Adjusting parameters in physiological closed-loop control based mechanical ventilation

Abstract

A controller in a physiological closed loop mechanical ventilation system can receive (301) at least one signal representative of a patient's blood oxygen saturation from an oximetry sensor, determine (303) the oxygen saturation based on the received at least one signal, continuously adjust (305) a fraction of inspired oxygen (FIO2) parameter of a gas delivery apparatus based at least in part on the received signals, wherein the FIO2 parameter includes a percentage of oxygen in gas delivered to the patient in accordance with one or more FIO2 parameter adjustment criteria, detect (307) one or more oscillations in at least one of the determined oxygen saturation and / or the FIO2 parameter by applying at least one oscillation detection algorithm, and modify (309) the one or more FIO2 parameter adjustment criteria of the gas delivery apparatus responsive to detecting the one or more oscillations.

Description

Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WOADJUSTING PARAMETERS IN PHYSIOLOGICAL CLOSED-LOOP CONTROL BASED MECHANICAL VENTILATIONCROSS REFERENCE TO RELATED APPLICATIONS

[0001] This patent application claims the benefit of U.S. Patent Application No. 63 / 775,257 filed March 20, 2025, and entitled “Adjusting Parameters in Physiological Closed-Loop Control Based Mechanical Ventilation,” which is hereby incorporated herein by reference in its entirety.TECHNICAL FIELD

[0002] The present disclosure is related to a mechanical ventilation device.BACKGROUND

[0003] Mechanical ventilation systems can be used to provide a patient or subject with breathing assistance. Some mechanical ventilation systems include physiological closed-loop control-based systems which vary oxygenation provided to a patient based on a setting which is adjusted responsive to a physiological parameter measured from the patient. For example, some systems may vary oxygenation provided to a patient based on a fraction of inspired oxygen (FIO2) setting which is adjusted responsive to a measured oxygenation level of a patient’s blood (SpCh). In another example, some systems may vary ventilation provided to a patient based on a minute volume setting (VM) which is adjusted responsive to a measured end-tidal carbon dioxide (EtCCh). Systems for mechanical ventilation that utilize physiological closed-loop control based on physiological parameters such as SpC>2 or EtCCh can develop oscillations that may provide suboptimal treatment to a patient.SUMMARY

[0004] Disclosed are improved mechanical ventilation systems including physiological closed-loop control which detect oscillations and modify one or more parameters of the mechanical ventilation system to provide improved oxygenation to a patient.

[0005] In some aspects, a mechanical ventilator apparatus includes: a gas delivery apparatus configured to deliver a gas to a patient and including a patient interface; an oximetry sensor configured to provide at least one signal representative of an oxygen saturation of the patient's blood; and a controller, including a processor and a memory, in communication with the gas delivery apparatus and the oximetry sensor, the controller configured to: receive the at leastZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO one signal representative of the oxygen saturation of the patient's blood provided by the oximetry sensor; determine an oxygen saturation of the patient's blood based on the received at least one signal; continuously adjust a fraction of inspired oxygen (FIO2) parameter of the gas delivery apparatus based at least in part on the received signals representative of the oxygen saturation of the patient's blood, wherein the FIO2 parameter includes a percentage of oxygen in the gas delivered to the patient in accordance with one or more FIO2 parameter adjustment criteria; detect one or more oscillations in at least one of the oxygen saturation of the patient's blood and / or the FIO2 parameter by applying at least one oscillation detection algorithm to at least one of: the determined oxygen saturation and / or the FIO2 parameter; and modify the one or more FIO2 parameter adjustment criteria of the gas delivery apparatus responsive to detecting the one or more oscillations.

[0006] In some aspects, a mechanical ventilator apparatus includes: a gas delivery apparatus configured to deliver a gas to a patient and including a patient interface; a capnography sensor configured to provide at least one signal representative of an amount of carbon dioxide in a patient's exhaled air; and a controller, including a processor and a memory, in communication with the gas delivery apparatus and the capnography sensor, the controller configured to: receive the at least one signal representative of the carbon dioxide in the patient's exhaled air provided by the capnography sensor; determine a carbon dioxide concentration (EtCO2) of the patient's exhalation based on the received at least one signal; cause adjustment of a minute volume (VM) parameter of the gas delivery apparatus based at least in part on the determined carbon dioxide concentration in accordance with one or more VM adjustment criteria; detect one or more oscillations in at least one of: the carbon dioxide concentration of the patient's exhalation and / or the VM parameter of the gas delivery apparatus by applying at least one oscillation detection algorithm to at least one of: the determined carbon dioxide concentration of the patient's exhalation and / or the VM parameter; and modify the one or more VM adjustment criteria of the gas delivery apparatus responsive to detecting the one or more oscillations.

[0007] In some aspects, a mechanical ventilator apparatus includes: a gas delivery apparatus configured to deliver a gas to a patient and including a patient interface; an oximetry sensor configured to provide at least one signal representative of an oxygen saturation of the patient's blood; and a controller, including a processor and a memory, in communication with the gas delivery apparatus and the oximetry sensor, the controller configured to: receive the at least one signal representative of the oxygen saturation of the patient's blood provided by the oximetry sensor; determine an oxygen saturation of the patient's blood based on the received at least one signal; receive at least one signal representative of a signal fidelity from the oximetry sensor;Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO based on one or more potential false desaturation event criteria, identify a potential false desaturation event as an event that may or may not be a desaturation event; and adjust one or more fraction of inspired oxygen (FIO2) adjustment criteria for the gas delivery apparatus responsive to detecting the potential false desaturation event.

[0008] In some aspects, a mechanical ventilator apparatus includes: a gas delivery apparatus, having a user interface, configured to deliver a gas to a patient; and a controller, including a processor and a memory, in communication with the gas delivery apparatus, the controller configured to: control one or more ventilation parameters using closed loop control, receive user input via one or more controls of the user interface indicating a gain adjustment relating to the closed loop control of the one or more ventilation parameters; and implement the gain adjustment based on the received user input.

[0009] In some aspects, a controller, comprising a processor and a memory, in communication with a gas delivery apparatus, the controller configured to: receive at least one signal representative of a physiological parameter of a patient, control one or more ventilation parameters based at least in part on the physiological parameter, wherein changes to the one or more ventilation parameters are further controlled based on a pattern of changes, such as oscillations, detected in the at least one physiological parameter and / or the one or more ventilation parameters. In some aspects, the controller is part of a medical device, such as a ventilator apparatus. In some examples, the at least one physiological parameter is indicative of oxygen saturation. In some examples, the one or more ventilation parameters includes fraction of inspired oxygen (FIO2) parameter. In some examples, the controller is configured to provide ongoing control of the fraction of inspired oxygen (FIO2) parameter based on the oxygen saturation. In some examples, the at least one physiological parameter is indicative of carbon dioxide concentration (EtCCh). In some examples, the controller is configured to provide ongoing control of the one or more ventilation parameters based on the carbon dioxide concentration (EtCCh). In some examples, the controller is configured to receive an indication of signal fidelity in relation to the physiological parameter, wherein said ongoing control is modified based on said indication of signal fidelity.

[0010] In one or more example embodiments, the mechanical ventilator apparatus and / or the controller recited in the aspects above may be provided with, or have the functionality of, one or more of the following example features. The oximetry sensor comprises at least one pulse oximetry sensor. The pulse oximetry sensor comprises an SpC>2 sensor. The oxygen saturation of the patient’s blood is an oxygen saturation. The gas is a breathing gas.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0011] In one or more example embodiments, the FIO2 parameter adjustment criteria comprises at least one of: proportional gain parameter, a target SpCh parameter, and / or a derivative gain parameter. The detected oscillation is in the oxygen saturation of the patient’s blood and / or the FIO2 parameter.

[0012] In one or more example embodiments, the modified one or more FIO2 parameter adjustment criteria comprises at least one of: a default FIO2 change rate, a reduction in a FIO2 change rate, a reduction in a maximum FIO2 change rate, a time value for a modified FIO2 setting, and / or a temporal pause. The modified one or more FIO2 parameter adjustment criteria comprises the temporal pause at a current FIO2 setting. The modified one or more FIO2 parameter adjustment criteria comprises the temporal pause at an average FIO2 setting for a predetermined number of full oscillation cycles.

[0013] In one or more example embodiments, the modified one or more FIO2 parameter adjustment criteria comprises at least one of: an adjustment to a proportional gain, an adjustment to a derivative gain, an adjustment to both a proportional gain and a derivative gain, and / or an adjustment to an overall gain.

[0014] In one or more example embodiments, the modified one or more FIO2 parameter adjustment criteria is based on a severity of the detected one or more oscillations. The severity is determined based on a rate of full range crossings per hour, a peak-to-peak amplitude of the oscillations, and / or a magnitude of an SpC>2 error. The severity is a numerical value between 0 to 1.

[0015] In one or more example embodiments, the modified one or more FIO2 parameter adjustment criteria comprises disabling a patient response time-based adjustment in an FIO2 change rate. The modified one or more FIO2 parameter adjustment criteria comprises a change in at least one of: a response time coefficient or a SpC>2 response time in a patient response time-based adjustment criteria.

[0016] In one or more example embodiments, the at least one oscillation detection algorithm comprises determining a count for full range crossings in a predetermined time period based on the determined oxygen saturation of the patient’s blood and detecting one or more oscillations when the determined count for full range crossings exceeds a predetermined threshold of maximum full range crossings. A severity of the detected oscillation is based on a rate of the determined count for full range crossings and / or a peak-to-peak amplitude of the determined oxygen saturation of the patient’s bloodZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0017] In one or more example embodiments, the at least one oscillation detection algorithm comprises determining a SpO2 error for a time window based on the determined oxygen saturation of the patient’s blood and detecting one or more oscillations when a standard deviation for the determined SpO2 error exceeds a predetermined threshold of maximum SpO2 error standard deviation, when a cumulative value of the SpO2 error for the time window exceeds a predetermined threshold of maximum SpO2 error, and / or when a rate of SpO2 error crossing exceeds a predetermined threshold of SpO2 error crossing rate. A severity of the detected oscillation is based on a magnitude of the standard deviation of the SpCh error or a magnitude of the cumulative value of the SpC>2 error and / or rate of SpCh error crossing.

[0018] In one or more example embodiments, the at least one oscillation detection algorithm comprises determining an SpO2 error for a time window based on the determined oxygen saturation of the patient’s blood and detecting one or more oscillations when a similarity factor between the determined SpO2 error for the time window is within a threshold of a historical SpO2 error, wherein the similarity factor comprises at least one of: an integral absolute error (IAE) and time between zero-crossing (TBZC). A severity of the detected oscillation is based on a magnitude of the integral absolute error (IAE).

[0019] In one or more example embodiments, the at least one oscillation detection algorithm comprises determining an SpO2 signal based on the determined oxygen saturation of the patient’s blood, generating a transformed SpO2 signal by applying a fast Fourier transform (FFT) to the determined SpO2 signal, and detecting one or more oscillations by identifying one or more peaks in the transformed SpO2 signal within a predetermined frequency range. A severity of the detected oscillation is proportional to at least one of: an amplitude or a power of a largest peak identified within the predetermined frequency range. The predetermined frequency range comprises a frequency between 0.00556 Hz and 0.0167 Hz.

[0020] In one or more example embodiments, the controller is configured to control one or more ventilation parameters using closed loop control.

[0021] In one or more example embodiments, the one or more oscillations are attributed at least in part by an FIO2 change rate. For the one or more oscillations attributed at least in part by the FIO2 change rate indicates that the FiO2 change rate exceeds a rate sufficient to induce the one or more oscillations

[0022] In one or more example embodiments, the controller is configured to detect the one or more oscillations in the oxygen saturation of the patient’s blood and the FIO2Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO parameter. Detecting the one or more oscillations, in the oxygen saturation of the patient’s blood and the FIO2 parameter, is used in confirming that the detected oscillations are caused at least in part by an FIO2 change rate. When an oscillation is detected in one of the oxygen saturation of the patient’s blood or the FIO2 parameter, the other of the oxygen saturation of the patient’s blood or the FiO2 parameter is checked for oscillations.

[0023] In one or more example embodiments, the capnography sensor is configured to provide a signal representative of a partial pressure of expired gas from the patient.

[0024] In one or more example embodiments, the one or more oscillations are detected in the carbon dioxide concentration of the patient’s exhalation and / or the one or more oscillations are detected in the VM parameter.

[0025] In one or more example embodiments, the controller comprises a proportional-derivative minute volume controller configured to modulate VM to reach a target end-tidal carbon dioxide (EtCO2).

[0026] In one or more example embodiments, the VM adjustment criteria comprises a proportional term and a derivative term. The proportional term comprises an end-tidal carbon dioxide (EtCCh) error based at least on a difference between a target end-tidal carbon dioxide (EtCCh) and a measured end-tidal carbon dioxide (EtCCh). The derivative term comprises a difference between a measured end-tidal carbon dioxide (EtCCh) for a first time window and a measured end-tidal carbon dioxide (EtCCh) for a previous time window. The VM adjustment criteria comprises a corrected minute volume (corrected VM) comprising a weighted sum of the proportional term and the derivative term. The VM adjustment criteria comprises one or more parameters configured to achieve the corrected minute volume (corrected VM). the VM adjustment criteria comprises at least one of: a respiratory rate (RR), and / or a target tidal volume (VT).

[0027] In one or more example embodiments, the controller continuously modifies the one or more VM adjustment criteria. The controller periodically modifies the one or more VM adjustment criteria.

[0028] In one or more example embodiments, the at least one oscillation detection algorithm comprises determining an end-tidal carbon dioxide (EtCO2) signal based on the received at least one signal representative of the carbon dioxide in the patient’s exhaled air provided by the capnography sensor, determining a count for EtCO2 crossings for a predefined target range for a time window, and detecting one or more oscillations in the carbon dioxideZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO concentration of the patient’s exhalation when the determined count for EtCO2 crossings exceeds a predetermined threshold.

[0029] In one or more example embodiments, the at least one oscillation detection algorithm comprises determining an end-tidal carbon dioxide (EtCO2) error for a time window based on the received at least one signal representative of the carbon dioxide in the patient’s exhaled air provided by the capnography sensor and detecting one or more oscillations in the carbon dioxide concentration of the patient’s exhalation when a standard deviation for the determined EtCO2 error exceeds a predetermined threshold of maximum EtCO2 error standard deviation.

[0030] In one or more example embodiments, modification of the one or more VM adjustment criteria further comprises adjusting a weight for the proportional term in the weighted sum. Modification of the one or more VM adjustment criteria further comprises maintaining the minute volume for a predetermined period of time. Modification of the one or more VM adjustment criteria further comprises maintaining the minute volume at an average minute volume for a predetermined number of cycles.

[0031] In one or more example embodiments, the one or more false desaturation event criteria comprise at least one signal fidelity criterion. The at least one signal fidelity criterion comprises a signal strength level and a signal confidence level.

[0032] In one or more example embodiments, the event is identified as a desaturation event when the determined oxygen saturation of the patient’s blood is below a predefined threshold for a predefined period of time. The predefined threshold is 88% and the predefined period of time is 10 seconds. The predefined threshold and the predefined period of time is based on the signal fidelity. The predefined period of time is increased when the signal fidelity decreases. The predefined threshold and the predefined period of time is based on historical data of oxygen saturation in the patient’s blood.

[0033] In one or more example embodiments, adjustment of the one or more FIO2 adjustment criteria comprises a stepwise increase in a target FIO2 value. Adjustment of the one or more FIO2 adjustment criteria comprises an increase in a target FIO2 value followed by an increase in a proportional gain coefficient for a predetermined time. Adjustment of the one or more FIO2 adjustment criteria comprises setting a target FIO2 value to 100% followed by an incremental decrease of the target FIO2 value when an oxygen saturation value meets a predetermined threshold. The predetermined threshold for the oxygen saturation value is 97%.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0034] In one or more example embodiments, the gain adjustment comprises an adjustment to at least one of: an overall gain, a proportional gain, and a derivative gain.

[0035] In one or more example embodiments, the mechanical ventilator apparatus comprises a gain for a fraction of inspired oxygen (FIO2) and / or a gain for a minute volume (VM). The gain adjustment comprise a rate of adjustment for a gain setting, wherein the rate of adjustment is aggressive, moderate, or conservative. The implemented gain adjustment is modified based on the received gain adjustment. The implemented gain adjustment is superseded by the received gain adjustment.

[0036] In one or more example embodiments, the mechanical ventilator apparatus further comprising displaying in the user interface at least one of a fraction of inspired oxygen (FIO2) value. The mechanical ventilator apparatus further comprising displaying in the user interface at least one oscillation of a fraction of inspired oxygen (FIO2) value.

[0037] In one or more example embodiments, the controls of the user interface comprise one or more knobs, input fields, and / or selection buttons.BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Various aspects of embodiments of the present disclosure are discussed below with reference to the accompanying figures, which are not intended to be drawn to scale. The figures are included for illustrative purposes and a further understanding of the various aspects and examples and are incorporated in and constitute a part of this specification but are not intended to limit the scope of the disclosure. The drawings, together with the remainder of the specification, serve to explain principles and operations of the described and claimed aspects and examples. In the figures, identical or nearly identical components that are illustrated in various figures may be represented by like numerals. For purposes of clarity, not every component may be labeled in every figure. Herein, where a single element is recited, it is implied that one or more may be included in various embodiments.

[0039] FIG. 1 depicts an example system incorporating physiological closed-loop control (PCLC) with a response time procedure in mechanical ventilation of a patient, in accordance with some embodiments of the present disclosure.

[0040] FIG. 2 shows an example of a control diagram for a closed-loop physiological control-based ventilation system, in accordance with some embodiments of the present disclosure.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0041] FIG. 3 shows a method for detecting oscillations in a FIO2 signal and / or SpCh signal and mitigating the detected oscillations, in accordance with some embodiments of the present disclosure.

[0042] FIG. 4 shows a process for detecting oscillations in an SpC>2 signal using full range crossings that can be performed by a controller, in accordance with some embodiments of the present disclosure.

[0043] FIG. 5 shows a process for detecting oscillations in an SpC>2 signal using full range crossings, in accordance with some embodiments of the present disclosure.

[0044] FIG. 6 shows an alternative method for detecting an oscillation in which the variation of the patient’s SpC>2 is quantified based on the Target SpC>2, in accordance with some embodiments of the present disclosure.

[0045] FIG. 7 shows an alternative method for detecting an oscillation based on the cumulative absolute SpC>2 error and an SpC>2 error crossing rate, in accordance with some embodiments of the present disclosure.

[0046] FIG. 8 shows an alternative method for detecting an oscillation based on an integral absolute error and the time between zero-crossings, in accordance with some embodiments of the present disclosure.

[0047] FIG. 9 shows an alternative method for detecting an oscillation using fast Fourier transforms, in accordance with some embodiments of the present disclosure.

[0048] FIG. 10 shows example results from a patient simulation where FIO2 parameter adjustments are modified due to a detected oscillation, in accordance with some embodiments of the present disclosure.

[0049] FIG. 11 shows an example intervention to resolve oscillations using FIO2 time, in accordance with some embodiments of the present disclosure.

[0050] FIG. 12A shows a modification to a patient response time coefficient that indicates a return to a default “slow” FIO2 change rate, where there is no adjustment for patient response time (PRT), in accordance with some embodiments of the present disclosure.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0051] FIG. 12B shows a modification to a patient response time coefficient, where the patient response time-adjusted FIO2 change rate is decreased, but not all the way back to default, in accordance with some embodiments of the present disclosure.

[0052] FIG. 12C illustrates a parameter modification where the maximum FIO2 change rate is decreased, by decreasing KI, max for proportional gain, in accordance with some embodiments of the present disclosure.

[0053] FIG. 13 provides a flow-chart for a method of adjusting parameter settings for a physiological closed loop control ventilation system that includes patient response time when oscillations are detected in a FIO2 signal and / or SpC>2 signal in order to mitigate the detected oscillations, in accordance with some embodiments of the present disclosure.

[0054] FIG. 14 shows a method for detecting oscillations in one of the EtCCh and / or VM parameters and modifying a VM adjustment criteria of the gas delivery apparatus accordingly, in accordance with some embodiments of the present disclosure.

[0055] FIG. 15 provides a demonstration of the effects of modifying proportional gain for a cardiopulmonary computational model to demonstrate the effect of different controller speeds, in accordance with some embodiments of the present disclosure.

[0056] FIG. 16 is an illustration of the impact of high proportional gain, in accordance with some embodiments of the present disclosure.

[0057] FIG. 17 is an illustration of the activity of the EtCCh and VM over time when comparing a system with the default gain coefficient and high gain coefficients, in accordance with some embodiments of the present disclosure.

[0058] FIG. 18 is a flowchart for an oscillation detection method, in accordance with some embodiments of the present disclosure.

[0059] FIG. 19 shows a method for detection of oscillations in an EtCCh signal based on a frequency of full range crossings, in accordance with some embodiments of the present disclosure.

[0060] FIG. 20 shows alternative approach to detecting oscillations in a patient’s EtCCh signal based on the standard deviation of EtCCh error, in accordance with some embodiments of the present disclosure.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0061] FIG. 21 shows method for improved specificity in determining a desaturation event, in accordance with some embodiments of the present disclosure.

[0062] FIG. 22 provides data for the patient at a shorter time frame to show more details of a single desaturation event, in accordance with some embodiments of the present disclosure.

[0063] FIG. 23 shows a method for identifying potential false desaturation events and adjusting FIO2 criteria accordingly, in accordance with some embodiments of the present disclosure.

[0064] FIG. 24 is an illustration of modifications to the FIO2 adjustment criteria responsive to detection of a desaturation event, in accordance with some embodiments of the present disclosure.

[0065] FIG. 25 shows a method to implement a gain adjustment, in accordance with some embodiments of the present disclosure.

[0066] FIG. 26 is an illustration of user-controlled gain settings and their resulting proportional gain coefficient, and estimated SpC>2 response time, in accordance with some embodiments of the present disclosure.

[0067] FIG. 27A illustrates a portable ventilator with a user interface, in accordance with some embodiments of the present disclosure.

[0068] FIG. 27B illustrates a portable ventilator with a user interface, in accordance with some embodiments of the present disclosure.

[0069] FIG. 27C provides an example of a user interface for a portable ventilator, in accordance with some embodiments of the present disclosure;

[0070] FIG. 27D provides an example of a user interface for a portable ventilator, in accordance with some embodiments of the present disclosure;

[0071] FIG. 28 illustrates a portable ventilator with a user interface, in accordance with some embodiments of the present disclosure.

[0072] FIG. 29 illustrates a portable ventilator with a user interface, in accordance with some embodiments of the present disclosure.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0073] FIG. 30 illustrates a portable ventilator with a user interface, in accordance with some embodiments of the present disclosure.

[0074] FIG. 31 illustrates a portable ventilator with a user interface, in accordance with some embodiments of the present disclosure.

[0075] FIG. 32 illustrates a portable ventilator with a user interface, in accordance with some embodiments of the present disclosure.

[0076] FIG. 33 illustrates an example schematic of a portable ventilation system or ventilator 3300, incorporating physiological closed-loop control, in accordance with some embodiments of the present disclosure.

[0077] FIG. 34 illustrates an example portable ventilator 3400, in accordance with some embodiments of the present disclosure.

[0078] FIG. 35 illustrates aspects of an example pneumatic system 3500 that can be used with a portable ventilator, in accordance with some embodiments of the present disclosure.

[0079] FIG. 36 illustrates aspects of an example external gas supply system 3600 that can be used with a portable ventilator 3608, in accordance with some embodiments of the present disclosure.

[0080] FIG. 37 illustrates aspects of example patient circuits 3700 that can be used with a portable ventilator 3714, in accordance with some embodiments of the present disclosure.DETAILED DESCRIPTION

[0081] Some embodiments include use of physiological closed loop control (PCLC) during mechanical ventilation being provided to a patient. This may include, for example, algorithmic control of an FIO2 setting in order to ongoingly optimize patient SpO? (e.g., so that it is within a target range or as close as possible to a target level) and / or control of a VM setting in order to ongoingly optimize patient EtCCh. For example, an algorithmically controlled direction (increase or decrease) and rate of change of FIO2 may be ongoingly adjusted in order to maintain (or achieve) patient SpO2 within a target range. In some embodiments, algorithmic gain factors, such as proportional and / or derivative gain, as described herein, may be adjusted for this purpose. Optimizing patient SpO2 and / or EtCO2 (or, e.g., EtCO2 and VM) may provide more optimized patient oxygenation and lead to better clinical outcomes for patients.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0082] In some embodiments, the algorithmically controlled rate of change of FIO2, for example, takes into account a measured patient response time. For example, a patient response time, with regard to SpC>2, may reflect an amount of time that it takes for an adjustment to an FIO2 setting to be reflected or sufficiently reflected by a corresponding change in the patient’s SpC>2. The patient response time may depend, for example, on factors including the physiology and current condition of the specific patient.

[0083] In some embodiments, optimal control, for example, of FIO2 (e.g., in order to maintain the patient’s SpC>2 within a target range) may include increasing or maximizing a rate of change of FIO2 while eliminating or avoiding oscillations in SpO 2 and / or FIO2. Maximizing or increasing the rate of change of FIO2, within a certain limit, may be desirable in order to most effectively maintain the patient’s SpC>2 in a target range, or to more rapidly move the patient’s SpO2into the target range. However, if the rate of change of FIO2 is too rapid, it may overtake the patient’s ability to respond rapidly enough with a corresponding desired change in the patient’s SpC>2. This may lead to the patient’s SpC>2 not being able to keep up, in a sense, with the rapid FIO2 change rate. As a result, for example, FIO2 may be ongoingly increased due to the patient’s SpC>2 being too low, but, given the delay in the patient’s response time, the patient’s SpO2may then overshoot the target range. FIO2 may then be too rapidly decreased, analogously leading to the patient’s SpC>2 dropping below the target range, which may again lead to FIO2 being too rapidly increased. This cycle may repeat, leading to oscillations in one or both of patient’s SpC>2 and FIO2.

[0084] The described oscillations, which may be caused by an overly rapid rate of change of FIO2, can lead to suboptimal patient oxygenation and ventilation, for example, with the patient’s SpC>2 repeatedly and cyclically moving too high or too low. Oscillations are known to be a problematic condition, such as in control theory, since they tend to disrupt stability.

[0085] As such, some embodiments include detection of oscillations. Once detected (e.g., detection of oscillations in patient SpO2), for example, a response may be determined and provided. In some embodiments, the response may include, for example, a reduction in a rate of change of FIO2 as necessary to eliminate the detected oscillations. For example, in some embodiments, the reduction may be determined so as to be great enough to remove the oscillations, but not unnecessarily or inappropriately great, since, absent oscillations, a higher rate of change may better optimize patient oxygenation and optimally maintain the patient’s SpO2within a target range.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0086] Disclosed is a mechanical ventilation system that can respond to oscillations that develop during the physiological closed-loop control of its parameters. Mechanical ventilation refers to the use of a device, such as a ventilator, to provide patients with breathing assistance. In mechanical ventilation systems that utilize physiological closed-loop control, parameters for the mechanical ventilation system can be adjusted based on physiological input (e.g., physiological parameters of the patient receiving ventilation). During this process, some physiological closed-loop control systems can experience oscillations. These oscillations can in turn lead to sub-optimal treatment being provided to a patient. Accordingly, the disclosed mechanical ventilation system provides an improvement to existing physiological closed-loop control mechanical ventilation systems by detecting oscillations and modifying one or more parameters for the mechanical ventilation system in order to mitigate the detected oscillations.

[0087] For example, a physiological closed-loop control system that varies oxygenation provided by a ventilation treatment (e.g., an FIO2 setting provided by a ventilator) responsive to a measured oxygenation level of a patient’s blood (e.g., SpCh) can experience oscillations in both the FIO2 and / or SpC>2. Disclosed are systems, methods, and apparatus that modify parameters for a mechanical ventilation system that is responsive to oscillations that develop during the closed loop control of parameters for mechanical ventilation. Modification of parameters for the mechanical ventilation system to mitigate the detected oscillations can include adjustments to the rate of change of the FIO2 setting.

[0088] In another example, similar oscillations can be detected in end-tidal carbon dioxide (EtCCh). Responses to oscillations may include adjusting the rate of change in the FIO2 setting, VM and the like. For example, oscillations in the EtCCh may be caused by overly rapid change in the FIO2 setting, VM and the like, which can lead to suboptimal patient oxygenation and ventilation, for example, with the patient’s EtCCh repeatedly and cyclically moving too high or too low.

[0089] Additionally, physiological closed-loop control systems for mechanical ventilation may respond to desaturation events that are often falsely detected due to inaccurate pulse oximetry readings. In conventional systems this can lead to over-oxygenation of the patient because when desaturation events are detected the patient oxygenation settings are typically increased and held for some time. Additionally, it may take a long time for patient oxygenation settings to be reduced and during that time there is over oxygenation of the patient. Accordingly, the current disclosure provides techniques for improved detection of desaturation events. The improved detection of desaturation events can lead to fewer false positive detections andZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO increases in the specificity of detection by incorporating signal information into the determination of the desaturation event, adjusting time requirements for detecting a desaturation event, and the like.

[0090] Physiological closed-loop control (PCLC) ventilation may refer to a ventilation system where aspects of the mechanical ventilation provided to a patient is controlled based on the patient’s physiological values.

[0091] For example, in various embodiments, the fraction of inspired oxygen (FIO2) provided to a patient by a ventilator system may be continuously adjusted based on a measured patient peripheral oxygen saturation (SpCh), which is used as an indicator of patient blood oxygen saturation. Generally, a lower SpC>2, or decreasing SpC>2 (as may be determined, for example, based on a single or current SpC>2 measurement, or several SpC>2 measurements over a recent period of time) may tend to indicate a “sicker” patient, or patient with more impaired lung or respiratory system disfunction, who is in need of more oxygenation support. In some embodiments, generally, when a patient’s SpC>2 is below a target level (such as a pre-determined SpO2value), and potentially also based at least in part on how much below, and / or a rate of decrease, FIO2 may procedurally tend to be increased in order to increase support of a patient’s oxygenation. When SpC>2 is above the target level, and potentially also based at least in part on how much above, FIO2 may procedurally tend to be decreased, since the patient may not need as much oxygenation support. As such, FIO2 may be increased or decreased based at least in part on the need of the patient as indicated at least in part by SpC>2 and / or, for example, some other indication(s), such as one or more other non-invasively sensed, measured or determined indications of patient oxygen saturation. In some PCLC systems, procedurally determined factors, such as derivative gain and proportional gain factors, may affect a direction (increase or decrease) and amount of FIO2 adjustment. Specifically with regards to the closed loop control of the FIO2 provided to a patient by a ventilator system, changes to the FIO2 levels may be performed at a relatively slow rate to bring the measured SpC>2 from its current level to a target level. The slow rate of change to the ventilator’s FIO2 level may be done in order to safely accommodate all patients, including those with slower response times to the change in the FIO2 level. While proportional and derivative gains are described herein, it is envisioned that alternative gains can be used in a physiological closed-loop control system.

[0092] In another example, the ventilation system can adjust a minute volume (VM) parameter of the ventilation apparatus based at least in part on the determined carbon dioxide concentration (EtCCh) of the patient’s exhalation.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0093] Alternatively, in some embodiments, a ventilation system can also include a response time procedure in which the rate of change to the ventilator’s FIO2 level may take into account a patient response time, or the patient’s SpCh response time. The SpCh response time expresses the delay between a change in oxygenation in the lungs (generally considered to be the same time that a change is made to the FIO2 level or the time when a next breath is taken after changing the FIO2 level) and when that change is reflected in a measurement of blood oxygen saturation at the measurement site (e.g., a pulse oximeter measurement made at a finger or earlobe). A patient’s SpC>2 response time is dependent on several factors, including the measurement site used, patient cardiopulmonary physiology, and vasoconstriction or vasodilation. Accordingly, the SpC>2 response time is specific to the patient. Various methods and systems for a physiological closed loop control system that incorporate patient response time can be used.

[0094] Herein, in some instances, variations of a term may be utilized that may refer to the same or similar concepts, and certain terms may have meanings that are informed by a particular context. Various ventilation-related terms or abbreviations, including FIO2, SpC>2, positive end-expiratory pressure (PEEP), and others, may refer to ventilation related settings, even though the word “setting” may or may not be stated, or blood oxygen measurements.Furthermore, reference to a ventilation parameter or parameter setting may be used to refer to the parameter in a conceptual or definitional sense, or the value associated with a particular setting (e.g., “FIO2 of 95%”). A user, as described herein, may include an individual operating, supervising or in whole or in part responsible for operation of a device such as a portable ventilator in support of the patient’s need for respiratory support, even if, during a particular period of time while the device is operating, the user may not be interacting with the device.

[0095] An alert or alarm, as used herein, may be presented for the attention of a user, such as by being visually or audibly presented, such as via a display, graphical user interface (GUI) or speaker of a device. However, an alert or alarm may also include reference to alert or alarm conditions that are procedurally identified, recognized or determined by a computerized device and not necessarily presented or displayed. Herein, the term optimizing may include, for example, improvement or improved operation in one or more aspects, for example, relative to an actual, potential or hypothetical less optimized situation or less optimized operation.

[0096] Herein, a ventilator can include, for example, a ventilator or ventilation device, apparatus or system, whether or not portable, and whether or not functionality other than ventilation aspects is provided by the device, apparatus or system. Herein, the term adjusting canZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO include changing as well as not changing or maintaining without change, as may be appropriate. Herein, a determined parameter value can include a determined estimated or determined approximated value for the parameter. Herein, the term monitoring can refer to or include, for example, monitoring or tracking performed by a computerized device utilizing one or more processes and not by a person or user, or monitoring by a person or user, or both. Herein, the term continuous can include, among other things, on a periodic basis (with identical or different periods), on a frequent basis, on a repeated basis, or cyclically, for example.

[0097] Herein, terms such as hypercapnia, hypocapnia and normocapnia are not intended to be limited to particular ranges or clinical meanings, but are used in a relative sense, such as to indicate relatively high, relatively low, or intermediate, in a particular embodiment, for example. Furthermore, in some embodiments, associated ranges, or some of them, may overlap. In some embodiments, normocapnia may have a lower EtCCh threshold of, e.g., in mm Hg, 20, 25, 30, 35, 40, 45 or 50 and an upper threshold of, e.g., in mm Hg, 30, 35, 40, 45, 50, 55 or 60. Hypercapnia may include an EtCCh of at or above a threshold of, e.g., in mm Hg, 30, 35, 40, 45, 50, 55 or 60. Hypocapnia may include an EtCCh of at or below a threshold of, e.g., in mm Hg, 20, 25, 30, 35, 40, 45 or 50.

[0098] The term physiological closed-loop control, as used herein, may refer to control of one or more ventilation related or patient related parameters, such as with relatively little or no required user action, participation or intervention, and can include reference to, but is not limited to reference to, fully automated or fully automatically regulated control. Physiological closed-loop control may include, for example, device facilitated or procedurally facilitated tracking, control and adjustment of one or more parameters, which may or may not include user involvement or participation. Where user involvement or participation is included, it may include, for example, confirming a suggested or recommended ventilation setting change or configuration, deciding on implementing a course of action, selecting one of several suggested courses of action, responding to a presented alert or alarm, or other decisions, choices or actions. User involvement or participation could also include, for example, setting or changing a parameter, where a physiological closed-loop control process proceeds from there, initially according to the user-set or user-changed parameter setting. In various embodiments, if there is user involvement, it may be, for example, among other things, in whole or in part user-initiated, or in whole or in part prompted, suggested, recommended or required.

[0099] In some embodiments, physiological closed-loop control may be utilized but may be subject to manual adjustment or override by the user. For example, in someZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO embodiments, although FIO2 may be procedurally and automatically controlled by the ventilator based on measured patient SpC>2 and a patient response time, a user may be able to intervene and manually change the FIO2 setting and / or the patient response time. In some embodiments, following any manual adjustments, physiological closed-loop control of FIO2 may resume from that point, at least until any further manual adjustments are made.

[0100] FIG. 1 is an example system 100 that incorporates physiological closed-loop control (PCLC) with mechanical ventilation of a patient. The example system 100 incorporates physiological closed-loop control 124, as conceptually represented by a dashed circle, in mechanical ventilation of a patient 104, in accordance with some embodiments of the present disclosure. While a portable (e.g., may be carried or practically carried or taken by a care provider to a patient at an out-of-hospital or pre-hospital location) ventilator 102 is shown, embodiments are contemplated in which a non-portable ventilator is provided or utilized. When operating, the portable ventilator 102 may provide breathing gas to a patient 104 via a gas delivery apparatus 106, including a patient circuit 108 that includes a facemask 110, though, in some embodiments, ventilation may be provided via intubation rather than via a facemask. A user 122 is also shown. The portable ventilator 102 may be coupled with an oxygen source 112. Oxygen sources include, but are not limited to oxygen tanks, oxygen reservoir bags and the like. In some implementations a high-pressure oxygen tank 113 can be attached to the high-pressure oxygen input located at the top of the portable ventilator 102. An oxygen tank may also be coupled or integrated with other devices. The portable ventilator 102 may also include various sensing, measuring, computerized, electrical, mechanical, coupling and output components. As depicted, the portable ventilator 102 includes an oximetry sensor 114, such as a pulse oximeter or other sensor for providing a direct or indirect measurement, estimation or indication of oxygen saturation (SpO2) or other blood oxygen content or concentration related parameter, a capnographic sensor 116 or capnograph, and a blood pressure sensor / monitor 118, and may also include one or more flow sensors such as pneumotachometers, or pressure sensors, among other things.

[0101] The portable ventilator 102 includes a display and user interface 120 that may provide data relating to various patient physiological, respiratory and ventilation related parameters, and may include other output or presentation components, such as a speaker. In some embodiments, the display and user interface 120, or other output devices, may provide a display that is integrated to include data relating to operation of other coupled devices that may also be in use with the patient, such as, for example, a critical care monitor or monitor / defibrillator. The display and user interface 120 may also allow user interaction, including obtaining or displayZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO data, change settings, accept suggested or recommended settings changes, or view or respond to alarms or alerts, among other things.

[0102] The portable ventilator 102 is capable of providing physiological closed-loop control 124 of one or more ventilation or patient related parameters, as described with regard to various embodiments herein. Accordingly, ventilator 102 may include a controller that executes one or more processes in implementing methods described herein. The location or setting depicted in FIG. 1 may include, among other things, a pre-hospital or non-hospital location or setting, which could include an emergency vehicle setting or other venue or location. The portable ventilator 102 may, for example, be stored at or near the location or setting, or may be carried or taken to the location or setting to provide emergency care to the patient 104.

[0103] According to some embodiments, the portable ventilator 102 is also capable of executing a response time procedure (RTP) 126 to determine an SpC>2 response time for the patient 104. RTP 126 may be a procedure that is executed within the physiological closed-loop control 124 process. In some examples, RTP 126 is executed independently of the physiological closed-loop control 124 process.

[0104] According to some embodiments, the portable ventilator 102 is also capable of detecting oscillation sin the ventilation settings and / or physiological outputs and adjusting physiological closed-loop control system accordingly to mitigate oscillations.

[0105] FIG. 2 is an example of a control diagram for a closed-loop physiological control-based ventilation system. As illustrated in FIG. 2, a ventilation system 200 can include a ventilator 201 configured to provide breaths to a patient 203. A physiological monitoring device 205 can be configured to measure a physiological parameter from the patient. For example, a pulse oximeter can be configured to measure a SpO? value for the patient. The measured physiological parameter (e.g., SpO? value) can be provided to a physiological closed-loop controller 207, which adjusts a setting (e.g., FIO2 setting) for the ventilator 201 based in part on a calculated difference 209 between a target value for the physiological parameter (e.g., target SpO2) 211 and the measured value of the physiological parameter (e.g., SpC>2 value).

[0106] In some implementations, the ventilator 101 can be referred to as an actuator, that outputs a manipulated variable such as the delivered FIO2. The patient 203 may be impacted by a patient disturbance variable vpsuch as one or more of a shunt, cardiac output, dead space, change in position, etc. The patient 203 may output a physiologic variable y such as SaC>2, arterial oxyhemoglobin saturation, that is measured by a pulse oximeter and provides a feedbackZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO variable f such as SpCh - pulse oximeter measured oxyhemoglobin saturation. A comparing element can calculate a difference 209 by using an error function e that takes a difference between the feedback variable SpCh f and the reference variable (i.e., target SpCh w). The error function e can be provided to the controller logic.

[0107] FIGS. 3- 13 illustrate mechanical ventilator system and apparatus that is configured to detect oscillations and modify the mechanical ventilator’s parameters to mitigate the detected oscillations.

[0108] For example, a mechanical ventilator apparatus can include a gas delivery apparatus configured to deliver a gas to a patient (e.g., breathing gas) and including a patient interface, an oximetry sensor configured to provide at least one signal representative of an oxygen saturation of the patient’s blood, and a controller including a processor and a memory, that is in communication with the gas delivery apparatus and the oximetry sensor. For example, the oximetry sensor may be configured to generate at least one signal representative of an oxygen saturation of the patient’s blood. The controller may be analogous to the controller 207 of FIG. 2 and can be configured to perform the method 300 illustrated in FIG. 3. In some embodiments, the oximetry sensor includes at least one of a pulse oximetry sensor, and a SpC>2 sensor. In some embodiments, the oxygen saturation of the patient’s blood is an oxygen saturation. The controller can be configured to control one or more ventilation parameters using closed loop control.

[0109] FIG. 3 is a method 300 for detecting oscillations in a FIO2 signal and / or SpC>2 signal and mitigating the detected oscillations. A controller may receive the at least one signal representative of the oxygen saturation of the patient’s blood provided by the oximetry sensor 301, determine an oxygen saturation of the patient’s blood based on the received at least one signal 303, continuously adjust a fraction of inspired oxygen (FIO2) parameter of the gas delivery apparatus based at least in part on the received signals representative of the oxygen saturation of the patient’s blood, wherein the FIO2 parameter comprises a percentage of oxygen in the gas delivered to the patient in accordance with one or more FIO2 parameter adjustment criteria 305, detect one or more oscillations in at least one of the oxygen saturation of the patient’s blood and / or the FIO2 parameter by applying at least one oscillation detection algorithm to at least one of the determined oxygen saturation and / or the FIO2 parameter 307, and modify the one or more FIO2 parameter adjustment criteria of the gas delivery apparatus responsive to detecting the one or more oscillations 309. It will be appreciated that in other examples the controller provides for one or more automatic adjustments of FiO2 during operation.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0110] As described herein, a physiological closed loop control system can be configured to continuously adjust a fraction of inspired oxygen (FIO2) parameter of the gas delivery apparatus based at least in part on the received signals representative of the oxygen saturation of the patient’s blood. In the described system, when an oscillation is detected in at least one of the oxygen saturation of the patient’s blood and / or the FIO2 parameter, one or more of the parameters used to adjust the gas delivery apparatus are modified to mitigate the detected oscillation.

[0111] For example, the FIO2 parameter adjustment criteria can include at least one of proportional gain parameter, a target SpC>2 parameter, and / or a derivative gain parameter. The FIO2 parameter adjustment criteria can include a proportional FIO2 gain which may refer to how fast FIO2 is algorithmically increased or decreased, based on patient SpC>2. In one implementation, this may include use of two different gain factors: (1) proportional gain and (2) derivative gain. The proportional gain parameter may refer to the speed of increasing or decreasing of the FIO2 parameter value based on a difference between the measured SpC>2 and a target (i.e., desired) SpC>2. In proportional gain, if the SpC>2 is far from the target SpC>2, FIO2 may be changed more rapidly. Whereas, in proportional gain, if SpC>2 is closer to the target SpC>2, FIO2 may be changed less rapidly.

[0112] The FIO2 parameter adjustment criteria can include a derivative gain that causes the FIO2 to increase more rapidly (be “boosted”) when the patient’s SpC>2 is decreasing (which may indicate that the patient needs urgent oxygen support). However, in derivative gain, the FIO2 is not decreased more rapidly when the patient’s SpC>2 is increasing. In some embodiments, gain may be asymmetric in the sense that the derivative gain coefficient is different depending on whether SpO2 is increasing or decreasing, for example.

[0113] In some implementations, a physiological closed-loop controller adjusts the FIO2 setting to achieve a target SpC>2 (default: 94%, adjustable between 94% and 98%) for the patient. The controller can be a modified proportional -derivative (PD) controller configured to calculate how much to change the FIO2 setting based on how far the patient SpC>2 is from the Target SpC>2 (i.e., proportional term), and, if the patient’s SpC>2 is decreasing, how quickly the SpO2is decreasing (i.e., derivative term). Specifically, FIO2 Correction = (SpC>2 Error * Proportional Gain) + (Derivative Error * Derivative Gain), where SpC>2 Error is defined as Target SpO2- SpO2. The new FIO2 setting equals the previous FIO2 setting plus the FIO2 correction.

[0114] In some implementations, an oscillation can be detected in the oxygen saturation of the patient’s blood (e.g., SpCh). For example, oscillations can be detected in theZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO signal produced by an oximetry sensor detecting signals from a patient. In some implementations, the oscillation(s) can be detected in the FIO2 parameter. In some implementations, the oscillation(s) can be detected in both the oxygen saturation of the patient’s blood and the FIO2 parameter.

[0115] Various methods for detecting oscillations are discussed in FIGS. 4-9.Detection of oscillations in accordance with the methods illustrated in FIGS. 4-9 can result in the triggering of an alarm, adjustment of one or more parameter settings for a physiological closed loop control ventilation system and / or the like.

[0116] FIG. 4 illustrates a process 400 for detecting oscillations in an SpC>2 signal using full range crossings (e.g., crossings into and out of a defined range) that can be performed by a controller. The controller can obtain an ongoing SpC>2 signal that is related to a waveform 401. Optionally, the controller can generate a moving average waveform (e.g., 60 seconds) to reduce the impact of signal noise 403. The resulting signal can be monitored for SpO2 full range crossings 409. In some embodiments, the controller may receive a target SpO2 range for use in oscillation detection and a threshold number of full range crossings over a specified period of time . In some embodiments, the target SpC>2 range and the threshold number of full range crossings can be predefined. Monitoring of the SpC>2 signal can be performed continuously until the number of SpC>2 full range crossings per hour is reached or the SpC>2 oscillations threshold is surpassed 411, in which case SpC>2 oscillations are detected 413. One or more parameter settings for a physiological closed loop control ventilation system can be adjusted responsive to SpO2 oscillations being detected 415.

[0117] In some implementations, the full range crossings can indicate that the signal has crossed into and out of a defined range. For example, a defined range can span a target SpO2 value modified by a percentage range (i.e., defined range for full range crossings = target range +x percentage / - y percentage). For example, the target range can be between 90-98% and / or the modifying percentage range can be between 0.25 and 4%. In such an example, when the SpC>2 value crosses from below to above the target range and / or from above to below the target range a full range crossing can be detected (e.g., 86 to 98.25 %). The number of full range crossings over a specified period of time can be determined. For example, the specified period of time can be on the range of minutes or hours (e.g., 5 minutes, 10 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, etc.). In some implementations, the threshold number of full range crossings can be 2 crossings per hour, 3 crossings per hour, 4 crossings per hour, ... 40 crossings per hour, 50 crossings per hour, 60 crossings per hour, etc.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0118] FIG. 5 illustrates a process for detecting oscillations in an SpCh signal using full range crossings. A method to detect oscillations may quantify the frequency of SpC>2 crossings into and out of a defined target SpCh range.

[0119] Data from a simulated patient with the following characteristics is illustrated in FIGS. 5-10. In the illustrated example, the simulation patient has a tidal volume VT = 450 ml; breaths per minute BPM = 15 1 / min; Weight = 70 kg; dead space ventilation VD = 200 ml; shunt fraction fshunt = 50%; cardiac output CO = 101 / min; dVCO2,met = 2.8 ml / kg / min; SpO2 Bias = 0%; SpO2Noise Amp = 1.5%; respiratory quotient RQ = 0.8; and physiological delay = 180 s.

[0120] Detecting oscillations to quantify the frequency of SpO2 crossings into and out of the target SpO2 range can include removing high frequency noise from the SpO2 signal, defining a target range of SpO2, identifying the times that the filtered SpO2 crosses a range (i.e., a range crossing), quantifying the rate of range crossings, and detecting oscillations when the quantified rate of range crossings exceeds a threshold.

[0121] In some implementations, high frequency noise can be removed from the SpO2signal obtained from a pulse oximeter and the like. The high frequency noise can be removed using a moving average, a lowpass filter, or the like. For example, as illustrated in FIG.5, a moving average of 60 seconds is applied.

[0122] FIG. 5 illustrates a FIO2 values 501 and SO2 values 503 for a patient. As shown in FIG. 5, a target range for the SpC>2 value can be defined. The target range can be predetermined or input by a user. In the illustrated example, the target range for the Target SpC>2 is defined as (94%) ± 2% (i.e., 92-96%) 505.

[0123] When physiological closed loop control is used to drive the FIO2 setting of the ventilator, range crossings in the filtered SpC>2 signal can be identified. For example, the times that the filtered SpC>2 crosses from “in range” to “out of range” and vice versa are identified 507. The range crossings can be further categorized by their respective type. The four categories or types of range crossings include: (a) Into range from above (e.g., 97% -> 95%), (b) Into range from below (e.g., 91% -> 93%), (c) Out of upper end of range (e.g., 95% -> 97%), and (d) Out of lower end of range (e.g., 93% -> 91%). Range crossings from all four types 509 are illustrated in FIG. 5. Some examples, may use one or more of these types in the determination of oscillations.

[0124] A patient with an SpO2 that crosses into and out of the range (e.g., from above 96% to below 92% or below 92% to above 96%) might be particularly likely to be experiencing SpO2oscillations which is illustrated as a Full-Range Crossing. A full range crossing is differentZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO from a patient that is simply oscillating into and out of one end of the range (e.g., between 95.5% and 96.5%).

[0125] The rate of range crossings can be quantified over a set time. For example, in the illustrated embodiment in FIG. 5, the rate of all range crossings is 37 per hour and the rate of full range crossings is 10 per hour.

[0126] When the rate of full range crossings exceeds a threshold, the system may detect oscillations. For example, if the rate of full range crossings is above a threshold of 5 crossings per hour, the system would determine that oscillations are present. The threshold for the rate of full range crossings can be set by a user, predetermined by a manufacturer of the ventilation device, and the like. For example, in some implementations the threshold for the rate of full crossings can be based on clinical data. In some implementations, the threshold may be set to dynamically vary in that depending on a particular condition or situation being met, the threshold can be adjusted (e.g., increased or decreased). For example, the threshold may vary depending on a measured response time, average SpCh, oscillation size, number of recent desaturation events and the like. In some implementations the rate of crossings over time may be monitored and an alert can be issued if it is determined to be increasing. In some implementations, the rate of crossings over time can be monitored. In some implementations, it may be preferable for the rate of crossings to increase over time or decrease over time. In some implementations, the alerts triggered by the detection of an oscillation can be escalated or deescalated based on whether the rate of crossings is increasing or decreasing. For example, the triggering of an adjustment in the physiological closed-loop control gain, escalating alarm, and / or warning transmission sent to the user can be based on whether the rate of crossings increases and / or decreases. In some implementations, the actions initiated when the threshold is reached can vary. Actions include an adjustment in the physiological closed-loop gain, a series of escalating alarms, warning transmissions, and the like.

[0127] As illustrated in FIG. 5, in some implementations the oscillation detection algorithm determines a count for full range crossings in a predetermined time period based on the determined oxygen saturation of the patient’s blood and detects one or more oscillations when the determined count for full range crossings exceeds a predetermined threshold of maximum full range crossings.

[0128] In some implementations a severity of the detected oscillation can be determined based on a rate of the determined count for full range crossings. In other words, aZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO higher rate of the determined count for full range crossings may correspond to the patient experiencing more severe oscillations.

[0129] FIG. 6 illustrates an alternative method for detecting an oscillation in which the variation of the patient’s SpCh is quantified based on the Target SpCh. FIG. 6 illustrates a FIO2 signal 601, an SpCh signal 603, a corresponding SpCh error signal 605, and the standard deviation of the SpCh error 607. The oscillation can be detected by determining a SpCh error for a time window based on the determined oxygen saturation of the patient’s blood and detecting one or more oscillations when a standard deviation for the determined SpCh error exceeds a predetermined threshold of maximum SpC>2 error standard deviation.

[0130] The SpO2error can be calculated by the controller based on a difference between the target SpC>2 and the measured SpC>2. For example, SpC>2 Error = Target SpC>2 -Measured SpC>2. The resulting SpC>2 error can be filtered to remove noise and artifacts. For example, FIG. 6 illustrates an SpC>2 error signal 605 where a 2ndorder Butterworth bandpass lowpass filter (lower cutoff = 0.001 Hz, upper cutoff = 0.01 Hz) has been applied. The lower cutoff of the bandpass filter acts to remove the fixed bias.

[0131] As illustrated in FIG. 6, the moving standard deviation over a fixed time window can be determined. For example, 607 illustrates the standard deviation over the previous thirty -minute window. The fixed time window can span any suitable time period including, for example, five minutes, ten minutes, fifteen minutes, thirty minutes, one hour, two hours, etc. Oscillations can be detected when the standard deviation of the SpO2 error exceeds a predefined value or threshold. In the illustrated example, oscillations can be detected when the standard deviation of the SpO2 Error is greater than a predefined value (e.g., 1%) 609. For example, in some implementations, oscillations are detected when the standard deviation of the SpO Error is greater than 0.5%, 1%, 2%, ...5%, and the like.

[0132] In some implementations the severity of the detected oscillation can be determined based on a magnitude of the standard deviation of the SpC>2 error. For example, adjustments in physiological closed-loop gain, an escalation in a set of alarms or transmissions sent can be based on the severity of the detected oscillations and / or whether the severity increases or decreases over time.

[0133] FIG. 7 illustrates an alternative method for detecting an oscillation or oscillations based on the cumulative absolute SpC>2 error and an SpC>2 error crossing rate.Illustrated is the FIO2 signal 701, SpC>2 signal 703, the absolute value of the SpC>2 error 705, theZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO cumulative value of the SpCh error for a time window 707, and the zero crossing rate 709. For example, an oscillation can be detected when a cumulative value of the SpCh error for the time window exceeds a predetermined threshold of maximum SpC>2 error, and / or when a rate of SpCh error crossing exceeds a predetermined threshold of SpCh error crossing rate.

[0134] As discussed above, the SpCh Error signal can be calculated as the difference between the Target SpC>2 and the measured SpC>2. The SpC>2 Error signal can be filtered to remove bias and / or noise. For example, in FIG. 7, a 2ndorder Butterworth bandpass lowpass filter (lower cutoff = 0.001 Hz, upper cutoff = 0.01 Hz) is applied to the SpC>2 Error signal. A lower cutoff of the bandpass filter acts to remove the fixed bias. The rate of zero crossings (i.e., where the SpO2error signal crosses a zero-value) for the filtered SpC>2 error signal can be calculated 711. The cumulative absolute value of the SpC>2 error over time can also be calculated. The cumulative absolute value of the SpC>2 error can be expressed as the cumulative sum of the SpC>2 error normalized by the cumulative sum of the time.

[0135] If the cumulative absolute SpC>2 Error is greater than a predetermined value (e.g., 2% / h) and / or if the rate of SpC>2 Error Crossing rate is greater than a predetermined value (e.g., 0.01 1 / h), then oscillations are detected. In some implementations the predetermined value can be based on annotated clinical datasets. The predetermined value (or threshold) can be set by a user or a manufacturer of the device, and the like. In some implementations the predetermined value for the cumulative absolute SpC>2 Error can be between 0.1% / h to 10% / h and the like. In some implementations, the predetermined value for the rate of SpC>2 Error Crossing rate can be between 0.005 to 0.5 1 / h.

[0136] The severity of the detected oscillation can be determined based on a magnitude of the cumulative value of the SpC>2 error and / or rate of SpC>2 error crossing. For example, a higher magnitude of the cumulative value of the SpC>2 error and / or rate of SpC>2 error crossing can be correlated with a higher severity in the detected oscillation.

[0137] FIG. 8 illustrates an alternative method for detecting an oscillation based on an integral absolute error and the time between zero-crossings. Oscillations can be detected by determining an SpO2 error for a time window based on the determined oxygen saturation of the patient’s blood, and detecting one or more oscillations when a similarity factor between the determined SpO2 error for the time window is within a threshold of a historical SpO2 error, where the similarity factor comprises at least one of an integral absolute error (IAE) and time between zero-crossing (TBZC).Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0138] Illustrated is the FIO2 signal 801, SpO2signal 803, the absolute value of the SpO2error 805, the area under the curve (AUC) between pairs of zero crossings 807, and a similarity parameter h 809.

[0139] The SpO2error can be defined as a difference between the target SpO2value and a measured SpO2value. The SpO2error signal can be filtered to remove bias. For example, the SpO2signal 803 is filtered using a 2ndorder Butterworth bandpass lowpass filter (passband: 0.001 to 0.01 Hz). The lower cutoff of the bandpass filter acts to remove a bias in SpO2Error. The time between zero crossings (TBZC) of the filtered SpO2Error signal can be calculated separately for positive and negative errors. The method can also calculate the integrals (i.e., area under the curve (AUC)) between pairs of zero crossings (integral absolute error, IAE), separately for positive (light gray shading) 811 and negative errors (dark gray shading) 813.

[0140] A similarity parameter h can be calculated based on the above. The similarity parameter h can be defined as the proportion of paired zero-crossing in which IAE and TBZC are “similar” to the IAE and TBZC of the previous pair. If SpO2Error is near periodic, then IAE and TBZC will not vary much over time, h will be close to 1 and defined as oscillating. For example, in some implementations, oscillations can be indicated when the similarity parameter h is greater than 0.8. The severity of the detected oscillation is based on a magnitude of the integral absolute error (IAE).

[0141] FIG. 9 illustrates an alternative method for detecting an oscillation using fast Fourier transforms. Oscillations can be detected by determining an SpO2signal based on the determined oxygen saturation of the patient’s blood, generating a transformed SpO2signal by applying a fast Fourier transform (FFT) to the determined SpO2signal, and detecting one or more oscillations by identifying one or more peaks in the transformed SpO2signal within a predetermined frequency range. In some implementations, the predetermined frequency range spans a frequency between 0.00556 Hz and 0.0167 Hz which correspond to periods of 30 minute and 1 minute, respectively.

[0142] Single-sided amplitude spectrums for the FIO2and SpO2signals are illustrated in FIG. 9. The amplitude of FFT of SpO2and / or FIO2setting signals can be calculated over the previous predetermined period of time (e.g., 30, 60, 120 min). In FIG. 9 the FFT amplitudes are plot for SpO2and FIO2signals over duration that a PCLC algorithm is active (60 min). If a large peak or peaks are observed within a frequency range of interest (e.g., 0.00556 - 0.0167 Hz, which corresponds to oscillations with periods of 30 min and 1 min, respectively), thenZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO oscillations are detected. A peak is observed at 0.00167 Hz (i.e., 10 min period) for the patient simulated in FIG. 9.

[0143] The severity of the detected oscillation can be based on the peak-to-peak amplitude of the determined oxygen saturation of the patient’s blood. For example, a larger peak-to-peak amplitude can be indicative that the detected oscillation has a higher severity.Alternatively, or additionally, the severity of the detected oscillation is proportional to at least one of an amplitude or a power of a largest peak identified within the predetermined frequency range.

[0144] In some implementations, one or more FIO2 parameter adjustment criteria of the gas delivery apparatus can be modified responsive to detecting the one or more oscillations. Various methods for modifying the FIO2 parameter adjustment criteria are illustrated in FIGS.10-12. In some implementations, the modified response can be based on a severity of the oscillations detected by the methods described above.

[0145] In some implementations, modifying one or more FIO2 parameter adjustment criteria includes at least one of a default FIO2 change rate, a reduction in a FIO2 change rate, a reduction in a maximum FIO2 change rate, a time value for a modified FIO2 setting, and / or a temporal pause. A default FIO2 change rate may refer to the rate at which the default value of the FIO2 parameter is changed. A reduction in a FIO2 change rate may refer to reducing how fast the FIO2 value is adjusted. A reduction in a maximum FIO2 change rate may refer to reducing the value at which the FIO2 setting is set. A time value for a modified FIO2 setting may refer to how long the FIO2 setting is applied for. A temporal pause may refer to a time period for which there are no changes made to the FIO2 setting which corresponds to a pause in the change in FIO2 parameter settings. For example, the FIO2 parameter adjustment criteria can be paused for a time period at a current FIO2 setting. In another example, the FIO2 parameter adjustment criteria can be paused at an average FIO2 setting for a predetermined number of full oscillation cycles.

[0146] In some implementations, modifying the FIO2 parameter adjustment criteria includes an adjustment to timing, FIO2 parameters, and in some implementations, gain. In some implementations, modifying the FIO2 parameter adjustment criteria includes an adjustment to a proportional gain, an adjustment to a derivative gain, an adjustment to both a proportional gain and a derivative gain, and / or an adjustment to an overall gain.

[0147] In some implementations, modifying the FIO2 parameter adjustment criteria may be based on the severity of the detected one or more oscillations. For example, the severityZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO can be determined based on a rate of full range crossings per hour, a peak-to-peak amplitude of the oscillations, a magnitude of an SpCh error. The severity can be expressed as a numerical value between 0 to 1.

[0148] FIG. 10 illustrates results from a patient simulation where FIO2 parameter adjustments are modified due to a detected oscillation. Illustrated is the FIO2 signal 1001, SpC>2 signal 1003 and the proportional gain 1005. In the illustrated embodiment, when oscillations in the FIO2 signal and / or the SpC>2 signal are detected, the proportional gain Kp is adjusted. As illustrated, the proportional gain Kp is adjusted to a value of 1, which may indicate a return to a default “slow” FIO2 change rate. This decrease in the proportional gain Kp resolves the oscillations in the SpC>2 and FIO2 signals. Because the proportional gain Kp is changed less quickly at the default “slow” FIO2 change rate, rapid changes are not observed and oscillations in the SpO2and FIO2 signals are avoided.

[0149] FIG. 11 illustrates an intervention to resolve oscillations using FIO2 time. For example, the FIO2 parameter adjustment can be set to an average FIO2 level. In some implementations, the FIO2 controller can be completely paused, keeping FIO2 level steady either for the remainder of treatment or for some predetermined period of time. The value that the FIO2 controller setting 1101 is paused on may be the current FIO2 level 1103 or based on an average FIO2 level 1105 of a predetermined number of full oscillations cycles.

[0150] In some implementations, the described systems for detecting an oscillation and modifying FIO2 parameter adjustment criteria can be integrated with a ventilation system that includes patient response time. In an implementation of a PCLC system with Response Time, the speed of the PCLC algorithm can be determined based on an estimate of the patient’s SpO2Response Time. Accordingly, a PCLC system with Response time can be prone to oscillations if the method underestimates the patient’s SpC>2 Response Time and / or the patient’s SpO2Response Time changes over time, which results in the controller adjusting FIO2 too quickly, therefore leading to the possibility of oscillations in FIO2 and SpC>2. The disclosed methods and systems detect such oscillations and modify FIO2 parameter adjustment criteria to mitigate such oscillations due to integration of patient Response Time.

[0151] Accordingly, in some implementations, when an oscillation or oscillations are detected, one or more FIO2 parameter adjustment criteria can be modified to disable a patient response time-based adjustment in an FIO2 change rate. In some implementations the one or more FIO2 parameter adjustment criteria can be modified to change at least one of a response time coefficient or a SpC>2 response time in a patient response time-based adjustment criteria.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0152] FIGS 12A-12C illustrate various interventions or modifications that can be applied upon detecting an oscillation.

[0153] FIG. 12A illustrates a modification to a patient response time coefficient that indicates a return to a default “slow” FIO2 change rate, where there is no adjustment for patient response time (PRT). In some implementations the modification may include temporarily remaining at the “slow” FIO2 change rate for a pre-determined amount of time (e.g., 10 min, 20 min, 30 min, etc.) and then returning to a patient- response-time adjusted FIO2 change rate.

[0154] FIG. 12B illustrates a modification to a patient response time coefficient, where the patient response time-adjusted FIO2 change rate is decreased, but not all the way back to default. By reducing patient response time coefficient by some percentage, oscillations can be mitigated. The amount that the patient response time-adjusted FIO2 change rate is decreased can be correlated with the severity of the oscillations. The severity of the oscillations can be based on a measured magnitude of the detected oscillations. For example, oscillation severity could be defined on a scale from 0 (low severity) to 1 (high severity). For low severity (i.e., severity = 0), Ki,max might remain unchanged while for high severity (i.e., severity = 1), Ki,max might decrease all the way to Ki ,min.

[0155] FIG. 12C illustrates a parameter modification where the maximum FIO2 change rate is decreased, by decreasing KI, max for proportional gain. This decreases the patient response-time coefficient for a given SpC>2 response time.

[0156] FIG. 13 provides a flow-chart for a method of adjusting parameter settings for a physiological closed loop control ventilation system that includes patient response time when oscillations are detected in a FIO2 signal and / or SpC>2 signal in order to mitigate the detected oscillations. FIG. 13 illustrates the change in the proportional gain (Kp) over time. Prior to the patient response time being estimated 1301, the proportional gain (Kp) is set to a default value of 1. After the patient response time is estimated 1301 and a relationship between the patient response time and the proportional gain is determined 1303, the proportional gain Kp can be set to a new value (e.g., 8). When oscillations are detected 1305, an intervention such as an adjustment to the proportional gain can be taken 1307 and the proportional gain Kp can be set back to the default value (e.g., 1). Various embodiments are described in which Kp may be set back to a default value (e.g., 1). However, as described, in some embodiments, Kp may be set to some value lower than a current value but greater than the default value. In some implementations, when oscillations are detected 1305, an alarm (e.g., visual, auditory) can be presented to a user indicating that oscillations were detected.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0157] In some implementations, the mechanical ventilator apparatus can be configured to detect oscillations in either the SpCh and / or FIO2 signal based on the techniques described above. In some embodiments, the oscillations can be caused by an FIO2 change rate. For example, when the FIO2 change rate crosses a threshold, it may trigger oscillations.

[0158] In some implementations, when oscillations are detected in an FIO2 parameter and / or a SpC>2 parameter the other of the SpC>2 signal and the FIO2 signal can be checked to confirm the presence of oscillations. If oscillations are present in both the SpC>2 signal and the FIO2 signal, the oscillations are likely being caused by FIO2 change rate being too high.Alternatively, if oscillations are detected on one of the SpC>2 signal and the FIO2 signal but not the other, it could be an indication that the oscillations are not being caused by too rapid an FIO2 change rate. For example, an oscillating FIO2 signal without a corresponding oscillation in the SpO2signal could be, in rare cases, indicative of a problem with the operation of the FIO2 PCLC algorithm or the ventilator itself. An oscillating SpC>2 signal without a corresponding oscillation in the FIO2 signal could be, in rare cases, indicative of some associated cyclic patient physio condition or parameter.

[0159] In some implementations, methods for detecting oscillations can be applied to the FIO2 signal instead of the SpC>2 signal. The FIO2 signal has a wider range of values and is generally less subject to confounding perturbation and can detect oscillations.

[0160] FIGS. 14-20 illustrate examples for a mechanical ventilator apparatus that detects one or more oscillations in at least one of the carbon dioxide concentration of the patient’s exhalation (EtCCh) and / or the minute volume (VM) parameter of the gas delivery apparatus by applying an oscillation detection algorithm and modifies one or more VM adjustment criteria of the gas delivery apparatus responsive to detecting oscillations.

[0161] The mechanical ventilator apparatus can include a gas delivery apparatus configured to deliver a gas to a patient and include a patient interface, a capnography sensor configured to provide at least one signal representative of an amount of carbon dioxide in a patient’s exhaled air, and a controller, comprising a processor and a memory, in communication with the gas delivery apparatus and the capnography sensor. The capnography sensor can be configured to provide a signal representative of a partial pressure of expired gas from the patient. In the illustrated example, the controller includes a proportional-derivative minute ventilation controller configured to modulate VM to reach a target end-tidal carbon dioxide (EtCCh). The controller is configured to control one or more ventilation parameters using closed loop control.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0162] FIG. 14 is a method 1400 for detecting oscillations in one of the EtCCh and / or VM parameters and modifying a VM adjustment criteria of the gas delivery apparatus accordingly.

[0163] A controller can be further configured to perform the steps illustrated in the method 1400. The method 1400 can include the steps of: receiving at least one signal representative of the carbon dioxide in the patient’s exhaled air provided by the capnography sensor 1401, determining a carbon dioxide concentration (EtCCh) of the patient’s exhalation based on the received at least one signal 1402, causing adjustment of a minute volume (VM) parameter of the gas delivery apparatus based at least in part on the determined carbon dioxide concentration in accordance with one or more VM adjustment criteria 1403, detecting one or more oscillations in at least one of the carbon dioxide concentration of the patient’s exhalation and / or the VM parameter of the gas delivery apparatus by applying at least one oscillation detection algorithm to at least one of the determined carbon dioxide concentration of the patient’s exhalation and / or the VM parameter 1404; and modifying the one or more VM adjustment criteria of the gas delivery apparatus responsive to detecting the one or more oscillations 1405.

[0164] One or more oscillations may be detected in the carbon dioxide concentration of the patient’s exhalation (EtCO?), in the detected VM parameter, or both. In some implementations, the controller can modify one or more VM adjustment criteria that is used by the controller to modulate VM in order to reach a target end-tidal carbon dioxide (EtCCh).Modifications may be made when oscillations are detected. The VM adjustment criteria can include a proportional term and a derivative term. In some implementations, the proportional term includes an end-tidal carbon dioxide (EtCCh) error based at least on a difference between a target end-tidal carbon dioxide (EtCCh) and a measured end-tidal carbon dioxide (EtCCh). In some implementations the derivative term includes a difference between a measured end-tidal carbon dioxide (EtCCh) for a first time window and a measured end-tidal carbon dioxide (EtCCh) for a previous time window.

[0165] In some implementations, concepts described above for detecting and resolving oscillations in SpCh and FIO2 for an FIO2 controller can be analogously applied to EtCCh and minute volume (VM) for a minute ventilation controller and vice-versa.

[0166] In some implementations, the controller may include a proportional -derivative (PD) minute ventilation controller. In particular, the controller may modulate VM to reach a target end-tidal carbon dioxide (EtCCh) using a proportional-derivative (PD) controller. The proportional term is calculated based on the difference between the target EtCCh (EtC O2target, default = 35 mmHg) and 1 -minute average of EtCCh (EtCO2Error = EtCO2 target— EtCO^.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO The derivative term is calculated based on change in the average EtCCh from 119 to 60s prior and the average EtCCh over the immediate previous 60 seconds (Derivative EtCO2Error = then calculated as:Derivaive EtCO2Error * Kd VM).

[0168] The Proportional Gain term is a product of two coefficient (KPI,VM and kP2,vM). One term (KP2,VM) is the default coefficient (-0.005 ml / min / mmHg / sec). The other term (KP2,VM) is a scalar of the default term to increase or decrease the speed VM is changed. If KPI,VM = 1, VM will be adjusted at the default speed. KPI,VM could be increased to allow for faster changes in VM or decreased if oscillations in EtCO2 or VM or detected. The default Derivative Gain coefficient is 0.005 ml / min / mmHg / sec.

[0169] The proposed updated VM is calculated as New VM= VM+ VMCorrection. The controller then checks to ensure the New VM is within preset V VM boundaries (Min VM,Pred, default = 100% VM,Pred, and Max VM,Pred, default = 250% VM,Pred). If the new VM is within the VM boundaries, the VM setting is updated. If the new VM is outside the limits, a low priority alarm triggers and the VM is set to the appropriate limit.

[0170] The algorithm may then determine whether to change rate (RR), target tidal volume (VT), or both RR and VT to achieve the new VM. For example, if the change in VM is positive (i.e., increasing), the new VT can be calculated as new VM / RR. If the new calculated VT is less than the maximum allowable VT (Vr,max, default = 8 ml / kg), then the new target VT is set and RR remains the same. If the new VT > Vr,max, then RR is instead increased to new RR = ceiling(new VM / Vr,max) and VT is adjusted to obtain the correct VM (i.e., new VT = new VM / new RR).

[0171] If the change in VM is negative (i.e., decreasing), the system first calculates the new VT as new VM / RR. If the new calculated VT is greater than the minimum allowable VT (Vr,min, default = 4 ml / kg), then the new target VT is set and RR remains the same. If the new VT < r min, then RR is instead decreased to new RR = floor(new VM / r min) and VT is adjusted to obtain the correct VM (i.e., new VT = new VM new RR).

[0172] The speed at which the minute ventilation controller modulates VM can be adjusted if an oscillation is detected. If the speed at which the minute ventilation controller modulates the minute volume is too slow there is a risk of the patient spending an unnecessarilyZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO long time outside of target EtCCh range and therefore experiencing hypocapnia or hypercapnia. If the speed at which the minute ventilation controller modulates the minute volume is too quick there is a risk of developing oscillations in minute volume and / or EtCCh. Accordingly, modifications to the speed at which the minute ventilation controller modulates VM requires precision.

[0173] FIG. 15-17 show the outputs of a cardiopulmonary computational model to demonstrate the effect of different controller speeds. In the illustrations, during the first ten minutes of the simulation PCLC is turned off while the model reaches a steady-state condition.

[0174] In FIG. 15, the SpCh, EtCCh, pressure, tidal volume (VT), VM, and breath rate over time is shown. The simulation time course demonstrates a minute ventilation controller with default proportional gains (KPI,VM = 1) resulting in no oscillations in VM and EtCCh. When PCLC is turned on at Time = 10 minutes proportional gain terms for the minute ventilation controller are set to their default values. When PCLC is turned on at Time = 10 minutes, VM increases relatively slowly over the next 20-30 minutes to drive the EtCCh value towards the Target EtCCh value of 35 mmHg. The algorithm achieves this increased VM through changes in both tidal volume (VT) and breath rate. VT corresponds to tidal volume, VM corresponds to minute volume, PEEP corresponds to positive end-expiratory pressure, PIP corresponds to peak inspiratory pressure, and Pplat corresponds to plateau pressure.

[0175] FIG. 16 illustrates the impact of high proportional gain. In FIG. 16, the SpCh, EtCCh, pressure, tidal volume (VT), VM, and breath rate over time is shown. In the simulation, the proportional gain terms for the minute ventilation controller are set to value ten times the default (KPI,VM= 10). When PCLC is turned on at Time = 10 minutes, VM increases quickly, eventually driving EtCCh below the Target EtCCh and resulting in oscillations in both EtCCh and VM. The amplitude of the oscillations decrease over the course of the simulation.

[0176] FIG. 17 illustrates the activity of the EtCCh and VM over time when comparing a system with the default gain coefficient and high gain coefficients. As shown the high gain coefficient system 1701 can result in oscillations in the EtCCh and the VM. By contrast, when the default gain coefficient is applied 1703, no oscillations are visible in the activity of the EtCCh and VM over time.

[0177] FIG. 18 is a flowchart for an oscillation detection method. Similar methods for detecting oscillations in the SpCh and / or FICh can be used to detect oscillations in the EtCCh and / or VM. FIG. 18 illustrates a process for detecting oscillations in an EtCCh signal using fullZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO range crossings that can be performed by a controller. The controller can obtain an ongoing EtCCh signal that is related to a waveform 1801. Optionally, the controller can generate a moving average waveform (e.g., 60 seconds) to reduce the impact of signal noise 1803. The resulting signal can be monitored for EtCO? full range crossings 1805. In some embodiments, the controller may receive a target EtCO? range for use in oscillation detection and a threshold number of full range crossings over a specified period of time . In some implementations the target EtCCh range and the threshold number of full range crossings can be predefined based on clinical data, experimental data, user input, and the like. In some embodiments, the target EtCCh range and the threshold number of full range crossings can be predefined. Monitoring of the EtCCh signal can be performed continuously until the number of EtCCh full range crossings per hour is reached or the EtCCh oscillations threshold is surpassed, in which case EtCCh oscillations are detected 1813.

[0178] FIGS. 19 and 20 illustrate various methods for detecting oscillations in the EtCCh and / or VM signal.

[0179] FIG. 19 illustrates detection of oscillations in an EtCCh signal based on a frequency of full range crossings. Shown are an EtCCh signal 1901 and a corresponding minute volume (VM) signal 1905. The method quantifies the frequency of EtCCh crossings into and out of the target EtCCh range. High frequency noise can be removed from an EtCCh signal obtained by the controller by using a moving average, lowpass filter and the like. In the illustrated example, a moving average of 60 s is applied. A target range of EtCCh can be defined via user input, or predefined values by a device manufacturer or the like. The target range can specify a preferred range within which it is beneficial to maintain the EtCCh. In the illustrated example the target range is based on a Target EtCCh (35 mmHg) ± 2.5 mmHg (i.e., 32.5-37.5 mmHg) 1903. The oscillation detection method can be configured to identify the times that the EtCCh signal (or filtered EtCCh signal) crosses from “in range” to “out of range” when compared to the target range. The identified times can be considered range crossings 1905.

[0180] The range crossings 1905 can be classified into four different types based on their directionality. For example, the range crossings 1905 can be classified as: (a) Into range from above (e.g., 38 -> 37 mmHg), (b) Into range from below (e.g., 32 -> 33 mmHg), (c) Out of upper end of range (e.g., 37 -> 38 mmHg), and (d) Out of lower end of range (e.g., 33 -> 32 mmHg). Some examples, may use one or more of these types in the determination of oscillations. A patient with an EtCO? that crossing into and out of the full range in a full-range crossing (e.g., from above 37.5 to below 32.5 mmHg or below 32.5 to above 37.5 mmHg) might be particularlyZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO likely to be experiencing EtCCh oscillations 1907. Patients experiencing full-range crossings 1907 are more likely to be experiencing oscillations than a patient that is simply oscillating into and out of one end of the range (e.g., between 37 and 38 mmHg). The rate of range crossings can then be quantified over a set time (e.g., per hour, per thirty -minutes, per two hours, etc.). In the illustrated example, the rate of all range crossings is 10.8 per hour, and the rate of full-range crossings is 4.8 per hour. If the rate is above a predetermined threshold of full range crossings, the system may determine oscillations are present (e.g., Rate of Full Range Crossing > 3 per hour). The predetermined threshold can be input by a user, be set by a device manufacturer or be based on prior historical information regarding range crossings.

[0181] In the illustrated method for detecting oscillations, the controller determines an end-tidal carbon dioxide (EtCCh) signal based on at least one signal representative of the carbon dioxide in the patient’s exhaled air provided by the capnography sensor and received by the controller, determines a count for EtCCh crossings for a predefined target range for a time window, and detects one or more oscillations in the carbon dioxide concentration of the patient’s exhalation when the determined count for EtCCh crossings exceeds a predetermined threshold.

[0182] FIG. 20 provides an alternative approach to detecting oscillations in a patient’s EtCCh signal based on the standard deviation of EtCCh error. Shown are an EtCCh signal 2001 and a corresponding minute volume (VM) signal 2003. This method may detect oscillations by quantifying the variation of the patient’s EtCCh from the Target EtCCh. The method for detecting oscillations can calculate the ETCCh error based on a difference between a Target ETCCh and the measured ETCCh (i.e., ETCCh Error = Target EtCCh - Measured EtCCh). The resulting ETCCh error can be filtered to remove artifacts and / or bias. In the illustrated example, a 2ndorder Butterworth bandpass lowpass filter (lower cutoff = 0.001 Hz, upper cutoff = 0.01 Hz) was applied. A moving standard deviation over a fixed time window can be calculated for the ETCCh error. For example, FIG. 20 illustrates a calculated standard deviation over the previous 30 minutes 2007 for the calculated ETCCh error 2005. Oscillations can be detected when the standard deviation of the EtCO? Error is greater than a predefined threshold value. A threshold value 2009 of 3 mmHg is illustrated in FIG. 20. The predefined threshold value can be set by a user and / or device manufacturer.

[0183] In the example illustrated in FIG. 20, the oscillation detection algorithm may be run on a controller that is configured to determine an end-tidal carbon dioxide (EtCO?) error for a time window based on at least one signal representative of the carbon dioxide in the patient’s exhaled air provided by the capnography sensor and received at the controller, andZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO detect one or more oscillations in the carbon dioxide concentration of the patient’s exhalation when a standard deviation for the determined EtCCh error exceeds a predetermined threshold of maximum EtCCh error standard deviation.

[0184] If oscillations are detected in VM and / or EtCCh, the system will respond to attempt to resolve these oscillations. Like the FIO2 controller, there are multiple possible responses when oscillations are detected. For example, in some implementations, the EtCCh controller may adjust the minute volume adjustment criteria to slow the minute volume change rate (e.g., set KPI,VM to 1 or to some value less than a current value but greater than 1). In another implementation, the EtCCh controller may adjust the minute volume adjustment criteria to pause for a predetermined amount of time or for the remainder of the treatment. During the pause, the EtCCh controller may adjust the minute volume adjustment criteria at the current VM level, or at an average VM level determined from a predetermined number of full oscillations cycles.

[0185] In some implementations, the VM adjustment criteria includes a corrected minute volume (corrected VM) that is expressed as a weighted sum of the proportional term and the derivative term. The VM adjustment criteria includes one or more parameters configured to achieve the corrected minute volume (corrected V VM). Example parameters include a respiratory rate (RR), a target tidal volume (VT), and the like.

[0186] In some implementations, the controller can be configured to continuously modify the one or more VM adjustment criteria. Alternatively, the controller periodically modifies the one or more VM adjustment criteria. Modifications of the one or more VM adjustment criteria further includes adjusting a weight for the proportional term in the weighted sum, maintaining the minute volume for a predetermined period of time, and / or maintaining the minute volume at an average minute volume for a predetermined number of cycles.

[0187] FIGS. 21-24 are directed towards a method for improved specificity in determining a desaturation event. A desaturation event refers to when a patient experiences a blood oxygen saturation level below a certain level. A desaturation event may be attributed to problems in the ventilation treatment.

[0188] Mechanical ventilation systems may be prone to falsely determining that a desaturation event has taken place due to noise in the SpC>2 signal and / or poor SpC>2 signal quality. To address these problems, in some implementations, information regarding the signal used to determine whether a desaturation event has occurred and / or the signal strength can be incorporated into detecting desaturation events with more accuracy and specificity. AdditionalZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO methods for responding to desaturation events in a manner that does not trigger oscillations in the SpO2and / or FIO2 signal are discussed.

[0189] In some implementations, a physiological closed loop control system for mechanical ventilation can be configured to include a fallback mode when the patient’s SpO2remains below a desaturation threshold for a desaturation time threshold. For example, a desaturation event may be detected when a desaturation of less than 88% (i.e., the desaturation threshold) is maintained for at least ten seconds (i.e., the desaturation time threshold).

[0190] In response to a desaturation event or potential desaturation event, in some implementations a controller may execute an algorithm to automatically increases the FIO2to 100% to quickly increase the patient’s SpO2and the PD controller pauses until the SpO2rises above the desaturation threshold. If a patient experiences two desaturation events within a 60-minute period, the controller may automatically modify the target SpO2to increase by 1%.However, such implementations may result in false positive detections. False positive detections may be due to noise in the SpO2signal and / or poor SpO2signal quality.

[0191] FIG. 21 illustrates data from a physiological closed loop controller that defines a desaturation as SpO2continuously less than or equal to the desaturation threshold for at least 10 seconds. In the illustrated example, SpO2values 2101, FIO2values 2103, and change in FIO2values 2105 for a single patient over a timespan of approximately 14 hours is shown. In the illustrated example, the patient appears to have experienced eight desaturation events, where the FIO2was automatically increased to 100% each time. After each of these desaturations, the patient’s SpO2increased to near 100% and the controller weaned the patient back down to an FIO2of < 40% over a future time period. This, including the fact that eight desaturation events occurred during the time period, suggests that these desaturations might have been false positives due to inaccurate pulse oximetry readings. Because sub-optimal patient outcomes are correlated with increases in the length of time a patient is on a ventilator, it is beneficial to remove a patient from mechanical ventilation as soon as possible. In the illustrated example, the eight desaturation events are followed by a change in FIO2was automatically increased to 100% each time, which may require a greater amount of time to be reduced to a more appropriate FIO2level for the patient which can lead to weaning the patient from the mechanical ventilator. Accordingly, in some implementations the disclosed systems provide a way to detect a suspected false desaturation event and do not inappropriately raise the FIO2value to 100% right away, because it may not be truly needed by the patient.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0192] FIG. 22 illustrates data for the patient of FIG. 21 at a shorter time frame to show more details of a single desaturation event. In the illustrated example, SpCh values 2201, FIO2 values 2203, and change in FIO2 values 2205 for the patient of FIG. 21 are illustrated. As shown, the SpC>2 drops from approximately 99% down to less than 88% within approximately 1 minute, which is physiologically unlikely, and thus indicative of a potentially false positive reading.

[0193] Physiological closed loop controller systems for mechanical ventilation can have improved performance in detecting and mitigating desaturation events by improving the specificity and / or by improving the way the controller responds when a desaturation event or potential desaturation event is detected. Examples of these improvements are described below.

[0194] In some implementations, desaturation events or potential desaturation events can be detected with greater specificity by incorporating the use of an indicator of the confidence level of SpO2measurements and / or signal strength in modifying a desaturation threshold and / or desaturation time threshold. For example, if there is low confidence in the SpO2, measurements and / or signal strength the desaturation threshold can be decreased (e.g., from 88% to 86%). Alternatively, or additionally, if there is a low confidence in the SpO2, measurements and / or signal strength the desaturation time threshold can be increased (e.g., from 10 s to 30 s).

[0195] The desaturation threshold can be any suitable value. For example, in some embodiments, the desaturation threshold can be adjustable by the user between 88% and 92%, in increments of 1%.

[0196] The desaturation time threshold can be any suitable value. For example, in some embodiments, the desaturation time threshold can be 10 seconds, 20 seconds, 30 seconds,..., 60 seconds, and the like. In some implementations, the desaturation time threshold can be set by a user.

[0197] In some implementations a signal identification and quality indicator can be incorporated into determining the desaturation threshold and / or desaturation time threshold. The signal identification and quality indicator can express an indication of the confidence level of the SpO2measurements being output by a pulse oximeter being used with a mechanical ventilation system. The signal identification and quality indicator may reflect patient behavior and / or environmental factors. For example, the signal identification and quality indicator may include a low value that indicates that there is higher probability that the SpC>2 reading are erroneous for patients exhibiting excessively high motion, patients with low perfusion, environmentalZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO interference, or improper sensor placement. The pulse oximeter may output the signal identification and quality indicator as a numerical value. The signal identification and quality indicator may also help indicate if the pulse oximeter sensor is properly positioned.

[0198] Similarly, in some implementations a signal strength indicator may be output by the pulse oximeter.

[0199] The signal identification and quality indicator and the signal strength indicator can be referred to as signals representative of signal fidelity.

[0200] In some implementations, an improved system may include a desaturation detection algorithm that incorporates the signal identification and quality value obtained from the pulse oximeter. For example, for a low value signal identification and quality reading, the desaturation time threshold or the minimum time required to detect a desaturation event can be increased. For example, if Signal IQ is in the “low” range and / or Signal Strength is less than a value (e.g., <2, on a scale from 0 to 20), the minimum time SpCh was required to be below 88% could be increased (e.g., 20 s instead of 10 s).

[0201] In some implementations an improved system may include a desaturation detection algorithm that adjusts the desaturation threshold and / or desaturation time threshold dynamically based on SpC>2 history, and / or SpCh variation.

[0202] For example, SpCh history such as the oxygenation levels over a past period of time (e.g., average, median, or maximum SpCh over the previous 60 seconds) can be used to modify the desaturation time threshold. For example, if the maximum SpCh over the previous 60 seconds was 98%, the controller might increase the desaturation duration from 10 s to 60 s, because if the SpCh was recently high, it is less likely that a Desaturation event would occur soon after.

[0203] In another example, measures of SpC>2 variation (e.g., moving standard deviation of SpC>2 after last 60 s) can be used to modify the desaturation time threshold. A higher SpO2variation might indicate less confidence in the measurement and therefore greater sensitivity can be achieved by increasing the minimum desaturation time threshold.

[0204] In some implementations an improved system may include a desaturation detection algorithm that adjusts the desaturation threshold and / or desaturation time threshold dynamically based on SpC>2 history, and / or SpC>2 variation, in connection with a signal strength indicator and / or a signal identification and quality indicator from a pulse oximeter.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0205] In some implementations, responses to a detected desaturation event can be improved by adjusting one more FIO2 adjustment criteria for the gas delivery apparatus of the mechanical ventilator. For example, while in some mechanical ventilation systems the controller may be configured to respond to a desaturation event by immediately increasing the FIO2 to 100% with the goal of minimizing risk of patient hypoxia. However, this increases the risk of hyperoxia and potentially wastes O2. Accordingly, in some implementations, a controller of a mechanical ventilator system can be configured to adjust one or more FIO2 adjustment criteria in a measured way. In some implementations, the adjustment to the FIO2 adjustment criteria can be based on identifying desaturation events using signals representative of signal fidelity. FIO2 adjustment criteria may include one or more values for various FIO2 parameters along with a timeline of when the parameters are determined.

[0206] FIG. 23 illustrates a method for identifying potential false desaturation events and adjusting FIO2 criteria accordingly. In the illustrated example, a mechanical ventilator apparatus can include a gas delivery apparatus configured to deliver a gas to a patient and include a patient interface, an oximetry sensor configured to provide at least one signal representative of an oxygen saturation of the patient’s blood, and a controller, having a processor and a memory, in communication with the gas delivery apparatus and the oximetry sensor. The controller can be configured to control one or more ventilation parameters using closed loop control. The controller can be configured to receive at least one signal representative of the oxygen saturation of the patient’s blood provided by the oximetry sensor 2301, determine an oxygen saturation of the patient’s blood based on the received at least one signal 2303, receive at least one signal representative of a signal fidelity from the oximetry sensor 2305, identify a potential false desaturation event as an event that may or may not be a desaturation event based on one or more potential false desaturation event criteria 2307, and adjust one or more fraction of inspired oxygen (FIO2) adjustment criteria for the gas delivery apparatus responsive to detecting the potential false desaturation event 2309.

[0207] In some implementations false desaturation evens may be determined based on at least one signal representative of the oxygen saturation of the patient’s blood. For example, the false desaturation may be determined based on a measurement of the SpO2 variation, or a standard deviation in the SpO2 signal. For example, a high variation in the standard deviation of the SpO2 signal may serve as a surrogate for confidence in the signal as a higher variation in the standard deviation may indicate less confidence in the signal. In some implementations, the false desaturation may be determined based on the history of SpO2 values. For example, if the SpO2 was recently high (e.g., >=98%), then it may be less likely to be a true desaturation event.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO However, if the SpO2 was in a low range prior to the detected desaturation event, the detected desaturation event may be more likely to be a true desaturation event.

[0208] As discussed above, in some implementations the one or more false desaturation event identification criteria can include at least one signal fidelity criterion, such as a signal strength level, and / or a signal confidence level. An event may be identified as a desaturation event when the determined oxygen saturation of the patient’s blood is below a predefined threshold for a predefined period of time. For example, the predefined threshold may be 88% and the predefined period of time is 10 seconds. As discussed above, the predefined threshold and / or the predefined period of time can be based on the signal fidelity. For example, the predefined period of time can be increased when the signal fidelity decreases. The predefined threshold and the predefined period of time can be based on historical data of oxygen saturation in the patient’s blood.

[0209] Adjusting one or more fraction of inspired oxygen (FIO2) adjustment criteria for the gas delivery apparatus responsive to detecting the potential false desaturation event can include implementing a stepwise increase in FIO2 to a value greater than the current FIO2 but less than 100% followed by a temporary adjustment to the proportional gain coefficient.

[0210] In some implementations, adjustment of the one or more FIO2 adjustment criteria comprises a stepwise increase in a target FIO2 value. For example, the controller may initiate a step increase in the FIO2 to a value greater than the current FIO2 but less than 100% in order to provide more oxygenation to the patient, while reducing the risk of hyperoxia and wasted O2. For example, if the FIO2 when the desaturation event is detected is 40%, the algorithm might increase the FIO2 by 20% to 60% (or, for example, half of the distance between the current FIO2 and 100% (i.e., FIO2 = 70%). The controller could then monitor SpC>2 at that increased FIO2 for a period of time (e.g., 60 s). If the SpC>2 is still not above the desaturation threshold after that period of time, the controller could do another step increase in the FIO2 (e.g., from 60% to 80%) and continue to monitor the SpC>2. These step increases could continue until the desaturation event is resolved or the FIO2 setting is at 100%. The proportional derivative controller would continue to be active during these step changes and monitoring periods.

[0211] In some implementations, adjustment of the one or more FIO2 adjustment criteria includes an increase in a target FIO2 value followed by an increase in a proportional gain coefficient for a predetermined time. For example, following the increase in FIO2 (either to 100% or lower value as described above) in response to a desaturation event, the proportional gain coefficient(s) could be temporarily increased (e.g., increase the gains by a factor 2) in order toZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO attempt to wean the patient more quickly. In this method, the controller may still respond quickly to potential desaturation events while also minimizing the time spent with an unnecessarily high FIO2 setting in the case of a false positive.

[0212] In some implementations, adjustment of the one or more FIO2 adjustment criteria comprises setting a target FIO2 value to 100% followed by an incremental decrease of the target FIO2 value when an oxygen saturation value meets a predetermined threshold. For example, the controller may initially increase the FIO2 to 100% and then gradually reduce the FIO2 setting over time in steps. Each step or FIO2 value can be maintained for a predetermined amount of time and / or so long as the SpC>2 remains above a threshold (e.g., 97%) for a set amount of time.

[0213] Modifications to the FIO2 adjustment criteria responsive to detection of a desaturation event is illustrated is illustrated in FIG. 24. Shown is a FIO2 signal 2401 and a SpC>2 signal 2403 for a patient. In the illustrated example, after a desaturation event is detected the FIO2 setting is increased to 75.5% which is halfway between the current FIO2 (51.0%) and 100%, and then gradually reduced over time.

[0214] In some implementations, a user can provide manual adjustment of gain. For example, in some implementations there may be one or more physical controls on the ventilator or virtual controls on a display or GUI in communication with the ventilator that allows a user to adjust FIO2 gain (such as proportional gain, derivative gain or both). The manual input provided by the user could override, or be addition to, algorithmic gain control, such as that disclosed above. In various embodiments, the controls may be included on a ventilator and / or one or more communicatively connected devices, such as a computing device, portable computing device (e.g., tablet), remote computing system or platform, or another medical or monitoring device (e.g., defibrillator, AED, patient monitoring or monitoring device, headworn device, wristworn device).

[0215] A mechanical ventilator such as those described herein can include a gas delivery apparatus, having a user interface, configured to deliver a gas to a patient, and a controller having a processor and a memory that is in communication with the gas delivery apparatus.

[0216] As illustrated in FIG. 25 in some implementations a controller for a mechanical ventilator apparatus may be configured to control one or more ventilation parameters using closed loop control 2501, receive user input via one or more controls of the user interfaceZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO indicating a gain adjustment relating to the closed loop control of the one or more ventilation parameters 2503, and implement the gain adjustment based on the received user input 2505.

[0217] For example, in some implementations the gain adjustment can include an adjustment to at least one of an overall gain, a proportional gain, and a derivative gain. The gain adjustment can be applied to the FIO2 and / or the VM.

[0218] In some implementations, the user may provide a gain adjustment that includes a rate of adjustment for the gain setting, and indicates whether the gain should be adjusted aggressively, moderately, or conservatively.

[0219] Examples of user-controlled gain settings and their resulting proportional gain coefficient, and estimated SpC>2 response time are illustrated in FIG. 26. For example, a user may indicate that the gain should be adjusted aggressively 2601, moderately 2603, or conservatively 2605. Aggressive gain could lead to fastest FIO2 change rates.

[0220] In some implementations, the gain implemented by the controller may be modified based on the received gain adjustment, or alternatively, the gain implemented by the controller can be superseded by the received gain adjustment.

[0221] A user interface can display the FIO2 values, SpC>2 values, EtCCh values, and / or VM values for the user. The user interface can also be configured to be interactive graphical user interface and receive an input from the user. Examples of input include the gain adjustment. In some embodiments, a user interface can include knobs and / or selection buttons that allow for input of a gain adjustment.

[0222] In some implementations, detection of oscillations could result in reduction in gain which can be modified via user selection. Additionally and / or alternatively, a user can use manual control of gain settings to reduce or eliminate oscillations that are detected using the methods described herein. In some implementations, the visibly detected oscillations can be displayed to a user.

[0223] A user may modify gain adjustment of FiO2, gain adjustments for minute volume, and other parameters.

[0224] FIGS. 27A and 27B are examples of a portable ventilator with a user interface 2701. As illustrated the user interface is configured to show a status of the closed loop controller along with various parameters of the ventilation treatment and monitoring such as HR, SpC>2, FIO2, PEEP, PIP, VT, BPM, and the like.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0225] FIGS. 27C and 27D provide examples of the user interface 2700 with parameter windows 2703, with a window 2709 that can provide alarm messages and / or images of waveforms, a shared icon area 2707 which can also provide icons indicating alarm status (e.g., alarm severity, alarm detections), and auxiliary parameter boxes 2705.

[0226] FIG. 28 is a portable ventilator 2801 which includes a knob or switch 2803 a user can use to adjust the FIO2 gain and indicate whether it should be increased or decreased. In some implementations, the user can manually adjust one or more parameters of the portable ventilator. In some implementations, the user can manually adjust one or more parameters of the portable ventilator in a manner that overrides the execution of the physiological closed-loop control process described herein.

[0227] FIG. 29 is a portable ventilator with a knob or switch 2901 a user can use to adjust the VM gain and indicate whether it should be increased or decreased.

[0228] FIG. 30 is a portable ventilator with includes a knob or switch 3001 a user can use to adjust the FIO2 gain and indicate whether it should be slow (conservative), moderate, or fast (aggressive).

[0229] FIG. 31 is a portable ventilator with a user interface that includes a plurality of FIO2 gains that can be set by a user such as the overall FIO2 gain 3101, proportional gain 3105, and / or derivative gain 3103.

[0230] FIG. 32 is a portable ventilator with a user interface that enables a user to enter or set various parameters such as overall gain— FIO2 and VM 3201, gain- FIO23203, and / or gain-VM 3205.

[0231] FIG. 33 illustrates an example portable ventilation system or ventilator 3300, incorporating physiological closed-loop control, in accordance with some embodiments of the present disclosure.

[0232] The ventilation system or ventilator 3300 may include various components, such as patient sensors and monitoring components 3321, system sensors and monitoring components 3344, and other components 3351. The patient sensors and monitoring components 3321 may include an oximetry sensor 3322, such as a pulse oximeter or other sensor for providing a direct or indirect measurement, estimation or indication of oxygen saturation (SpCh) or other blood oxygen content or concentration related parameter, a CCh / EtCCh sensor / capnograph 3324, an ECG component 3326, a patient blood flow sensor 3328 patientZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO airway pressure sensor 3330, patient blood pressure sensor 3340, and patient temperature sensor 3342. In another embodiment that ventilation and monitoring system could be the result of series of devices (ventilator, critical care monitor, other therapeutic devices and / or sensors) that work interoperably as a single life support and monitoring system.

[0233] Various combinations of these components are used in performing physiological closed-loop control of ventilation parameters according to various embodiments, such as, for example, while ventilation is being provided to a patient via a gas delivery apparatus and using a facemask coupled with the patient, or using an invasive airway such as an endotracheal tube. For example, measured patient SpCh (such as may be measured, for example, using an oximetry sensor such as a pulse oximeter coupled with the patient) is used in determining FIO2 updates. In some embodiments, measured EtCCh (such as may be measured using a capnographic sensor or capnograph, coupled with the patient) is used in determining parameter updates, including VT, Ve, respiratory rate (RR) and PIP, such as in connection with patient hypercapnia, hypocapnia and normocapnia conditions. Patient hemodynamics, such as measures of blood flow including systolic blood pressure, may be used in connection with PEEP change eligibility (such as may be measured, for example, using a blood pressure sensor or monitor coupled with the patient).

[0234] The system sensors and monitoring components 3344 may include a temperature sensor 3346, a barometric sensor 3348 and flow sensor(s) 3350 such as those that utilize pneumotachometer(s), or other types of sensed parameters. Other components 3351 include an external and / or internal power supply 3352, patient circuits 3354, including inspiratory and exhalation circuits, other mechanical components 3356, other electrical components 3358, other computer or computerized components, such as one or more central processing units, processors and memories 3360, an oxygen / Ch supply 3362, and a display / GUI and potentially other output components 3364.

[0235] Also included is ventilation control software 3310 with various operation modes for the ventilator including physiological closed-loop control capability, which may be stored in whole or in part in the one or more memories 3306 of the minute ventilation controller 3302 and executed in whole or in part by the one or more processors 3304 of the physiological closed-loop control of mechanical ventilation control system.

[0236] The physiological closed-loop control of mechanical ventilation system software includes components including an initiation period 3370, a test breaths period 3372, a response time procedure 3374, and a ventilation period / active period engine 3376. Various otherZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO software may be included, including software that may be stored or executed in whole or in part outside of the portable ventilator or ventilation system 3300.

[0237] The active period engine 3376 includes a minute ventilation control engine 3312, an FIO2 control engine 3318 and a PEEP control engine 3320, where each or some of these engines 3312, 3318, 3320 may be in coordination with a central control engine 3316 or operate independently, and each may or may not also be in coordination with each other or some of the other engines, such as with response time procedure engine 3374. Different aspects of the physiological closed-loop control of mechanical ventilation may be activated, for example, minute ventilation control 3312, FIO2 control 3318, and / or PEEP control 3320 may be activated alone or in combination. In some embodiments, FIO2 closed-loop control is activated without PEEP closed-loop control, such that PEEP is manually adjusted by the user; or the minute volume closed-loop while the user has responsibility for the control of FIO2 and PEEP.

[0238] As discussed above, FIO2 physiological closed-loop control can provide advantages including minimizing the time that a patient’s SpC>2 is below or substantially below a target value, providing rapid oxygenation response to patient SpC>2 desaturation events and helping prevent patient hypoxia / hypoxemia and hyperoxia / hyperoxemia. Furthermore, incorporating the patient response time into the FIO2 closed-loop control allows for some patients (e.g., those with faster response times) to be brought to their target SpC>2 level even faster. The patient response time may be determined by ventilator 3300 by way of response time procedure engine 3374. Oscillations can be detected and incorporated into the FIO2 closed-loop control.

[0239] It is noted that, while the modules and engines are depicted separately for conceptual purposes, they may be implemented in a combined, integrated or different manner, such as embodiments in which aspects of the roles of each of the operational phases or engines are distributed differently or combined in various ways. Moreover, other conceptual frameworks may also be utilized in various embodiments.

[0240] In some embodiments, the ventilator system or ventilator 3300 may be operated in one of several control schemes based on the user, patient and / or area or circumstance of operation (e.g., remote environment rescue, aeromedical transport, prolonged field care, etc.). One (or several) such schemes may include physiological closed-loop control of ventilation, PEEP, and FIO2, which may collectively be referred to as a VPFC system. According to some embodiments, initiation period 3370, test breaths period 3372, active period (or ventilation period) 3376, and response time procedure 3374 may occur in a particular order and represent phases of operation in the VPFC system. In some embodiments, after turning on the ventilatorZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO 3300, the user may select the VPFC system from amongst other types of control schemes.However, embodiments are contemplated in which VPFC system is entered into or begun without user selection or input.

[0241] In various embodiments, various types of physiological closed-loop control, such as the VPFC system, can be started or engaged, as well as stopped or disengaged, in different ways. In some embodiments, VPFC or other aspects of physiological closed-loop control may start automatically, such as at the onset of active period ventilation. In some embodiments, the ventilator 3300 may include a control component, such as a physical button, control knob or graphical user interface (GUI) component, which the user may press, engage or actuate in order to start, select or turn on the VPFC system or a particular aspect or engine of physiological closed-loop control based on the patient’s condition, or the circumstances referenced above. For example, in some embodiments, the user may be provided with options to select and initiate, for example, specific VPFC system engines, closed-loop control of FIO2 but manual PEEP control or adjustment, or closed-loop control of minute ventilation and FIO2 but manual PEEP control or adjustment. Furthermore, in some embodiments, the user may be provided with options to start, stop or re-start various types of closed-loop control at different times, so that the VPFC system or other aspects of closed-loop control are available, but also subject to disengagement, and so are made to be essentially on-demand as required to manage the patient or circumstance. Also, as mentioned previously, in some embodiments, during operation of aspects of closed-loop control, the user may be able to change a particular setting or settings, such as FIO2 or PEEP, and then the physiological closed-loop control may resume from that point and initially with that setting or those settings as could be the case when the patient requires additional FIO2 to facilitate endotracheal suctioning. Furthermore, in some embodiments, a user may be provided with an option to stop or disengage the VPFC system or some other aspect of physiological closed-loop control (or the physiological closed-loop control may be automatically stopped), and later the user may restart it as could be the case when the patient is disturbed during movement to or from a vehicle which could cause transient physiological disturbances. These features could also trigger automatically when an accelerometer(s) detect characteristic movement patterns. In some embodiments, a user may select to initiate the response time procedure 3374, thus pausing any physiological closed-loop control being performed within active period 3376 and returning to the physiological closed-loop control upon the completion of the response time procedure 3374. Still further, in some embodiments, multiple or different users may oversee or operate the ventilator, such as at different times, and each user may take different actions.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0242] In some embodiments, for example, a user, such as a minimally trained user, may initiate active period ventilation with the VPFC system (or another aspect of physiological closed-loop control). At some point during active period ventilation, that user or another user, such as a more trained user, may change from the full VPFC system (or another aspect of physiological closed-loop control) to manual, or more manual, operation. Alternatively, active period ventilation may be initiated without the VPFC system or some other aspect of physiological closed-loop control, and the VPFC system or some other aspect of physiological closed-loop control may be started or engaged later, such as if the user becomes distracted (or during the period of user distraction), or by a less trained user who may later arrive at the scene, for example. In some embodiments, the VPFC system may activate automatically if the sensor / monitoring system detects a physiologic pattern that represents a threat to the patient’s wellbeing. Such a case could be the automated initiation of FIO2 physiological closed-loop control when the ventilator system detects significant changes is altitude which would be associated with aeromedical transport. In this case, the VPFC system would initiate the FIO2 control engine to ensure that the patient’s oxygen saturation is maintained as the cabin pressure is reduced during the flight.

[0243] The following provides an exemplary overview of operation of the VPFC system, according to some embodiments. Further details, regarding various aspects and in various embodiments, are provided with reference to later figures.

[0244] In some embodiments, at the start of the execution of initiation period 3370, or after the user selects the VPFC system, the user may be prompted (via a display of the ventilator 3300) to enter the patient’s sex and height. From this, the controller 3302 may determine an associated bodyweight, which may be called the patient’s PBW. However, the determined bodyweight may not be the patient’s actual bodyweight, and may represent an ideal bodyweight, approximated, typical or other associated bodyweight to be used, for example, in determination or optimization of certain ventilation settings. Predicted bodyweight may be used, as opposed to actual bodyweight, for example, since actual bodyweight may fluctuate substantially from person to person, and even between individuals of similar characteristics such as height and sex, due to different amounts of muscle and fat from person to person, while lung volume, capacity and function remain relatively unaffected by such factors. As such, in some embodiments, PBW may be used at least in part as an indicator associated with an individual’s respiratory capacity and may generally be a better indicator than actual patient bodyweight.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0245] During the execution of initiation period 3370, the controller 3302 may utilize the PBW in determining one or more ventilation parameter settings to be used for one or several operational breaths to be delivered to the patient, which may be utilized, for example, in confirming correct operation of the ventilator 3300, which may include confirming that there are no leaks, or significant leaks, in the circuit. For example, PBW may be used in setting initial VT, such as may be set as VT (in ml) = A*PBW (in kg), where A may be, e.g., 5, 6, 7, 8 or 9 (in ml / kg). Furthermore, for example, initial minute volume (VM in ml / min) may be set as B*PBW, where B (in ml / (min*kg) may be, e.g., 80, 90, 100, 110, 120 or 150.

[0246] Once the execution of the initiation period 3370 is successfully completed, the ventilator 3300 may execute test breaths period 3372. During the execution of test breaths period 3372, one or more test breaths are delivered to the patient and respiratory data is obtained. The respiratory data is used in determining one or more patient respiratory parameters, such as estimated patient respiratory system compliance (Crs) and, in some embodiments, one or more additional parameters, such as estimated patient respiratory system resistance (Rrs). In some embodiments, if Crs cannot be estimated or sufficiently estimated then a default value, such as 100 ml / cm H2O may be used. The determined patient Crs is then used in determining an initial peak inspiratory pressure (PIP(0)) setting to be used at the start of active period 3376.

[0247] In some embodiments, the ventilator 3300 may execute response time procedure 3374 following the completion of test breaths period 3372 and before the execution of the active period 3376. The patient response time may be determined by response time procedure 3374. In some embodiments, the ventilator 3300 first proceeds to active period 3376 following the completion of test breaths period 3372 and proceeds from active period 3376 where the response time procedure 3374 activates once the FIO2 and SpC>2 levels have reached a steady state during the physiological closed-loop control of active period 3376. Ventilator 3300 may pause the physiological closed-loop control during active period 3376 at any time to execute response time procedure 3374, returning to active control 3376 at the conclusion of the response time procedure 3374.

[0248] In some embodiments, active period 3316 may include physiological closed-loop control of FIO2 and PEEP, and possibly one or more other parameters. During physiological closed-loop control of mechanical ventilation 3376, active period control 3316, in coordination with minute ventilation control 3312, FIO2 control 3318 and PEEP control 3320, sets or adjusts ventilation settings including FIO2, PEEP, PIP, VT, VM, R, and / or inspiratory: expiratory ratio (I:E). However, in some embodiments, one or more of minute ventilation control 3312, FIO2Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO control 3318, PEEP control 3320, or other components, may set or adjust, or participate in the setting or adjusting of, certain of those or other ventilation settings.

[0249] As described above, the controller 3302 may utilize a target SpCh, such as 94% (however, in various embodiments, the target SpC>2 may be, e.g., between 92%-98%, between 92%-96% or between 96%-98%). On a continuous basis, actual measured patient SpO? may be used as input in adjusting the FIO2 setting of the ventilator.

[0250] In some embodiments, determined parameters including patient end-tidal carbon dioxide (EtCO2), a determined patient airway pressure waveform (P), patient airway flow waveform (V), and volume waveform (V) may be used in determining active period initial settings for VT, Vm, PIP, RR and I:E, and / or, in some embodiments, parameters can be used that are derived at least in part from the V and V waveforms, which can include plateau pressure, driving pressure, Crs and Rrs. Furthermore, the controller 3302 may continuously use determined patient Crs and Rrs in determining adjustments to VT, such as may maintain VT at a safe level. The controller 3302 may also continuously adjust RR, such as to maintain VM at a constant level when VT is adjusted, where VM =VT*RR.

[0251] FIG. 34 illustrates an example portable ventilator 3400, in accordance with some embodiments of the present disclosure. Portable ventilator 3400 includes features such as pulse oximeter connector 3401, fresh gas / emergency air intake 3402, handle 3406, power switch 3409, battery compartment 3410, user selection dial 3411, control panel 3412, manual breath / plateau pressure button 3413, menu button 3419, parameter buttons 3408, oxygen inlet 3434 and a display and user interface screen 3416.

[0252] The fresh gas / emergency air intake 3402 provides a gas path and allows ambient air into the device’s internal compressor. Built-in filters are used to protect the compressor and patient from particulate matter. The intake 3402 also acts as an anti -asphyxia path that enables the patient to breathe ambient air, should the ventilator fail. The intake 3402 further contains a particulate filter and permits the user to connect either a bacteria / viral or a chemical / biological filter, depending on ambient conditions. Furthermore, an oxygen reservoir bag assembly may be connected to the intake 3402 to allow for low-flow oxygen use with the ventilator 3400 in order to provide a source of supplemental oxygen to patients during ventilation. For example, low-flow oxygen sources can be obtained based on a flow meter or an oxygen concentrator. Oxygen may be delivered through the intake 3402 when the ventilator’s internal compressor cycles deliver breaths.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO

[0253] A top panel of the ventilator 3400 may have components including, in addition to the intake 3402 and the pulse oximeter connector 3401, a high-pressure oxygen input, a gas output, a power cord connector for external AC / DC power, a USB port, an exhalation valve port, an exhaust valve and a pressure transducer port. The pulse oximeter connector 3401 is used to connect a pulse oximeter that may provide continuous non-invasive monitoring of SpCh and pulse rate. The portable ventilator 3400 may be operable using external AC / DC power or a battery, such as an internal lithium-ion battery.

[0254] Furthermore, the portable ventilator 3400 may include at least one display and user interface screen 3416, which may, for example, include a liquid crystal display (LCD). Among other things, the display and user interface 3416 may provide a user with data relating to patient parameters and ventilation parameters, including current ventilator settings, which may be continuously updated. Furthermore, the display and user interface 3416 may include, among other things, various GUI aspects, allowing user interaction, such as to access particular data, change ventilator selections or settings, confirm suggested displayed changes to ventilator settings, receive and respond to alarms, etc. In particular, as shown, the display and user interface screen 3416 includes parameter and alarm indicators 3407, an alarm message center / waveform window 3418, and auxiliary parameter boxes 3414.

[0255] In some embodiments, the display and user interface screen 3416 may be divided into a number of sections. For example, as depicted, the top left area of the display and user interface screen 3416 may include airway pressure, flow, volume, capnography and plethysmography (pleth) waveform plots. This section may include displayed plots for airway pressure as well as, when a pulse oximeter is connected, the pleth waveform, and when a CO2 sensor is connected, the capnogram. When a plot is useful to facilitate a parameter adjustment by the user, a message area may display both the plot and a context menu that the user may use to make selections to obtain displayed context relating to the parameter.

[0256] The display and user interface screen 3416 also includes a menu display section in the top left area. This section may be used to display a menu after the user presses a menu button on the ventilator’s control panel, and may be used to display context menus associated with the operational status of the ventilator, alarm configuration, alarm history, audible alarm volume, LCD brightness / contrast, etc.

[0257] The display and user interface screen 3416 also includes an alarm message center / waveform window 3418 in the upper left area, in which visible alarms may at times be displayed. Some alarms may instruct the user to consult a physician, for example. In someZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO embodiments, alarms may be categorized into different levels of priority, such as based on the level and / or urgency of the risk that the particular alarm condition may pose to the patient.Multiple alarms, along with their priorities, that have occurred recently may be available for display to a user, where the user may view the recent alarms by scrolling in a GUI, for example. In some embodiments, if the FIO2 setting is increased by a certain amount, such as 10% (or, e.g., 5-15%) during a predetermined period of time, such as 10 minutes (or, e.g., 5-15 minutes), an alarm is generated. Furthermore, in some embodiments, certain alarms may cause some or all physiological closed-loop control aspects, or VPFC system including FIO2, minute volume, and PEEP closed-loop control engines, to pause until the user clears the alarm. In some embodiments, during the time of the pause and before the alarm is cleared, the ventilator may operate using current parameter values, such as for FIO2 and PEEP, that were being used at the time that the pause was initiated.

[0258] In some implementations, the alarm can include a priority (e.g. low priority, medium priority, or high priority) which may correspond to the severity of oscillations detected by the system.

[0259] The display and user interface screen 3416 may also include pop-up windows that may provide a user with context-sensitive guidance, such as in connection with manual adjustment of parameter values, for example.

[0260] The display and user interface screen 3416 also includes various parameter windows on the right side. Displayed parameters may include, e.g., SpC>2, EtCCh, FIO2, PEEP, PIP, VT, BPM and blood pressure, for example. In some embodiments, the patient’s measured response time may be displayed in one or more of the parameter windows. Each parameter window may display a primary parameter as well as secondary parameters, such as parameters that may be related to the primary parameter or with associated alarm limits. In some embodiments, solid text may be displayed for primary and secondary parameter values that can be adjusted by the user, while outlined text may be used for patient-dependent measured parameters, for example. Primary parameters may also include mode, which may include a user selectable mode of operation including assist / control (AC), SIMV (synchronized Intermittent Mandatory Ventilation), continuous positive airway pressure (CPAP) and bilevel (BL).

[0261] Furthermore, the mode parameter may be associated with secondary parameter choices including volume targeting and pressure targeting. Volume targeting (V) aim to deliver a constant volume to the patient in the inspiratory time using a constant flow. During volume targeting, the measured PIP parameter is displayed or highlighted. Pressure targeting (P) aims toZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO achieve a constant airway pressure for the duration of the inspiratory time. During pressure targeting, the measured VT parameter is displayed or highlighted.

[0262] The display and user interface screen 3416 also includes device-related icons section in the lower left area. This section may include icons that represent, and may provide status information on, for example, the ventilator’s power source (which may indicate whether the ventilator is operating on external power or its battery), a battery charging status icon, an oxygen supply attachment icon, and an icon that indicates whether audible alarms or permitted or muted.

[0263] The display and user interface 3416 may also include an auxiliary parameter boxes section 3414, which may be located toward the bottom. This section may display parameter boxes that allow the user to adjust a particular parameter using a context menu associated with the parameter.

[0264] In some embodiments, a user may take the following steps in setting up. The patient circuit may be attached to the ventilator’s top panel. A high-pressure oxygen supply, if it is to be used, is attached. The user inspects the fresh gas / emergency air intake filters and may attach other items, such as an oxygen reservoir bag, and biological and chemical filters. The user may choose a power source, such as an external or internal power source. The user may connect the power supply to the ventilator. Once preliminary steps are completed, the user may power on the ventilator 3400 using the ventilator’s power switch or button. Once powered on, the ventilator 3400 may perform a self-check, to check for potential alarm conditions as well as the operation of the pneumatic system, power system and internal communications system. During normal start-up, the ventilator’s alarms may be muted for, e.g., 2 minutes, to allow the user to connect items including the patient circuit and pulse oximeter, and to perform operational tests.

[0265] In some embodiments, after powering on the ventilator 3400, the user may choose from the settings defaults, such as adult, pediatric, mask CPAP, custom (includes use of saved settings values), and last settings (includes use of last-used settings values). Alternatively, these setting defaults would include VFPC or a subset of the physiological closed-loop control engines described herein. The user may select one of the defaults, in which case ventilation will be initiated using the default settings associated with the selection. Alternatively, the user may manually set settings using any of the parameter buttons 3408 or select a mode of operation.

[0266] The parameter and alarm indicators 3407 may include information specifying current parameter values and may also display other related information such as alarm thresholdZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO values 3420, which may indicate, for example, threshold beyond which an alarm may be triggered. The parameter and alarm indicators 3407 may include an SpC>2 parameter display aspect 3403, an FIO2 parameter display aspect 3404 and a PEEP / PIP parameter display aspect 3405.

[0267] In the SpO2parameter display aspect 3403, the current patient SpC>2 is displayed as “95”, meaning 95%. A target symbol, along with the displayed numbers “94” and “88” indicate that the SpC>2 target is set to 94% and the desaturation threshold of SpC>2 is set to 88%.

[0268] In the FIO2 parameter display aspect 3404, the current FIO2 is displayed as “99”, meaning 99%. Double arrows 3415 (which, in some embodiments, may be animated as displayed), indicate that FIO2 PCLC is currently active and operating. The displayed “O2 Use” text indicates that an attached oxygen supply is being used and the rate of oxygen use in L / min.

[0269] In some embodiments, various alerts or warnings may be displayed to the user on the display and user interface screen 3416 before the user initiates FIO2 PCLC. For example, the user may be warned not to use FIO2 PCLC if the user suspects that pulse oximetry may not operate correctly or may not be available, or if the patient has carboxyhemoglobin poisoning (i.e., carbon monoxide poisoning), in which case the user may be advised to follow the local standard of care. The user may also be warned not to use FIO2 PCLC for patients with a core temperature of less than 35 degrees Celsius. Furthermore, in some embodiments, pulse oximetry and a high-pressure oxygen source may be required for FIO2 PCLC, and failure of availability of either of these resources may cause FIO2 PCLC to be paused and may cause an associated alarm to be displayed to the user.

[0270] In the PEEP / PIP parameter display aspect 3405, the current PIP is displayed as 28, meaning 28 cm H2O, and the current PEEP is displayed at 5, meaning 5 cm H2O. PIP alarm threshold levels are also displayed.

[0271] FIG. 35 illustrates aspects of an example pneumatic system 3500 that can be used with a portable ventilator, in accordance with some embodiments of the present disclosure. As shown, the pneumatic system 3500 includes a high-pressure oxygen connector 3508, patient circuit tubing 3510 that may include patient inhalation and exhalation circuit components, an exhalation valve 3512, a radial compressor 3506 or other gas moving component such as a blower, an oxygen valve 3504 and components 3502 associated with control and / or measurement of oxygen pressure, oxygen flow, ambient pressure, air flow, intake pressure and patient airwayZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO pressure, which may include programmable-gain amplifiers (PGAs), analog-to-digital converters (ADCs), and other components.

[0272] The oxygen valve 3504 and the compressor 3506 may provide the appropriate gas mixture for the patient during ventilation. The pneumatic system 3500 may include transducers for pressure measurements including oxygen input supply and barometric pressure. The patient circuit tubing 3510 may include an inspiratory portion that provides gas to the patient, as well as an expiratory portion that exhausts gas directly to the atmosphere without return to the pneumatic system 3500. The pneumatic system 3500 pneumatically controls the exhalation valve 3512. A transducer within the pneumatic system 3500 measures the airway pressure during ventilation.

[0273] An external high-pressure oxygen source connects to the pneumatic system 3500 using a high-pressure oxygen input port. The source may be a medical grade piped oxygen system or oxygen cylinder supply, for example.

[0274] In some embodiments, a portable ventilator may be coupled with a supplemental oxygen source (some examples of types of oxygen sources are provided). In various embodiments, the portable ventilator may be capable of supplying oxygen, using the supplemental oxygen source, in a number of different ways, or the portable ventilator may be capable of supplying oxygen in any one of several different ways. In various embodiments, the manner in which oxygen is supplied may be determined without user selection, or may be selected by a user, and may or may not require user confirmation.

[0275] In some embodiments, a reservoir bag may be used that allows entrainment of oxygen from a low-pressure oxygen source. For example, a user may adjust the flow rate of oxygen based at least in part on current SpC>2 (such as, for example, may be measured using an oximetry sensor such as a pulse oximeter coupled with the patient).

[0276] In some embodiments, the portable ventilator includes and uses a variable rate regulatory valve, in which an oxygen output rate allowed or facilitated by the variable rate regulatory valve may be varied and changed to a particular oxygen flow rate of a range of possible oxygen flow rates, such as may range from 01 / min to 2001 / min (or, e.g., up to 220, 250 or 275 1 / min). The variable rate regulatory valve may be used in providing a variable and controllable oxygen flow rate for gas provided by a gas delivery apparatus (such as, for example, gas delivery apparatus) of the portable ventilator, such as using a facemask, coupled with the patient, or using an invasive airway such as an endotracheal tube, during the providing ofZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO mechanical ventilation. In some embodiments, the variable rate regulatory valve may attach to a gas inlet (such as, for example, oxygen inlet) of the portable ventilator and a high-pressure oxygen source, and potentially one or more other devices and / or sensing or monitoring components.

[0277] In some embodiments, the variable rate regulatory valve may be controlled automatically or without need for user interaction. For example, this may be based at least in part on the patient’s continuously monitored SpCh and in accordance with an FIO2 setting or adjustment that may be determined based at least in part on the current SpC>2. In some embodiments, this arrangement may be used in providing FIO2 PCLC. In some embodiments, a portable oxygen concentrator (POC) may be used. FIO2 PCLC may be used in controlling and regulating the output of the POC for entrainment of oxygen into the gas delivery apparatus during mechanical ventilation. Furthermore, in some embodiments, including embodiments in which the variable rate regulatory valve or a POC is used, PEEP PCLC may also be included in control of the gas delivery apparatus. In some embodiments, PEEP PCLC may be based least in part on a current FIO2 setting and a current PEEP setting.

[0278] FIG. 36 illustrates aspects of an example external gas supply system 3600 that can be used with a portable ventilator 3608, in accordance with some embodiments of the present disclosure. Depicted components include an oxygen tank 3602 or other oxygen output 3604, high pressure hose 3606 for use with the oxygen supply, and low flow oxygen source 3610 shown coupled to the portable ventilator 3608.

[0279] FIG. 37 illustrates aspects of example patient circuits 3700 that can be used with a portable ventilator 3714, in accordance with some embodiments of the present disclosure. Depicted components include an adult circuit 3710, including an inspiratory line 3702 and an expiratory line 3706, and an infant / pediatric circuit 3712, including an inspiratory line 3704 and an expiratory line 3708.

[0280] Various embodiments described herein may apply to, for example, out-of-hospital or pre-hospital patient care (although not limited to such care). Some aspects of embodiments described herein take into account practical factors relating to such care contexts. For example, in pre-hospital patient care, the care provider may be less trained than a hospitalbased care provider. Furthermore, no support or less support from other care providers and / or hospital systems may be available. Also, pre-hospital care may involve less patient and equipment physical stability and may involve movement or transport. Additionally, pre-hospital patient care may extend for long periods of time, sometimes extending to many hours, a day orZoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO several days. During this time, the resulting physical and mental stress, and overall exhaustion, of the patient and the care provider can be significant factors to consider in determining optimal ventilator operation, procedures and processes. As such, in some embodiments, these pre-hospital conditions are taken into account, such as in connection with determination of parameter values, ranges and thresholds, frequency of change of parameters, overall simplicity, and balances between parameter stability and the need for adjustment. In some embodiments, such balances and optimization approaches may be thought of as providing or favoring a form of conceptual “guardrails” in view of the particular concerns and elevated potential risks that tend to accompany pre-hospital care contexts and situations.

Claims

Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO CLAIMS1. A mechanical ventilator apparatus comprising:a gas delivery apparatus configured to deliver a gas to a patient and comprising a patient interface;an oximetry sensor configured to provide at least one signal representative of an oxygen saturation of the patient’s blood; anda controller, comprising a processor and a memory, in communication with the gas delivery apparatus and the oximetry sensor, the controller configured to:receive the at least one signal representative of the oxygen saturation of the patient’s blood provided by the oximetry sensor;determine an oxygen saturation of the patient’s blood based on the received at least one signal;continuously adjust a fraction of inspired oxygen (FIO2) parameter of the gas delivery apparatus based at least in part on the received signals representative of the oxygen saturation of the patient’s blood, wherein the FIO2 parameter comprises a percentage of oxygen in the gas delivered to the patient in accordance with one or more FIO2 parameter adjustment criteria;detect one or more oscillations in at least one of the oxygen saturation of the patient’s blood and / or the FIO2 parameter by applying at least one oscillation detection algorithm to at least one of: the determined oxygen saturation and / or the FIO2 parameter; andmodify the one or more FIO2 parameter adjustment criteria of the gas delivery apparatus responsive to detecting the one or more oscillations.

2. The mechanical ventilator apparatus of claim 1, wherein the oximetry sensor comprises at least one pulse oximetry sensor.

3. The mechanical ventilator apparatus of claim 2, wherein the pulse oximetry sensor comprises an SpC>2 sensor.

4. The mechanical ventilator apparatus of claim 1, wherein the oxygen saturation of the patient’s blood is an oxygen saturation.

5. The mechanical ventilator apparatus of claim 1, wherein the gas is a breathing gas.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO 6. The mechanical ventilator apparatus of claim 1, wherein the FIO2 parameter adjustment criteria comprises at least one of: proportional gain parameter, a target SpCh parameter, and / or a derivative gain parameter.

7. The mechanical ventilator apparatus of claim 1, wherein the detected oscillation is in the oxygen saturation of the patient’s blood.

8. The mechanical ventilator apparatus of claim 1, wherein the detected oscillation is in the FIO2 parameter.

9. The mechanical ventilator apparatus of claim 1, wherein the detected oscillation is in both the oxygen saturation of the patient’s blood and the FIO2 parameter.

10. The mechanical ventilator apparatus of claim 1, wherein the modified one or more FIO2 parameter adjustment criteria comprises at least one of: a default FIO2 change rate, a reduction in a FIO2 change rate, a reduction in a maximum FIO2 change rate, a time value for a modified FIO2 setting, and / or a temporal pause.

11. The mechanical ventilator apparatus of claim 10, wherein the modified one or more FIO2 parameter adjustment criteria comprises the temporal pause at a current FIO2 setting.

12. The mechanical ventilator apparatus of claim 10, wherein the modified one or more FIO2 parameter adjustment criteria comprises the temporal pause at an average FIO2 setting for a predetermined number of full oscillation cycles.

13. The mechanical ventilator apparatus of claim 1, wherein the modified one or more FIO2 parameter adjustment criteria comprises at least one of: an adjustment to a proportional gain, an adjustment to a derivative gain, an adjustment to both a proportional gain and a derivative gain, and / or an adjustment to an overall gain.

14. The mechanical ventilator apparatus of claim 1, wherein the modified one or more FIO2 parameter adjustment criteria is based on a severity of the detected one or more oscillations.

15. The mechanical ventilator apparatus of claim 14, wherein the severity is determined based on a rate of full range crossings per hour, a peak-to-peak amplitude of the oscillations, and / or a magnitude of an SpC>2 error.

16. The mechanical ventilator apparatus of claim 14, wherein the severity is a numerical value between 0 to 1.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO 17. The mechanical ventilator apparatus of claim 1, wherein the modified one or more FIO2 parameter adjustment criteria comprises disabling a patient response time-based adjustment in an FIO2 change rate.

18. The mechanical ventilator apparatus of claim 1, wherein the modified one or more FIO2 parameter adjustment criteria comprises a change in at least one of: a response time coefficient or a SpC>2 response time in a patient response time-based adjustment criteria.

19. The mechanical ventilator apparatus of claim 1, wherein the at least one oscillation detection algorithm comprises:determining a count for full range crossings in a predetermined time period based on the determined oxygen saturation of the patient’s blood; anddetecting one or more oscillations when the determined count for full range crossings exceeds a predetermined threshold of maximum full range crossings.

20. The mechanical ventilator apparatus of claim 19, wherein a severity of the detected oscillation is based on a rate of the determined count for full range crossings and / or a peak-to-peak amplitude of the determined oxygen saturation of the patient’s blood.

21. The mechanical ventilator apparatus of claim 1, wherein the at least one oscillation detection algorithm comprises:determining a SpC>2 error for a time window based on the determined oxygen saturation of the patient’s blood; anddetecting one or more oscillations when a standard deviation for the determined SpO2error exceeds a predetermined threshold of maximum SpC>2 error standard deviation, when a cumulative value of the SpC>2 error for the time window exceeds a predetermined threshold of maximum SpC>2 error, and / or when a rate of SpC>2 error crossing exceeds a predetermined threshold of SpC>2 error crossing rate.

22. The mechanical ventilator apparatus of claim 21, wherein a severity of the detected oscillation is based on a magnitude of the standard deviation of the SpC>2 error.

23. The mechanical ventilator apparatus of claim 21, wherein a severity of the detected oscillation is based on a magnitude of the cumulative value of the SpC>2 error and / or rate of SpO2error crossing.

24. The mechanical ventilator apparatus of claim 1, wherein the at least one oscillation detection algorithm comprises:Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO determining an SpC>2 error for a time window based on the determined oxygen saturation of the patient’s blood; anddetecting one or more oscillations when a similarity factor between the determined SpCh error for the time window is within a threshold of a historical SpC>2 error, wherein the similarity factor comprises at least one of: an integral absolute error (IAE) and time between zero-crossing (TBZC).

25. The mechanical ventilator apparatus of claim 24, wherein a severity of the detected oscillation is based on a magnitude of the integral absolute error (IAE).

26. The mechanical ventilator apparatus of claim 1, wherein the at least one oscillation detection algorithm comprises:determining an SpC>2 signal based on the determined oxygen saturation of the patient’s blood;generating a transformed SpC>2 signal by applying a fast Fourier transform (FFT) to the determined SpC>2 signal; anddetecting one or more oscillations by identifying one or more peaks in the transformed SpC>2 signal within a predetermined frequency range.

27. The mechanical ventilator apparatus of claim 26, wherein a severity of the detected oscillation is proportional to at least one of: an amplitude or a power of a largest peak identified within the predetermined frequency range.

28. The mechanical ventilator apparatus of claim 26, wherein the predetermined frequency range comprises a frequency between 0.00556 Hz and 0.0167 Hz.

29. The mechanical ventilator apparatus of claim 1, wherein the controller is configured to control one or more ventilation parameters using closed loop control.

30. The mechanical ventilator apparatus of claim 1, wherein the one or more oscillations are attributed at least in part by an FIO2 change rate.

31. The mechanical ventilator apparatus of claim 30, wherein for the one or more oscillations attributed at least in part by the FIO2 change rate indicates that the FiO2 change rate exceeds a rate sufficient to induce the one or more oscillations.

32. The mechanical ventilator apparatus of claim 1, comprising detecting the one or more oscillations in the oxygen saturation of the patient’s blood and the FIO2 parameter.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO 33. The mechanical ventilator apparatus of claim 32, wherein detecting the one or more oscillations, in the oxygen saturation of the patient’s blood and the FIO2 parameter, is used in confirming that the detected oscillations are caused at least in part by an FIO2 change rate.

34. The mechanical ventilator apparatus of claim 1, wherein when an oscillation is detected in one of the oxygen saturation of the patient’s blood or the FIO2 parameter, the other of the oxygen saturation of the patient’s blood or the FiO2 parameter is checked for oscillations.

35. A mechanical ventilator apparatus comprising:a gas delivery apparatus configured to deliver a gas to a patient and comprising a patient interface;a capnography sensor configured to provide at least one signal representative of an amount of carbon dioxide in a patient’s exhaled air; anda controller, comprising a processor and a memory, in communication with the gas delivery apparatus and the capnography sensor, the controller configured to:receive the at least one signal representative of the carbon dioxide in the patient’s exhaled air provided by the capnography sensor;determine a carbon dioxide concentration (EtCCh) of the patient’s exhalation based on the received at least one signal;cause adjustment of a minute volume (VM) parameter of the gas delivery apparatus based at least in part on the determined carbon dioxide concentration in accordance with one or more VM adjustment criteria;detect one or more oscillations in at least one of: the carbon dioxide concentration of the patient’s exhalation and / or the VM parameter of the gas delivery apparatus by applying at least one oscillation detection algorithm to at least one of: the determined carbon dioxide concentration of the patient’s exhalation and / or the VM parameter; andmodify the one or more VM adjustment criteria of the gas delivery apparatus responsive to detecting the one or more oscillations.

36. The mechanical ventilator apparatus of claim 35, wherein the capnography sensor is configured to provide a signal representative of a partial pressure of expired gas from the patient.

37. The mechanical ventilator apparatus of claim 35, wherein the one or more oscillations are detected in the carbon dioxide concentration of the patient’s exhalation.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO 38. The mechanical ventilator apparatus of claim 35, wherein the one or more oscillations are detected in the VM parameter.

39. The mechanical ventilator apparatus of claim 35, wherein the one or more oscillations are detected in both the carbon dioxide concentration of the patient’s exhalation and the VM parameter.

40. The mechanical ventilator apparatus of claim 35, wherein the controller comprises a proportional-derivative minute ventilation controller configured to modulate VM to reach a target end-tidal carbon dioxide (EtCCh).

41. The mechanical ventilator apparatus of claim 35, wherein the VM adjustment criteria comprises a proportional term and a derivative term.

42. The mechanical ventilator apparatus of claim 41, wherein the proportional term comprises an end-tidal carbon dioxide (EtCCh) error based at least on a difference between a target end-tidal carbon dioxide (EtCCh) and a measured end-tidal carbon dioxide (EtCCh).

43. The mechanical ventilator apparatus of claim 41, wherein the derivative term comprises a difference between a measured end-tidal carbon dioxide (EtCCh) for a first time window and a measured end-tidal carbon dioxide (EtCCh) for a previous time window.

44. The mechanical ventilator apparatus of claim 41, wherein the VM adjustment criteria comprises a corrected minute volume (corrected VM) comprising a weighted sum of the proportional term and the derivative term.

45. The mechanical ventilator apparatus of claim 44, wherein the VM adjustment criteria comprises one or more parameters configured to achieve the corrected minute volume (corrected VM).

46. The mechanical ventilator apparatus of claim 43, wherein the VM adjustment criteria comprises at least one of: a respiratory rate (RR), and / or a target tidal volume (VT).

47. The mechanical ventilator apparatus of claim 35, wherein the controller continuously modifies the one or more VM adjustment criteria.

48. The mechanical ventilator apparatus of claim 35, wherein the controller periodically modifies the one or more VM adjustment criteria.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO 49. The mechanical ventilator apparatus of claim 35, wherein the at least one oscillation detection algorithm comprises:determining an end-tidal carbon dioxide (EtCCh) signal based on the received at least one signal representative of the carbon dioxide in the patient’s exhaled air provided by the capnography sensor;determining a count for EtCCh crossings for a predefined target range for a time window; anddetecting one or more oscillations in the carbon dioxide concentration of the patient’s exhalation when the determined count for EtCCh crossings exceeds a predetermined threshold.

50. The mechanical ventilator apparatus of claim 35, wherein the at least one oscillation detection algorithm comprises:determining an end-tidal carbon dioxide (EtCCh) error for a time window based on the received at least one signal representative of the carbon dioxide in the patient’s exhaled air provided by the capnography sensor; anddetecting one or more oscillations in the carbon dioxide concentration of the patient’s exhalation when a standard deviation for the determined EtCCh error exceeds a predetermined threshold of maximum EtCCh error standard deviation.

51. The mechanical ventilator apparatus of claim 44, wherein modification of the one or more VM adjustment criteria further comprises:adjusting a weight for the proportional term in the weighted sum.

52. The mechanical ventilator apparatus of claim 42, wherein modification of the one or more VM adjustment criteria further comprises:maintaining the minute volume for a predetermined period of time.

53. The mechanical ventilator apparatus of claim 42, wherein modification of the one or more VM adjustment criteria further comprises:maintaining the minute volume at an average minute volume for a predetermined number of cycles.

54. The mechanical ventilator apparatus of claim 35, wherein the controller is configured to control one or more ventilation parameters using closed loop control.

55. A mechanical ventilator apparatus comprising:Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO a gas delivery apparatus configured to deliver a gas to a patient and comprising a patient interface;an oximetry sensor configured to provide at least one signal representative of an oxygen saturation of the patient’s blood; anda controller, comprising a processor and a memory, in communication with the gas delivery apparatus and the oximetry sensor, the controller configured to:receive the at least one signal representative of the oxygen saturation of the patient’s blood provided by the oximetry sensor;determine an oxygen saturation of the patient’s blood based on the received at least one signal;receive at least one signal representative of a signal fidelity from the oximetry sensor;based on one or more potential false desaturation event criteria, identify a potential false desaturation event as an event that may or may not be a desaturation event; andadjust one or more fraction of inspired oxygen (FIO2) adjustment criteria for the gas delivery apparatus responsive to detecting the potential false desaturation event.

56. The mechanical ventilator apparatus of claim 55, wherein the one or more false desaturation event criteria comprise at least one signal fidelity criterion.

57. The mechanical ventilator apparatus of claim 56, wherein the at least one signal fidelity criterion comprises a signal strength level and a signal confidence level.

58. The mechanical ventilator apparatus of claim 55, wherein the event is identified as a desaturation event when the determined oxygen saturation of the patient’s blood is below a predefined threshold for a predefined period of time.

59. The mechanical ventilator apparatus of claim 58, wherein the predefined threshold is 88% and the predefined period of time is 10 seconds.

60. The mechanical ventilator apparatus of claim 58, wherein the predefined threshold and the predefined period of time is based on the signal fidelity.

61. The mechanical ventilator apparatus of claim 60, wherein the predefined period of time is increased when the signal fidelity decreases.Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO 62. The mechanical ventilator apparatus of claim 58, wherein the predefined threshold and the predefined period of time is based on historical data of oxygen saturation in the patient’s blood.

63. The mechanical ventilator apparatus of claim 55, wherein adjustment of the one or more FIO2 adjustment criteria comprises a stepwise increase in a target FIO2 value.

64. The mechanical ventilator apparatus of claim 55, wherein adjustment of the one or more FIO2 adjustment criteria comprises an increase in a target FIO2 value followed by an increase in a proportional gain coefficient for a predetermined time.

65. The mechanical ventilator apparatus of claim 55, wherein adjustment of the one or more FIO2 adjustment criteria comprises setting a target FIO2 value to 100% followed by an incremental decrease of the target FIO2 value when an oxygen saturation value meets a predetermined threshold.

66. The mechanical ventilator apparatus of claim 65, wherein the predetermined threshold for the oxygen saturation value is 97%.

67. The mechanical ventilator apparatus of claim 60, wherein the controller is configured to control one or more ventilation parameters using closed loop control.

68. A mechanical ventilator apparatus comprising:a gas delivery apparatus, having a user interface, configured to deliver a gas to a patient; anda controller, comprising a processor and a memory, in communication with the gas delivery apparatus, the controller configured to:control one or more ventilation parameters using closed loop control, receive user input via one or more controls of the user interface indicating a gain adjustment relating to the closed loop control of the one or more ventilation parameters; andimplement the gain adjustment based on the received user input.

69. The mechanical ventilator apparatus of claim 68, wherein the gain adjustment comprises an adjustment to at least one of: an overall gain, a proportional gain, and a derivative gain.

70. The mechanical ventilator apparatus of claim 68, comprising a gain for a fraction of inspired oxygen (FIO2) and / or a gain for a minute volume (VM).Zoll Ref.: Z20874WO-01 / Mintz Ref.: 059624-534001WO 71. The mechanical ventilator apparatus of claim 68, wherein the gain adjustment comprise a rate of adjustment for a gain setting, wherein the rate of adjustment is aggressive, moderate, or conservative.

72. The mechanical ventilator apparatus of claim 68, wherein the implemented gain adjustment is modified based on the received gain adjustment.

73. The mechanical ventilator apparatus of claim 68, wherein the implemented gain adjustment is superseded by the received gain adjustment.

74. The mechanical ventilator apparatus of claim 68, further comprising:displaying in the user interface at least one of a fraction of inspired oxygen (FIO2) value.

75. The mechanical ventilator apparatus of claim 69, further comprising:displaying in the user interface at least one oscillation of a fraction of inspired oxygen (FIO2) value.

76. The mechanical ventilator apparatus of claim 68, wherein the controls of the user interface comprise one or more knobs, input fields, and / or selection buttons.

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