阅读说明：本技术 机械通气的自动peep选择 (automatic PEEP selection for mechanical ventilation ) 是由 F·比卡里奥 R·布伊扎 W·A·特鲁什切尔 于 2018-02-22 设计创作，主要内容包括：本公开涉及一种被配置为在机械通气(800)期间自动设置呼气末正压(PEEP)的系统(10)。所述系统使用测量的跨肺压(804)与肺容量(808)之间的关系来设置PEEP,以便将机械辅助呼吸更有效地递送到开放气道(例如,潮气呼吸将被递送到包括在呼气未最终没有收缩或坍缩的肺泡的气道)(810)。此外,所述系统被配置为感测(18、804)何时肺可能过度扩张和/或经历周期性肺不张,以防止对肺纤维组织的创伤或损伤。所述系统被配置为执行PEEP设置的恢复和/或连续监测和调整以维持肺开放。(The present disclosure relates to a system (10) configured to automatically set a Positive End Expiratory Pressure (PEEP) during mechanical ventilation (800). The system uses the relationship between measured cross-lung pressure (804) and lung volume (808) to set PEEP in order to more efficiently deliver mechanically assisted breathing to an open airway (e.g., tidal breathing will be delivered to an airway including alveoli that do not eventually contract or collapse upon exhalation) (810). Further, the system is configured to sense (18, 804) when the lung may be over-expanded and/or experience periodic atelectasis to prevent trauma or injury to lung fibrous tissue. The system is configured to perform recovery of PEEP settings and/or continuous monitoring and adjustment to maintain lung patency.)

1. a mechanical ventilator system (10) configured to control Positive End Expiratory Pressure (PEEP) of a subject (12), the mechanical ventilator system comprising:

A pressure generator (14) configured to generate a pressurized flow of breathable gas for delivery to the airway of a subject;

one or more sensors (18) configured to generate output signals conveying information related to respiration of the subject; and

one or more hardware processors (20) coupleable to the pressure generator and the one or more sensors, the one or more hardware processors configured by machine-readable instructions to:

Determining a tidal volume and a transpulmonary pressure of the subject based on the information in the output signals;

Determining a target PEEP level based on a lung volume and the cross-lung pressure, the lung volume determined based on the tidal volume; and is

causing the pressure generator to adjust the pressurized flow of breathable gas to maintain the determined target PEEP level.

2. The system of claim 1, wherein the one or more hardware processors are configured such that determining the target PEEP level based on the lung volume and the cross-lung pressure comprises:

Determining a curve of lung volume versus cross-lung pressure based on the information in the output signal;

Identifying one or more inflection points in the curve; and is

Determining the target PEEP level from the one or more inflection points.

3. The system of claim 2, wherein the one or more hardware processors are configured such that determining the target PEEP level based on the lung volume and the cross-lung pressure further comprises:

identifying a dip inflection point in the curve;

Causing the pressure generator to adjust the pressurized flow of breathable gas to reduce therapeutic PEEP levels in the subject in individual breaths in a series of subsequent breaths until a concave upward inflection point is identified;

Causing the pressure generator to adjust the pressurized flow of breathable gas to increase a therapeutic PEEP level to a level between the lower concave inflection point and the upper concave inflection point proximate the lower concave inflection point in at least one other breath; and is

In at least one second additional breath, setting the target PEEP level to a level proximate the concave inflection point between pressures corresponding to the concave and concave inflection points to maintain an open airway of the subject.

4. the system of claim 2, wherein the one or more hardware processors are configured such that determining the target PEEP level based on the lung volume and the cross-lung pressure further comprises:

Identifying a concave up inflection point in the curve; and is

Causing the pressure generator to adjust the pressurized flow of breathable gas to increase a therapeutic PEEP level in the subject in individual breaths in a series of subsequent breaths until the concave upward inflection point is no longer identified in a portion of the curve corresponding to a most recent breath.

5. the system of claim 2, wherein the one or more physical processors are further configured to:

Identifying concave-up and concave-down inflection points in the curve; and is

Automatically suggesting lung restitution in response to:

At a constant PEEP level, a decrease in compliance over time, the decrease in compliance over time being determined based on the information in the output signal; and/or

A change in a position of the inflection point.

6. The system of claim 1, wherein the one or more sensors are configured such that the information related to the breathing of the subject includes a flow rate (Q) of the pressurized flow of breathable gas and a pressure (Pao) of breathable gas at the mouth of the subject, and

wherein the one or more hardware processors are configured such that determining the cross-lung pressure of the subject based on the information in the output signals comprises:

Determining airway resistance (R) and elasticity (E) based on Q and Pao;

Determining alveolar pressure (Pal) and muscle pressure (Pmus) of the subject based on R and E; and is

Determining the transpulmonary pressure based on Pal and Pmus.

7. The system of claim 1, wherein the one or more sensors comprise: a flow rate sensor configured to generate output signals conveying information related to a flow rate of the pressurized flow of breathable gas; and a pressure sensor that conveys information related to the pressure of the breathable gas at the mouth of the subject.

8. The system of claim 1, wherein the one or more hardware processors are configured to determine a transmural pressure in lieu of a transpulmonary pressure, and determine the target PEEP level based on the lung volume and the transmural pressure.

9. A method of controlling Positive End Expiratory Pressure (PEEP) of a subject (12) using a mechanical ventilator system (10) including a pressure generator (14), one or more sensors (18), and one or more hardware processors (20), the method comprising:

Generating, with the pressure generator, a pressurized flow of breathable gas for delivery to the airway of the subject;

Generating output signals with the one or more sensors, the output signals conveying information related to respiration of the subject;

Determining, with one or more hardware processors, a tidal volume and a transpulmonary pressure of the subject based on the information in the output signals;

Determining, with the one or more hardware processors, a target PEEP level based on a lung volume and the cross-lung pressure, the lung volume determined based on the tidal volume; and is

Causing, with the one or more hardware processors, the pressure generator to adjust the pressurized flow of breathable gas to maintain the determined target PEEP level.

10. the method of claim 9, wherein determining the target PEEP level based on the lung volume and the transpulmonary pressure comprises:

Determining a curve of lung volume versus cross-lung pressure based on the information in the output signal;

Identifying one or more inflection points in the curve; and is

determining the target PEEP level from the one or more inflection points.

11. the method of claim 10, wherein determining the target PEEP level based on the lung volume and the transpulmonary pressure further comprises:

Identifying a dip inflection point in the curve;

Causing the pressure generator to adjust the pressurized flow of breathable gas to reduce therapeutic PEEP levels in the subject for individual breaths in a series of subsequent breaths until a concave upward inflection point is identified;

Causing the pressure generator to adjust the pressurized flow of breathable gas to increase a therapeutic PEEP level to a level between the concave inflection point and the concave inflection point proximate the concave inflection point in at least one additional breath; and is

In at least one second additional breath, setting the target PEEP level to a level proximate the concave inflection point between pressures corresponding to the concave and concave inflection points to maintain an open airway of the subject.

12. the method of claim 10, wherein determining the target PEEP level based on the lung volume and the transpulmonary pressure further comprises:

Identifying a dip inflection point in the curve; and is

Causing the pressure generator to adjust the pressurized flow of breathable gas to increase a therapeutic PEEP level in a subject in individual breaths in a series of subsequent breaths until the concave upward inflection point is no longer identified in a portion of the curve corresponding to a most recent breath.

13. The method of claim 10, further comprising:

Identifying concave-up and concave-down inflection points in the curve; and is

Automatically suggesting lung restitution in response to:

at a constant PEEP level, a decrease in compliance over time, the decrease in compliance over time being determined based on the information in the output signal; and/or

A change in a position of the inflection point.

14. The method of claim 9, wherein the information related to the breathing of the subject comprises: a flow rate (Q) of the pressurized flow of breathable gas and a pressure (Pao) of breathable gas at the mouth of the subject, and

Wherein determining the cross-lung pressure of the subject based on the information in the output signal comprises:

Determining airway resistance (R) and elasticity (E) based on Q and Pao;

Determining alveolar pressure (Pal) and muscle pressure (Pmus) of the subject based on R and E; and is

Determining the transpulmonary pressure based on Pal and Pmus.

15. The method of claim 9, wherein the one or more sensors comprise: a flow rate sensor configured to generate output signals conveying information related to a flow rate of the pressurized flow of breathable gas; and a pressure sensor that conveys information related to the pressure of the breathable gas at the mouth of the subject.

Technical Field

the present disclosure relates to a method and mechanical ventilator system for and controlling Positive End Expiratory Pressure (PEEP) in a subject.

Background

Mechanical ventilators assist in breathing by pushing air into the lungs of the patient. The ventilator may operate in different control modes. The method of dynamically and automatically combining lung renaturation with proper selection and maintenance of PEEP requires a static view of the lung volume to which pressure is applied. These methods are cumbersome and do not allow real-time assessment of alveolar recovery, thus requiring constant observation of the patient to prevent over-dilatation, atelectasis, or circulatory clipping of the alveoli.

Disclosure of Invention

accordingly, one or more aspects of the present disclosure relate to a mechanical ventilator system configured to control Positive End Expiratory Pressure (PEEP) in a subject. The mechanical ventilator system includes a pressure generator, one or more sensors, one or more hardware processors, and/or other components. The pressure generator is configured to generate a pressurized flow of breathable gas for delivery to the airway of a subject. The one or more sensors are configured to generate output signals conveying information related to respiration of the subject. One or more hardware processors can be coupled to the pressure generator and the one or more sensors and configured by machine readable instructions to: determining a tidal volume and a transpulmonary pressure of the subject based on the information in the output signals; determining a lung volume from the tidal volume; determining a target PEEP level based on the lung volume and the transpulmonary pressure; and cause the pressure generator to adjust the pressurized flow of breathable gas to maintain the determined target PEEP level.

another aspect of the present disclosure relates to a method for controlling PEEP in a subject with a mechanical ventilator system. The mechanical ventilator system includes a pressure generator, one or more sensors, one or more hardware processors, and/or other components. The method comprises the following steps: generating, with the pressure generator, a pressurized flow of breathable gas for delivery to the airway of the subject; generating, with the one or more sensors, output signals conveying information related to respiration of the subject; determining, with one or more hardware processors, a tidal volume and a transpulmonary pressure of the subject based on the information in the output signals; determining, with the one or more hardware processors, a lung volume based on the tidal volume; determining, with the one or more hardware processors, a target PEEP level based on the lung volume and the cross-lung pressure; and causing, with the one or more hardware processors, the pressure generator to adjust the pressurized flow of breathable gas to maintain the determined target PEEP level.

Yet another aspect of the present disclosure is directed to a system for controlling PEEP in a subject. The system comprises: means for generating a pressurized flow of breathable gas for delivery to the airway of the subject; means for generating output signals conveying information related to respiration of the subject; means for determining a tidal volume and a transpulmonary pressure of the subject based on the information in the output signals; means for determining, with the one or more hardware processors, a lung volume based on the tidal volume; means for determining a target PEEP level based on the lung volume and the cross-lung pressure; and means for causing the means for generating the pressurized flow of breathable gas to adjust the pressurized flow of breathable gas to maintain the determined target PEEP level.

These and other features and characteristics of the present invention, as well as the methods of operation and functions of the related elements of structure and the combination of parts and economies of manufacture, will become more apparent upon consideration of the present invention and the appended claims with reference to the accompanying drawings, all of which form a part of this specification, wherein like reference numerals designate corresponding parts in the various figures. It is to be expressly understood, however, that the drawings are for the purpose of illustration and description only and are not intended as a definition of the limits of the disclosure.

Drawings

Fig. 1 is a schematic illustration of a system configured to control Positive End Expiratory Pressure (PEEP) of a subject;

FIG. 2 schematically illustrates Pao, R, Q, Pa1, E, and Pmus in a respiratory mechanics system represented as a single-chamber linear model;

FIG. 3 is an input-output diagram illustrating the determination of parameters R, Pal, E, and Pmus based on Pao and Q;

FIG. 4 illustrates airway compliance as a function of increased PEEP levels;

FIG. 5 illustrates an example p-v curve for a lung of a subject;

FIG. 6 illustrates another example p-v curve for a lung of a subject;

FIG. 7 illustrates a set of possible operations performed by the system to determine a target PEEP level; and is

Fig. 8 illustrates a method for controlling PEEP in an object.

Detailed Description

As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. The statement that two or more parts or components are "coupled" as used herein shall mean that the parts are joined together or work together either directly or indirectly (i.e., through one or more intermediate parts or components, so long as a connection occurs). As used herein, "directly coupled" means that two elements are in direct contact with each other. As used herein, "fixedly coupled" or "fixed" means that two components are coupled to move as one while maintaining a fixed orientation relative to each other.

the word "integral" as used herein means that the components are created as a single piece or unit. That is, a component that comprises multiple pieces that are created separately and then coupled together as a unit is not a "unitary" component or body. As used herein, the statement that two or more parts or components "engage" one another shall mean that the parts exert a force on one another either directly or through one or more intermediate parts or components. The term "plurality" as used herein shall mean one or an integer greater than one (i.e., a plurality).

directional phrases used herein, such as, but not limited to, top, bottom, left, right, upper, lower, front, rear, and derivatives thereof, relate to the orientation of the elements shown in the drawings and are not limiting upon the claims unless expressly recited therein.

Fig. 1 is a schematic diagram of a mechanical ventilator system 10 configured to control Positive End Expiratory Pressure (PEEP) in a subject 12. In some embodiments, controlling PEEP comprises selecting and maintaining a target PEEP level in subject 12. The collapsed lung requires the application of pressure to expand the alveoli. Once an alveolus is open, it tends to interact with and remain open to adjacent alveolus. Lung refolding is used to open the collapsed lungs of a dyspnea subject and improve its mechanical ventilation. PEEP is controlled during lung atelectasis and/or at other times to prevent circulatory collapse (as part of an open lung ventilation procedure) to increase end-tidal lung volume, improve gas exchange, reduce ventilator and/or other cause-induced lung injury (VILI). Lung remodeling involves temporarily increasing airway pressure to open collapsed alveoli. For example, failure of recovery may result from poor ventilation, insufficient PEEP, and/or chest wall instability. Alveolar collapse may lead to poor gas exchange and increased risk of VILI. Some alveoli may collapse during breathing, collapse periodically and expand again as the person breathes, and/or collapse at other times. Also, due to high tidal volumes and high pressures, other alveoli in the lungs may remain inflated and/or over inflated, causing trauma. For example, pulmonary renaturation may be used in subjects with severe Acute Respiratory Distress Syndrome (ARDS) and/or other subjects, may be part of a pulmonary protective ventilation strategy, and/or may be used as part of an open lung ventilation method.

the system 10 is configured to dynamically and automatically select and maintain a target PEEP level for and/or during lung renaturation. Previous methods require a static view of the lung volume and applied pressure of the subject. These previous methods are cumbersome and do not allow real-time assessment of alveolar recovery, thus requiring constant observation of the subject to prevent over-dilation, atelectasis, or cyclic shearing of the alveoli. With the development of subjects with acute respiratory distress, there is an occasional need for periodic lung renaturation to keep the lungs open. The desired target PEEP level during these procedures may vary over time (e.g., caused by surfactant treatment, natural production of lipids contained in the surfactant to reduce surface tension in the alveoli, and/or other factors). During mechanical ventilation management, the need to assess and adjust target PEEP levels is constantly changing, which is a heavy burden on any caregiver.

Existing tools available to caregivers cannot keep the lungs open. For example, a pressure/volume (p-v) loop generated by a typical ventilator system plots tidal volume versus mouth pressure. Such a loop contributes to transmural pressure affecting the alveoli by not accounting for the effects of resistive pressure drops on the airway of the subject and (e.g., muscle) effort by the subject. As a result, the caregiver needs to interpret the p-v loop, and typically, static operation by the caregiver (e.g., manually increasing the pressure and observing the resulting tidal volume) is necessary to characterize the p-v relationship of the lung itself. Manually performed lung restitution requires the presence of skilled personnel. As a result, such manipulation is rarely performed. The lack of continuous monitoring of PEEP further exacerbates the problem of infrequent lung renaturation.

advantageously, the system 10 is configured to determine the target PEEP level based on a p-v curve, wherein the lung volume is plotted against the cross-lung pressure, i.e. the pressure difference across the elastic compartments (lung and chest wall) of the respiratory system. Performing pulmonary renaturation typically involves pulmonary hypertension. The system 10 is configured to monitor alveolar (and, hence, transpulmonary) pressure rather than oral pressure and ensure that it is maintained within safe limits. The system 10 is configured to determine a p-v curve (lung volume versus transpulmonary pressure) in real time and/or near real time to facilitate maintaining automatic lung manipulation at a set target PEEP level and throughout mechanical ventilation. The system 10 is configured to assist caregivers in their daily management of subjects by eliminating the need to perform artificial lung restitution, among other advantages. The system 10 is also useful during, for example, a catastrophic event in which many people may need to be ventilated without skilled caregivers.

in some embodiments, system 10 includes one or more of pressure generator 14, subject interface 16, one or more sensors 18, one or more processors 20, user interface 22, electronic storage 24, and/or other components.

Pressure generator 14 is configured to generate the pressurized flow of breathable gas for delivery to the airway of subject 12. Pressure generator 14 may control one or more ventilation parameters of the flow of gas (e.g., rate, pressure, volume, temperature, composition, etc.) for therapeutic purposes and/or other purposes. Pressure generator 14 is configured to control one or more ventilation parameters of the pressurized flow of breathable gas in accordance with a prescribed mechanical ventilation therapy regime and/or other therapy regime. As non-limiting examples, pressure generator 14 may be configured to control respiratory rate, flow rate, oral pressure waveform, Positive End Expiratory Pressure (PEEP), tidal volume, minute volume, inspiratory to expiratory respiratory phase ratio (e.g., I: E ratio), and/or other ventilation parameters of the gas flow.

pressure generator 14 receives a flow of gas from a gas source, such as the ambient atmosphere, and raises and/or lowers the pressure of the gas for delivery to the airway of subject 12. Pressure generator 14 is and/or includes any device capable of raising and/or lowering the pressure of gas received for delivery to a patient, such as a pump, blower, piston, or bellows. Pressure generator 14 may include servo-controlled valves and/or motors, one or more other valves and/or motors for controlling the pressure and/or flow rate of the gas, and/or other components. The present disclosure also contemplates controlling the operating speed of the blower, either alone or in combination with such valves, to control the pressure and/or flow rate of the gas provided to subject 12.

subject interface 16 is configured to deliver the pressurized flow of breathable gas to the airway of subject 12. As such, subject interface 16 includes conduit 30, interface appliance 32, and/or other components. Conduit 30 is configured to deliver a pressurized flow of gas to interface appliance 32. Conduit 30 may be a length of flexible hose, or other conduit that places interface appliance 32 in fluid communication with pressure generator 14. Interface appliance 32 is configured to deliver a flow of gas to the airway of subject 12. In some embodiments, interface appliance 32 is non-invasive. In this manner, the interface device 32 non-invasively engages the subject 12. Non-invasive engagement includes removably engaging one or more areas (e.g., nostrils and/or mouth) surrounding one or more external orifices of the airway of subject 12 to communicate gas between the airway of subject 12 and interface appliance 32. Some examples of non-invasive interface appliance 32 may include, for example, a nasal cannula, nasal mask, nasal/oral mask, full face mask, or other interface appliance in airflow communication with the airway of the subject. The present disclosure is not limited to these examples, and contemplates delivery of airflow to a subject using any interface appliance, including invasive interface appliances such as endotracheal tubes and/or other appliances.

Sensor 18 is configured to generate output signals conveying information related to respiration and/or other gases and/or respiratory parameters of subject 12. In some embodiments, the information related to the breathing of subject 12 includes the flow rate of the pressurized flow of breathable gas (and/or information related to the flow rate), the pressure and/or other location of the pressurized flow of breathable gas at the mouth of subject 12, and/or other information. In some embodiments, information related to respiration of subject 12 may include information related to volume (e.g., tidal volume, minute volume, etc.), pressure (e.g., inhalation pressure, exhalation pressure, etc.), composition (e.g., concentration) of constituent gas (es), gas temperature, gas humidity, acceleration, velocity, acoustics, parameters indicative of changes in respiratory effort by subject 12, and/or other parameters. In some embodiments, the sensor 18 may generate the output signal substantially continuously at predetermined intervals in response to the occurrence of a predetermined event and/or at other times. In some embodiments, the predetermined intervals, events, and/or other information may be determined at the time of manufacture based on user input via user interface 22 and/or based on other information.

sensor 18 may include one or more sensors that directly measure these parameters (e.g., via fluid communication with the airflow in subject interface 16). The sensor 18 may include one or more sensors that indirectly generate output signals related to one or more parameters of the gas flow. For example, one or more of sensors 18 may generate an output based on an operating parameter of pressure generator 14 (e.g., valve driver or motor current, voltage, rotational speed, and/or other operating parameters).

Although sensor 18 is illustrated as being located at (or in communication with) a single location within conduit 30 between interface appliance 32 and pressure generator 14, this is not intended to be limiting. Sensors 18 may include sensors disposed in a plurality of locations, e.g., within pressure generator 14, within (or in communication with) interface appliance 32, in communication with subject 12, and/or in other locations. For example, sensors 18 may include flow rate sensors, pressure sensors that convey information related to the pressure of the breathable gas at the mouth and/or other locations of subject 12, volume sensors, temperature sensors, acoustic sensors, gas composition (e.g., SpO2 sensors) sensors, and/or other sensors located at various locations in system 10.

Processor 20 is configured to provide information processing capabilities in system 10. As such, the processor 20 may include one or more of the following: a digital processor, a logic processor, a digital circuit designed to process information, a logic circuit designed to process information, a state machine, and/or other mechanisms for electronically processing information. Although processor 20 is shown in fig. 1 as a single entity, this is for illustration purposes only. In some implementations, processor 20 may include multiple processing units. These processing units may be physically located within the same device (e.g., pressure generator 14), or processor 20 may represent processing functionality of multiple devices operating in conjunction.

As shown in fig. 1, processor 20 is configured to execute one or more computer program components. The one or more computer program components may include one or more parameter components 40, PEEP components 42, control components 44, and/or other components. Processor 20 may be configured to execute components 40, 42, and/or 44 via software; hardware; firmware; some combination of software, hardware, and/or firmware; and/or other mechanisms for configuring processing capabilities on processor 20. In some embodiments, processor 20 may perform one or more of the operations described below and/or other operations substantially continuously (e.g., in real-time and/or near real-time) at predetermined intervals, in response to the occurrence of predetermined events, and/or at other times. In some embodiments, the predetermined intervals, events, and/or other information may be determined at the time of manufacture based on user input via user interface 22 and/or based on other information.

It should be understood that although components 40, 42, and/or 44 are illustrated in fig. 1 as being co-located within a single processing unit, in implementations in which processor 20 includes multiple processing units, one or more of components 30, 40, 42, and/or 44 may be located remotely from the other components. The functionality described below as not being provided by the same components 40, 42, and/or 44 is for illustrative purposes, and is not intended to be limiting, as components 40, 42, and/or 44 may provide more or less functionality than is described. For example, one or more of components 40, 42, and/or 44 may be eliminated, and some or all of its functionality may be provided by other components 40, 42, and/or 44. As another example, processor 20 may be configured to execute one or more additional components that may perform some or all of the functionality attributed below to one of components 40, 42, and/or 44.

Parameter component 40 is configured to determine a tidal volume, a lung volume, a transpulmonary pressure, a PEEP, and/or other parameters related to the pressurized flow of breathable gas and/or the breathing of subject 12. In some embodiments, tidal volume, lung pressure, PEEP, and/or other parameters are determined based on information in the output signals, a determination of one or more other parameters, and/or other information. For example, lung volume may be determined based on tidal volume by stitching together several measurements of tidal volume. In some embodiments, the information related to the breathing of subject 12 (e.g., information in the output signals) includes the flow rate (Q) of the pressurized flow of breathable gas, the pressure of the breathable gas at the mouth of the subject (PAO), and/or other information. In some embodiments, determining the tidal volume of subject 12 based on the information in the output signals includes multiplying the flow rate by a time period corresponding to a given breath. In some embodiments, determining the transpulmonary pressure of subject 12 based on the information in the output signals includes determining airway resistance (R) and elasticity (E) based on Q and Pao, determining alveolar pressure (Pal) and muscle pressure (Pmus) in subject 12 based on R and E, and determining the transpulmonary pressure based on Pal and Pmus.

fig. 2 schematically shows how the above parameters are dynamically related to each other. The respiratory system of the patient is modeled as a single compartment, represented in fig. 1 as an electrical simulation 200. The lung and chest wall are modeled as elastic compartments served by a single resistive path (airway). The pressure at the entrance of the resistive path corresponds to the airway opening pressure (Pao 202), while the pressure in the elastic compartment represents the alveolar pressure (Pal 208). The system is subjected to an external pressure (Pmus 212) which represents the equivalent pressure of the force exerted by the respiratory muscle. The dynamics of the flow Q through the different components of the respiratory system are driven by the pressure difference Pao-Pmus. The elastic properties of the elastic compartment are described by an elasticity parameter E210 and the resistive properties of the resistive component are described by a resistance parameter R204.

Using the model shown in fig. 2, the transpulmonary pressure or the pressure on the transrespiratory elastic compartment can be determined by subtracting Pmus from Pal, where the elastic element E210 comprises the lung and the chest wall. Determining the resistance (R) and elasticity (E) based on Q and Pao (e.g., based on information in the output signal from sensor 18) may be performed according to the formula(s) shown below and/or other formulas. For example, over a time sample t during expiration of the ventilator providing the set PEEP

τ＝median(-(V(t)-V(t))/(Q(t)-Q(t)))。

also:

E ═ E (Pao (teoi) -Pao (t0))/(τ (Q (teoi) -Q (t0)) + (V (teoi) -V (t 0))); and is

R＝τE,

where t0 is the time at which the patient starts breathing (or the ventilator if the patient is passive), and tEOI is the time at which the ventilator is off. τ is the respiratory system time constant, which can be estimated as the median (as above) or, for example, by the ordinary least squares method. Determining alveolar pressure (Pal) and muscle pressure (Pmus) in subject 12 based on R and E may be performed according to the formulas shown below and/or other formulas. For example,

pal (t) ═ pao (t) -rq (t); and is

Pmus(t)＝Pao(t)-RQ(t)-E(V(t)-(V(t0))-Pal(t0).

As described above, the transpulmonary pressure P can be determined transpulmonary based on Pa1 and Pmus according to the formula shown below and/or other formulas.

P transpulmonary (t) ═ pal (t) -pmus (t)

By way of non-limiting example, fig. 3 is an input-output diagram 300 illustrating determining 302 (e.g., using the above formula) parameters R204, Pal208, E210, and Pmus 212 based on Pao 202 and Q206. As shown in fig. 3, system 10 (fig. 1) is configured such that only measurements of air flow rate (Q206) and pressure (Pao 202) based on information in output signals from sensors 18 positioned in communication with subject interface 16 at the mouth of subject 12 are required to make breath-by-breath estimates of R204, E210, Pal208, Pmus 212, and/or other parameters. In some embodiments (e.g., during non-invasive ventilation), the flow rate and pressure at the mouth of the subject are estimated based on flow rate and pressure measurements obtained using sensors located in the ventilator.

In some embodiments, a transmural pressure (Pal-pleural pressure (Ppl)) is determined instead of and/or in addition to a transpulmonary pressure, and a target PEEP level is determined based on lung volume, transmural pressure, and/or other information (e.g., as described herein). In such embodiments, subject interface 16 (fig. 1) and/or sensor 18 (fig. 1) may include one or more invasive components configured to facilitate measurement of pleural pressure (e.g., via an esophageal catheter and/or other components).

Returning to fig. 1, PEEP component 42 is configured to determine a target PEEP level. The target PEEP level is determined based on information in the output signal from sensor 18, parameters determined by parameter component 40 (e.g., including lung volume, cross-lung pressure, and/or other parameters), and/or other information. In some embodiments, PEEP component 42 is configured to determine a target PEEP level and determine airway compliance C (e.g., 1/E as described above) for individual PEEP levels by controlling pressure generator 14 to generate the pressurized flow of breathable gas to achieve a range of increased PEEP levels in subject 12 over a range of breaths of subject 12. In some embodiments, PEEP component 42 is configured to cause breaths with increased PEEP levels to be controlled in tidal volume and/or to limit alveolar pressure during breathing to ensure safety of subject 12 (e.g., where necessary safety determinations are made based on limits and/or other inputs and/or selections made through user interface 22, and/or based on other information, in accordance with information in the output signals from sensors 18). Tidal volume controlled and alveolar pressure limited breathing refers to breathing under pressure support or increasing pressure until the inhaled volume reaches the prescribed volume threshold.

Fig. 4 illustrates airway compliance C400 as a function of increasing PEEP 401 levels 402, 404, 406, and 408. In such embodiments, based on the compliance versus PEEP information (e.g., the information in fig. 4), the PEEP component 42 (fig. 1) is configured to set the target PEEP level at or near the PEEP level that generates the maximum or near maximum lung compliance for the subject 12 (fig. 1). Using fig. 4 as an example, maximum lung compliance (or minimum elasticity) 410 is reached at or near PEEP levels 404 and 406, so PEEP component 42 sets target PEEP level 412 to a level equal to or near PEEP levels 404 and/or 406.

In some embodiments, determining the target PEEP level based on the lung volume and the cross-lung pressure includes determining a curve of the lung volume (e.g., by stitching together multiple measurements of tidal volume) versus the cross-lung pressure (e.g., determined as described above) based on information in the output signal, parameters determined by parameter component 40 (fig. 1), and/or other information. In some embodiments, the lung volume portion of the curve is generated by stitching together many measurements of tidal volume and biasing them by starting volume at the beginning of a breath and/or by other methods. Fig. 5 shows an example of a lung volume (V)500 versus transpulmonary pressure (pstranspulmonary) 502 curve 504 for subject 12 (fig. 1). In some embodiments, PEEP component 42 (fig. 1) is configured to determine curve 504 by controlling pressure generator 14 (fig. 1) to generate the pressurized flow of breathable gas to achieve a series of increased PEEP levels 506, 508, 510, and 512 in subject 12 over a series of breaths 514, 516, 518, and 520 of subject 12, and to plot lung volume versus cross-lung pressure (e.g., determined as described above) for individual breaths 514 and 520. As shown in fig. 5, the information generated for the individual breath 514 and 520 is used to determine the corresponding portion 522 and 528 of the curve 504.

The cross-lung pressure p-v curve of the lungs of subject 12 (fig. 1) has three main regions. At low pressures, the curve is generally flat (e.g., a large pressure change is required to achieve a relatively small volume change). This corresponds to low lung compliance. The central region of the curve is characterized by higher lung compliance and corresponds to a range of pressures over which the lungs operate at their optimal state without collapse or over-extension of the alveoli. At higher pressures, the p-v curve flattens out, since again a larger pressure change is required to achieve a relatively smaller volume change.

Fig. 6 illustrates another example p (cross-lung) -v (lung) curve 600 of the lungs of subject 12 (e.g., alveoli maintain their own hysteresis and/or interaction once open are not shown in fig. 6 for simplicity). Fig. 6 illustrates a lower region 602 in which the curve 600 is generally flat at low pressures (e.g., requiring a large pressure change to achieve a relatively small volume change). Fig. 6 shows a central region 604 of the curve 600, characterized by higher lung compliance, and a higher region 606, where the p-v curve 600 flattens out at higher pressures, since again a larger cross-lung pressure change is required to achieve a relatively smaller volume change. As shown in fig. 6, region 602 transitions to region 604 at an upper concave inflection point 608 in curve 600, and region 604 transitions to region 606 at a lower concave inflection point 610 in curve 600. Also in fig. 6, P shows the pressure across the elastic compartment of the respiratory system (e.g., Pal-Pmus, where the elastic elements include the lungs and chest wall) across the pulmonary axis.

returning to fig. 1, in some embodiments, PEEP component 42 is configured such that determining a target PEEP level based on lung volume and cross-lung pressure includes identifying one or more inflection points (e.g., 608 and/or 610 shown in fig. 6) in a p (cross-lung) -v (lung) curve, determining a target PEEP level based on the one or more inflection points, and/or performing other operations. In some embodiments, PEEP component 42 determines an inflection point in the p (cross lung) -v (lung) curve by, for example, detecting a change in a value of a derivative of curve 600. In some embodiments, the PEEP component 42 is configured such that the derivative may be calculated locally (i.e., point-by-point along the curve 600) using a Savitzky-Golay smoothing filter and/or other techniques.

in some embodiments, determining the target PEEP level based on lung volume and cross-lung pressure further comprises: identifying an upwardly concave inflection point in the curve and/or causing pressure generator 14 to adjust the pressurized flow of breathable gas to increase the therapeutic PEEP level in subject 12 for individual breaths in a series of subsequent breaths until an upwardly concave inflection point is no longer identified in the portion of the curve corresponding to the most recent breath. In some embodiments, determining the target PEEP level based on lung volume and cross-lung pressure further comprises: identifying a concave inflection point in the curve; causing the pressure generator 14 to adjust the pressurized flow of breathable gas to reduce a therapeutic PEEP level of subject 12 for individual breaths in a subsequent series of breaths until a concave upward inflection point is identified; causing the pressure generator 14 to adjust the pressurized flow of breathable gas to increase a therapeutic PEEP level to a level between a lower concave inflection point and an upper concave inflection point in at least one additional breath; and setting the target PEEP level to a pressure corresponding to the foveal inflection point and the therapeutic PEEP level for at least one additional breath to keep the airway of subject 12 open.

For example, fig. 7 illustrates a set of possible operations 700 performed by PEEP component 42 (fig. 1) to determine a target PEEP level. As described above, PEEP component 42 may cause pressure generator 14 (fig. 1) to generate the pressurized flow of breathable gas to achieve a range of PEEP levels (e.g., PEEP1-PEEP7) in subject 12 (fig. 1) over a range of breaths (e.g., 1-7) by subject 12. Fig. 7 shows: identifying a concave downward inflection point in the curve 702; causing the pressure generator 14 to adjust the pressurized flow of breathable gas to reduce a therapeutic PEEP level (e.g., PEEP 2-PEEP 5) of subject 12 for individual breaths (e.g., breaths 2-5) in a subsequent series of breaths until a concave upward inflection point 704 is identified; causing pressure generator 14 to adjust the pressurized flow of breathable gas to increase a therapeutic PEEP level (e.g., PEEP6) for at least one additional breath (e.g., PEEP6) to a level between lower concave inflection point 702 and upper concave inflection point 704, closer to 702; and finally sets the target PEEP level to a level between lower concave inflection point 702 and upper concave inflection point 704 (e.g., PEEP7) closer to 704 to maintain an open airway of subject 12.

Returning to fig. 1, in some embodiments, PEEP component 42 is configured to perform one or more of the operations described above such that the target PEEP level is determined one or more times per breath by subject 12, such that the target PEEP level is determined in real-time and/or near real-time (e.g., such that a plot similar to the plot shown in fig. 6 may be generated and/or updated for individual breaths of subject 12). In some embodiments, PEEP component 42 is configured to perform one or more of the above operations in response to detecting an upper concave inflection point in the p (cross-lung) -v (lung) curve. In some embodiments, PEEP component 42 is configured to perform one or more of the operations described above in response to one or more parameters determined by parameter component 40 violating a threshold level. For example, the PEEP component 42 may be configured to perform one or more of the above operations to determine the target PEEP level in response to the parameter indicating the low ventilation alarm condition (e.g., one or more parameters violating a low ventilation alarm threshold), the SpO2 level breaching a SpO2 alarm threshold level, and/or in response to other parameters violating other thresholds. In some embodiments, PEEP component 42 is configured to determine the target PEEP level at predetermined intervals, which may or may not correspond to the breathing of subject 12, to perform one or more of the above-described operations. In some embodiments, PEEP component 42 is configured to perform one or more of the above-described operations to determine a target PEEP level in response to manual instructions received from a user (e.g., such instructions selected via user input and/or via user interface 22 and/or other components of system 10). In some embodiments, the timing of the target PEEP level determination is set at the time of manufacture (e.g., in real-time, near real-time, in response to a threshold breach, at predetermined intervals, in response to a manual command, etc.), determined and/or adjusted based on user input via the user interface 22, and/or determined by other methods.

Control component 44 is configured to control pressure generator 14 to generate the pressurized flow of breathable gas. The pressurized flow of gas generated by pressure generator 14 is controlled to replace and/or supplement the normal breathing of subject 12. In some embodiments, control component 44 is configured to cause pressure generator 14 to generate the pressurized flow of breathable gas in accordance with a prescribed mechanical ventilation therapy regime. In such embodiments, control component 44 is configured to cause pressure generator 14 to control one or more ventilation parameters of the pressurized flow of breathable gas in accordance with a prescribed mechanical ventilation therapy regime (e.g., as described above). In some embodiments, control component 44 may be configured to control pressure generator 14 to generate a flow of gas in accordance with a ventilation and/or positive airway pressure support therapy regime in addition to and/or in lieu of a mechanical ventilation therapy regime. As non-limiting examples, control component 44 may control pressure generator 14 such that the pressure support provided to subject 12 via the flow of gas includes continuous positive airway pressure support (variable CPAP), variable bi-level positive airway pressure support (BPAP), proportional positive airway pressure support (PPAP), and/or other types of pressure support therapies.

In some embodiments, control component 44 is configured to cause pressure generator 14 to adjust the pressurized flow of breathable gas to provide the therapeutic PEEP level described herein (e.g., the adjusted PEEP level described above for determining the target PEEP level) and/or to maintain the determined target PEEP level. Maintaining the determined target PEEP level may facilitate maintenance of an open airway in subject 12 such that oxygen and carbon dioxide may be more easily exchanged, requiring little and/or no effort from subject 12 to facilitate gas exchange. Control component 44 is configured to control pressure generator 14 based on information related to output signals from sensors 18, information determined by PEEP component 42 and/or parameter component 40, information input and/or selected by a user via user interface 22, and/or other information.

By way of a non-limiting practical example of operation of components 40, 42, and/or 44 of processor 20, and/or other components of system 10 described herein, system 10 may deliver a pulmonary repopulation (e.g., triggered automatically by system 10 and/or manually by an external user) comprising a series of controlled tidal volumes and alveolar pressure limited breaths (pressures) that increase toward subject 12, e.g., 15cmH2O to begin an initial PEEP. As described above, tidal volume controlled and alveolar pressure limited breathing is breathing at pressure support and/or ramped pressure until the inspiratory volume reaches a prescribed volume threshold (e.g., 6cc/kg Ideal Body Weight (IBW), e.g., entered via user interface 22 and/or selected by other components of system 10) and/or until alveolar pressure reaches, e.g., 30cmH2O, after which the pressure is reduced back to the PEEP setting. System 10 may cause one or more of these breaths to be delivered in order to stabilize the above-described parameter estimation algorithm, and/or to establish a robust estimate of the corresponding p (cross-lung) -v (lung) curve segment (e.g., by averaging determinations from different breaths). If an upwardly concave inflection point is detected in the estimated p-v curve segment, PEEP may be increased to a pressure level corresponding to the inflection point plus 2cmH2O, for example. The delivery of breaths may then continue at the new PEEP level while other respiratory parameters continue to be determined and the above process repeated until the determined p-v curve segment does not have a lower inflection point (concave upward inflection point).

If the detected inflection point is concave, the system 10 is configured to decrease the PEEP level setting by the desired amount of cmH2O to move the p-v curve downward and cause the upper inflection point (concave inflection point) to vanish for a given curve segment (e.g., segments 524 and 526 in FIG. 5). Thereafter, a continuous decrease in PEEP level (with continuous delivery of breaths) was performed until the emergence of the concave upward inflection point. This level of PEEP corresponds to atelectasis, and the system 10 sets the target PEEP level above this pressure. The recovery procedure is repeated (increasing the level of PEEP step by step), but then PEEP is reduced to a level of 2cm H20, e.g. above the level of learning of PEEP leading to atelectasis. It should be noted that atelectasis can be detected at any time by the system 10 by detecting the lower inflection point (the upper concave inflection point) during administration of mechanical ventilation. As described above, in response to detection of a foveal inflection point and/or other event by the system 10 (e.g., the PEEP component 42), the system 10 (e.g., the PEEP component 42 and/or the pressure generator 14) is configured to perform lung refocusing according to the procedures described herein.

User interface 22 is configured to provide an interface between system 10 and object 12 and/or other users, through which object 12 and/or other users provide information to system 10 and receive information from system 10. Other users may include caregivers, physicians, family members, decision makers, and/or other users. User interface 22 enables data, cues, results, and/or instructions, and any other communicable items, collectively referred to as "information," to be communicated between a user (e.g., subject 12) and pressure generator 14, sensors 18, processor 20, electronic storage, and/or other portions of system 10. Examples of interface devices suitable for inclusion in the user interface 22 include keypads, buttons, switches, keyboards, knobs, levers, display screens, touch screens, speakers, microphones, indicator lights, audible alerts, printers, haptic feedback devices, and/or other interface devices. In some embodiments, the user interface 22 may include a plurality of separate interfaces. In some embodiments, user interface 22 includes at least one interface provided integrally with pressure generator 14.

It should be understood that other communication technologies, whether hardwired or wireless, are also contemplated by the present disclosure as user interface 22. For example, the present disclosure contemplates that user interface 22 may be integrated with a removable storage interface provided by electronic storage device 24. In this example, information may be loaded into system 10 from a removable storage device (e.g., a smart card, flash memory, a removable disk, etc.) that enables the user(s) to customize the operation of system 10. One example input device and technique suitable for use with system 10 as user interface 22 includes, but is not limited to, an RS-232 port, an RF link, an IR link, a modem (telephone, cable, or other). In short, the present disclosure contemplates any technique for communicating information with system 10 as user interface 22.

In some embodiments, electronic storage 24 comprises electronic storage media that electronically stores information. The electronic storage media of electronic storage 24 may include one or both of system memory that is provided integrally (i.e., substantially non-removable) with system 10 and/or removable memory that is removably connectable to system 10 via, for example, a port (e.g., a USB port, a firewire port, etc.) or a drive (e.g., a disk drive, etc.). The electronic storage device 24 may include one or more of the following: optically readable storage media (e.g., optical disks, etc.), magnetically readable storage media (e.g., magnetic tape, magnetic hard drive, floppy drive, etc.), electrical charge-based storage media (e.g., EPROM, RAM, etc.), solid-state storage media (e.g., flash drive, etc.), and/or other electronically readable storage media. Electronic storage 24 may store software algorithms, information determined by processor 20, information received via user interface 22, and/or other information that enables system 10 to function as described herein. Electronic storage 24 may be (in whole or in part) a separate component within system 10, or electronic storage 24 may be provided (in whole or in part) integrally with one or more other components of system 10 (e.g., user interface 22, processor 20, etc.).

fig. 8 illustrates a method 800 for controlling PEEP in a subject with mechanical ventilator system control. The mechanical ventilator system includes a pressure generator, one or more sensors, one or more hardware processors, and/or other components. The one or more hardware processors are configured by machine-readable instructions to execute computer program components. The computer program components include a parameter component, a PEEP component, a control component, and/or other components. The operations of method 800 presented below are intended to be illustrative. In some embodiments, method 800 may be accomplished with one or more additional operations not described, or without one or more of the operations discussed. Additionally, the order in which the operations of method 800 are illustrated in fig. 8 and described below is not intended to be limiting.

In some embodiments, method 800 may be implemented in one or more processing devices (e.g., a digital processor, a logic processor, a digital circuit designed to process information, a logic circuit designed to process information, a state machine, and/or other mechanisms for electronically processing information). The one or more processing devices may include one or more devices that perform some or all of the operations of method 800 in response to instructions stored electronically in an electronic storage device medium. The one or more processing devices may include one or more devices configured by hardware, firmware, and/or software to be specifically designed to perform one or more of the operations of method 800.

At operation 802, a pressurized flow of breathable gas is generated for delivery to the airway of a subject. In some embodiments, operation 802 is performed by one or more pressure generators that are the same as or similar to pressure generator 14 (shown in fig. 1 and described herein).

At operation 804, output signals conveying information related to the breathing of the subject are generated. In some embodiments, operation 804 is performed by one or more sensors that are the same as or similar to sensor 18 (shown in fig. 1 and described herein). In some embodiments, the one or more sensors comprise: a flow rate sensor configured to generate output signals conveying information related to a flow rate of the pressurized flow of breathable gas; a pressure sensor that conveys information related to a pressure of breathable gas at a mouth of the subject; and/or other sensors.

At operation 806, a lung volume and a cross-lung pressure of the subject are determined. The lung volume and the cross-lung pressure are determined based on the one or more determined parameters, based on information in the output signals, and/or based on other information (e.g., the lung volume may be determined based on the tidal volume, the tidal volume may be determined based on the output signals, the lung volume may be determined based on the tidal volume; and the cross-lung pressure may be determined according to the above parameters and formulas). In some embodiments, the information related to the breathing of the subject includes the flow rate (Q) of the pressurized flow of breathing gas, the pressure (Pao) of the breathing gas at the mouth of the subject, and/or other information. In some embodiments, determining the cross-lung pressure of the subject based on the information in the output signal comprises: determining airway resistance (R) and elasticity (E) based on Q and Pao; determining alveolar pressure (Pal) and muscle pressure (Pmus) of the subject based on R and E; and determining the transpulmonary pressure based on Pal and Pmus. In some embodiments, the transmural pressure is determined instead of the transpulmonary pressure, and the target PEEP level is determined based on lung volume, transmural pressure, and/or other information (e.g., as described herein). In some embodiments, operation 806 is performed by one or more processors that are the same as or similar to parameter component 40 (shown in fig. 1 and described herein).

At operation 808, a target PEEP level is determined. The target PEEP level is determined based on lung volume, cross-lung pressure, and/or other information. In some embodiments, determining the target PEEP level based on the lung volume and the transpulmonary pressure comprises: determining a lung volume versus pulmonary artery pressure curve from the information in the output signal, the determined parameter, and/or other information; identifying one or more inflection points in the curve; and determining a target PEEP level from the one or more inflection points. In some embodiments, determining the target PEEP level based on the lung volume and the transpulmonary pressure further comprises: identifying a concave inflection point in the curve; causing the pressure generator to adjust the pressurized flow of breathable gas to reduce a therapeutic PEEP level of the subject for individual breaths in a subsequent series of breaths until an inflection point is identified; causing the pressure generator to adjust the pressurized flow of breathable gas to increase a therapeutic PEEP level to a level between a lower concave inflection point and an upper concave inflection point in at least one additional breath; and setting the target PEEP level to a pressure corresponding to the foveal inflection point and the therapeutic PEEP level for at least one additional breath to keep the airway of the subject open. In some embodiments, determining the target PEEP level based on the lung volume and the transpulmonary pressure further comprises: identifying an upper concave inflection point in the curve; and causing the pressure generator to adjust the pressurized flow of breathable gas to increase the therapeutic PEEP level in the subject in individual breaths in a series of subsequent breaths until the concave upward point is no longer identified in the portion of the curve corresponding to the most recent breath. In some embodiments, operation 808 is performed by one or more hardware processors that are the same as or similar to PEEP component 42 (shown in fig. 1 and described herein).

at operation 810, the pressure generator is caused to adjust the pressurized flow of breathable gas to maintain the determined target PEEP level. In some embodiments, operation 810 is performed by one or more hardware processors that are the same as or similar to control component 44 (shown in fig. 1 and described herein).

Although the description provided above provides details for the purpose of illustration based on what is currently considered to be the most preferred and practical embodiments, it is to be understood that such details are solely for that purpose and that the disclosure is not limited to the specifically disclosed embodiments, but, on the contrary, is intended to cover modifications and equivalent arrangements that are within the spirit and scope of the appended claims. For example, it is to be understood that the present disclosure contemplates that, to the extent possible, one or more features of any embodiment can be combined with one or more features of any other embodiment.

In the claims, any reference signs placed between parentheses shall not be construed as limiting the claim. The word "comprising" or "comprises" does not exclude the presence of elements or steps other than those listed in a claim. In the device claim enumerating several means, several of these means may be embodied by one and the same item of hardware. The word "a" or "an" preceding an element does not exclude the presence of a plurality of such elements. In any device-type claim enumerating several means, several of these means may be embodied by one and the same item of hardware. Although specific elements are recited in mutually different dependent claims, this does not indicate that a combination of these elements cannot be used to advantage.