A system for adaptive cough detection and adaptive mechanical inflation-deflation (MIE) therapy

Abstract

A mechanical ventilation system (1) includes a mechanical ventilator (2) configured to deliver ventilation to a patient. An electronic controller (13) is programmed to control the mechanical ventilator to perform a mechanical insufflation-exsufflation (MI-E) treatment method (100) that includes performing an MI-E cycle that includes: (i) during an insufflation cycle, delivering pressure to the patient at a positive insufflation gauge pressure; (ii) during an exsufflation cycle after step (i), delivering pressure to the patient at a negative exsufflation gauge pressure, and detecting whether an upper airway collapse occurs; and (iii) if an upper airway collapse is detected in step (ii), decreasing a magnitude of the negative exsufflation gauge pressure.

Description

[0001] Cross-references to related applications

[0002] This patent application claims priority to U.S. Provisional Application No. 63 / 066,572, filed August 17, 2020, pursuant to 35 U.S.SC §119(e), the contents of which are incorporated herein by reference.

[0003] The following text generally covers ventilation therapy techniques, especially mechanical ventilation (MI-E) therapy and related techniques. Background Technology

[0004] Mechanical insufflation and expulsion (MI-E) therapy has been used for secretion management since the early 1950s. MI-E therapy aims to enhance weak or ineffective coughs in patients with neuromuscular diseases (NMD) or high spinal cord injuries (significant loss of innervation of major respiratory muscles). MI-E therapy is delivered non-invasively via a face mask or gauze, or, if necessary, via tracheostomy or an endotracheal adapter.

[0005] MI-E helps clear lung secretions by applying positive pressure during inhalation (inflation) to generate a large volume of air (targeting inspiratory capacity) and then rapidly shifting to negative pressure (exhalation) to create a pressure gradient that increases expiratory flow rate. Clinical evidence indicates that the critical threshold for effective secretion clearance peak expiratory flow (PEF; also known as peak expiratory flow rate (PEFR) or peak cough flow (PCF) is 160 LPM (see, e.g., Bach JR, Saporito LR. Criteria for extubation and tracheostomy tube removal for patients with ventilatory failure. A different approach to weaning. Chest 1996; 110:1566-71). For NMD patients, MI-E is recommended once their PCF begins to decrease to below 270 L / min to help support their declining muscle strength and to help patients adapt to the device (see, e.g., Bach JR, Ishikawa, Kim H. Prevention of pulmonary morbidity for patients with Duchenne Muscular dystrophy. Chest 1997; 112(4):1024-1028).

[0006] Patients with amyotrophic lateral sclerosis (ALS) are considered a primary target for inclusion in MI-E therapy as part of a holistic respiratory support strategy. ALS is associated with the loss of motor neurons in the cortex, brainstem, and spinal cord, leading to muscle weakness and atrophy. Approximately 20–30% of patients diagnosed with ALS have bulbar symptoms at onset; however, almost all of the remaining 70–80% of ALS patients will develop bulbar symptoms as the disease progresses (see, for example, Simonds A. Progress in respiratory management of bulbar complications of motor neuron disease / amyotrophic lateral sclerosis. Thorax March 2017 Vol 72 No 3). Bulbar symptoms include dysarthria, dysphagia, difficulty clearing oropharyngeal secretions, weakened cough, laryngospasm, and aspiration. Increasing evidence supports that MI-E therapy can improve PCF and, when combined with noninvasive ventilation (NIV), can prolong survival in ALS patients. However, in patients with bulbar ALS, this therapy has proven to be highly ineffective. In these patients, the application of negative pressure during the exhalation phase of MI-E treatment led to upper airway collapse (see, for example, Anderson T et al. Laryngeal response patterns influence the efficacy of mechanical assisted cough in ALS. Thorax 2016; 0:1-9; Sancho J, Servera E, Diaz J, Marin J. Efficacy of mechanical insufflation-exsufflation in medically stable patients with amyotrophic lateral sclerosis. Chest 2004; 125(4):1400-1405), and often resulted in a feeling of suffocation, which rendered the treatment ineffective and often intolerable.

[0007] Upper airway closure and compression have been described in clinical literature using invasive methods such as fiberoptic bronchoscopy (see, for example, Anderson T, Sandnes A, Fondenes O, Nilsen R, Tysnes OB, Heimdal JH et al. Laryngeal Responses to Mechanically Assisted Cough in Progressing Amyotrophic Lateral Sclerosis. Resp Care May 2018;63(5):538-549).

[0008] The following section discloses some improvements to overcome these and other problems. Summary of the Invention

[0009] On one hand, the mechanical ventilation system includes a mechanical ventilator configured to deliver ventilation to a patient. An electronic controller is programmed to control the mechanical ventilator to perform an MI-E treatment method, the method comprising performing an MI-E cycle, the MI-E cycle comprising: (i) delivering pressure to the patient at a positive inflator pressure during an inflator cycle; (ii) delivering pressure to the patient at a negative exhaust pressure during an exhaust cycle following step (i), and detecting whether upper airway collapse has occurred; and (iii) if upper airway collapse is detected in step (ii), reducing the magnitude of the negative exhaust pressure.

[0010] On the other hand, the mechanical ventilation system includes a mechanical ventilator configured to deliver ventilation to a patient. An electronic controller is programmed to control the mechanical ventilator to perform a MI-E treatment method, the method including performing an MI-E cycle comprising: (i) delivering pressure to the patient at a positive inflator pressure during an inflator cycle; and (ii) delivering pressure to the patient at a negative exhaustor pressure during an exhaustor cycle following step (i); and (iii) analyzing one or more respiratory measurements of the patient during the delivery of pressure at a negative exhaustor pressure.

[0011] In another aspect, a non-transitory computer-readable medium stores instructions made by an electronic controller of a mechanical ventilator for controlling the mechanical ventilator to perform MI-E treatment, the method comprising performing an MI-E cycle, the MI-E cycle comprising: (i) delivering pressure to the patient at a positive inflator pressure during an inflator cycle; (ii) delivering pressure to the patient at a negative exhaust pressure during an exhaust cycle following step (i); (iii) reducing the magnitude of the negative exhaust pressure to zero during step (ii); and (iv) increasing the magnitude of the negative exhaust pressure during delivery if analysis predicts that upper airway collapse will not occur during the exhaust cycle.

[0012] One advantage is that MI-E treatment can be used more widely by preventing upper airway collapse in patients.

[0013] Another advantage is that it provides a mechanical ventilator with a negative pressure process that can adjust the negative pressure to prevent the patient's upper airway from collapsing.

[0014] Another advantage is that it provides a non-invasive method for adjusting the mechanical inflation-deflation settings of a mechanical ventilator that provides ventilation therapy to patients.

[0015] Another advantage is that the ventilation therapy delivered to the patient can be non-invasively measured, regardless of whether the treatment is delivered in a clinical, rehabilitation, or home setting.

[0016] Another advantage is that MI-E therapy can be used more widely to treat patients with medullary ALS.

[0017] The given embodiments may provide zero, one, two, more or all of the foregoing advantages, and / or may provide other advantages that will be apparent to those skilled in the art upon reading and understanding this disclosure. Attached Figure Description

[0018] This disclosure can take various forms of components and component arrangements, as well as various forms of steps and step arrangements. The accompanying drawings are for illustrative purposes only and should not be construed as limiting this disclosure.

[0019] Figures 1 to 4 The diagram illustrates the flow and pressure curves of patients during cough adjunctive therapy.

[0020] Figure 5 An illustrative apparatus for a ventilator system according to this disclosure is shown in the diagram.

[0021] Figure 6 It shows the result of Figure 5 Example flowchart of the appropriate operations performed by the system.

[0022] Figure 7 The acceptance was shown Figure 6 The patient's flow and pressure curves during the procedure.

[0023] Figure 8 It shows the result of Figure 5 Another example flowchart of the operations that the system should perform appropriately.

[0024] Figure 9 and Figure 10 The acceptance was shown Figure 8 The patient's flow and pressure curves during the procedure.

[0025] Figure 11 It shows the result of Figure 5 Another example flowchart of the operations that the system should perform appropriately.

[0026] Figures 12 to 16 The acceptance was shown Figure 11 The patient's flow and pressure curves during the procedure.

[0027] Figure 17 It shows the result of Figure 5 Another example flowchart of the operations that the system should perform appropriately.

[0028] Figure 18 The acceptance was shown Figure 17 The patient's flow and pressure curves during the procedure.

[0029] Figures 19 to 22 It shows the result of Figure 5 The patient curves generated by the algorithm implemented by the system module.

[0030] Figure 23 and 24 It shows the result of Figure 5 The patient curves are generated by an algorithm implemented in another module of the system. Detailed Implementation

[0031] As used herein, unless the context clearly indicates otherwise, the singular forms “a / an” and “the” include plural references. As used herein, statements of two or more parts or components being “connected,” “joined,” or “joined” will mean as long as a link exists. These parts are directly or indirectly (i.e., through one or more intermediate parts or components) combined, operated, or act together. Directional phrases used herein, such as, but not limited to, top, bottom, left, right, up, down, front, back, and their derivatives, refer to the orientation of elements shown in the accompanying drawings and, unless explicitly stated in the drawings, do not limit the scope of the claimed invention. The terms “comprising” or “including” do not exclude the presence of elements or steps other than those described herein and / or listed in the claims. In an apparatus comprising several devices, several of these devices may be implemented by one and the same hardware item.

[0032] Unless otherwise stated, all pressure values ​​in this document are gauge pressure values, where zero pressure corresponds to atmospheric pressure.

[0033] The embodiments disclosed herein provide a method for assessing the upper airway response to MI-E therapy by evaluating flow and pressure waveforms generated by an MI-E device (e.g., the Philips 70 series (i.e., CoughAssist) device available from Koninklijke Philips NV; Eindhoven, the Netherlands). The disclosed method advantageously addresses various aspects of airway clearance therapy (ACT).

[0034] refer to Figures 1 to 4 The graph shows various flow pattern curves for ALS patients. Figure 1 The graphs showing the changes in "normal" airway flow rate over time (top) and "normal" airway pressure over time (bottom) in cough patients are shown. Following the initial gas decompression peak, peaks in both expiratory flow rate and expiratory pressure are observed after three coughing efforts. The maximum cough flow peak (PCF) occurs during the first effort, when lung and chest wall recoil pressures are at their highest. ALS patients with medullary symptoms exhibit two main expiratory flow patterns associated with disease progression.

[0035] like Figure 2 As shown, the first expiratory flow pattern appears early in the development of medullary symptoms and leads to the loss of the patient's ability to close the glottis (i.e., the patient is no longer able to produce the compression phase of a cough and is also no longer able to speak). Due to the loss of the ability to cough, the expiratory flow pattern becomes smooth and rounded, and no longer has the multiple expiratory flow spikes characteristic of a normal cough effort, such as... Figure 1 As shown. Simultaneously, the expiratory pressure peak (also associated with glottal closure, such as...) Figure 1 The double-ended arrow (as indicated by the arrow) is no longer obvious.

[0036] Figure 2 The study shows that in patients with medullary tract obstruction, the expiratory flow curve becomes smoother as the patient loses the ability to close the glottis, representing the disappearance of the compression phase of coughing. Furthermore, as pulmonary backflow pressure decreases and negative pressure enters the airway, at some point the upper airway collapses, and expiratory flow suddenly drops.

[0037] about Figure 2 The initial loss of glottal control and the resulting steady expiratory flow pattern are illustrated. The disclosed system and method aim to delay or even prevent upper airway collapse in patients with upper airway instability during the negative pressure expiratory phase of MI-E therapy. Reduction of upper airway collapse is achieved by identifying significant flow attenuation after PEF (e.g., Figure 2 This is achieved (as shown by the vertical line in the diagram), and the decay does not continue to gradually decay to zero or ambient flow conditions during the allocated expiratory time. For example... Figure 3As shown, a sudden drop in expiratory flow can be addressed by using a servo controller to rapidly reduce the negative pressure to a point where the expiratory flow continues to gradually decay to the zero flow line during the set expiratory time.

[0038] Figure 3 An example is shown of how manual titration with negative pressure can prolong expiratory flow beyond the initial collapse point. The titration process adjusts the negative pressure to optimize it while avoiding upper airway collapse. Although Figure 3 An example is manual sequential breath titration, but as disclosed herein, this process can be replaced by an automated process performed over several breaths, or by a fast servo mechanism that can automatically titrate the negative pressure over a single breath (or several sequential breaths) instead of the manual titration process.

[0039] Figure 3 The pressure titration steps are shown in 5 cmH2O increments, starting from -40 cmH2O and proceeding up to -5 cmH2O. For simplicity and space reasons, only three pressure increments (-35 cmH2O, -20 cmH2O, and 5 cmH2O) are shown. When the pressure gradient is highest (+40 cmH2O to -35 cmH2O), the peak expiratory flow rate is highest at the first increment of -35 cmH2O and decreases slightly with decreasing pressure. Due to the decreasing negative pressure, the expiratory time before airflow occurs gradually lengthens. After adding active coughing, the optimal PCF occurs at a pressure setting of -20 cmH2O.

[0040] Figure 4 This illustrates a second expiratory flow pattern that appears later in the development of medullary symptoms, characterized by the almost complete disappearance of the expiratory flow curve (i.e., the absence of a smooth expiratory flow pattern). Instead, Figure 4 The curve shows an initial gas decompression spike, followed by an almost flat expiratory flow rate curve with little or no evidence of expiratory flow (or even passive flow). This characteristic is a result of complete loss of upper airway muscle tone and subsequent collapse upon exposure to negative pressure during the expiratory phase of MI-E. (To maximize the effectiveness of the algorithm, an automatic titration to maximize the target inspiratory pressure occurs first. Increasing the maximum inspiratory pressure increases lung and chest wall recoil pressure and shifts the point of negative pressure where collapse occurs.)

[0041] Figure 4 This shows that when glottal control is completely lost, the upper airway is prone to collapse when exposed to negative pressure. Figure 4 In the middle, when negative pressure is applied, it almost completely collapses, and the expiratory flow trace consists of a gas decompression spike followed by an almost flat expiratory flow curve.

[0042] refer to Figure 5This illustrates a mechanical ventilator system 1 that provides ventilation therapy for the associated patient P. (Example) Figure 5 As shown, system 1 includes a mechanical ventilator 2 configured to perform MI-E treatment. For example, mechanical ventilator 2 may be a CoughAssist airway clearing device (available from Koninklijke Philips NV). Mechanical ventilator 2 includes an outlet (not shown) connected to patient breathing circuit 5 to deliver mechanical ventilation to patient P to perform MI-E treatment. Patient circuit 5 includes an air hose 6, patient port 8, and one or more respiratory sensors, such as a gas flow meter 10, a pressure sensor or pressure sensor 11, an end-tidal carbon dioxide (etCO2) sensor (not shown), etc. Alternatively, some or all of sensors 10, 11 may be internal to mechanical ventilator 2. Patient port 8 may be implemented differently. For non-invasive ventilation, patient port 8 is suitably a mask strapped to the patient's face. For invasive ventilation, patient port 8 may be an endotracheal tube, tracheostomy tube, etc.

[0043] The mechanical ventilator 2 includes an air inlet (not shown) for inhaling atmospheric air and delivering it to an air hose 6 to provide MI-E treatment to the patient. For example, the ventilator 2 may include a blower 12 to deliver air to the air hose 6. (Note that the blower 12 is in...) Figure 5 (Illustrated in the diagram, as it is located inside the housing of the mechanical ventilator 2 and is therefore obscured from view). The mechanical ventilator 2 includes an electronic processor or electronic controller 13, a display 14, and a non-transitory computer-readable medium 15 storing instructions executable by the electronic process 13 to perform mechanical inflation-deflation (MI-E) treatment methods 100, 200, 300, 400, as described in more detail below.

[0044] refer to Figure 6 And continue to refer to Figure 5An example embodiment of the MI-E treatment method 100 is illustrated as a flowchart. The MI-E treatment method 100 includes a titration protocol with a negative pressure scheme for eliminating upper airway collapse (UAC) during one or more MI-E cycles. To begin method 100, in operation 102, ventilation is delivered to patient P via mechanical ventilator 2 according to the treatment settings. The treatment settings may be a target inspiratory pressure, which may be set to the maximum value that the patient can tolerate, with the aim of maximizing inspiratory capacity (MIC). For example, the target inspiratory pressure may be 40 cmH2O (metered pressure) or slightly higher. Values ​​of 60 cmH2O or higher have been reported in the literature (see, for example, Esquinnas AM, Fiorentino G, Considerations about the effect of Cough Assist on Laryngeal Function in Neuroologic Disease. Letter to the editor. Respir Care Nov 2018; 63(11):1459), and pulmonologists are reluctant to prescribe values ​​much higher than 40 cmH2O due to the potential risk of pneumothorax. In one example, in a DMD patient with pneumonia, the target pressure was set to 50 cmH2O, a setting that resulted in pneumothorax. Maximizing the target inspiratory pressure (P) for the patient also maximizes the lung recoil pressure supporting the positive cavitation pressure used to prevent upper airway collapse. In normal subjects and patients with severe medullary injury, the upper airway remained open and did not collapse when no negative pressure was applied. Typically, by completely removing the negative pressure and relying solely on passive lung recoil, patients can achieve PCF values ​​higher than the 160 L / min level required for support clearance. Furthermore, if patients use their expiratory muscles to support a cough, this further increases the PCF they can achieve without a negative pressure phase.

[0045] In operation 104, during an inhalation cycle, the mechanical ventilator 2 is configured to deliver pressure to the patient at the positive inhalation gauge pressure (i.e., the target inhalation pressure set in operation 102).

[0046] In operation 106, during the exhaust cycle following the inhalation cycle, the mechanical ventilator 2 is configured to deliver pressure to the patient at a negative exhaust pressure gauge reading. For example, the negative exhaust pressure gauge reading can be delivered in increments of -5 cmH2O, and exhaust can be paused after each increment.

[0047] In operation 108, negative pressure delivery operation 106 continues until UAC is detected. In some embodiments, once UAC is detected, the patient P may be required to actively cough or exhale.

[0048] This operation 108 can be performed in several automated ways. In one example, operation 108 includes measuring the airway flow rate of patient P using flow meter 10 at a predetermined time or time interval in the exhaust cycle, and comparing the measured airway flow rate with a predetermined threshold to detect whether a UAC has occurred. In another example, operation 108 includes measuring the volume of air inhaled by patient P using flow meter 10 at a predetermined time in the exhaust cycle 106, and comparing the measured volume of air with a predetermined threshold to detect whether a UAC has occurred. In yet another example, operation 108 includes measuring the rate of change of airway flow using flow meter 10 at a predetermined time or time interval in the exhaust cycle 106, and comparing the measured rate of change of airway flow with a predetermined threshold to detect whether a UAC has occurred. In yet another example, operation 108 includes measuring the rotational speed of the blower 12 of mechanical ventilator 2 at a predetermined time or time interval in the exhaust cycle, and comparing the measured blower rotational speed with a predetermined threshold to detect whether a UAC has occurred. In another example, operation 108 includes measuring the pressure generated by blower 12 at a predetermined time or time interval in the exhaust cycle, and comparing the measured pressure generated by the blower with a predetermined threshold to detect whether a UAC has occurred. In yet another example, operation 108 includes measuring the patient's airway flow rate using flowmeter 10 and measuring the patient's airway pressure using pressure gauge 11, determining airway reactance from the measured airway flow rate and the measured airway pressure, and detecting whether a UAC has occurred based on the determined airway reactance. In yet another example, operation 108 includes superimposing an AC oscillation onto the pressure delivered to the patient P at a negative exhaust pressure. When the AC oscillation is superimposed, the respiratory measurement includes (i) the patient's airway flow rate, which can be measured using flowmeter 10, or (ii) the patient's airway pressure, which can be measured using pressure gauge 11. UAC can be detected in part based on the AC component of the measured respiratory measurement.

[0049] In operation 110, if UAC is detected in UAC detection operation 108, the magnitude of the negative exhaust pressure gauge reading is reduced. More specifically, in illustrative operation 108, the next cycle is adjusted according to the following formula (denoted as P). _exs(下一次循环) Exhaust pressure:

[0050] P _exs(下一次循环) =P _exs(最后一次循环) +5cmH2O

[0051] Where P _exs(最后一次循环) This is the exhaust pressure used in the last cycle. Note that due to P... _exsThe value is a negative gauge pressure, therefore a +5cmH2O adjustment will decrease the magnitude of the (negative) gauge pressure. Thus, the negative exhaust gauge pressure decreases by a predetermined pressure increment, for example, 5cmH2O. Continue operations 104-108 until no UAC is detected (e.g., ...). Figure 6 (As shown in operation 112). In operation 112, the negative exhaust pressure when no UAC is detected can be confirmed by delivering ventilation to patient P at the negative exhaust pressure when no UAC is detected, 5 cmH2O above that value, and 5 cmH2O below that value, to confirm the optimal pressure.

[0052] In some embodiments, the MI-E method 100 may include detecting a critical closure pressure (Pcrit) value for the upper airway (see, for example, Eckert et al., Phenotypic approaches to obstructive sleep apnea-Newpathways for targeted therapy. Sleep Medicine Review, 2018:45-49). This value will represent a patient-specific starting point for initiating treatment delivery. In this example, the ventilation delivery process will reduce the magnitude of the negative pressure so that it is less than the Pcrit value, and then verify upper airway occlusion.

[0053] The MI-E treatment method 100 is a dynamic process influenced by several opposing forces. In one example, positive cavitary pressure is defined as the combined elastic recoil force of the lungs and chest wall supported by the maximum target inspiratory pressure to support maintaining airway occlusion, and the patient's ability to supplement this force through their own active breathing is a result of any expiratory muscle force they can actively generate. In another example, the opposite of positive cavitary pressure is the negative pressure (defined as negative cavitary pressure) exerted by MI-E during the expiratory phase.

[0054] Therefore, when these two forces are nearly equal, the relaxed structures of the upper airway may vibrate, such as Figure 7 As shown, this results in audible expiratory grunting that may be noticed by the patient, caregiver, or clinician. This is a clear symptom indicating that the current setup has created luminal pressure very close to the point of collapse. Further reducing the negative pressure near this point will open the airway, eliminate vibration, reduce patient discomfort, and improve PCF. Figure 7 The image shows a patient in the medulla oblongata who exhibits this vibration or groaning.

[0055] refer to Figure 8 And continue to refer to Figure 5 and Figure 6An example embodiment of the MI-E treatment method 200 is illustrated as a flowchart. The MI-E treatment method 200 is similar to the MI-E treatment method 100, except as described below. The MI-E treatment method 200 may include a gradual reduction under negative exhaust pressure.

[0056] Method 200 begins with operations 102 to 108 of method 100 described above. In operation 108, if UAC is detected, method 200 proceeds to operation 202, in which the magnitude of the negative exhaust gauge pressure is reduced to zero (instead of being reduced by a predetermined amount as in operation 110).

[0057] Once the negative exhaust pressure gauge reading decreases to zero, method 200 continues with operations 204, 206, 208, and 210, which essentially correspond to operations 102, 104, 106, and 108. In operation 204, the mechanical ventilator 2 delivers ventilatory treatment to patient P with updated treatment settings. In operation 206, pressure is delivered to patient P with a positive inflation gauge reading during an inflation cycle. In operation 208, pressure is delivered to patient P with a negative exhaust pressure gauge reading during an exhaust cycle. In operation 210, negative pressure delivery operation 204 continues until a UAC is detected.

[0058] If UAC is not detected in operation 210, then in operation 212, the magnitude of the negative exhaust gas gauge pressure is increased. The magnitude of the negative exhaust gas gauge pressure can be increased by a predetermined amount, such as an increase of 5 cmH2O. These operations 204 to 212 are repeated until UAC is detected.

[0059] If UAC is not detected in operation 208, then in operation 214, the magnitude of the negative exhaust gauge pressure is reduced by a predetermined pressure reduction increment (e.g., 2 cmH2O). After this increase, method 200 proceeds to operations 216, 218, 220, and 222 (these operations essentially correspond to operations 204 to 210, and for the sake of brevity, their details will not be repeated).

[0060] In operation 222 (corresponding to UAC detection operation 210), if no UAC is detected, then in operation 224, the negative exhaust pressure is maintained.

[0061] Repeat steps 216 to 222 until UAC is detected. Once UAC is detected, method 200 proceeds to step 226, in which the negative exhaust gauge pressure is reduced by a predetermined pressure increment (again, 2 cmH2O).

[0062] In addition to operation 226, in operation 228, when UAC is detected, the negative exhaust pressure is recorded as the negative exhaust pressure (i.e., Pcrit value) for subsequent MI-E cycles for MI-E treatment.

[0063] As previously stated, method 200 can be viewed as a gradual reduction of negative pressure during the multiple venting stages of method 100. Figure 9 As shown, a slow pressure response algorithm or process is triggered when the zero flow point (i.e., UAC) occurs at the start of the exhaust phase and there is no flow reversal to indicate an active cough during glottal closure. Once triggered, the algorithm or process reduces the negative pressure setting in increments of 5 cmH2O before each exhaust phase until the zero flow point equals the exhalation time setting. For example, if a rapid UAC occurs with inspiratory and expiratory pressures of + / -40 cmH2O, the electronic controller 13 will reduce the negative pressure setting to -35 cmH2O before the next exhaust phase and assess the location of the zero flow point. The negative pressure setting will continue to decrease towards ambient pressure until the zero flow point equals the exhalation time setting. Figure 10 This demonstrates the reduction in negative pressure.

[0064] In an alternative embodiment, the rapid UAC can reset the negative pressure setting to 0 cmH2O for the next delivery exhaust phase. Once the negative pressure is set to ambient pressure, each subsequent exhaust phase will increase by -5 cmH2O to increase the delivery / setting negative pressure until a zero flow point is predicted to occur before the end of the exhaust time. The zero flow point prediction during the exhaust time will generate a Pcrit negative pressure upper limit and stop any further increase in negative pressure. Once Pcrit is established, the negative pressure will decrease by 2 cmH2O, thus setting a new negative pressure baseline. For example, if Pcrit occurs at 25 cmH2O, the new baseline negative pressure will be set at -23 cmH2O.

[0065] exist Figure 6 and Figure 8 In one embodiment, the titration of negative pressure is typically performed over several MI-E cycles, with one adjustment of negative pressure per MI-E cycle. While this is effective, it can be unpleasant for the patient because he or she experiences (typically) multiple UAC events before the titration reaches the final negative pressure that provides effective nebulization therapy without inducing a UAC event during the exhaust cycle. In the following embodiment, rapid titration is performed within a single exhaust cycle by dynamically detecting, at the initial stage of the exhaust cycle, whether UAC collapse is likely to occur later in the cycle, and if UAC collapse is detected, reducing the magnitude of the negative pressure during the same exhaust cycle to prevent the detected potential UAC collapse.

[0066] refer to Figure 11 And continue to refer to Figures 5 to 7 An example embodiment of the MI-E treatment method 300 is illustrated as a flowchart. The MI-E treatment method 300 is similar to the MI-E treatment method 100, except as described below.

[0067] In operation 302, pressure is delivered to patient P using a positive pressure gauge (similar to operations 104 and 206).

[0068] In operation 304, after the gas injection cycle, pressure is delivered to patient P at a negative pressure gauge reading (similar to operations 106 and 208).

[0069] During pressure delivery to the patient at a negative exhaust pressure gauge, one or more respiratory measures of the patient P are analyzed. In one example, at operation 306, the respiratory measures may include determining whether a rapid UAC is occurring (similar to operations 108 and 210). If no rapid UAC is detected (as indicated in 310), another iteration of operations 302 through 306 occurs (as indicated in operation 312). These operations are repeated until a rapid UAC is detected.

[0070] In some examples, UAC is primarily determined by reaching a zero-flow point before the end of the expiratory phase and maintaining zero flow for the remainder of the expiratory phase. Characterizing cough effort helps distinguish between active cough (i.e., glottal closure) and UAC, as both involve a zero-flow point or zero-crossing element. Various methods can be used to differentiate between the two in order to accurately respond to true upper airway closure. For example, one way to do this is to ensure that there are at least two zero-crossings to indicate that the individual is coughing (i.e., no UAC is occurring), so the controller does not respond with a negative pressure reduction. Another approach is to introduce a brief time-delay filter that introduces a brief pause once the zero-flow point occurs to identify whether the zero-flow point is subsequently associated with flow reversal. If flow reversal is present, the instantaneous zero pressure point is generated by glottal closure associated with coughing (not UAC), and the controller does not respond with a negative pressure reduction. On the other hand, if a zero pressure point is reached but no flow reversal is identified, this would meet the criteria for UAC, and the controller would respond with a reduction in the amount of negative pressure reduction.

[0071] In another example of analyzing the respiratory measurements of patient P, in operation 308, the respiratory measurements may include a cough measurement indicating whether the patient is coughing. If the cough measurement indicates that patient P is coughing, the magnitude of the exhaust pressure is not adjusted.

[0072] On the other hand, if operation 306 indicates that a UAC may be imminent, and no cough is detected in operation 308, method 300 continues to operation 314, in which the magnitude of the negative exhaust pressure is reduced during delivery of the (same) exhaust cycle in an effort to prevent the predicted UAC from occurring. For this purpose, the magnitude of the negative exhaust pressure is multiplied by a constant k less than 1. Method 300 then proceeds to operation 312, where operations 302 through 306 are repeated. In some cases, the exhaust pressure adjustment in operation 314 may be sufficient to prevent the UAC predicted in operations 306, 308 from actually occurring in that exhaust cycle. However, even if UAC cannot be prevented in that exhaust cycle, the exhaust pressure will be further reduced with each subsequent exhaust cycle via further operation 314. By adjusting within the same exhaust cycle in which UAC is predicted to occur, faster titration is achieved, and the patient is predicted to experience fewer (or even no) actual UAC events.

[0073] Method 300 includes expiratory flow trace mapping to be based on expiratory time (T) within a breath-by-breath measurement window. E An anchored initial PEFR is set to track and predict the expiratory zero flow point. In a patient profile showing an initial expiratory flow pattern with relatively slow PEFR decay (no glottal closure), indicating that the zero flow point will occur before the end of the expiratory time (when upper airway closure is imminent), the response of the rapid response algorithm or method 300 will be triggered. Figure 12 As shown, the critical threshold of the fast response algorithm of triggering method 300 will include the absence of back pressure spikes in the pressure waveform.

[0074] The back pressure spike indicates an active cough during glottal closure, such as... Figure 13 As shown. In addition to backpressure spike detection, if zero flow is reached during the exhalation phase, a pressure response delay can be introduced to determine whether rapid flow reversal (glottis opening, active cough) has occurred. The flow reversal filter in this algorithm prevents the rapid pressure response algorithm from being triggered by active cough and glottis closure, even if a zero flow point occurs during the exhalation phase.

[0075] The fast-response algorithm of Method 300 is a servo-controlled reduction of the delivery negative pressure setting during the exhaust phase. The reduction in negative pressure depends on the degree of exhaled flow rate decay and the prediction of the zero flow point. The pressure reduction may be proportional to the decrease in PEFR, or it may continue to rise to 0 cmH2O (ambient pressure) before the exhaust phase ends. Therefore, as... Figure 14 As shown, when triggered, the fast pressure algorithm creates (3) different pressure distributions for a single mechanically assisted cough effort.

[0076] In another embodiment, the MI-E waveform is modified from a two-stage (i.e., stage 1 is positive pressure and stage 2 is negative pressure) waveform to a three-stage waveform, which includes positive pressure during the inspiratory phase, followed by a negative pressure delivery set at the initial portion of the exhalation phase, which, once PEFR is identified, slowly rises to ambient pressure (i.e., 0 cmH2O) at the end of the exhalation phase. Figure 15 As shown.

[0077] The rapid reduction in negative pressure can conceptually be applied to all breathing, provided that within a single mechanically assisted cough (MAC), the PCF value consistently decreases after the initial PEFR and any subsequent coughing efforts by the patient. Figure 16 As shown, the sharp drop in PCF during multiple coughs within a single MAC is due to a significant decrease in lung volume with each cough. A fine-tuned exhaust algorithm that focuses on a single maximum PEFR and then raises the negative pressure to 0 cmH2O will serve as a protective mechanism to mitigate UA collapse, conceptually without affecting the device's effectiveness. The PCF filter can delay the rise in negative pressure until a low PCF threshold (e.g., 160 lpm) is reached.

[0078] refer to Figure 17 And continue to refer to Figure 5 and Figure 11 An example embodiment of the MI-E treatment method 400 is shown in the form of a flowchart. The MI-E treatment method 400 is similar to the MI-E treatment method 300, except as described below.

[0079] In operation 402, pressure is delivered to patient P using a positive pressure gauge (similar to operations 104, 206, and 302).

[0080] In operation 404, after the gas injection cycle, pressure is delivered to patient P at a negative pressure gauge reading (similar to operations 106, 208, and 304).

[0081] In operation 406, during the exhaust cycle, the magnitude of the negative exhaust gauge pressure is set to zero (similar to operation 202).

[0082] In operation 408, negative pressure delivery operation 406 continues until UAC is detected (similar to operations 108, 210 and 306).

[0083] If no UAC is detected, in operation 410, the magnitude of the negative exhaust gauge pressure is increased during the delivery of the exhaust cycle. To increase the negative exhaust gauge pressure, a constant value (constant k) is added to the negative exhaust gauge pressure.

[0084] If UAC is detected, then in operation 412, the negative exhaust gauge reading pressure is recorded as the negative exhaust gauge reading pressure Pcrit for subsequent MI-E cycles of MI-E treatment method 400.

[0085] Furthermore, when UAC is detected, a second cycle of MI-E method 400 is performed, which includes an injection cycle operation 414 similar to operation 402. Pressure is delivered to patient P at a positive injection gauge reading. In exhaust cycle operation 416, pressure is delivered to patient P at a recorded negative exhaust gauge reading (from operation 412).

[0086] Method 400 can be facilitated by introducing a Pcrit measurement tool. Clinical evidence suggests that Pcrit decreases during peak inspiration (i.e., UA is less prone to collapse) and increases during expiration (i.e., UA is more prone to collapse) (see, for example, Cao Y, McGuire M, Liu C, Malhotra A, Ling L: Phasic respiratory modulation of pharyngeal collapsibility via neuromuscular mechanisms in rats. J Appl Physiol 2012; 112(5):695–703). Therefore, a Pcrit tool will be used during the exhaust phase to determine and set the optimal negative pressure setting while avoiding the zero flow point (UA collapse) during exhaust. As the upper airway becomes more collapsible, automatic adjustment of negative pressure will help to alter the disease state, allowing the controller to deliver negative pressure that is increasingly closer to the ambient environment. In a preferred embodiment, the patient receives a target inspiratory pressure, followed by a negative expiratory pressure that begins to rise from ambient pressure and decreases toward a maximum negative pressure, which can be applied within the limits of the expiratory time setting, or can be applied until a change in the expiratory flow pattern indicates UA compression. A series of assessment breaths will help increase the delivered peak negative pressure to the upper limit of the negative pressure (set inspiratory pressure setting value) or until a zero flow point indicating the Pcrit value is reached. The Pcrit value will be used to set the negative pressure setting for the next exhaust phase (i.e., ≤ target inspiratory pressure setting), such as... Figure 18 As shown. Patient feedback tools such as mask seals and detection of active effort (i.e., coughing) during the exhalation phase can further improve the effectiveness of the Pcrit negative pressure controller algorithm of method 400.

[0087] Another embodiment may include a key function to prevent lung decompensation: an automated expiratory timing control algorithm. Assessing peak expiratory flow to determine the optimal time for circulatory closure of negative pressure will prevent the lungs from being exposed to unnecessarily negative pressure after expiratory flow has decayed to zero. This feature also helps prevent UA collapse, particularly for patients with initial expiratory flow rates that result in UA closure during the expiratory phase. If premature termination of the expiratory phase leads to the development of intrinsic PEEP, the patient's overall risk is considered low because intrinsic PEEP will resolve as soon as possible after the short MI-E treatment period ends.

[0088] Refer again Figure 5 To perform the UAC or cough detection procedure described herein, the electronic controller 13 of the mechanical ventilator 2 may include a UAC detector module 16 and an active cough detector module 18. Specifically, the UAC detector module 16 is programmed to perform a UAC detection operation 108, as described in more detail below.

[0089] UAC detector module 16 is programmed to execute a flow thresholding method, wherein the exhaust flow rate value is compared with any minimum flow threshold within any time window to determine the UAC condition. For example, as Figure 19 As shown, any minimum flow threshold is set to 5% or 10 lpm of the peak cough flow within each cough cycle, whichever is higher. Any time window is set to 30% of the set exhaust time.

[0090] UAC detector module 16 is programmed to execute a volume thresholding method, in which the exhaust volume is compared with any minimum volume threshold over the entire exhaust time, or with any portion of the injection volume, to determine the UAC conditions. For example, as Figure 20 As shown, any minimum exhaust volume threshold is set to 50% or 200ml of the injection volume, whichever is larger.

[0091] UAC detector module 16 is programmed to perform a slope method, whereby the change in flow over time is compared to an arbitrary maximum slope deviation threshold within an arbitrary time window to determine UAC conditions. For example, as Figure 21 As shown, the arbitrary flow rate slope deviation threshold is set to -0.25 or less. The arbitrary time window is set to 30% of the set exhaust time.

[0092] UAC detector module 16 is programmed to perform a revolutions per minute (RPM) pressure deviation method, wherein the change in the RPM or pressure of the blower 12 (or airflow generator source) over time is compared with an arbitrary maximum slope deviation threshold within an arbitrary time window to determine UAC conditions. For example, as Figure 22As shown, any RPM threshold is set to 20,000 or 80% of the exhaust pressure target. Any time window is set to 30% of the exhaust time.

[0093] The UAC detector module 16 is programmed to perform a convolutional neural network (CNN) method employing artificial intelligence (AI) processes. Deep learning and AI techniques have been used to classify various medical images. A CNN with fully connected artificial neural networks (ANNs) is used to build a classifier to distinguish between normal exhaust waveforms and exhaust waveforms with UAC. Sample MI-E waveforms used for the CNN model can be provided from expert-annotated real patient waveform data or a benchtop airway model with a collapsible airway for simulating UAC. Below is an example of using the CNN method with Python.

[0094]

[0095]

[0096]

[0097] UAC detector module 16 is programmed to perform the Forced Oscillation Technique (FOT) Delta Xrs method. Expiratory flow restriction can be determined through respiratory impedance analysis. During a normal airway opening in the exhaust cycle, low-frequency reactance measurements reflect the resilience of the respiratory system. During UAC, a blockage point forms around the collapsible upper airway. The oscillating signal cannot pass through this blockage point, thus significantly reducing respiratory reactance, which indicates UAC. The following is an example of the FOT Delta Xrs method, including the selection of the oscillation frequency, sampling method, filtering, and averaging calculation.

[0098] 1. A 6Hz single-frequency superposition of a 2cmH2O sinusoidal waveform onto MI-E therapeutic respiration.

[0099] 2. Pressure and flow signals are sampled at 1024Hz with a 0.5-second window and a 50% overlap window, resulting in a time resolution of 0.25 seconds.

[0100] 3. Apply a 25Hz fourth-order low-pass filter to eliminate noise.

[0101] 4. Apply a 2Hz 6th-order high-pass filter to eliminate MI-E respiratory cycles.

[0102] 5. Apply a 6th-order bandpass filter with a center frequency of 6Hz and a frequency of + / -1Hz.

[0103] 6. Apply the FFT function to extract the coefficients of each pressure and flow signal at 4Hz.

[0104] 7. Calculate Xrs (6Hz) for the injection and exhaust cycles: Xrs = FFT(pressure) / FFT(flow rate)

[0105] 8. Calculate Delta Xrs, which is equal to the difference between injection Xrs and exhaust Xrs.

[0106] 9. If Delta Xrs is greater than, for example, 3 cmH2O / L / S, then UAC is detected.

[0107] In addition to Delta Xrs, the following other parameters using FOT can be used to estimate the degree of UAC: Zi, Ri, Xi, Ze, Re, Xe, Fr.

[0108] Zi: Inhalation breathing resistance

[0109] Ri: Inhalation breathing resistance

[0110] Xi: Inhalation respiration response

[0111] Ze: Exhaust breathing resistance

[0112] Re: Exhaustion and Breathing Resistance

[0113] Xe: Exhaust breathing reactance

[0114] Fr: Resonance frequency

[0115] The active cough detector module 18 is programmed to perform a flow-based oscillation detection method. For flow-based active cough effort detection, the AC connection flow signal is analyzed. Various signal filtering schemes can be combined to improve signal integrity. A pause time can be added at the start of the exhalation phase to eliminate transient noise. The zero-crossing counter will only increment if the signal crosses a specified hysteresis band within the exhalation time frame. Active cough effort is detected if the number of zero-crossings in the signal is greater than any other number. The zero-crossing sum is cleared at the start of each respiratory phase. The flow oscillation detection process is as follows: Figure 23 As shown.

[0116] The active cough detector module 18 is programmed to perform a pressure-based oscillation detection method. Similar to a flow-based active cough effort detection method, it analyzes the AC connection pressure signal. Various signal filtering schemes can be combined to improve signal integrity. In this non-limiting example, a bandpass filter and signal rectification process are employed. The sum of the rectified signals is updated whenever the signal exceeds a specified minimum threshold. Active cough effort is detected when the summed signal exceeds the specified threshold. Pressure oscillations are cleared at the beginning of each respiratory phase. These outputs are as follows: Figure 24 As shown.

[0117] The active cough detector module 18 is programmed to execute a fast-response UAC triggering method, which can be obtained from the UAC detection method: flow rate, volume, and flow rate slope method. Fast-response UAC conditions can be declared within the exhaust time window when each flow rate, volume, and flow rate slope signal crosses an arbitrary threshold.

[0118] The disclosed system and method provide, for the first time, a technique that enables the MI-E device to be used clinically to support the clearance of secretions in neuromuscular patients presenting with medullary symptoms. Previously, the application of negative pressure in medullary patients was a significant obstacle, rendering the device ineffective.

[0119] The disclosed systems and methods support the complete removal of the negative pressure phase in very severe medullary patients, thereby preventing upper airway collapse. Patients are more likely to achieve PCF supporting lung clearance when the maximum target inspiratory pressure is used in conjunction with MIC support and active expiratory effort (i.e., coughing). This use of maximum target inspiratory pressure is entirely contrary to currently published recommendations for reducing inspiratory pressure in medullary patients. In this application, reducing inspiratory pressure is part of a strategy to reduce inspiratory flow, thereby reducing inspiratory adduction in ALS, particularly medullary ALS. However, if inspiratory flow control is successfully provided, reducing the target inspiratory pressure as a method of reducing inspiratory flow is no longer necessary. Flow controller 13 will allow inspiratory flow reduction to prevent inspiratory collapse while allowing the target inspiratory pressure to be maximized to achieve the MIC. This will significantly improve PCF in medullary patients.

[0120] The invention has been described with reference to preferred embodiments. Modifications and variations may arise in others after reading and understanding the foregoing detailed description. It is intended that the exemplary embodiments be construed as including all such modifications and variations, provided they fall within the scope of the appended claims or their equivalents.

Claims

1. A mechanical ventilation system (1), comprising: A mechanical ventilator (2) is configured to deliver ventilation to the patient; as well as An electronic controller (13) is programmed to control the mechanical ventilator to perform a mechanical insufflation-exhaust (MI-E) therapy (100), the method comprising performing an MI-E cycle, the MI-E cycle comprising: (i) During the inflation cycle, pressure is delivered to the patient using a positive inflation gauge; (ii) During the exhaust cycle following step (i), pressure is delivered to the patient at a negative exhaust pressure gauge; and (iii) Determine whether the zero-flow point during the exhaust cycle is caused by active coughing or upper airway collapse, based on the presence of a back pressure spike during the exhaust cycle; and (iv) If it is determined in step (iii) that the zero flow point is caused by upper airway collapse, then reduce the magnitude of the negative exhaust gauge pressure used for subsequent exhaust cycles.

2. The mechanical ventilation system (1) according to claim 1, wherein step (iv) reduces the magnitude of the negative exhaust pressure by a predetermined pressure magnitude reduction increment.

3. The mechanical ventilation system (1) according to claim 2, wherein the value of the incremental decrease in the predetermined pressure is 5 cm H2O.

4. The mechanical ventilation system (1) according to claim 1, wherein the treatment method is programmed to be repeated until no upper airway collapse is detected.

5. The mechanical ventilation system (1) according to claim 1, wherein the treatment method comprises: If upper airway collapse is detected, the magnitude of the negative exhaust pressure gauge is reduced to zero, and thereafter the magnitude of the negative exhaust pressure gauge is gradually increased.

6. The mechanical ventilation system (1) according to claim 5, wherein the gradual increase in the magnitude of the negative exhaust pressure continues until a second upper airway collapse is detected.

7. The mechanical ventilation system (1) according to claim 6, wherein the treatment method comprises: After detecting the second upper airway collapse, the magnitude of the negative exhaust gas meter pressure is reduced by a predetermined increment to a new negative exhaust gas meter pressure, and if no upper airway collapse is subsequently detected, the new negative exhaust gas meter pressure is maintained.

8. The mechanical ventilation system (1) according to claim 7, wherein the treatment method comprises: After upper airway collapse is detected using the new negative exhaust pressure gauge, the magnitude of the new negative exhaust pressure gauge is reduced by using the predetermined increment.

9. The mechanical ventilation system (1) according to claim 1, wherein the active cough includes glottal closure of the patient.

10. The mechanical ventilation system (1) according to claim 1, wherein determining whether the zero flow point is caused by active coughing or by upper airway collapse includes: Determine whether the zero flow point is included in one of at least two zero crossings during the exhaust cycle.

11. The mechanical ventilation system (1) according to claim 1, wherein determining whether the zero flow point is caused by active coughing or by upper airway collapse includes: Determine whether the zero flow point is instantaneous or associated with flow reversal.

12. A non-transitory computer-readable medium (15) storing instructions performed by an electronic controller (13) of a mechanical ventilator (2) to control the mechanical ventilator to perform a mechanical injection-exhaust (MI-E) therapy (400), the method comprising performing an MI-E cycle, the MI-E cycle comprising: (i) During the inflation cycle, pressure is delivered to the patient using a positive inflation gauge; (ii) During the exhaust cycle following step (i), pressure is delivered to the patient at a negative exhaust pressure gauge; (iii) Determine whether the zero flow point in the exhaust cycle is caused by active coughing or by upper airway collapse, based on whether a back pressure spike exists during the exhaust cycle; (iv) If it is determined in step (iii) that the zero flow point is caused by upper airway collapse, then reduce the magnitude of the negative exhaust gauge pressure used for subsequent exhaust cycles; as well as (v) If the analysis predicts that no upper airway collapse will occur during the exhaust cycle, the magnitude of the negative exhaust gauge pressure is increased during the delivery.

13. The non-transitory computer-readable medium (15) of claim 12, wherein the increase comprises: if the analysis at step (v) predicts that upper airway collapse will not occur during the exhaust cycle, the increase comprises: The magnitude of the negative exhaust pressure is increased by a constant value by adding a constant value to the negative exhaust pressure.

14. The non-transitory computer-readable medium (15) of claim 13, wherein the MI-E cycle comprises: if the analysis at step (v) predicts that upper airway collapse will not occur during the exhaust cycle: The negative exhaust pressure is recorded as the negative exhaust pressure for subsequent MI-E cycles of the MI-E treatment method (400).

15. The non-transitory computer-readable medium (15) of claim 14, wherein the MI-E treatment method (400) further comprises responding to the detection of upper airway collapse in step (v): A second MI-E cycle is executed after step (v), the second MI-E cycle comprising: (vi) During the inflation cycle, pressure is delivered to the patient at the pressure indicated by the positive inflation gauge; (vii) During the exhaust cycle following step (iv), pressure is delivered to the patient at the recorded negative exhaust gauge pressure.

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