Apparatus and method for diaphragmatic stimulation

Abstract

Some systems and methods described herein are directed to controlling, activating, and otherwise interacting with a patient's phrenic nerve, thereby interacting with the diaphragm, while the patient is undergoing mechanical ventilation. Some embodiments of the systems and methods described herein are configured to achieve phrenic nerve stimulation in a controlled manner that adequately tailors respiratory therapy to various patients.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Patent Application No. 63 / 397,143, filed August 11, 2022, and U.S. Provisional Patent Application No. 63 / 441,300, filed January 26, 2023, the disclosures of which are incorporated herein by reference.

[0002] The present disclosure relates to medical devices, systems, and methods for use in respiratory care, such as those involving mechanical ventilation. Some implementations described herein are directed to providing electrical stimulation of the phrenic nerve in patients undergoing respiratory augmentation, such as through mechanical ventilation, assisted breathing techniques in which the patient may initiate a breath, the use of continuous positive airway pressure (CPAP), or applications involving sleep apnea. Such techniques can facilitate ventilation and patient recovery, for example, by mitigating the effects of ventilator-induced diaphragmatic dysfunction.

[0003] The present disclosure relates to medical devices, systems, and methods for use in respiratory care, such as those involving mechanical ventilation. Some implementations described herein are directed to providing electrical stimulation of the phrenic nerve in patients undergoing respiratory augmentation, such as through mechanical ventilation, patient-initiated assisted breathing techniques, continuous positive airway pressure (CPAP) use, and applications involving sleep apnea. Such techniques can facilitate ventilation and patient recovery, for example, by mitigating the effects of ventilator-induced diaphragmatic dysfunction. [Background technology]

[0004] Respiratory augmentation techniques, such as mechanical ventilation, can be used clinically to maintain gas exchange in patients and help maintain adequate alveolar ventilation. It can be desirable to avoid prolonged mechanical ventilation and to help wean patients off assisted breathing. For example, while mechanical ventilation can be a life-saving treatment for patients suffering from respiratory failure, prolonged mechanical ventilation can promote diaphragmatic atrophy and contractile dysfunction, referred to as ventilator-induced diaphragmatic dysfunction. In some situations, mechanical ventilation of a patient for only a few days can be sufficient to cause ventilator-induced diaphragmatic dysfunction.

[0005] Phrenic nerve stimulation is a technique for facilitating respiratory augmentation and can be used to maintain a level of diaphragm activity in patients on mechanical ventilation. When patients are on a ventilator and unable to generate their own inspiratory effort, phrenic nerve pacing can be used to induce activity in the diaphragm muscles to reduce or reverse atrophy, especially in severe cases where patients become ventilator dependent and require a form of pacing training to strengthen their own muscles. Summary of the Invention [Problem to be solved by the invention]

[0006] Some embodiments of the systems and methods described herein are configured to achieve phrenic nerve stimulation in a controlled manner that adequately adapts respiratory therapy to a variety of patients, including those experiencing changes in the level of patient respiratory effort over time. In certain implementations, the system can provide such control in an efficient and rapid manner so that dynamic responses (computationally and otherwise) can be achieved. Some examples detailed herein provide a system for diaphragmatic stimulation that is specifically programmed to monitor one or more sensor signals in real time during the patient's inspiratory phase and controllably adapt the stimulation intensity level during the next stimulated breath in a manner that avoids abrupt changes to stimulation intensity and accounts for momentary outliers from the sensor signal. [Means for solving the problem]

[0007] Certain embodiments described herein include a phrenic nerve stimulation system including a phrenic nerve stimulation control console and a phrenic nerve stimulation lead assembly. The phrenic nerve stimulation control console may be configured to control a stimulation intensity of a phrenic nerve stimulation signal deliverable to at least one phrenic nerve during mechanical ventilation. The phrenic nerve stimulation lead assembly may include at least one electrode lead positionable in proximity to at least one phrenic nerve for outputting the phrenic nerve stimulation signal from the phrenic nerve stimulation control console to a corresponding phrenic nerve. In some optional implementations, in response to a detected level of patient respiratory effort being outside a predetermined range, the phrenic nerve stimulation control console controllably increases or decreases the stimulation intensity of the phrenic nerve stimulation signal by a preset differential value.

[0008] In further embodiments, the phrenic nerve stimulation system may include a phrenic nerve stimulation control console, a phrenic nerve stimulation lead assembly, and a muscle activity sensor. The phrenic nerve stimulation control console may be configured to control a stimulation intensity of a phrenic nerve stimulation signal deliverable to at least one phrenic nerve during mechanical ventilation. The phrenic nerve stimulation lead assembly may include at least one electrode lead positionable in proximity to at least one phrenic nerve to output the phrenic nerve stimulation signal from the phrenic nerve stimulation control console to the corresponding phrenic nerve. The muscle activity sensor may be in communication with the phrenic nerve stimulation control console to provide feedback indicative of muscle activity in at least one of the shoulder and the neck. In some optional implementations, in response to a detected level of muscle activity being greater than a predetermined threshold, the phrenic nerve stimulation control console may decrement the stimulation intensity of the phrenic nerve stimulation signal by a preset delta value.

[0009] Additional embodiments described herein include a method for controlling phrenic nerve stimulation. The method may include delivering a first cycle of phrenic nerve stimulation at a first intensity level from a phrenic nerve stimulator to at least one stimulation lead proximate to at least one phrenic nerve, followed by delivering a second cycle of phrenic nerve stimulation at the first intensity level from the phrenic nerve stimulator to at least one stimulation lead proximate to the at least one phrenic nerve. Optionally, the method may also include outputting a warning via a user interface of the phrenic nerve stimulator indicating readiness to wean from mechanical ventilation in response to detecting that a parameter indicative of diaphragmatic contraction force is greater during the second cycle than during the first cycle.

[0010] Some embodiments described herein include a method of phrenic nerve stimulation. The method may include delivering a phrenic nerve stimulation signal for an entire stimulation period during a first stimulated breath of a patient in which at least one phrenic nerve is electrically stimulated by the phrenic nerve stimulation signal delivered from a phrenic nerve stimulation control console to at least one stimulation lead positioned proximate to the at least one phrenic nerve. The method may also include detecting a level of patient respiratory effort during the first stimulated breath. Furthermore, the method may include delivering a notched stimulation signal from the phrenic nerve stimulation control console to at least one stimulation lead positioned proximate to the at least one phrenic nerve during a second stimulated breath of the patient, such that electrical stimulation is temporarily terminated for a portion of the entire stimulation period. The method may include outputting a warning via a user interface of a phrenic nerve stimulation device in response to detecting a particular condition, the warning indicating readiness to wean from mechanical ventilation. Optionally, detecting the specific condition may be either detecting that the decrease in airflow characteristics during the notch stimulation signal is below a threshold, or detecting that the magnitude of the decrease in airflow characteristics during the notch stimulation signal is equal to or less than a previous magnitude detected during a previous delivery of the notch stimulation signal.

[0011] Some embodiments described herein include a mechanical ventilator configured to deliver breathable air to a patient's lungs. The mechanical ventilator may include a ventilator control console configured to control selected pressure or flow parameters of respiratory therapy breaths during mechanical ventilation. The mechanical ventilator may also include a breathing circuit tubing for directing the respiratory therapy breaths to the patient. In some optional implementations, the mechanical ventilator may include a phrenic nerve stimulation lead assembly connected to the ventilator control console via a cable and including at least one electrode lead positionable adjacent to at least one phrenic nerve to output a phrenic nerve stimulation signal during respiratory therapy breaths. The ventilator control console of the mechanical ventilator may optionally include a graphical user interface for controlling the stimulation intensity of the phrenic nerve stimulation signal deliverable to the at least one phrenic nerve during mechanical ventilation.

[0012] Further embodiments described herein include a stimulation electrode and a stimulation circuit for stimulating a patient's diaphragm, the stimulation circuit capable of delivering electrical energy via the stimulation electrode to the patient's phrenic nerve at a stimulation intensity, including incrementally increasing or decreasing the stimulation intensity by predetermined incremental amounts to maintain the patient's characteristic respiratory airflow parameter within a target range.

[0013] In some embodiments described herein, a device may include a stimulation circuit for applying stimulation via one or more electrodes and a control circuit, which may optionally be configured to deliver electrical energy via the stimulation circuit to the patient's phrenic nerve coincident with inspiration to stimulate the patient's diaphragm, to record and track the patient's amount of respiratory effort for a given intensity level of the electrical stimulation, and to generate and output an indicator signal in response to the patient achieving a target level of respiratory effort.

[0014] Additionally or alternatively, some embodiments include a device comprising a stimulation circuit for applying stimulation via one or more electrodes and a control circuit, which may optionally be configured to assess the patient's respiratory effort for a given intensity level of electrical stimulation applied to the patient's phrenic nerve via the stimulation circuit, and to generate and output an indication in response to the assessed respiratory effort reaching a plateau of decreasing gain in effort for the given stimulation intensity over time.

[0015] Further embodiments described herein include devices comprising a stimulation circuit for applying stimulation via one or more electrodes and a control circuit, which may optionally be configured to increase the rate at which the patient's diaphragm is strengthened or rehabilitated by stimulating the patient's diaphragm with electrical energy delivered to the patient's phrenic nerve via the stimulation circuit in successive breaths using a predetermined pattern of varying stimulation intensity levels.

[0016] In some embodiments, the device includes a stimulation circuit for applying stimulation via one or more electrodes and a control circuit, which may optionally be configured to provide a diaphragm pacing function to stimulate the patient's diaphragm through delivery of electrical energy to the patient's phrenic nerve coincident with inspiration based on representative airflow parameters indicative of the patient experiencing hypoventilation or central sleep apnea.

[0017] Certain embodiments described herein include a device including a lead circuit and a processing circuit. The lead circuit can be configured to couple stimulation energy to a phrenic nerve of a patient having a diaphragm. The processing circuit can be configured to stimulate the diaphragm by delivering stimulation energy to the phrenic nerve via the lead circuit, including incrementally increasing or decreasing the stimulation energy by predetermined amounts in subsequent breaths of the patient based on characteristic respiratory airflow parameters of the patient and target ranges for the parameters.

[0018] One or more of the embodiments described herein may be configured to achieve several advantages. First, some embodiments of a phrenic nerve stimulation system may be configured to provide adaptive stimulation during mechanical ventilation, including a control system that is adaptive to a detected level of patient respiratory effort. Second, certain embodiments described herein may be configured to prospectively predict a patient's readiness for weaning from mechanical ventilation, for example, based on sensor data input to the control system over time. Third, some embodiments of a phrenic nerve stimulation system may be connected to and controlled by a mechanical ventilator console. Fourth, in some implementations, the phrenic nerve stimulation system may accept user input indicating a delta value for a change to stimulation intensity and then implement an automatic delta change to the stimulation intensity level (e.g., an increase or decrease in the delta value) based on the detected level of patient respiratory effort, thereby providing a safe degree of adaptive control configured to avoid large or uncomfortable fluctuations in stimulation intensity from one stimulated breath to the next. Fifth, some embodiments of the phrenic nerve stimulation system can efficiently and automatically detect an operating range of stimulation intensity levels (e.g., including a maximum level of stimulation intensity customized for a particular patient) based on a detected level of patient respiratory effort during mechanical ventilation. Fifth, some embodiments of the phrenic nerve stimulation system can be configured to automatically decrement the stimulation intensity level in response to sensing muscle activity in at least one of the patient's neck and shoulders. Sixth, some embodiments of the phrenic nerve stimulation system can advantageously include a user interface that outputs a warning indicating the patient's readiness to wean from mechanical ventilation in response to detecting, for example, a change in sensed diaphragmatic contraction force. Seventh, in some variations, the phrenic nerve stimulation system can be controlled to implement a predetermined training pattern for stimulating the phrenic nerve using a succession of different stimulation intensity levels during a training period.

[0019] The above summary is not intended to describe each embodiment or every implementation of the present disclosure. The figures, detailed description, and claims that follow also exemplify various embodiments. Other features, objects, and advantages will be apparent from the description and drawings, and from the claims. [Brief explanation of the drawings]

[0020] [Figure 1] FIG. 1 is a perspective view of a system for diaphragmatic stimulation, according to some embodiments. [Figure 2] FIG. 2 is a perspective view of a phrenic nerve stimulator of the system of FIG. 1. [Figure 3A] 2 is another perspective view of the phrenic nerve stimulator of the system of FIG. 1. [Figure 3B.3C.3D] FIG. 3B is a perspective view of an alternative stimulation lead of the phrenic nerve stimulator of FIG. 3A. [Figure 4] FIG. 10 is a perspective view of an alternative system for diaphragmatic stimulation according to a further embodiment. [Figure 5A] 1 is a flow diagram of an exemplary process for stimulus control, according to some embodiments. [Figure 5B] FIG. 5B is a diagram of an example phrenic nerve stimulation signal from the process of FIG. 5A. [Figure 6] 1 is a flow diagram of an exemplary process for stimulus control, according to some embodiments. [Figure 7] 1 is a flow diagram of an exemplary process for stimulus control, according to some embodiments. [Figure 8A] 1 is a flow diagram of an exemplary process for detecting readiness to wean from mechanical ventilation, according to some embodiments. [Figure 8B] FIG. 8B is an example diagram of a phrenic nerve stimulation signal from the process of FIG. 8A. [Figure 9A] 1 is a flow diagram of an exemplary process for detecting readiness to wean from mechanical ventilation, according to some embodiments. [Figure 9B] FIG. 9B is an example diagram of a phrenic nerve stimulation signal from the process of FIG. 9A. [Figure 10]1 is a flow diagram of an exemplary process for delivering phrenic nerve stimulation in combination with mechanical ventilation, according to some embodiments. [Figure 11] 1 is a flow diagram of an exemplary process for delivering phrenic nerve stimulation in combination with mechanical ventilation, according to some embodiments. [Figure 12A] 1 is a flow diagram of an exemplary process for stimulus control, according to some embodiments. [Figures 12B-12C] FIG. 12B is an example diagram of a phrenic nerve stimulation signal from the process of FIG. 12A. [Figure 13] FIG. 10 illustrates example respiratory sensor signals, including airway flow and pressure signals, that may be displayed on a graphic user interface of some exemplary systems disclosed herein, in accordance with certain embodiments. DETAILED DESCRIPTION OF THE INVENTION

[0021] Like numbers in the various drawings indicate like elements. Furthermore, the various diagrams and graphs as shown may be utilized independently, in conjunction with one another, or modified in accordance with other aspects disclosed herein.

[0022] 1-3D , some embodiments of a system 10 for diaphragm stimulation include a phrenic nerve stimulator 100 and a mechanical ventilator device 200. The phrenic nerve stimulator 100 may include a control console 110 in communication with a respiratory sensor 120 and an electrical stimulation lead assembly 130. The respiratory sensor 120 may be in the form of a Y-shaped sensor coupled to an airflow path extending between an intubation conduit 125 positioned in the airway of the patient 105 and breathing circuit tubing 225 of the mechanical ventilator 200. The lead assembly 130 may include one or more leads configured to output electrical stimulation to a corresponding phrenic nerve. In the depicted embodiment, the lead assembly 130 includes two percutaneous leads 132 and 134 (e.g., a right lead and a left lead; see also Figures 2-3D) configured for percutaneous insertion into the neck 106 of the patient 105 such that a selected electrode pair of the right lead 132 captures the right phrenic nerve and another selected electrode pair of the left lead 134 captures the left phrenic nerve.

[0023] As described in more detail below, the control console 110 comprises a graphic user interface 112 (e.g., a touch screen and, optionally, mechanical switches for user input), a computer-readable memory and central processing unit positioned within the housing of the console 110 and configured to control stimulation of the patient's diaphragm according to implementation examples detailed below, a number of connection ports for receiving sensor data (e.g., from the Y-sensor 120, from several optional EMG sensors 140, from optional force sensors 142 worn on the patient's body, and others), a connection port for data communication with the mechanical ventilator 200, and one or more ports for connection to corresponding cables 135 of the lead assembly 130. The control console 110 is programmed to deliver electrical current to the lead assembly 130 in response to one or more sensed conditions for the purpose of electrically stimulating one or both of the phrenic nerves 108 ( FIG. 3A ) and thereby activating the patient's diaphragm 109 while the patient 105 is receiving mechanical ventilation (from the ventilator 200). The wye sensor 120 may optionally include at least one flow sensor configured to detect several respiratory characteristics (e.g., pressure, flow direction, volume, etc.) that are input to the control console 110 and used to monitor the patient and determine whether a sufficient level of stimulation is being applied to the patient's diaphragm 109. For example, the wye sensor 120 may be pneumatically connected to the breathing circuit tubing 225 of the mechanical ventilator 200 to measure both flow and pressure using standard differential and gauge pressure sensors within the desired operating range. In this embodiment, the wye sensor 120 is electrically coupled to the control console 110 via a cable 125. As described above, the control console 110 houses a processing unit and computer readable memory that controls the integrated pulse generator to provide electrical output that is delivered to the leads 132 and 134 via corresponding lead cables 135.In some embodiments, data received from the Y-sensor 120, lead assembly 130, optional EMG sensor 140, body-worn sensor 142, and ventilator 200, as well as pulse generator output parameters, may be displayed on a touchscreen display of control console 110. A computer-readable memory device housed within control console 110 stores software that implements stimulation control tasks, including, for example, reading input data from the sensors, performing algorithmic calculations, and setting outputs based on user-set inputs and algorithmic calculations. In some optional implementations, control console 110 may be configured to export patient data, including sensor data and historical phrenic nerve stimulation data, to an external memory device (e.g., a USB memory device or external hard drive) or an external computing device (e.g., via a wireless network connection, a Bluetooth connection, or a cable connection). For example, in certain implementations, patient data may be exported for purposes of real-time data processing on an external computing device configured for greater computational load or other predictive models capable of assessing when a patient is ready to be weaned from mechanical ventilation so that the external computing device can communicate back to the control console 110 for outputting alerts or other information in the graphic user interface 112.

[0024] 3A-3D, lead assembly 130 can include one or more stimulation leads, and in the depicted example of FIG. 3A, right lead 132 and left lead 134 each include a single lead body having a distal end with multiple electrodes and a proximal end having a set of four terminals for connection to control console 110 (via a corresponding cable 135). In this embodiment, each lead 132 and 134 is a multipolar lead having at least four electrodes (axially spaced apart) exposed along percutaneous insertion tips 136 and 138 of leads 132 and 134, respectively. Alternatively, each lead 132 and 134 shown in FIG. 3A can instead have five annular electrodes 133 axially spaced apart from one another (e.g., as depicted in FIG. 3B). In another alternative, each lead 132 and 134 shown in Figure 3A may include a percutaneously insertable paddle-shaped electrode lead tip 137 (e.g., as depicted in Figure 3C) having an array of electrodes along a flat surface (in this example, a 2 x 8 array of 16 electrodes). Alternatively, each lead 132 and 134 shown in Figure 3A may include multiple segmented electrodes 139 (e.g., as depicted in Figure 3C) spaced along a cylindrical portion of the lead tip, with additional sets of segmented electrodes spaced axially from each other (e.g., providing a total of 12 sets of electrodes in the depicted example). In some implementations, different types of electrode leads 132 and 134 (see examples in Figures 3A, 3B, 3C, and 3D) may be provided to the user, and the user may select a particular type of electrode lead depending on the lead insertion orientation of the percutaneous insertion tip for each lead 132 and 134 and the specific anatomical structure in the patient's neck 106.

[0025] 3A-3D , at least one pair of electrodes along each lead 132 and 134 can be anchored in proximity to the phrenic nerve 108 such that the selected electrode pair is positioned across the phrenic nerve 108 in the neck 106 and can electrically capture the nerve 108 (in response to delivery of an electrical stimulation signal output from the selected electrode pair) for purposes of stimulating the diaphragm 109. For example, the control console can be configured to activate several electrode pair options and initiate an electrode selection process that detects a level of stimulation for each of the electrode pair options (e.g., via detected work of breathing, via an EMG sensor, or a combination thereof), in which case the control console can automatically select one of the electrode pair options that sufficiently captures the phrenic nerve at a lower current input level (to activate the diaphragm). Alternatively, the control console can provide a recommendation for one of the electrode pair options, and the user can manually select the recommended electrode pair using the touchscreen interface 112. Additionally or alternatively, the user may manually initiate stimulation of the electrode pair options and then manually select (using the touchscreen interface 112) one of the electrode pair options that adequately captures the phrenic nerve at a lower current input level (to activate the diaphragm). The control console 110 may be implemented to provide both monopolar and bipolar stimulation options using lead assemblies, with both anodal and cathodal stimulation available for use in therapy. The control console 110 may also be implemented to provide both monophasic balanced current stimulation and unbalanced biphasic current stimulation; in the example depicted in FIG. 3A, the control console 110 is configured to deliver biphasic stimulation from the selected electrode pair (in each of the leads 132 and 134) to achieve a satisfactory level of work of breathing (as calculated by the control console 110, described below). The selected electrode pair may also be changed (e.g., to select a different pair) after a period of time or in response to detecting that the leads 132, 134 have moved relative to the nerve 108 over time.

[0026] In use, the control console 110 of FIGS. 1-3A can be configured to deliver phrenic nerve stimulation during a subset of breaths while the patient is exposed to mechanical ventilation from the ventilator 200. A person's breath has an inspiratory phase characterized by the static pressure flow of air through the Y-sensor 120 to the patient, and an expiratory phase that begins when the flow through the Y-sensor reverses (e.g., when the flow value drops below zero and turns negative) as the patient exhales the inhaled volume. This end of the inspiratory event typically initiates the outflow portion of the respiratory cycle. In operation, the control console 110 is programmed to deliver electrical stimulation beginning with the inspiratory phase (of a designated stimulated breath) when flow exceeds a first predetermined level and to terminate stimulation before the start of the expiratory phase when flow drops below a second predetermined level. It is not necessary for all of a patient's breaths during mechanical ventilation to be stimulated breaths. In many embodiments, the control console 110 will deliver phrenic nerve stimulation only during designated stimulation breaths between preceding and following breaths of the mechanical ventilator. Electrical stimulation pulses are delivered at a preset pulse rate within the designated breath. The selection of the count of designated stimulation breaths can be a simple ratio, such as the selected stimulation breath occurring every other breath (1:2), every fourth breath (1:4), or every 20 breaths (1:20).

[0027] Some embodiments of the control console 110 can advantageously communicate with a mechanical ventilator such that the control console 110 can receive input that is useful when assessing a patient's work of breathing and other respiratory characteristics. For example, a ventilator data cable 205 can provide data communication between the control console 110 and the control console of the mechanical ventilator 200 during ventilated breaths of the patient 105 (or alternatively, the data communication connection between the control console 110 and the ventilator 200 can be wireless communication using Bluetooth data communication or a wireless network connection). The control console 110 can receive data from the ventilator 200 that indicates the type of ventilator breath being output to the patient. In this embodiment, the ventilator 200 can be configured to deliver flow-controlled ventilation (FCV) breaths, pressure-controlled ventilation (PCV) breaths, or a combination of both. The control console 110 can receive data from the ventilator 200 indicative of the type of ventilator breath, and further facilitates interpretation of the flow and pressure measurement trajectories detected during each breath and depicted on the touchscreen interface 112 of the control console 110. In some embodiments in which the control console 110 receives data communication from the ventilator 200 (e.g., via cable 205 or wireless data communication), the control console 110 can receive sensed breath characteristics (e.g., pressure, flow direction, volume, etc.) from the ventilator 200 rather than from the wye sensor 120. Optionally, in such situations, the system 10 can operate with or without a separate wye sensor 120 directly connected to the control console 110.

[0028] 4, some alternative embodiments of the system 30 for diaphragmatic stimulation may include an enhanced mechanical ventilator 300 that incorporates control of phrenic nerve stimulation into the control console of the ventilator 300. For example, the features and operation of the control console 110 (FIGS. 1-3) described herein may be implemented in the control console 310 of the mechanical ventilator 300, and the flow-sensing operation of the wye-sensor 120 (FIGS. 1-3) may also be implemented by one or more flow sensors housed within the mechanical ventilator 300. The control console 310 of the mechanical ventilator 300 may include an enhanced user interface 312 with additional display graphics and user input fields for controlling phrenic nerve stimulation and outputting detected characteristics of stimulated breaths (and, optionally, work of breathing values ​​calculated by the control console 310 of the ventilator 300 during each stimulated breath), in addition to control screens for setting and monitoring the patient's mechanical ventilation. The control console 310 of the improved mechanical ventilator 300 can include a port for connection to the lead assembly 130, which includes one or more percutaneous leads 132 and 134 connected to the ventilator 300 via a cable 135. The lead assembly 130 operates as described above in connection with FIGS. 1-3 , and an internal pulse generator housed within the control console 310 of the mechanical ventilator 300 can be configured to deliver stimulation current to selected electrode pairs on each of the leads 132 and 134 to capture the nearby phrenic nerve in the patient's neck 106 and activate the diaphragm during mechanical breaths delivered from the ventilator 300 (such that the ventilator 300 operates as a control console for both mechanical ventilation control and phrenic nerve stimulation). The control console 310 of the improved mechanical ventilator 300 may also include ports for connection to optional EMG sensors, optional body-worn force sensors 142, or a combination thereof.

[0029] Both systems 10 (FIGS. 1-3D) and 30 (FIG. 4) can be implemented in a manner that implements automatic stimulation control and other control features for phrenic nerve stimulation during mechanical ventilation (including, for example, those detailed below in FIGS. 5A-12). In various variations, control settings, user interfaces, and graphical overviews (including, for example, graphs of respiratory characteristics during breathing) can be implemented via control console 110 (FIGS. 1-3A) or via control console 310 (FIG. 4).

[0030] Referring now to FIG. 5A , some embodiments of a system for diaphragmatic stimulation (e.g., system 10 or system 30) can be implemented to achieve method 400, which provides an automatic stimulation control feature. In a specific example, the system can respond to a patient's respiratory effort during a breath, such as a stimulated breath while a control console (e.g., 110 or 310) delivers an electrical stimulation signal to stimulate the patient's phrenic nerve. Optionally, the system can dynamically respond by lowering or increasing the stimulation intensity level by a predetermined difference value, which can remain the same both when the detected level of patient respiratory effort is only slightly outside a predetermined range or when it is significantly outside the predetermined range. In such an example, the stimulation intensity can be automatically adjusted over time by a controlled, fixed difference, rather than the substantial, variable adjustments that might otherwise occur from one stimulated breath to the next (e.g., due to outlying measurements of patient respiratory effort).

[0031] 5A, method 400 may include operation 405 in which the control console stores an operating range for stimulation intensity, a predetermined stimulation intensity difference value, or both. In some embodiments, the stimulation intensity may be a value associated with the electrical stimulation signal delivered to leads 132, 134, such as amplitude, pulse width (PW), frequency, electrode pair, or a combination thereof. The operating range for stimulation intensity stored by the control console may be manually determined during an electrode pair mapping period (described above) based on a diaphragmatic contraction threshold on the lower end and a supramaximal diaphragmatic stimulation level (or a maximum tolerable level for the patient) on the higher end. In one example, the electrode mapping period may specify the following characteristics for the stimulation signal and electrode pair combination (shown are two configurations based on two different electrode pair combinations):

[0032] [Table 1]

[0033] In such an example, the operating range for stimulation intensity stored by the control console may have a lower end of 1.1 mA with a 200 μs PW at 25 Hz (for configuration number 1), a higher end of 2.6 mA with a 200 μs PW at 25 Hz (for configuration number 2), a lower end of 3.4 mA with a 200 μs PW at 25 Hz, and a higher end of 5.9 mA with a 200 μs PW at 25 Hz (for configuration number 2). In certain embodiments, the predetermined stimulation intensity delta value stored by the control console (used to automatically increase or decrease stimulation, as described in more detail below) may be a percentage of the operating range, such as 10% current (mA). In this example, the delta values ​​would be 0.15 mA (for configuration number 1) and 0.25 mA (for configuration number 2). Alternatively, the predetermined stimulus intensity difference value can be a default value stored in the control console (e.g., 0.2 mA), which can be manually changed / selected by the user in a settings selection screen of the control console's graphic user interface. Also, in other embodiments, the predetermined stimulus intensity difference value stored by the control console can be a characteristic of the stimulus signal other than current amplitude, such as a difference in pulse width (PW) or frequency values.

[0034] 5A , method 400 may also include operation 410, in which the system delivers pacing stimulation at a set intensity level to one or more leads (e.g., leads 132, 134) proximate to the patient's phrenic nerve during the patient's breath. In such a situation, the breath is characterized as a stimulated breath that occurs during mechanical ventilation of the patient, e.g., as described above in connection with FIGS. 1-3D and 4 . The set intensity level includes stimulation characteristics that fall within an operating range for stimulation intensity stored by the control console. As described above, the set intensity level may have a stimulation intensity characterized by current amplitude, pulse width (PW), frequency, or a combination thereof.

[0035] Method 400 may also include operation 415, in which the system detects a level of patient respiratory effort during a breath. For example, during a stimulated breath from operation 410, the system may receive a sensor input (e.g., from the wye-sensor 120, from the EMG sensor 140, from the patient-worn sensor 142, or a combination thereof) indicating the level of effort achieved by the patient's diaphragm during the stimulated breath. The sensor input may be used directly as a detected level of patient respiratory effort, or alternatively, may be used by the control console to calculate a value for the level of patient respiratory effort. In one example, the control console may use the sensor input to calculate a value for work of breathing (WOB), which may be expressed as work per unit volume, such as joules / liter, or as a power rate, such as joules / minute. The control console may calculate WOB during a selected breath for purposes of identifying the level of energy expended to draw respiratory gas. In other examples, systems with lead stimulation activity may instead rely on different characteristics of detected levels of patient respiratory effort, such as a) peak inspiratory flow, b) average inspiratory flow, c) peak airway pressure compared to peak predicted airway pressure, or d) average airway pressure compared to average predicted airway pressure. As described above, these examples of different characteristics of detected levels of patient respiratory effort may be gathered directly from sensor inputs (e.g., from the wye sensor 120, from the EMG sensor 140, from the patient-worn sensor 142, or a combination thereof) without subsequent calculations (e.g., to calculate a WOB value), thereby providing a dynamic and potentially more rapid response from the control console (as described in more detail below).

[0036] For those particular embodiments in which the detected level of patient respiratory effort is a calculated WOB value, the equation for breathing motion is used to estimate patient WOB in electrically stimulated breaths. In breaths without electrical stimulation, WOB is calculated as: mus is 0 cmH2O, so it should be 0 J / L. According to the kinetic equation for the respiratory system, Pvent +P mus = elastance x volume + resistance x flow is.

[0037] Elastance is a measure of the tendency of a hollow organ to rebound toward its original dimensions upon removal of a distending or compressing force. It is the inverse of compliance. Resistance or airway resistance is the obstruction to flow caused by frictional forces. Resistance is defined as the ratio of the driving pressure to the rate of airflow. Elastance is measured in cmH2O / liter, volume is measured in liters, resistance is measured in cmH2O / Lpm, and flow is measured in Lpm. P vent is the pressure exerted by the ventilator, and P mus is the pressure exerted by the diaphragm muscle, both measured in cmH2O. This equation can be rearranged to show: P vent +P mus = elastance x volume + resistance x flow + PEEP P mus = elastance x volume + resistance x flow + PEEP-P vent where P vent =P wye Work = Pressure x Volume Work = ∫0 Vt Pmuscles*dV (Joules) where dV is the rate of change of volume and Vt is the inspired tidal volume.

[0038] This can also be expressed as follows: Work = ∫ t0 t1 Pmuscles*Qdt where Q is the instantaneous flow and t0 and t1 are the start and end of inspiration. WOB = Work / Liter = Work / Vt (Joules / Liter)

[0039] The systems 10, 30 may include mechanical ventilators 200, 300 configured to measure respiratory mechanics, such as static and dynamic compliance and resistance, for each individual patient. These values ​​may be advantageously communicated to the control console 110 in FIGS. 1-3A via cable 205 or a wireless data connection (or measured and stored using the integrated control console 310 in FIG. 4). Additionally or alternatively, the wye sensor 120 may be configured to measure the patient's respiratory mechanics, such as static and dynamic compliance and resistance, which are then stored by the control console 110, 310 for purposes of calculating the WOB value in some implementations. As described above in connection with FIGS. 1-3A and 4, the wye sensor 120 may be used to measure Pvent (Pwye) and flow in the wye (Qwye). Volume accumulation may be calculated by integrating Qwye over respiratory progression, beginning at the beginning of inspiration and stopping at the end of inspiration.

[0040] Referring again to FIG. 5A , method 400 may also include operations for determining whether a detected level of patient respiratory effort (e.g., a WOB value or a sensor value as described above) is outside a predetermined range (e.g., a selected safe range of patient effort during mechanical ventilation) and for dynamically responding accordingly by automatically adjusting the set stimulation intensity level by a pre-stored difference level. For example, in operation 420, the system may determine whether the detected level of patient respiratory effort is higher than the upper limit of the predetermined range of respiratory effort. If yes, method 400 may respond by proceeding to operation 425 to reduce the set intensity level (described in operation 410) by a predetermined intensity difference value (described in operation 405). As shown in FIG. 5B , the intensity signal may be reduced incrementally 525 in response to detecting that the level of patient respiratory effort is higher than the upper limit of the predetermined range, although subsequent breaths may optionally remain at the same stimulation level as long as the detected level of patient respiratory effort remains within the predetermined range. (In some implementations, one or more of the trajectories / plots depicted in FIG. 5B may be displayed on a user interface screen of the control console 110 or 310 during therapy.) Thus, referring again to FIG. 5A , operation 425 decrements the set intensity level, which may then be applied to the next stimulated breath when method 400 loops back to operation 410 (using the decremented intensity level as the new set intensity level). In this embodiment, the difference value is pre-saved (operation 405), so that the new stimulation intensity level (for the next stimulated breath) is not reduced by an amount that varies with how much higher the detected level of patient respiratory effort exceeds the upper limit of the predetermined range of respiratory effort. Rather, in this embodiment, the set intensity level is decremented by a pre-set amount regardless of whether the detected level of patient respiratory effort exceeds the upper limit by a small or more significant amount, thereby providing automatic control of stimulation intensity in a manner that avoids dramatic changes in the new stimulation level from the first breath to the next stimulated breath.

[0041] Similarly, in operation 430, the system may determine whether the detected level of patient respiratory effort is lower than the lower limit of a predetermined range of respiratory effort. If yes, method 400 may respond by proceeding to operation 435 to increase the set intensity level (described in operation 410) by a predetermined intensity difference value (described in operation 405). As shown in FIG. 5B, the intensity signal may be increased 535 in a stepwise manner in response to detecting that the level of patient respiratory effort is lower than the lower limit of the predetermined range, while subsequent breaths may optionally remain at the same stimulation level as long as the detected level of patient respiratory effort remains within the predetermined range. Thus, referring again to FIG. 5A, operation 435 may increment the set intensity level, which may then be applied to the next stimulated breath when method 400 loops back to operation 410 (using the stepwise increased intensity level as the new set intensity level). In this embodiment, the difference value is pre-saved (operation 405), so that the new stimulation intensity level (for the next stimulated breath) is not increased by an amount that varies with how far the detected level of patient respiratory effort falls below the lower limit of the predetermined range of respiratory effort. Rather, in this embodiment, the set intensity level is increased incrementally by a preset amount regardless of whether the detected level of patient respiratory effort falls below the lower limit by a small or a more significant amount, thereby again providing automatic control of stimulation intensity in a manner that avoids dramatic changes in the new stimulation level from the first breath to the next stimulated breath.

[0042] 5A, the method 400 may also determine that the detected level of patient respiratory effort remains within a predetermined range (e.g., operations 420 and 430 indicate that the detected level of patient respiratory effort does not exceed an upper limit and does not fall below a lower limit), in which case the set intensity level may be maintained 440. As shown in FIG. 5B, the stimulation signal may be maintained at the same level for subsequent stimulated breaths 540 in response to detecting that the level of patient respiratory effort falls within the predetermined range.

[0043] Referring now to FIG. 6 , some embodiments of a system for diaphragmatic stimulation (e.g., system 10 or system 30) can be implemented to achieve method 600, which provides an automatic stimulation delivery assessment to correlate stimulation intensity with an improvement in the value of the detected level of patient respiratory effort. In a specific example, the system can respond to the patient's respiratory effort during a breath, such as a stimulated breath during which a control console (e.g., 110 or 310) delivers an electrical stimulation signal to stimulate the patient's phrenic nerve. In some implementations, method 600 is used to controllably identify a stimulation intensity level for an individual patient at which the patient's respiratory effort substantially levels off, even as the stimulation level is increased. For example, in a system that calculates a WOB value for each stimulated breath, method 600 can be used to automatically identify the stimulation intensity level at which a plateau in the WOB level occurs with further increases in stimulation intensity. Such an assessment can indicate where the patient's diaphragm is maximally contacted for phrenic nerve stimulation therapy. From there, the console can store the value and report it to the user (e.g., via a graphical user interface) so that the user can select an initial level of stimulation intensity for the patient's treatment. Alternatively, the initial level of stimulation intensity can be automatically selected by the control console as a level below that which caused the maximal contraction, thereby helping to avoid muscle fatigue during the patient's phrenic nerve stimulation during mechanical ventilation.

[0044] As shown in FIG. 6 , the method can include operation 605, in which the system detects a first level of patient respiratory effort during delivery of pacing stimuli at a first intensity level to leads (e.g., leads 132 and 134) proximate to the patient's phrenic nerve. As described above, the set intensity level can have a stimulation intensity characterized by current amplitude, pulse width (PW), frequency, or a combination thereof. Then, during a subsequent stimulated breath, the method can include operation 610, in which the system detects a second level of patient respiratory effort during delivery of pacing stimuli at a second intensity level greater than the previous intensity level. In operation 615, the system determines whether the detected second level of patient respiratory effort is greater than the detected first level of patient respiratory effort by a threshold amount. If yes, method 600 automatically proceeds to operation 620, in which the first intensity level is reset to the value of the second intensity level, and the second intensity level is increased incrementally by the difference. From there, method 600 returns to operation 610 for the patient's next stimulated breath. This loop 610, 615, and 620 can continue until, in operation 615, the system determines that the second level of detected patient respiratory effort is not greater than the first level of detected patient respiratory effort by a threshold amount. The threshold amount can be set to a value indicative of the fact that the first and second levels of patient respiratory effort are substantially close to (or the same as) one another, indicating that the level of patient respiratory effort has leveled off (or otherwise not increased by a significant amount) despite the second stimulation intensity level being greater than the immediately preceding intensity level during the previous stimulated breath.

[0045] As shown in FIG. 6 , when operation 615 indicates that the second level of detected patient respiratory effort is not greater than the first level of detected patient respiratory effort by a threshold amount, the system proceeds to operation 625, where the system saves the value for the second intensity level as the maximum level of an operating range for the patient during phrenic nerve stimulation therapy (e.g., during mechanical ventilation as described above). Optionally, this maximum level of the operating range can also be used as an upper bound for the operating range described in connection with FIG. 5A (operation 405). As shown in FIG. 6 , in operation 630, the system can be configured to automatically set the administered intensity level to a value lower than the maximum level of the operating range. In operation 635, during the patient's selected breath, the system can deliver pacing stimulation at the administered intensity level to leads (e.g., leads 132 and 134) proximate to the phrenic nerve. Optionally, this administered intensity level can also be used as the set intensity level described in connection with FIG. 5A (operation 410).

[0046] 5A-5B and 6, the control console 110, 310 may also be configured to account for transitions of the leads 132 and 134 throughout the course of patient treatment. For example, the system may achieve automatic stimulation adjustments by monitoring changes in patient respiratory effort (e.g., calculated WOB values ​​or sensor values ​​as described above). Thus, in response to detecting a reduced level of patient respiratory effort in subsequent breaths, the system may automatically increase stimulation intensity (or varying electrode combinations) to maintain a target level of patient respiratory effort.

[0047] 7, some embodiments of a system for diaphragmatic stimulation (e.g., system 10 or system 30) can be implemented to achieve a method 700 of monitoring a patient's external muscle activity and responsively altering a stimulation signal to reduce the likelihood of such external muscle activity. Such a method 700 can be used, for example, as a supplement to the automatic control methods described above in connection with FIGS. 5A-5B and 6, or can be used on a periodic basis to monitor changes in patient positioning or lead 132, 134 transitions. In a particular variation of the method, the control console 110, 310 can monitor EMG activity of the patient's shoulder and neck muscles (e.g., using one or more EMG sensors 140 in FIGS. 1-3A and 4) and then automatically reduce the level of stimulation intensity (or change the electrode combination) to limit or eliminate external stimulation of the patient's shoulder or neck muscles. In some implementations, signals for such external stimulation may include strain sensors, ENG activity, ECG signals, acceleration measurements, bioimpedance or noise in airflow signals indicative of undesired external stimulation, and / or those obtained using external sources. As shown in FIG. 7, method 700 may include operation 705 in which the control console stores an operating range for stimulation intensity, a predetermined stimulation intensity delta value, or both. This operation 705 may be similar to (and simultaneous with) operation 405 detailed above in connection with FIG. 5A. In some embodiments, stimulation intensity may be a value associated with the electrical stimulation signal delivered to leads 132, 134, such as amplitude, pulse width (PW), frequency, electrode pair, or a combination thereof.

[0048] With further reference to FIG. 7, method 700 may also include operation 710, in which the system delivers pacing stimulation at a set intensity level to one or more leads (e.g., leads 132, 134) proximate to the patient's phrenic nerve during the patient's breathing. This operation 705 may be similar to (and simultaneous with) operation 410, detailed above in connection with FIG. 5A. In operation 715, the system may detect a level of muscle activity exceeding activity of the patient's diaphragm muscles, such as muscle activity in the patient's neck and / or shoulders. This detection 715 may occur during delivery of stimulation signals from pacing leads 132, 134 to the phrenic nerve (see, e.g., FIGS. 3A-3D), in which case the elevated level of muscle activity in the patient's neck and / or shoulders may be considered extraneous muscle activity. In operation 720, the system may determine whether the detected muscle activity (in the patient's neck and / or shoulders) is higher than a predetermined threshold level. If no, the method may return to operation 710 (described above). If yes, method 700 may include operation 725, which issues an alert via the user interface of the control console 110, 310. The alert may be an audible notification, a visual notification, or a combination thereof. In some implementations, the alert may also provide instructions for the user to visually monitor the patient's neck and shoulder muscles, to reposition the stimulation leads 132, 134, to select a different electrode pair for stimulation delivery, or a combination thereof. Optionally, method 700 may also include operation 730, in which, in response to determining in operation 720 that the detected muscle activity (in at least one of the patient's neck and shoulder) is higher than a predetermined threshold level, the control console may decrease the set intensity level by a predetermined threshold stimulation intensity delta value. Thus, operation 730 causes the set intensity level to be decremented and then applied in the next stimulated breath when method 700 loops back to operation 710 (described above).

[0049] In a further implementation of the automatic control method described in connection with FIGS. 5A-5B, 6, and 7, the control console 110, 310 can include at least one stimulation lead (e.g., lead 132 or 134, or optionally, a separate sensing lead) configured to measure ENG (neuroelectromyography) activity of the isophrenic nerve. Phase ENG activity can be detected and used to trigger the initiation of functional stimulation of the diaphragm through phrenic nerve stimulation or direct diaphragm stimulation. The functional stimulation pulse train may be blocked or filtered to continue detecting native ENG and determine when stimulation should be stopped at end-inspiration. Similarly, the level of native ENG activity may be used to control the intensity of functional diaphragm stimulation. When native ENG phase activity increases, the stimulation system can reduce the functional stimulation level to prevent excessive diaphragm contraction. When the detected level of innate phase ENG decreases, the functional stimulation intensity may be increased to maintain a target level of diaphragmatic stimulation (e.g., as measured through WOB or a surrogate signal). Innate ENG activity may be assessed in unstimulated breaths to avoid interference from the stimulation signal, or the stimulation signal may have a notch through which innate ENG activity may be assessed.

[0050] 8A-8B, some embodiments of a system for diaphragmatic stimulation (e.g., system 10 or system 30) can be implemented to perform a method 800 of detecting when a patient is ready to be weaned from mechanical ventilation and providing notification thereof to a user. Such method 800 can be used, for example, as a supplement to the automatic control methods described above in connection with FIGS. 5A-5B, 6, and 7, or can be implemented on a periodic basis to monitor changes in the patient's condition. In a particular variation of method 800, the system can identify when an improvement in diaphragmatic contraction force indicative of readiness to wean is met, such as by monitoring an improvement in a detected level of patient respiratory effort (e.g., a calculated WOB value or a sensor value as described above), which can be monitored over time (e.g., over the period of days 852, 854, and 856 depicted in FIG. 8B). Optionally, as shown in FIG. 8A , method 800 can include operations for alerting a user when the increase in detected levels of patient respiratory effort reaches a predetermined target value, which can indicate that the diaphragm muscle condition has reached a point where the diaphragm has sufficiently regained its original strength and weaning from mechanical ventilation can be attempted. In some embodiments, the system can use an effort belt (referring to body-worn sensor 142 in FIGS. 1-3A and 4 ), diaphragm EMG (referring to diaphragm EMG sensor 140 in FIGS. 1-3A and 4 ), or other sensor indicative of respiratory effort that can provide sensor feedback to the control console to indicate that an acceptable improvement in diaphragm health has occurred, thereby providing the user with data and notifications that enable successful weaning of the patient from mechanical ventilation.

[0051] 8A , method 800 may include operation 805, in which the system delivers a first cycle of pacing stimuli at a first intensity level to pacing leads (e.g., leads 132 and 134) proximate to the phrenic nerve. At operation 810, the method includes detecting a parameter indicative of diaphragmatic contraction force during the first cycle. As described above, the parameter may be a detected level of patient respiratory effort (e.g., a calculated WOB value or a sensor value as described above). Additionally or alternatively, the parameter may be a sensor value from an effort belt (referring to body-worn sensor 142 in FIGS. 1-3A and 4 ), diaphragmatic EMG (referring to diaphragmatic EMG sensor 140 in FIGS. 1-3A and 4 ), or a combination thereof that provides sensor feedback to a control console indicative of diaphragmatic contraction force. In operation 815, the system delivers a second cycle of pacing stimuli at the same first intensity level to pacing leads (e.g., leads 132 and 134) proximate to the phrenic nerve. In some implementations, the second cycle occurs one to three days after the first cycle. In operation 820, the method includes detecting a parameter indicative of diaphragm contraction force during the second cycle. In operation 825, the method includes comparing the detected parameter during the second cycle with the detected parameter during the first cycle. For example, in operation 825, the system can determine whether the detected parameter during the second cycle is greater than the detected parameter during the first cycle by a threshold amount. Alternatively, the system can determine whether the detected parameter during the second cycle is greater than the detected parameter during the first cycle and greater than a target value indicative of the patient's readiness to be weaned from mechanical ventilation.

[0052] If the determination from operation 825 is no, method 800 may loop back to operation 815 to evaluate a subsequent cycle of pacing stimulation at the first intensity level. If the determination from operation 825 is yes, method 800 may proceed to operation 830, where the control console outputs a warning from a graphical user interface indicating readiness to wean the patient from mechanical ventilation. As described above, the warning may be an audible notification, a visual notification, or a combination thereof.

[0053] Additionally or alternatively, the system described above in connection with FIGS. 8A-8B may be configured to identify improvements in diaphragm contraction strength by monitoring improvements in detected levels of patient respiratory effort (e.g., calculated WOB values ​​or sensor values ​​as described above) over time to identify when increases in those detected levels begin to decrease. In such a situation, the detected levels of patient respiratory effort may begin to plateau (e.g., over a period of 1-3 days), thereby indicating that the diaphragm muscle condition has reached a point of reduced effectiveness. In response to detecting such a situation, the graphical user interface of the control console 110, 310 may display a plotted curve of values ​​for the detected levels of patient respiratory effort (over a set of cycles occurring on different days), which may alert the user that the patient's diaphragm is regaining its original strength and that weaning can be attempted.

[0054] 9A-9B, some embodiments of a system for diaphragmatic stimulation (e.g., system 10 or system 30) can be implemented to achieve a method 900 that provides a notched pulse train delivery of phrenic nerve stimulation that can be used to accurately assess momentary improvements in the patient's detected level of respiratory effort (e.g., a calculated WOB value or a sensor value as described above). For example, the notched pulse train delivery can be output to leads 132, 134 in a manner such that the stimulation signal is temporarily terminated for a percentage of the inspiration period. The momentary change in the patient's detected level of respiratory effort (e.g., a calculated WOB value or a sensor value indicative of airflow characteristics as described above) during this notch assessment can be monitored over time to identify when the improvement in the patient's detected level of respiratory effort decreases (e.g., when diaphragmatic strength is approaching sufficient for weaning from mechanical ventilation). In this manner, method 900 can advantageously identify when the patient is ready to be weaned from mechanical ventilation and provide notification thereof to the user. Such a method 900 can be used, for example, as a supplement to the automatic control methods described above in connection with Figures 5A-5B, 6, and 7, or can be implemented on a periodic basis to monitor changes in the patient's condition.

[0055] As shown in FIG. 9A , some embodiments of method 900 may include operation 905, in which the control console delivers a pacing stimulation signal for an entire stimulation period to one or more leads (e.g., leads 132, 134) proximate to the patient's phrenic nerve during the patient's stimulated breath. The entire stimulation period may coincide with the inspiratory phase of the patient's breath or may be a selected portion of the inspiratory phase. In this embodiment of operation 905, the pacing stimulation signal is not notched (or otherwise temporarily terminated during a middle portion of the stimulation period); instead, stimulation pulses of the electrical stimulation signal are delivered constantly throughout the entire stimulation period of the stimulated breath. In operation 910, the control console detects the level of patient respiratory effort during the stimulated breath. As described above, the control console may receive sensor input (e.g., from the wye sensor 120, from the EMG sensor 140, from the patient-worn sensor 142, or a combination thereof) indicative of the level of effort achieved by the patient's diaphragm during the stimulated breath. The sensor input can be used directly as a detected level of patient respiratory effort, or alternatively, can be used by the control console to calculate a value for the level of patient respiratory effort (e.g., WOB). Method 900 can be implemented to perform many cycles of operations 905 and 910 before proceeding periodically (e.g., several times per day) to operation 915.

[0056] In operation 915, the control console can deliver a notched stimulation signal to the pacing lead during a subsequent stimulated breath, in which the stimulation signal is temporarily terminated for a portion of the total stimulation period (e.g., a portion midway through the inspiratory period of the stimulated breath). For example, as shown in FIG. 9B , the notched stimulation signal 950 is aligned with the patient's inspiratory period 952 during the stimulated breath, but the stimulation signal includes a “notch” 955 in which the stimulation pulse of the stimulation signal is temporarily terminated during the portion midway through the stimulated breath. (In some implementations, one or more of the trajectories / plots depicted in FIG. 9B can be displayed on a user interface screen of the control console 110 or 310 during therapy.) In response to the temporary termination of the stimulation pulse, the system can detect (e.g., via the wye sensor 120) a drop 957 in airflow characteristics, such as a momentary change in the detected flow volume or pressure. As described below, the magnitude of this decline in airflow characteristics can be monitored over time (e.g., operation 915 of method 900 is implemented several times during a day or over a period of several days) to provide an objective indication of when the measurable improvement in the patient's level of respiratory effort has plateaued (e.g., because the patient's diaphragm has reached sufficient strength to be ready for weaning from a mechanical ventilator).

[0057] Referring again to FIG. 9A , the method may include operation 920, in which the control console detects a level of patient respiratory effort during delivery of the notch stimulation signal (operation 915). In operation 925, method 900 detects whether there is a decline in airflow characteristics (e.g., from a wye sensor 120 detecting flow volume or pressure during the inspiratory phase) during delivery of the notch stimulation signal (operation 915). A decline in airflow characteristics may be identified by comparing the magnitude of the airflow characteristics measured during the notch stimulation signal to a previous magnitude of the same airflow characteristics measured during a regular stimulation signal previously delivered throughout the entire stimulation period. For example, the system may detect the absence of a decline in airflow characteristics if the magnitude of any decline in airflow characteristics during delivery of the notch stimulation signal is less than a predetermined low threshold. If no decline is detected in operation 925, the system may proceed to operation 940 to alert the user that the diaphragm muscle condition has reached a point where the diaphragm has sufficiently regained its original strength and that weaning from the mechanical ventilator may be attempted. If there is a drop detected in operation 925, the system can proceed to operation 930, where the magnitude of the drop is compared to a previously measured magnitude of the drop in airflow characteristics during a previous delivery of a notch stimulation signal (e.g., during a previous cycle of method 900 in which the previous example of operation 915 was implemented). If the detected drop in airflow characteristics during the most recent delivery of a notch stimulation signal is less than or equal to the previous magnitude of the drop in airflow characteristics during the previous delivery of a notch stimulation signal, the system proceeds to operation 940 and alerts the user that the diaphragm muscle state has reached a point where the diaphragm has sufficiently regained its original strength and weaning from the mechanical ventilator may be attempted. Otherwise, method 900 can loop back to operation 905 for continued treatment of the patient during mechanical ventilation.

[0058] 8A-8B and 9A-9B, the control console 110, 310 can include at least one lead (e.g., lead 132 or 134, or optionally, a separate sensing lead) configured to measure ENG activity of the phrenic nerve adjacent to the lead. In these embodiments, the measurement of ENG activity can be compared to the resulting diaphragmatic contraction level as an indication of the improved state of the diaphragm resulting from phrenic nerve stimulation training. Diaphragmatic health can be periodically monitored by measuring detected increases in the patient's level of respiratory effort (e.g., calculated WOB values ​​or sensor values ​​as described above) while the stimulation signal is terminated (e.g., temporarily terminated during a notched stimulation signal, as described above) to identify when these parameters reach specific target values ​​or plateaus that indicate that the target benefit of the stimulation therapy has been reached and that the patient's diaphragmatic strength has sufficiently increased. Additionally, an effort belt indicating respiratory effort (e.g., body worn sensor 142, diaphragmatic EMG sensor (e.g., sensor 140), or other sensor) can be used to provide feedback to the control console, which can compare ENG activity as a measure of improving or worsening diaphragmatic health.

[0059] 10-11 , some embodiments of a system for diaphragmatic stimulation (e.g., system 10 or system 30) may be implemented to achieve data communication between a stimulation control console and a control console of a mechanical ventilator (e.g., ventilator 200) or to achieve phrenic nerve stimulation control directly from an enhanced mechanical ventilator (e.g., ventilator 300). In such a situation, the system may implement enhanced automatic control of phrenic nerve stimulation, for example, using methods 1000 or 1100 described in FIGS. 10-11 . As previously described in connection with FIGS. 1-3A , some embodiments of control console 110 may advantageously receive data from ventilator 200 that is useful in assessing a patient's work of breathing and other respiratory characteristics. Control console 110 may also communicate data back to ventilator 200. In one example, ventilator data cable 205 can provide data communication between control console 110, which can receive data from ventilator 200 indicative of the type of ventilator breath being delivered to the patient. Control console 110 can receive data indicative of the type of ventilator breath from ventilator 200 and further facilitate interpretation of flow and pressure measurement trajectories detected by wye-sensor 120 during each breath and depicted on touchscreen interface 112 of control console 110. Additionally or alternatively, control console 110 can receive data from ventilator 200 indicative of patient-specific measures of respiratory mechanics, such as compliance and resistance of the patient's lungs. As described above in connection with FIG. 4, some variations of improved mechanical ventilator 300 can include a control console 310 for dictating both control of mechanical ventilation and control of phrenic nerve stimulation.In such cases, the control console 310 of the mechanical ventilator 300 may include an enhanced user interface 312 that includes (i) control screens / user input fields for configuring and monitoring the patient's mechanical ventilation, and (ii) control screens / user input fields for configuring and monitoring phrenic nerve stimulation and outputting detected characteristics of the stimulated breath.

[0060] As shown in FIG. 10 , some embodiments of method 1000 may be used during data communication between a phrenic nerve stimulation console (e.g., control console 110) and a mechanical ventilator (e.g., ventilator 200). The method may include operation 1005 for establishing a connection between the mechanical ventilator and the stimulation control console. As described above, the control console may be connected to the mechanical ventilator using a cable (e.g., cable 205) or a wireless data connection such as Bluetooth. In operation 1010, the system may deliver pacing stimulation to one or more leads proximate one or more phrenic nerves during respiratory therapy initiated by the mechanical ventilator. Method 1000 may also include operation 1015, in which the control console receives ventilator airflow and pressure signal information during delivery of respiratory therapy breaths. Optionally, the data connection between the stimulation control console and the ventilator can be used to transfer ventilator settings to the control console. For example, the control console can receive configuration information from the ventilator indicating the type of ventilator breath being delivered to the patient (e.g., flow-controlled ventilation (FCV) breath, pressure-controlled ventilation (PCV) breath, or a combination of both). In act 1020, the system can detect the level of patient respiratory effort based at least in part on the data received from the ventilator via the data connection (e.g., calculating a WOB value as described above or directly using sensor measurements). For example, via the data connection (act 1005), ventilator airflow and pressure signals can be sent to the stimulation control console for purposes of detecting the level of patient respiratory effort and can be used to automatically control stimulation intensity (as detailed in the example methods above), determine readiness to wean, or determine whether undesirable extraneous stimulation is present. The control console 110 can also receive configuration information from the ventilator 200 and then use such information to interpret the flow and pressure measurement trajectories detected during each breath and depicted on the control console's touchscreen interface.

[0061] As shown in FIG. 11 , some embodiments of method 1100 can be used in an improved mechanical ventilator (e.g., ventilator 300) having a control console that operates both mechanical ventilation control and phrenic nerve stimulation control. Method 1100 may include operation 1105, in which one or more phrenic nerve stimulation leads (e.g., leads 132 and 134) are connected to a mating connector port on the mechanical ventilator. In operation 1110, the system can initiate a respiratory therapy breath from the mechanical ventilator according to a selected ventilator mode. In operation 1115, during the respiratory therapy breath, the system can deliver pacing stimulation from the mechanical ventilator to one or more leads proximate one or more phrenic nerves. In operation 1120, the system can detect a level of patient respiratory effort (e.g., calculating a WOB value or directly using sensor measurements, as described above) based at least in part on information sensed by the ventilator (e.g., one or more flow sensors housed within the mechanical ventilator). For example, a ventilator may be equipped to detect airflow and pressure signals during mechanical ventilation of a patient, and the sensor information may be used by the ventilator's control console for purposes of detecting the level of patient respiratory effort, automatically controlling stimulation intensity (as detailed in the example methods above), determining readiness to wean, or determining whether undesirable extraneous stimulation is present.

[0062] 12A-12C, some embodiments of method 1200 can be implemented by a system for diaphragm stimulation (e.g., system 10 or system 30) to achieve a phrenic nerve stimulation training pattern that can be automatically selected by the control console or selected by the user for the purpose of improving the therapeutic effect of strengthening a patient's diaphragm during phrenic nerve stimulation therapy. In certain embodiments, the control console can be implemented to deliver stimulation in one of various selectable patterns. Such a system can improve the rate at which a patient's diaphragm strength is increased and, in some embodiments, facilitate an improved maximum level of diaphragm strength at the end of therapy. As shown in FIG. 12A, method 1200 can include operation 1205 in which the control console stores an operating range for stimulation intensity, a predetermined stimulation intensity difference value, or both. As described above in connection with FIG. 4, stimulation intensity can be a value associated with the electrical stimulation signal delivered to leads 132, 134, such as amplitude, pulse width (PW), frequency, electrode pair, or a combination thereof. The operating range for stimulation intensity stored by the control console may be manually determined during the electrode pair mapping period (described above) based on a diaphragmatic contraction threshold at the lower end and a supramaximal diaphragmatic stimulation level (or a maximum tolerable level for the patient) at the higher end. Method 1200 may also include operation 1210, in which the control console accepts input indicating a selected training pattern for phrenic nerve stimulation. For example, a user interface of the control console (e.g., console 110 or 310) may present selectable training options, such as a continuous pattern, a pyramidal pattern, or an interval pattern, and a user may select an option for a particular patient. In operation 1215, during the patient's stimulated breathing, the system may deliver pacing stimulation to one or more leads (e.g., leads 132 and 134) proximate to the phrenic nerve according to the selected training pattern (within the operating range described in operation 1205) and the set intensity level.For example, as shown in FIG. 12B, the training pattern implemented for a particular patient can be in the form of a “pyramid” training pattern 250a-250g, in which the delivered stimulation begins at a relatively low level 250a, rises to a peak value 250d, and then decreases back to the low level 250g at the end of the period for stimulation treatment. The increment and decrement of stimulation may occur on a breath-by-breath basis or may remain constant for several or more breaths before changing to the next level. The “pyramid” pattern can be repeated until the entire treatment period is completed. In another example, as shown in FIG. 12C, the training pattern implemented for a particular patient can be in the form of an “interval” training pattern, in which a lower stimulation intensity 260a is delivered for several breaths that provide a nominal level of diaphragmatic contraction, followed by one or more higher intensity stimuli 260b during the stimulated breath closer to the peak contraction of the diaphragm. The lower stimulation intensity 260a can then be returned for succession, resulting in an “interval” training regimen. In further examples, the training pattern implemented for a particular patient may be in the form of a higher stimulation intensity level applied for a shorter period (e.g., shorter than the normal period time), a longer stimulation period in which the normal intensity level is applied for a longer period than the normal period time, or an increased rate training period in which the frequency of stimulation breathing is increased during a shorter training period (e.g., shorter than the normal period time).

[0063] 12A , method 1200 may include operation 1220, in which the system detects a level of patient respiratory effort during stimulated breathing (e.g., delivery of pacing stimuli). The system can use this detected level of patient respiratory effort to provide adaptive training patterns for phrenic nerve stimulation therapy. In some examples, the control console may be configured to automatically adapt the set intensity level of the pacing stimulation during the training pattern, for example, by automatically adjusting the current magnitude for each stimulation signal in the training pattern.

[0064] For example, method 1200 can be used to determine whether a detected level of patient respiratory effort (e.g., a WOB value or a sensor value as described above) is outside a predetermined range (e.g., a selected safe range of patient effort during mechanical ventilation) and to dynamically respond accordingly by automatically adjusting the set stimulation intensity level across all stimulations for the training pattern. For example, in act 1225, the system can determine whether the detected level of patient respiratory effort is higher than the upper limit of a predetermined range of respiratory effort. If yes, method 1200 can respond by proceeding to act 1230 to reduce the set intensity level (described in act 1215) by a predetermined intensity difference value (described in act 1205), thereby decrementing the stimulation intensity for each stimulated breath in the selected training pattern. In this embodiment, the difference value is pre-saved (act 1205), so that the new stimulation intensity level (for the next stimulated breath) is not reduced by a variable amount. Rather, in this embodiment, the set intensity level is decremented by a preset amount regardless of whether the detected level of patient respiratory effort exceeds the upper limit by a small amount or a more significant amount, thereby providing automatic control of stimulation intensity in a manner that avoids dramatic changes in the new stimulation level from the first breath to the next stimulated breath.

[0065] Similarly, in act 1235, the system can determine whether the detected level of patient respiratory effort is below the lower limit of a predetermined range of respiratory effort. If yes, method 1200 can respond by proceeding to act 1240 to increase the set intensity level (described in act 1215) by a predetermined intensity difference value (described in act 1205), thereby incrementally increasing the stimulation intensity for each stimulated breath in the selected training pattern. Again, in this embodiment, the difference value is pre-stored (act 1205), so that the set intensity level is incrementally increased by a preset amount regardless of whether the detected level of patient respiratory effort is below the lower limit by a small amount or a more significant amount. In doing so, the system provides an adaptive training cycle for the patient in a manner that avoids dramatic changes in the new stimulation level from the first breath to the next stimulated breath. Also, if method 1200 determines that the detected level of patient respiratory effort remains within a predetermined range (e.g., if operations 1225 and 1235 indicate that the detected level of patient respiratory effort does not exceed an upper limit and does not fall below a lower limit), then the training pattern does not need to be adapted to a different intensity and the set intensity level may be maintained.

[0066] Referring to FIG. 13 , some embodiments of a system for diaphragmatic stimulation (e.g., system 10 or system 30) can be implemented relying on sensor feedback on the detected level of patient respiratory effort, which can provide a dynamic control response that does not rely on subsequent calculations of work of breathing (WOB). For example, an operator can set a pressure target for PawPred (predicted airway pressure). The stimulation level can be controlled on a sample-by-sample basis using a PID controller or similar methodology to determine whether the pressure target has been achieved. In such embodiments, the control console ( FIGS. 1-3A and 4 ) can be configured to automatically adjust the stimulation level to meet the pressure target. Additionally or alternatively, an operator can set a waveform for PawPred. A system or device as featured herein can control the stimulation level on a sample-by-sample basis using a PID controller or similar methodology to determine whether the waveform target has been achieved. In such embodiments, the control console ( FIGS. 1-3A and 4 ) can be configured to automatically adjust the stimulation level to meet the waveform target. Additionally or alternatively, the operator can set a negative pressure target for PDia (diaphragm-derived pressure), which is arithmetically PawMeasured (measured airway pressure) minus PawPred. A system or device as featured herein can control the stimulation level on a sample-by-sample basis using a PID controller or similar methodology to determine whether the pressure target has been achieved. In such embodiments, the control console (FIGS. 1-3A and 4) can be configured to automatically adjust the stimulation level to meet the pressure target. Additionally or alternatively, the operator can set a negative pressure waveform for PDia. A system or device as featured herein can control the stimulation level on a sample-by-sample basis using a PID controller or similar methodology to determine whether the waveform target has been achieved. In such embodiments, the control console (FIGS. 1-3A and 4) can be configured to automatically adjust the stimulation level to meet the waveform target.Additionally or alternatively, the operator can set a peak inspiratory flow (PIF) target or an inspiratory tidal volume (TVI) target. A system or device as featured herein can control the stimulation level on a sample-by-sample basis using a PID controller or similar methodology to determine whether the target is achieved. In such embodiments, the control console (FIGS. 1-3A and 4) can be configured to automatically adjust the stimulation level to meet the target. Additionally or alternatively, the operator can set a waveform for Vaw (measured airway flow). A system or device as featured herein can control the stimulation level on a sample-by-sample basis using a PID controller or similar methodology to determine whether the target is achieved. In such embodiments, the control console (FIGS. 1-3A and 4) can be configured to automatically adjust the stimulation level to meet the target.

[0067] Referring again to FIGS. 1-4, the control console 110 (FIGS. 1-3A) or 310 (FIG. 4) includes a graphical user interface (e.g., a touch screen and, optionally, mechanical switches for user input) along with a processing unit and computer-readable memory positioned within a housing configured to control stimulation of the patient's diaphragm according to the implementations detailed above. The memory contained within the control console 110 or 310 can provide mass storage for the system 100 or 300 and can be in the form of a computer-readable medium such as a solid-state memory device or a hard disk drive. In some options, the control console 110 or 310 can include a high-speed interface connecting to the memory and multiple high-speed expansion ports, and at least one port for accepting an external memory device (e.g., a USB drive or external hard drive). Each of the processing unit, memory, high-speed interface, and high-speed expansion port can be interconnected using various buses and can be mounted on a motherboard. The processing unit can process instructions for performing stimulation control operations and other tasks detailed above, including instructions stored in memory for displaying graphical information for the graphical user interface 112 or 312 (described in detail above). Accordingly, certain embodiments are directed to computer program products (e.g., non-volatile memory devices) that include machine- or computer-readable media having stored thereon instructions that can be executed by a computer (or other electronic device) to implement these operations / activities. For example, such products may be implemented with circuitry that is otherwise operable to facilitate breathing and may be implemented in accordance with one or more embodiments described herein.

[0068] Several embodiments have been described. Nevertheless, it will be understood that various modifications may be made without departing from the scope of the following claims. For example, multiple variations in activation time for control may be utilized, such as to adjust stimulation to various preset levels. Accordingly, other embodiments are within the scope of the following claims.

Claims

1. a phrenic nerve stimulation control console configured to control a stimulation intensity of a phrenic nerve stimulation signal deliverable to at least one phrenic nerve during mechanical ventilation; a phrenic nerve stimulation lead assembly including at least one electrode lead positionable adjacent to the at least one phrenic nerve for outputting the phrenic nerve stimulation signal from the phrenic nerve stimulation control console to a corresponding phrenic nerve; Equipped with In response to the detected level of patient respiratory effort being outside a predetermined range, the phrenic nerve stimulation control console controllably increments or decrements the stimulation intensity of the phrenic nerve stimulation signal by a preset delta value. Phrenic nerve stimulation system.

2. a respiratory sensor in communication with the phrenic nerve stimulation control console and configured to couple to an airflow path of a breathing circuit during mechanical ventilation; sensor information from the respiratory sensor is received at the phrenic nerve stimulation control console such that the phrenic nerve stimulation control console identifies a detected level of the patient's respiratory effort. The system of claim 1 .

3. 2. The system of claim 1, wherein the phrenic nerve stimulation control console controllably increments the stimulation intensity of the phrenic nerve stimulation signal by the preset differential value in response to the detected level of the patient's respiratory effort being less than the predetermined range.

4. 4. The system of claim 3, wherein the phrenic nerve stimulation control console controllably decrements the stimulation intensity of the phrenic nerve stimulation signal by the preset differential value in response to the detected level of patient respiratory effort being greater than the predetermined range.

5. The system of claim 4 , wherein the phrenic nerve stimulation control console includes a graphic user interface for accepting user input of a selected value for the preset difference value.

6. The system of claim 5 , wherein the graphical user interface of the phrenic nerve stimulation control is configured to accept customized selection of an operating range for the stimulation intensity of the phrenic nerve stimulation signal.

7. the phrenic nerve stimulation control console is configured to automatically identify a maximum level of stimulation intensity of an operating range for the stimulation intensity of the phrenic nerve stimulation signal; the phrenic nerve stimulation control console controllably increments or decrements the stimulation intensity by the preset delta value so that the stimulation intensity remains within the operating range. The system of claim 1 .

8. 10. The system of claim 1, wherein the phrenic nerve stimulation control console is integrated into a console of a mechanical ventilator such that a cable of the phrenic nerve stimulation lead assembly couples to the mechanical ventilator.

9. the at least one electrode lead of the phrenic nerve stimulation lead assembly includes a first electrode lead and a second electrode lead; 10. The system of claim 1, wherein each of the first and second electrode leads comprises one of a percutaneously insertable paddle-shaped electrode lead tip having an array of electrodes along a flat surface and a plurality of segmented electrodes along a cylindrical portion of the percutaneously insertable lead tip.

10. a phrenic nerve stimulation control console configured to control a stimulation intensity of a phrenic nerve stimulation signal deliverable to at least one phrenic nerve during mechanical ventilation; a phrenic nerve stimulation lead assembly including at least one electrode lead positionable adjacent to the at least one phrenic nerve for outputting the phrenic nerve stimulation signal from the phrenic nerve stimulation control console to a corresponding phrenic nerve; a muscle activity sensor in communication with the phrenic nerve stimulation control console for providing feedback indicative of muscle activity in at least one of the shoulder and neck; Equipped with In response to the detected level of muscle activity being greater than a predetermined threshold, the phrenic nerve stimulation control console decrements the stimulation intensity of the phrenic nerve stimulation signal by a preset delta value. Phrenic nerve stimulation system.

11. 11. The system of claim 10, wherein the phrenic nerve stimulation control console includes a graphical user interface that outputs a warning in response to the detected level of muscle activity being greater than a predetermined threshold.

12. a respiratory sensor in communication with the phrenic nerve stimulation control console and configured to couple to an airflow path of a breathing circuit during mechanical ventilation; sensor information from the respiratory sensor is received at the phrenic nerve stimulation control console such that the phrenic nerve stimulation control console identifies a detected level of patient respiratory effort. The system of claim 10.

13. 13. The system of claim 12, wherein the phrenic nerve stimulation control console controllably increments the stimulation intensity of the phrenic nerve stimulation signal by a preset delta value in response to the detected level of patient respiratory effort being less than the predetermined range.

14. 14. The system of claim 13, wherein the phrenic nerve stimulation control console controllably decrements the stimulation intensity of the phrenic nerve stimulation signal by the preset delta value in response to the detected level of patient respiratory effort being greater than the predetermined range.

15. 15. The system of claim 14, wherein the phrenic nerve stimulation control console includes a graphic user interface for accepting user input of a selected value for the preset difference value.

16. The system of claim 10 , wherein the phrenic nerve stimulation control console is integrated into a control unit of a mechanical ventilator.

17. delivering a first cycle of phrenic nerve stimulation at a first intensity level from a phrenic nerve stimulator to at least one stimulation lead proximate at least one phrenic nerve, and then delivering a second cycle of phrenic nerve stimulation at the first intensity level from the phrenic nerve stimulator to the at least one stimulation lead proximate the at least one phrenic nerve; outputting a warning via a user interface of the phrenic nerve stimulator indicating readiness to wean from mechanical ventilation in response to detecting that a parameter indicative of diaphragmatic contraction force is greater during the second cycle than during the first cycle; A method comprising:

18. The phrenic nerve stimulation device includes: a phrenic nerve stimulation control console configured to control a stimulation intensity of a phrenic nerve stimulation signal deliverable to the at least one phrenic nerve during mechanical ventilation; a phrenic nerve stimulation lead assembly including the at least one electrode lead positionable adjacent to the at least one phrenic nerve for outputting the phrenic nerve stimulation signal from the phrenic nerve stimulation control console; 18. The method of claim 17, comprising:

19. receiving respiratory sensor information from a respiratory sensor in communication with the phrenic nerve stimulation control console and coupled to an airflow path of a breathing circuit during mechanical ventilation; determining a detected level of patient respiratory effort based on the respiratory sensor information; 20. The method of claim 18, further comprising:

20. 20. The method of claim 19, further comprising controllably increasing or decreasing the stimulation intensity of the phrenic nerve stimulation signal by a preset differential value in response to the detected level of patient respiratory effort being outside a predetermined range.

21. delivering the phrenic nerve stimulation signal for an entire stimulation period during a first stimulated breath of a patient in which at least one phrenic nerve is electrically stimulated by a phrenic nerve stimulation signal delivered from a phrenic nerve stimulation control console to at least one stimulation lead positioned proximate to the at least one phrenic nerve; detecting a level of patient respiratory effort during said first stimulated breath; delivering a notch stimulation signal from a phrenic nerve stimulation control console to at least one stimulation lead positioned proximate to the at least one phrenic nerve such that electrical stimulation is temporarily terminated for a portion of the total stimulation period during the patient's second stimulated breath; outputting via a user interface of the phrenic nerve stimulator; detecting a decrease in airflow characteristic during the notch stimulation signal being below a threshold; or detecting that the magnitude of the decrease in the airflow characteristic during a notch stimulation signal is less than or equal to a previous magnitude detected during a previous delivery of the notch stimulation signal. and outputting a warning via a user interface of the phrenic nerve stimulator indicating readiness to wean from mechanical ventilation in response to any of the following: A method comprising:

22. receiving respiratory sensor information from a respiratory sensor in communication with the phrenic nerve stimulation control console and coupled to an airflow path of a breathing circuit during mechanical ventilation; determining a detected level of patient respiratory effort based on the respiratory sensor information; 22. The method of claim 21 further comprising:

23. 20. The method of claim 19, further comprising controllably increasing or decreasing the stimulation intensity of the phrenic nerve stimulation signal by a preset differential value in response to the detected level of patient respiratory effort being outside a predetermined range.

24. 1. A mechanical ventilator configured to deliver breathable air to the lungs of a patient, comprising: a ventilator control console configured to control selected pressure or flow parameters of respiratory therapy breaths during mechanical ventilation; a breathing circuit tube for directing the respiratory treatment breath to the patient; a phrenic nerve stimulation lead assembly connected to the ventilator control console via a cable, the phrenic nerve stimulation lead assembly including at least one electrode lead positionable in proximity to the at least one phrenic nerve for outputting a phrenic nerve stimulation signal during the respiratory treatment breath; Equipped with the ventilator control console includes a graphic user interface for controlling a stimulation intensity of the phrenic nerve stimulation signal deliverable to the at least one phrenic nerve during mechanical ventilation. Mechanical ventilator.

25. The ventilator control console is configured to adaptively adjust the stimulation intensity of the phrenic nerve stimulation signal in response to a detected level of patient respiratory effort being outside a predetermined range.

26. A stimulation electrode; a stimulation circuit for stimulating the patient's diaphragm by delivering electrical energy via the stimulation electrode to the patient's phrenic nerve at a stimulation intensity, including incrementally increasing or decreasing the stimulation intensity by predetermined incremental amounts to maintain the patient's characteristic respiratory airflow parameter within a target range; An apparatus comprising:

27. 27. The apparatus of claim 26, wherein maintaining the characteristic respiratory airflow parameter comprises selecting one of a plurality of stored differential amounts based on a detected value of the characteristic respiratory airflow parameter exhibited by a patient, and incrementally increasing or decreasing the stimulation intensity by the selected differential amount.

28. 27. The device of claim 26, wherein the stimulation intensity is increased or decreased by adjusting a characteristic of the stimulation intensity selected from the group consisting of current amplitude, voltage amplitude, pulse width, frequency, and combinations thereof.

29. 27. The apparatus of claim 26, wherein the characteristic respiratory airflow parameter is based on or selected from the group of: work of breathing (WOB), inspiratory pressure, inspiratory airflow, and combinations thereof.

30. 27. The device of claim 26, wherein the stimulation circuitry is configured to automatically increase or decrease the stimulation intensity by an amount that is a percentage of a range between a threshold stimulation level and a maximum intensity level.

31. 31. The device of claim 30, wherein the stimulation circuitry is configured to automatically establish the range by incrementing the stimulation intensity until a decreasing amount of an increase in the patient's respiratory effort is detected, and assigning the stimulation intensity level at which a decreasing amount of the increase in respiratory effort is detected as a maximum value of the range.

32. 27. The device of claim 26, wherein the stimulation circuitry is configured to gradually decrease the stimulation intensity in response to detecting an external stimulus through EMG of shoulder or neck muscles or heart rate measurement.

33. 33. The apparatus of claim 32, wherein the stimulation circuitry is configured to incrementally decrease the stimulation intensity with each subsequent breath until the detected extraneous stimulus is at or below a predetermined value.

34. delivering electrical stimulation energy to the patient's phrenic nerve in conjunction with each of the patient's inspirations to stimulate the patient's diaphragm; and automatically adjusting the stimulation energy applied during each one of said inspirations by a predetermined amount to maintain a characteristic non-respiratory parameter indicative of respiratory effort within a target range. An apparatus comprising a circuit.

35. 35. The apparatus of claim 34, wherein the non-respiratory parameters include parameters obtained via sensing techniques selected from the group of diaphragmatic EMG, phrenic nerve ENG, shoulder EMG, neck EMG, chest muscle EMG, external effort belt, motion sensor signals indicative of respiratory effort, and combinations thereof.

36. a stimulation circuit for applying stimulation via one or more electrodes; A control circuit comprising: delivering electrical energy via the stimulation circuit to the patient's phrenic nerve in response to inspiration to stimulate the patient's diaphragm; for a given intensity level of electrical stimulation, to record and track the amount of respiratory effort of said patient; and a control circuit configured to generate and output an indication signal in response to the patient achieving a target level of respiratory effort; An apparatus comprising:

37. 37. The apparatus of claim 36, wherein the control circuitry is configured to generate the indicator signal to indicate the patient's readiness to be weaned from mechanical ventilation or as an indication of the health and / or strength of the patient's diaphragm.

38. 37. The apparatus of claim 36, wherein the target level of respiratory effort is based on or selected from the group of work of breathing (WOB), inspiratory pressure, inspiratory airflow, and combinations thereof.

39. 37. The apparatus of claim 36, wherein the control circuitry is configured to prevent the delivery of the electrical energy during an inspiratory phase of the patient's ventilation so that the instantaneous amount of effort can be measured directly within a tidal breath.

40. 37. The apparatus of claim 36, wherein the amount of respiratory effort is detected using a technique selected from the group consisting of diaphragmatic EMG, shoulder EMG, neck EMG, chest EMG, an external effort belt, a motion sensor signal indicative of respiratory effort, and combinations thereof.

41. 37. The apparatus of claim 36, wherein the control circuitry is configured to generate and output an alert in response to the respiratory effort reaching a level that indicates the patient is ready to wean.

42. 42. The apparatus of claim 41, wherein the level of respiratory effort is detected based on comparing measured patient respiratory effort to measured patient phrenic nerve ENG, the comparison indicating an amount of diaphragmatic contraction achieved through functional stimulation.

43. a stimulation circuit for applying stimulation via one or more electrodes; A control circuit comprising: assessing the patient's respiratory effort for a given intensity level of electrical stimulation applied to the patient's phrenic nerve via the stimulation circuit; and generating and outputting an indication in response to the estimated respiratory effort reaching a plateau of decreasing gain in effort for a given stimulation intensity over time; a control circuit configured as An apparatus comprising:

44. a stimulation circuit for applying stimulation via one or more electrodes; a control circuit configured to increase the rate at which the patient's diaphragm is strengthened or rehabilitated by stimulating the patient's diaphragm with electrical energy delivered to the patient's phrenic nerve via the stimulation circuit in successive breaths using a predetermined pattern of varying stimulation intensity levels; An apparatus comprising:

45. 45. The device of claim 44, wherein the pattern of variation in stimulation intensity levels includes a progressively increasing intensity followed by a progressively decreasing intensity to create a pyramidal diaphragm exercise regimen.

46. 45. The device of claim 44, wherein the pattern of variation in stimulation intensity level includes groups of stimulated breaths at a lower level of intensity followed by a fewer number of breaths at a higher intensity to create an interval diaphragmatic exercise therapy.

47. The control circuit recording patient effort and corresponding diaphragm strength over time for a plurality of different varying patterns of stimulation intensity levels applied to the patient's diaphragm; comparing the improvement in the patient's diaphragmatic effort as achieved through each one of the plurality of different variation patterns; and selecting one of said different change patterns that shows the highest rate of improvement in diaphragmatic effort; 45. The apparatus of claim 44, comprising:

48. a stimulation circuit for applying stimulation via one or more electrodes; a control circuit configured to provide a diaphragm pacing function to stimulate the patient's diaphragm through delivery of electrical energy to the patient's phrenic nerve coincident with inspiration based on representative airflow parameters indicative of the patient experiencing hypoventilation or central sleep apnea; An apparatus comprising:

49. 49. The apparatus of claim 48, wherein the control circuitry is configured to increase the length of time the patient's diaphragm is stimulated in response to patient diaphragmatic effort indicating an improvement in patient respiratory effort that meets a predetermined criterion.

50. 49. The apparatus of claim 48, wherein the control circuitry is configured to decrease the amount of time the patient's diaphragm is stimulated in response to a worsening of the patient's diaphragm effort according to predetermined criteria indicating the diaphragm is fatigued.

51. A device according to one or more embodiments and / or claims herein, wherein a control circuit including software programmed circuitry is connected to the circuitry of a mechanical ventilator and configured to share the airflow parameter sensor signal with the mechanical ventilator.

52. An apparatus for stimulating a patient's diaphragm by utilizing one or more stimulation electrodes positioned adjacent to one or more phrenic nerves of the patient to deliver electrical energy to the phrenic nerves coincident with inspiration, according to one or more claims and / or embodiments of the present application.

53. A device according to one or more claims and / or embodiments of the present application, wherein the control circuitry and stimulation circuitry are integrated with the circuitry of a mechanical ventilator and configured to share the airflow parameter sensor signal with the circuitry of the mechanical ventilator.

54. a lead circuit for coupling stimulation energy to a phrenic nerve of a patient having a diaphragm; a processing circuit for delivering stimulation energy to the phrenic nerve via the lead circuit to stimulate the diaphragm, including incrementally increasing or decreasing the stimulation energy by predetermined amounts in subsequent breaths of the patient based on characteristic respiratory airflow parameters of the patient and target ranges for the parameters; and An apparatus comprising:

55. 1. A method comprising: stimulating the patient's diaphragm by delivering electrical energy via a stimulation circuit to the patient's phrenic nerve at a stimulation intensity, including incrementally increasing or decreasing the stimulation intensity by predetermined differential amounts to maintain the patient's characteristic respiratory airflow parameter within a target range.

56. 56. The method of claim 55, wherein maintaining the characteristic respiratory airflow parameter comprises selecting one of a plurality of stored differential amounts based on a detected value of the characteristic respiratory airflow parameter exhibited by a patient, and incrementally increasing or decreasing the stimulation intensity by the selected differential amount.

57. A method according to one or more embodiments featured in the present application.

58. 10. An apparatus according to one or more embodiments featured in the present application.

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