smaller a gas container for supplying the nitric oxide can be. This is preferred for distribution reasons.

[0090] As an alternative source of nitric oxide, nitric oxide can also be produced at the required location. Such production methods are known in the art. U.S. Pat. No. 5,396,882 discloses e.g. the application of an electric arc to enrich NO from air, whereas US 2006/172018 provides a method for obtaining NO by controlling the diffusion and/or dissolution of nitride salts or other precursor compositions. NO can also be derived through a reaction with reduction agents. An example of such a method can e.g. be found in US 2011/220103. The methods described here should not be appreciated such that these are limiting, but merely provide examples from a plurality of alternative methods known in the art.

[0091] In order to make sure that the patient is provided with the desired concentration of nitric oxide in the breathing gas offered to the patient, the concentrated gas supplied by the source of gaseous nitric oxide 3 needs to be diluted. Furthermore, the increased N.sub.2 content by the carrier gas in the gas supplied by the source of gaseous nitric oxide 3 needs to be supplemented by a suitable concentration of oxygen such that the patient does not suffer from low oxygen levels.

[0092] To provide a suitable mixture of gas which preferably comprises the oxygen content of ambient air, a supply of oxygen is provided which enables the addition of oxygen to the breathing gas which is offered under invasive mechanical ventilation to the patient.

[0093] However, the higher the concentration of nitric oxide in the source of gaseous nitric oxide 3, the lower the proportion of the carrier gas, for example nitrogen, such that it is no longer necessary to add oxygen in order to achieve a breathable gas. In other words, the carrier does not displace oxygen in a critical amount such that oxygen would not have to be added to the breathing gas for this reason alone.

[0094] In the invasive mechanical ventilator 2 the breathing curve of the patient is predefined and can be adjusted according to patient observation. Accordingly, the gas injector 4 is controlled by the controller 6 according to a predetermined scheme and preferable injects a mixture of nitric oxide and the carrier gas nitrogen upstream of a mixing channel 40 in which the gas is conducted in turbulent manner such as to ensure proper mixing.

[0095] The nitric oxide can be injected via the gas injector 4 just on the basis of the inhaled gas concentrations as determined by the gas sensor 5.

[0096] In FIG. 2 another device 1 for the prevention of ventilator-associated infections of the respiratory system is shown which has, in principle, the same setup as the one shown in FIG. 1. Additional preferred features of the device 1 are shown therein.

[0097] In a preferred embodiment, at the patient interface 20 a sample gas conduit 70 is provided which enables drawing test samples of air from the gas that is offered to the patient under positive airway pressure. The test samples can be analyzed in a gas sensor 7 such that the concentration of nitric oxide injected into the gas stream offered to the patient under positive airflow can be determined. The concentrations determined by the gas sensor 7 can be supplied to the controller 6 to further adjust the concentrations in order to ensure that the gas injector 4 injects the correct amount of nitric oxide such that the desired concentration is achieved at the patient interface 20 where the gas flows into the patient. The sample gas conduit 7 can be in communication or in-line with the pressure relief valve 24.

[0098] Furthermore, via the gas sensor 7 the occurrence of nitrogen dioxide in the invasive patient interface 20 can be monitored and if the concentration of nitrogen dioxide exceeds a predetermined level, the controller 6 lowers the concentration of nitric oxide injected into the gas flow, stops the injection of nitric oxide for one or more breathing cycles and/or triggers an alarm.

[0099] In a preferred embodiment, the gas sensor 7 also allows measuring the oxygen content of the gas offered to the patient under positive airway pressure upon invasive mechanical ventilation and sends feedback to the controller 6 such that the injection of additional oxygen supplied by an oxygen supply 80 via an oxygen injector 8 into the breathing gas of the patient can be adjusted accordingly. The oxygen concentration offered to the patient under positive airflow preferably resembles the oxygen concentration in ambient air, but can also be higher if the prescription calls for a higher concentration of oxygen.

[0100] The injection of oxygen into the flow of breathing gas takes place as close as possible to the patient interface 20 in order to reduce the contact of the oxygen with the nitric oxide to the least possible degree.

[0101] The controller 6 is preferably connected to a data communication module 60 as well as a monitoring module 62 which enables recording of the treatment data such that a doctor or control room in an intensive care unit can determine whether the patient was supplied with the prescribed doses of nitric oxide. The data communication module 60 can use any suitable form of communication with a doctor or control room such as, for example, wired data communication, wireless data communication or storage of data to a suitable data carrier. The format of the data communication preferably uses standard communication formats and protocols such as the internet protocol or any other telecommunication standards which enable communication of data between the device 1 and the doctor or control room.

[0102] Nitric oxide and nitrogen dioxide which is exhaled from the patient interface 20 can be treated before it is released to the environment. For the treatment of nitric oxide and nitrogen dioxide different methods and devices are available. However, in a regular setting, since the administered concentration of nitric oxide is below any toxic level, the exhaled gas from the patient interface 20 that is released into the surroundings does not require prior treatment because the overall concentrations of these gases are very low.

[0103] However, in case the gas exhaled by the patient as well as the gas withdrawn from the patient interface 20 is to be treated, the gases are collected via an output line 30 in a centralized waste gas treatment device 32 which treats the NO and nitrogen dioxide such that the treated gas can be released to the outside. In hospitals such devices for waste gas treatment are usually present.

[0104] In FIG. 4 a schematic diagram showing the interdependence between the concentration of NO supplied to the breathing gas of a patient and a treatment duration of a treatment interval. It can be seen that the treatment duration is longer when the concentration of NO is lower. However, when the concentration of NO increases, the treatment duration is shorter.

[0105] The graphs a, b, c show levels of different reduction of bacteria, viruses and fungi in a given setting. For example, graph a) shows a reduction of 90%, graph b) shows a reduction of 75% and graph c) shows a reduction of 50% of the bacteria, viruses and fungi in this setting. Accordingly, in order to achieve a higher reduction as shown with graph a, higher concentrations of NO would be necessary or longer treatment durations in a treatment interval.

[0106] Another parameter of a treatment regime would be the intermission between treatment intervals. This parameter, however, is not necessarily correlated with the concentrations and treatment durations of the administration of NO. It is rather determined on the basis of the growth rate of the bacteria, viruses and fungi considered harmful.

[0107] Starting from a situation after termination of a treatment interval, bacteria, viruses and fungi are at a low level. However, they start growing again such that they might approach a critical level again. Accordingly, before this critical level is reached the next treatment interval is to be initiated.

[0108] On the basis of these parameters, a treatment regime can be established which balances the positive and negative effects of NO and which helps achieve the goal of reducing or suppressing the occurrence of ventilator-induce pneumonia.

LIST OF REFERENCE NUMERALS

[0109] 1 device for ventilating a patient [0110] 2 invasive mechanical ventilator [0111] 20 invasive patient interface [0112] 22 source of breathing gas [0113] 24 pressure relief valve [0114] 26 hose [0115] 3 source of gaseous nitric oxide [0116] 30 output line [0117] 32 waste gas treatment [0118] 4 gas injector [0119] 40 mixing channel [0120] 5 gas sensor [0121] 6 controller [0122] 60 data communication module [0123] 62 monitoring module [0124] 7 gas sensor [0125] 70 sample gas conduit [0126] 8 oxygen injector [0127] 80 oxygen supply [0128] I inhalation phase [0129] II exhalation phase [0130] III inhalation phase [0131] IV exhalation phase [0132] L lower threshold [0133] U upper threshold [0134] p pressure