A device, system, and method for calibrating a blood pressure surrogate used when monitoring the blood pressure of a subject.

Abstract

The present invention relates to a device, system and method for calibrating a blood pressure surrogate for use in monitoring the blood pressure of a subject. The device comprises a BP input 51, a sensor input 52 and a processing unit 53, the processing unit being configured to calculate a pulse-related value from a first and a second time-dependent sensor signal using a first feature of a first time-dependent sensor signal and a second feature of a second time-dependent sensor signal during cuff inflation, the pulse-related value being a value of a Pulse Arrival Time PAT or a value of a Pulse Transit Time PTT, to select pairs of pulse-related values ​​and corresponding cuff pressure values ​​to calculate calibration parameters of a BP surrogate, the pairs comprising a pulse-related value and a corresponding time-related cuff pressure value, only those pairs of pulse-related values ​​and corresponding cuff pressure values ​​for which one or more predetermined conditions regarding BP and / or cuff pressure are met are selected, and to calculate the calibration parameters of the BP surrogate from the BP measurements and the selected pairs of pulse-related values ​​and corresponding cuff pressure values.

Description

[Technical Field]

[0001] The present invention relates to a device, system, and method for calibrating blood pressure (BP) surrogates used when monitoring the blood pressure of a subject. [Background technology]

[0002] Hemodynamic measurements in acute care generally tend to be more continuous, less invasive, and less intrusive. Blood pressure (BP) is a fundamental hemodynamic parameter used in all hospital settings to assess a patient's health status. Arterial pressure (ABP) is an important physiological parameter related to medical diagnosis, prevention, and treatment guidance. Invasive measurement—the gold standard—allows for the most accurate continuous measurement, but can only be performed by trained healthcare professionals and is primarily applied in acute settings where real-time alerts and extremely strict monitoring are required.

[0003] The established method for non-invasively measuring blood pressure is using an upper arm cuff (NIBP = non-invasive blood pressure). While NIBP measurements are practical, they are only intermittent and therefore need to be repeated (usually automatically) for monitoring purposes, for example, every few minutes during surgery or typically every 15 minutes in the ICU. Most NIBP measurements for patient monitoring are performed using standard cuff-based ABP measurements with automated oscillometry that enables intermittent measurements. The need for continuous and highly accurate non-invasive blood pressure measurement techniques remains unmet. To avoid missing the onset of hypotension (or hypertension) symptoms associated with adverse patient outcomes, the ability to obtain continuous non-invasive blood pressure information between measurement intervals is a crucial differentiating factor.

[0004] A sophisticated method to achieve this is to utilize continuous physiological signals, already available in acute care settings, and infer continuous blood pressure information (continuous BP surrogate parameters) from those signals. This minimizes additional costs and remains unaffected by the clinical workflow.

[0005] For continuous NIBP measurements, several specialized devices exist, such as finger cuff devices. However, these are not yet widely adopted in hospitals. This is due not only to various problems related to a lack of accuracy and robustness, but also to additional costs and negative impacts on the clinical workflow.

[0006] A continuous, non-invasive method of blood pressure measurement is based on BP surrogates. BP surrogates are well-known parameters such as pulse wave time (PTT) and pulse wave arrival time (PAT), pulse wave velocity, or combinations thereof. Using these parameters, blood pressure can be estimated non-invasively and continuously without the use of external pressure, except for reference or initialization purposes, often referred to as calibration. Calibration is a critical issue in practical applications in clinical settings and home environments.

[0007] U.S. Patent Application Publication 2010 / 160798A1 discloses a technique for continuously measuring blood pressure (BP) based on PTT, without requiring any external calibration. This technique is performed using a body-worn monitor that measures BP and other biometric information and transmits them wirelessly to a remote monitor. Typically, a network of body-worn sensors, positioned on the patient's right arm and chest, is connected to the monitor to measure time-dependent ECG, PPG, accelerometer, and pressure waveforms. The sensors may include a cuff featuring an inflatable air bladder coupled to a pressure sensor, three or more electrical sensors (e.g., electrodes), three or more accelerometers, a temperature sensor, and an optical sensor (e.g., a light source and photodiode) attached to the patient's thumb. A dedicated PTT change is obtained during a controlled decrease in transwall pressure under the cuff. [Overview of the project]

Problems to be Solved by the Invention

[0008] An object of the present invention is to provide a device, a system, and a method that can further improve the accuracy of continuous and non-invasive BP measurement using a BP surrogate.

Means for Solving the Problems

[0009] In one aspect of the present invention, there is provided a device for calibrating a BP surrogate used when monitoring the blood pressure of a subject, the device comprising: a BP input unit configured to obtain a value of a time-dependent cuff pressure during inflation of a cuff of a pressure delivery system attached to a body part of the subject and also to obtain a BP measurement value; a sensor input unit configured to obtain a first time-dependent sensor signal and a second time-dependent sensor signal, which are related to the heartbeat of the subject and are measured at different parts of the subject's body during inflation of the cuff; a processing unit wherein the processing unit is configured to: - use a first feature of the first time-dependent sensor signal and a second feature of the second time-dependent sensor signal during inflation of the cuff to calculate a value related to the pulse from the first and second time-dependent sensor signals, the value related to the pulse being a value of the pulse arrival time PAT or a value of the pulse transit time PTT; - select a pair of a value related to the pulse and a corresponding value of the cuff pressure for calculating a calibration parameter of the BP surrogate, the pair including a value related to the pulse and a corresponding temporally related value of the cuff pressure, and only pairs of a value related to the pulse and a corresponding value of the cuff pressure that satisfy one or more predetermined conditions regarding BP and / or the cuff pressure are selected; - calculate a calibration parameter of the BP surrogate from the BP measurement value and the selected pair of a value related to the pulse and a corresponding value of the cuff pressure is configured.

[0010] In a further aspect of the present invention, there is provided a system for calibrating a BP surrogate for use when monitoring the blood pressure of a subject, the system comprising: A pressure delivery system comprising a cuff configured to be attached to a body part of a subject and to deliver pressure to the body part of the subject by inflating the cuff; A pressure sensor configured to obtain a value of a time-dependent cuff pressure and to obtain or estimate a BP measurement value during inflation of the cuff of the pressure delivery system attached to the body part of the subject; A first sensor configured to be attached to a first part of the body of the subject and to obtain a first time-dependent sensor signal related to the heartbeat of the subject during inflation of the cuff; A second sensor configured to be attached to a second part of the body of the subject and to obtain a second time-dependent sensor signal related to the heartbeat of the subject during inflation of the cuff; The device that calculates calibration parameters for calibrating a BP surrogate from the BP measurement value, the value of the time-dependent cuff pressure, and the first and second time-dependent sensor signals and comprising.

[0011] In yet another aspect of the present invention, there is provided a corresponding method, a computer program having program code means which, when executed on a computer, causes the computer to execute the steps of the method disclosed herein, and a non-transitory computer-readable recording medium storing internally a computer program product which, when executed by a processor, causes the method disclosed herein to be executed.

[0012] Preferred embodiments of the present invention are defined in the dependent claims. It should be understood that the methods, systems, computer programs, and media described in the claims have preferred embodiments that are similar and / or identical to those defined in the dependent claims and disclosed herein for the devices specifically.

[0013] This invention enables a reliable, personalized calibration procedure (sometimes called an initiation or initialization procedure) by utilizing the fact that cuff inflation causes relevant changes in a well-defined blood pressure surrogate. Insights into the physiological effects during cuff inflation have resulted in optimized methods and procedures used to calculate one or more calibration parameters. A reliably calibrated blood pressure surrogate allows for highly accurate, non-invasive tracking of blood pressure. That is, by using a calibrated BP surrogate, a set of initially undetermined / undefined parameters can be translated into blood pressure with meaningful clinical parameters.

[0014] This invention is based on research showing that changes in PAT (or PTT) during cuff pressurization are distorted by dynamic filling effects resulting from venous occlusion in the forearm (or, more generally, the peripheral region of the body part of the subject to which the cuff is placed). This finding influences the method of acquiring one or more calibration parameters. For example, parameter regression, which is one of the preferred options for calculating one or more calibration parameters, is affected, and this must be addressed in order to estimate the sensitivity parameter. This effect has been observed and interpreted from invasively measured BP signals acquired peripherally to the cuff, e.g., the forearm if the cuff is placed on the upper arm, or the lower limb if the cuff is placed on the upper leg.

[0015] According to the present invention, one or more conditions (or criteria) are used to select pairs of pulse-related values ​​and corresponding cuff pressure values, which are used to calculate calibration parameters for the BP surrogate for later estimation of BP. These conditions relate to BP and / or cuff pressure. That is, depending on BP and / or cuff pressure, it is determined whether the pairs of pulse-related values ​​and corresponding cuff pressure values ​​are used to calculate the calibration parameters for the BP surrogate. There are several embodiments relating to such conditions, as will be described in detail below.

[0016] According to one embodiment, the processing unit is configured to calculate calibration parameters for the BP surrogate using only pairs of pulse-related values ​​and corresponding cuff pressure values, calculated from first and second time-dependent sensor signals measured during partial cuff inflation. It has been found that at high cuff pressures, unreliable pulse signals do not appear in the peripheral parts of the body where the cuff is placed, due to pulse distortion. This adversely affects the calculation of calibration parameters when pairs of values ​​calculated from sensor signals measured when the cuff is fully or nearly fully inflated are used. In this embodiment, since only pulse signals with a defined relationship to BP are considered, these adverse effects are avoided, thereby improving the accuracy of calibration and, ultimately, improving BP determination by using a calibrated BP surrogate.

[0017] The processing unit is configured, according to another embodiment, to calculate the calibration parameters for the BP surrogate using only pairs of pulse-related values ​​and corresponding cuff pressure values, where the peripheral BP is substantially constant, particularly with a variation of less than 10% or less than 5%. Other moderate values ​​are used in a similar manner. As described above, a similar effect can be obtained in this way, but different conditions are used for selecting the pairs of values ​​to be calculated.

[0018] The processing unit is configured to determine, based on the first and / or second time-dependent sensor signals, whether the peripheral BP is substantially constant. For this purpose, for example, a period is determined in which the amplitude of the second time-dependent signal is substantially constant, particularly when the fluctuation is less than 10% or less than 5% (or any other arbitrary reasonable threshold predetermined or set by the user) of the previously acquired average value. This previously acquired average value refers to the previous average value of the second time-dependent signal.

[0019] The processing unit is further configured to calculate the calibration parameters for the BP surrogate using only pairs of pulse-related values ​​and corresponding cuff pressure values ​​where the cuff pressure value is below the subject's diastolic BP, particularly the subject's most recent diastolic BP measured, or below the subject's average BP, particularly the subject's most recent average BP measured, or below a set cuff pressure threshold. This enables a fairly simple but efficient embodiment of the disclosed solution.

[0020] In another embodiment, the processing unit is configured to calculate the calibration parameters for the BP surrogate using only pairs of pulse-related values ​​and corresponding cuff pressure values, where the cuff pressure values ​​are within a range between a set minimum cuff pressure and a set maximum cuff pressure, particularly when the minimum cuff pressure is set to a range of 10 to 30 mmHg and the maximum cuff pressure is set to a range of 40 to 90 mmHg (or within a range defined by other reasonable values). This, likewise, enables a fairly simple but efficient embodiment of the disclosed solution.

[0021] In further embodiments, the processing unit is configured to calculate the calibration parameters for the BP surrogate using only pairs of pulse-related values ​​and corresponding cuff pressure values, provided that the pulse-related values ​​are substantially constant, particularly with a variation of less than 10% (or any other reasonable value), or until the gradient of the curve of the pulse-related values ​​over time exceeds a threshold. In such embodiments, other readily implementable conditions are utilized.

[0022] The processing unit is further configured to calculate control signals for controlling the pressure delivery system to inflate the cuff of the pressure delivery system, specifically to fully inflate the cuff to acquire BP measurements, and to partially inflate the cuff to acquire a first time-dependent sensor signal and a second time-dependent sensor signal. The device thus can actively control the inflation of the cuff as needed in acquiring sensor signals used for BP measurement or determination of calibration parameters. BP measurements used for calibration (i.e., calculation of calibration parameters) are acquired through BP measurement by the BP measurement device.

[0023] In a preferred embodiment, the first time-dependent sensor signal is an ECG signal, and / or the second time-dependent sensor signal is a photoplethysmography (PPG) signal, particularly a contact PPG signal or a remotely acquired PPG signal (e.g., acquired by a camera used in remote PPG). Other signals relating to the subject's heart rate and enabling the calculation of PAT and / or PTT can be used additionally or as substitutes. For example, bioimpedance or a cuff signal can be used instead of a PPG signal. ECG and PPG signals are commonly known signals, and PAT and / or PTT can be calculated from the ECG and PPG signals in a commonly known manner, which can also be used in the devices and methods of the present invention.

[0024] In one embodiment, the processing unit is more preferably configured to calculate calibration parameters using regression. The calibration parameters are calculated, for example, as the gradient of the dependence of the blood pressure relationship, which is a function of the blood pressure surrogate at zero cuff pressure. The regression derives a parameterized functional relationship between transwall blood pressure and the BP surrogate, which serves as a transfer function for estimating blood pressure from the BP surrogate when the cuff is not inflated (cuff pressure is zero). Further details are described, for example, in "Surrogate based continuous noninvasive blood pressure measurement", Pielmus, AG, Muhlsteff, J., Bresch, E., Glos, M., Jungen, C., Mieke, S., Zaunseder, S., Biomedical Engineering / Biomedizinische Technik, 66(3), pp. 231-245, 2021.

[0025] The processing unit is further configured to determine the BP value when pressure is not delivered to the subject's body by the pressure delivery system, using the calculated BP surrogate and first and second time-dependent sensor signals measured at different parts of the subject's body when pressure is not delivered to that part of the subject's body. This allows for unobtrusive determination of the subject's BP without inflating the cuff. In other words, the subject's BP can be continuously monitored without causing discomfort or injury to the patient by inflating the cuff.

[0026] The system described in the claims further comprises a control unit configured to control a pressure delivery system based, for example, on control signals supplied by the device or calculated by the system. The control unit is either part of the device or located externally.

[0027] The present invention may also be used in combination with one or more of the following embodiments.

[0028] In one embodiment, the processing unit is: - Calculate a control signal to control the pressure delivery system so that, with partial inflation, the cuff of the pressure delivery system is repeatedly inflated to a cuff pressure below the subject's systolic blood pressure (BP), - Using the first characteristic of the first time-dependent sensor signal and the second characteristic of the second time-dependent sensor signal, a pulse-related value is calculated from the first and second time-dependent sensor signals measured during repeated partial inflation of the cuff, and the pulse-related value is the pulse wave arrival time PAT or the pulse wave propagation time PTT. - The system is configured to calculate calibration parameters for the BP surrogate from BP measurements and pairs of pulse-related values ​​and corresponding cuff pressure values ​​calculated from first and second time-dependent sensor signals measured during repeated partial inflation of the cuff, the pair including a pulse-related value and a corresponding time-related cuff pressure value.

[0029] According to this embodiment, only low cuff pressure levels are used for calibration; that is, the cuff is only partially inflated for data acquisition. Repeated sampling at such appropriate cuff pressure levels can be performed over a sufficiently short period of time so that the BP level stabilizes and there are no changes that distort the calibration process. Furthermore, the repetition of inflation gradients (with or without pauses between gradients) is made possible by the low maximum pressure. There is no need to wait for the tissues and arteries to recover from high pressurization (i.e., there is no hysteresis effect).

[0030] Lower cuff pressure levels, especially those below diastolic pressure, are less disruptive to the patient, particularly an awake patient, resulting in less discomfort and skin stress than a full inflation gradient exceeding systolic pressure. Another advantage is that it does not impose extra requirements on the pressure delivery system of the NIBP device.

[0031] The BP measurements used for calibration (i.e., for calculating calibration parameters) are obtained through BP measurements using a BP measuring device.

[0032] There are various embodiments for controlling the pressure delivery system during repeated partial expansion. All embodiments contribute to improved calibration accuracy by further attempting to avoid the undesirable dynamic filling effects mentioned above, which ultimately improves BP determination by using a calibrated BP surrogate.

[0033] In one embodiment, the processing unit is configured to calculate a control signal for controlling the pressure delivery system to inflate the cuff of the pressure delivery system with partial expansion during periods when the peripheral BP is substantially constant, particularly when the variation is less than 10 percent or less than 5 percent. Other moderate values ​​are used similarly.

[0034] The processing unit is configured to determine whether the peripheral BP is substantially constant by determining, based on the first and / or second time-dependent sensor signals, that the amplitude of the second time-dependent signal is substantially constant, in particular, that the fluctuation is less than 10 percent or less than 5 percent (or any other arbitrary reasonable threshold predetermined or set by the user) of the previously acquired mean value. The previously acquired mean value refers to the previous mean value of the second time-dependent signal.

[0035] According to another embodiment, the processing unit is configured to calculate a control signal for controlling the pressure delivery system to inflate the cuff of the pressure delivery system in partial inflation to the subject's diastolic BP, in particular to the subject's most recent measured diastolic BP, the subject's average BP, in particular to the subject's most recent measured average BP, or to a set threshold BP. This enables a fairly simple but efficient embodiment of the solution described and disclosed in the claims.

[0036] The processing unit is configured to control the pressure delivery system and calculate a control signal to partially inflate the cuff of the pressure delivery system so that the PAT exceeds the PAT threshold, specifically the absolute threshold of PAT, or the relative threshold of PAT compared to the baseline PAT. The processing unit is thus configured to calculate the baseline PAT by averaging the PAT measurements over a period of time, specifically in the range of 10 seconds to 5 minutes (other appropriate values ​​are also possible). The appropriate threshold for relative change, i.e., PAT compared to the baseline PAT, is, for example, in the range of 10 to 60 milliseconds, e.g., 30 milliseconds.

[0037] In another embodiment, the processing unit is configured to calculate a control signal for controlling the pressure delivery system such that the cuff of the pressure delivery system is partially inflated to a cuff pressure where the amplitude of a second time-dependent signal exceeds an amplitude threshold, particularly an absolute or relative amplitude threshold. Such criteria can be easily set by the user or predetermined. A reasonable threshold for relative change is, for example, in the range of 5 to 20%, for example, 10%.

[0038] The processing unit is configured to calculate a control signal to control the pressure delivery system so that the cuff of the pressure delivery system is partially inflated at a predetermined inflation rate, or at an inflation rate that varies depending on one or more of the subject's heart rate, the subject's diastolic BP, the subject's mean BP, and the subject's systolic BP.

[0039] In actual embodiments, the processing unit is - Calculate a control signal to control the pressure delivery system so that the cuff of the pressure delivery system is deflated after each iteration of partial inflation. - i) For each iteration, use the respective regression to calculate one or more calibration parameters from the pairs of pulse-related values ​​obtained in each iteration and the corresponding cuff pressure values, average the respective calibration parameters calculated over two or more iterations to obtain one or more average calibration parameters for use with the BP surrogate, or - ii) Calculate one or more calibration parameters from pairs of pulse-related values ​​and corresponding cuff pressure values ​​obtained in a single regression over two or more iterations. It is structured in such a way.

[0040] Both options i) and ii) lead to improved accuracy, depending on the context and application of the disclosed device and method. Note that the applied cuff pressure causes a change in transwall pressure below the cuff.

[0041] In another embodiment, the processing unit is configured to use a BP surrogate to calculate a control signal for controlling the pressure delivery system to inflate the cuff of the pressure delivery system with a full inflation exceeding the subject's systolic BP, before and / or after one or more partial inflation repetitions, in order to obtain a time-dependent BP reference measurement for use when monitoring the subject's BP. The last measured BP value is used, among other things, to calculate calibration parameters.

[0042] The processing unit is further configured to control the number of times partial expansion is repeated based on a comparison of the regression error with the regression error threshold. The processing unit is also configured to control whether and when to perform a full expansion, according to a fixed or variable schedule, or if one or more calibration parameters have changed significantly in the last calculation, particularly by more than 10 percent (or more than 15 or 20 percent). Thus, a trade-off is made between additional measurement time / effort and improved calibration accuracy.

[0043] The processing unit is further configured to determine the BP value when pressure is not delivered to the subject's body by the pressure delivery system, using the calculated BP surrogate and first and second time-dependent sensor signals measured at various parts of the subject's body when pressure is not delivered to that part of the subject's body. This allows for uninterrupted determination of the subject's BP without inflating the cuff. In other words, the subject's BP can be continuously monitored without causing discomfort or injury to the patient by inflating the cuff.

[0044] In a preferred embodiment, the first time-dependent sensor signal is an ECG signal, and / or the second time-dependent sensor signal is a photoplethysmography (PPG) signal, particularly a contact PPG signal or a remote PPG signal. Other signals relating to the subject's heart rate and enabling the calculation of PAT and / or PTT can be used additionally or as an alternative. The ECG and PPG signals are commonly known signals, and PAT and / or PTT can be calculated from the ECG and PPG signals in a commonly known manner, which can also be used in the disclosed devices and methods.

[0045] These and other aspects of the present invention will become apparent from the embodiments described herein and will be clarified with reference to those embodiments. [Brief explanation of the drawing]

[0046] [Figure 1] This is a schematic diagram of one embodiment of the overall concept of the present invention. [Figure 2] This is a diagram showing the ECG signal and PPG signal, with PAT indicated. [Figure 3] This figure shows a comparison of robust versus non-robust regression in the case of a linear model. [Figure 4] This is an example of an increase in PAT caused during cuff inflation. [Figure 5] This is a diagram illustrating the overall concept of proofreading. [Figure 6] This is a schematic diagram of equipment commonly used in general concepts for acquiring invasively measured BP signals peripherally to a cuff. [Figure 7] This is a diagram of the signals measured using the equipment shown in Figure 5. [Figure 8] This figure shows an analysis of the inflation process that affects blood pressure measured at the posterior periphery of the cuff. [Figure 9] This is a diagram of transwall blood pressure versus measured PAT. [Figure 10] This is a diagram of one embodiment of the system according to the present invention. [Figure 11] This is a diagram of one embodiment of the device according to the present invention. [Figure 12] This is a diagram of one embodiment of the method according to the present invention. [Figure 13] This is a diagram showing the PAT value versus the Pcuff value during the entire cuff expansion process. [Figure 14] This figure shows another embodiment of a method using the present invention. [Figure 15] This figure shows that only the Pcuff / PAT value pair is used unless the PPG signal features indicate changes in pulse pressure in the peripheral arm. [Figure 16] This figure shows another embodiment of a method using the present invention. [Figure 17] This figure shows an example of fitting a parameterized model to pairs of measurement data obtained during the complete and partial expansion processes. [Figure 18] This is a diagram of another embodiment of the method according to the present invention. [Figure 19] This figure shows one embodiment of a cuff pressure profile, including two partial inflations followed by a full inflation. [Figure 20] This figure shows one embodiment of a cuff pressure profile, including full inflation and two subsequent partial inflations. [Figure 21] This figure shows one embodiment of a cuff pressure profile that allows for continuous tracking of the need for recalibration through repeated partial expansion. [Modes for carrying out the invention]

[0047] This invention relates to the development of an ABP measurement technique that enables accurate and continuous blood pressure monitoring. Interval BP tracking in standard cuff-based, non-invasive, intermittent blood pressure measurements is based on a recalibrated / initialized blood pressure surrogate. Calibration is performed using the NIBP measurement itself (systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MBP)), as well as the inflation / deflation process of the NIBP measurement, which introduces disturbances related to the controlled BP in the surrogate signal. The surrogate is acquired from, or using a combination of, features of signals related to the subject's heart rate, such as an electrocardiogram (ECG) or photoplethysmography (PPG). These signals are routinely acquired in such settings.

[0048] Since the sensor embodiment is small and lightweight and provides comfortable, nearly continuous, non-invasive ABP measurement, the present invention focuses on a method that assists in pulse wave velocity ABP measurement without other interference. An embodiment of this concept is schematically shown in Figure 1. In this embodiment, ECG signals and PPG signals are obtained (block 100), which are received or retrieved, for example, from the respective sensor (acquiring these signals) or from a buffer or memory (where these signals are buffered or stored), and used to continuously determine a BP surrogate (block 101). This BP surrogate can then be used as an indicator of BP change (block 102). At any time, or when a significant BP change is indicated (used as a trigger), the NIBP cuff is activated (block 103), the BP surrogate is recalibrated, and BP readings are obtained by an oscillometry method, for example, an accepted standard oscillometry method. The BP determination obtained by using cuff inflation and the BP surrogate is reported (block 104).

[0049] This concept does not require additional sensors, can use readily available sensors, can be implemented solely through software, and has low barriers to clinical acceptance. Advantages include early intervention through early detection of blood pressure changes, reduced complications by decreasing the use of arterial lines, and improved drug dosage setting through more appropriate tracking of blood pressure responses.

[0050] Embodiments of this method refer to the use of PAT, a BP surrogate. PAT is defined as the time interval between the peak of the R wave in an ECG and the rise of the pulse in a peripheral pulse wave analysis. PAT has been extensively studied as a surrogate measure of blood pressure and vascular stiffness. PAT is the sum of pre-ejection time (PEP) and pulse time to pulse time (PTT). PEP refers to the time required for isovolumetric ventricular contraction to aortic valve opening (AVO), while PTT is the intrinsic transit time of the pressure pulse over the long, heterogeneous vascular pathway along the arterial wall. Only PTT relates to the propagation of pressure-dependent arterial waves, modeled by the Maines-Korte-Beek equation. PEP is a variety of additional delays that are susceptible to stress, emotion, and physical effort. The main advantage of PAT over PTT is that only one transducer (e.g., a PPG sensor) that is susceptible to location-dependent issues needs to be precisely positioned.

[0051] Figure 2 shows the ECG signal 110 and PPG signal 111 (quoted from "An Optimization Study of Estimating Blood Pressure Models Based on Pulse Arrival Time for Continuous Monitoring," Shao, J. et al.), where PAT is shown as the time delay between the R peak of the ECG signal and the feature point of the peripheral PPG signal. In this example, the maximum derivative (Dmax) is selected as the feature point.

[0052] A system that uses PAT to continuously estimate BP between NIBP measurements requires no additional devices (hardware), assuming that time-synchronized PPG and ECG sensors (and / or corresponding signals) are available. This system therefore represents a software-only approach to continuous BP estimation in a clinical setting.

[0053] Changes in PAT are inversely proportional to changes in BP. When BP increases, transwall pressure in the artery increases, leading to decreased arterial wall extensibility. As a result, the propagation time of the blood pulse wave becomes faster, and therefore the time it takes for the pulse wave to reach the periphery decreases. Conversely, when BP decreases, PAT lengthens. The exact transfer function from BP to PAT depends on many factors, including the characteristics and geometry of the patient's arteries and the cardiac prodromal period (PEP). Furthermore, the transfer function is not static but changes over time as the patient's hemodynamic state, i.e., the characteristics of the arteries (e.g., arterial smooth muscle or PEP), changes.

[0054] However, the transfer functions of BP and PAT can be modeled by fairly simple models with two or three parameters (e.g., proportional-linear, logarithmic, reciprocal, inverse square, etc.). For example, considering a simple linear model (BP = m1·PAT + m2), the two patient-specific parameters are the offset parameter m2 and the sensitivity parameter (gradient) m1. In order to actually apply the transfer function to continuously estimate blood pressure from continuous PAT values, it is necessary to "learn" the patient-specific parameters. This is called calibration. Furthermore, it is preferable that changes in these parameters be tracked. That is, it is preferable that calibration be repeated when the model parameters (i.e., calibration parameters) are changing. This is called recalibration.

[0055] Model calibration is typically performed using parameter regression. That is, given multiple (BP, PAT) data pairs, a model curve can be fitted to the data points by applying some optimality criterion (such as least squares), and the optimal values ​​for the model parameters can be obtained based on the given data. The wider the range of BP and PAT values, the more appropriate (more accurate) the determined parameters become.

[0056] Figure 3 illustrates robust versus non-robust regression in the case of a linear model, specifically showing a linear model of a surrogate fitted to a data pair of blood pressure and a surrogate. Two parameters, offset and slope (or sensitivity parameter), are determined by the regression. The regression is not robust in the figure shown in Figure 3A because the values ​​of the data pair (indicated by x) are too similar. In contrast, the regression shown in Figure 3B is very robust because the available values ​​of the data pair are spread over a wider range.

[0057] In practice, achieving robust calibration of the model is a critical challenge in ensuring that BP surrogates can be reliably used for the uninterrupted determination and monitoring of a subject's blood pressure. Regression using multiple NIBP and PAT measurements taken over a short period presents a problem: the measured NIBP and PAT values ​​are too similar, resulting in a poorly fitting curve. Improving the curve's fit would require altering the patient's blood pressure level, which is usually impossible, harmful to the patient, and impractical without changing arterial wall stiffness.

[0058] Furthermore, since the transwall pressure of the arterial portion below the cuff decreases, an increase in PAT can be measured in relation to the applied cuff pressure. This is illustrated in Figure 4, which shows an example of an increase in PAT 120 caused during cuff inflation 121. Cuff pressure changes the transwall pressure of the arterial portion. The PAT value is acquired for each pulse in sync with the cuff pressure. More precisely, this sequence is applied to the arterial portion above the cuff. To estimate BP, a scaling factor must be incorporated to scale the entire arterial portion in which the distal pulse sensor is located.

[0059] Using the acquired PAT pair, along with the synchronously acquired cuff pressure and BP values, a PAT / BP sensitivity parameter S can be derived, thereby enabling BP tracking. This is illustrated in Figure 5, which shows a schematic diagram illustrating the overall concept of calibration. During cuff inflation, an increase in PAT occurs, from which, together with the synchronously acquired cuff pressure and derived BP (using oscillometry), a sensitivity parameter S for tracking BP is derived. The subject-specific scaling factor is expressed as k in the formula. Two examples of mathematical models using the estimated sensitivity parameter S for tracking BP are shown, and these are used according to embodiments of this disclosure.

[0060] Figure 6 shows a schematic diagram of exemplary equipment used in a general concept for acquiring an invasively measured BP signal acquired distal to the cuff. Note that invasive BP measurement is primarily shown here to clarify the change in BP distal to the cuff. New insights and understandings have been found in physiological processes that affect the calibration process and underlying assumptions for robust and accurate regression of the sensitivity parameter S. In particular, it has been found that changes in PAT during cuff inflation are distorted by venous occlusion (which affects arterial blood pressure and causes adverse effects) and the dynamic filling effect of the forearm, due to the venous capacity that stores blood in the arm. This finding affects the parameter regression and needs to be addressed in order to reliably infer the sensitivity parameter S.

[0061] Figure 7 shows the signals measured using the equipment shown in Figure 6. Figure 7A shows the ECG signal. Figure 7B shows the cuff signal. Figure 7C shows the radial BP / A-line (representing the invasive BP signal). Figure 7D shows the PPG signal.

[0062] Current calibration methods (applying cuff pressure to alter PAT subcuff) are affected by nonlinear dynamic filling effects in the peripheral artery tree of the arm. The observed process can be subdivided into various stages depending on its impact on mathematical modeling capabilities and the inclusion / exclusion of results in data pairs. Figure 8 shows an analysis of the inflation process with respect to blood pressure measured distally behind the cuff. Various processes affecting PAT can be identified. A fundamental assumption for successful calibration, independent of complex model assumptions, is that peripheral blood pressure in the peripheral arm is constant, which is assumed to exist only at lower cuff pressures.

[0063] These findings are shown in Figure 9, transwall blood pressure (SBP-P cuff Identify the various regions in the graph of the measured PAT (on the x-axis) versus the measured PAT (on the y-axis). A typical increase in PAT during cuff inflation is observed, and at least three zones A, B, and C can be distinguished. In zone A, the arm is compressed at a lower cuff pressure, and the arm volume changes significantly. Peripheral blood pressure does not change at this stage due to cuff inflation. In zone B, arterial peripheral blood pressure is still unaffected by cuff inflation. In zone C, a nonlinear dynamic process is observed in the peripheral blood pressure signal. Zone C is related to the cuff pressure region and the blood pressure in the peripheral arm changes, so it should not be included in the calibration procedure.

[0064] However, regression models assume a constant BP for a given transwall pressure during expansion at a specific moment in the pulse phase (e.g., systolic, mean, diastolic).

[0065] The wall pressure is P trans (t)=P arterial (t)-P cuff(t) is defined. An important condition for reliable regression during cuff expansion / contraction is the time-dependent P trans (t) is P cuff This means that it must depend on the time dependence of (t), and (for a specific moment of the pulse) P arterial = It only needs to be constant. This suggests that for reliable regression, the internal arterial pressure should not be affected by cuff inflation (explained in detail in Figure 9).

[0066] In one exemplary regression method described in U.S. Patent Application Publication 2010 / 160798A1, the PAT value is included only when the cuff pressure is higher than DBP. However, as shown in Figure 9 and indicated as Zone C, at such cuff pressures, peripheral arm blood pressure changes relative to BP at zero cuff pressure and also changes with cuff inflation. The calibration concept disclosed in U.S. Patent Application Publication 2010 / 160798A1 should therefore be improved, even if applicable within the scope of this disclosure. Considering the findings of the present invention, at cuff pressures higher than diastolic blood pressure, complex nonlinear regression models are applied that depend on the effects of vascular resistance, arterial occlusion, venous occlusion, and pulse distortion. Typically, such parameters are not available. To address these challenges, alternative strategies are needed for calibration methods.

[0067] Impacts on blood pressure monitoring include inaccurate blood pressure calibration leading to unreliable BP estimates that result in false alarms or delayed interventions, and delays in intervention, affecting the outcomes of the affected patients. In contrast to the current technology, this invention addresses a solution that includes PAT as calibration data only when appropriately defined criteria are valid.

[0068] Figure 10 shows a diagram of one embodiment of a system 1 for calibrating a BP surrogate used when monitoring the blood pressure of a subject, according to the present invention.

[0069] System 1 comprises a pressure delivery system 10 having a cuff 11 that is attached to a part of a subject's body and configured to deliver pressure to that part of the subject's body by inflating the cuff. The cuff 11 can be attached to the subject's limbs, specifically the upper arm, upper leg, or wrist, and such a pressure delivery system 10 is generally known in the art of NIBP measurement. The pressure delivery system generally comprises a pressure generating unit, e.g., a pump or accumulator, configured to inflate the cuff 11, a valve configured to deflate the cuff 11, and a processor configured to control the pressure generating unit and valve and to determine the subject's blood pressure based on the measured cuff pressure. A user interface is provided, for example, including one or more of a display, keypad, speaker, and touchpad, to output the measured BP value in a visible and / or audible form.

[0070] System 1 further comprises a pressure sensor 20 configured to acquire a time-dependent cuff pressure value during cuff inflation of a pressure delivery system attached to a part of the subject's body, thereby obtaining a BP measurement. Typically, the pressure sensor 20 is not attached directly to the subject's body, but rather the cuff 11 is attached to the body, and the pressure sensor 20 is attached (in the pressure delivery system) to an air tube from the cuff 11. Thus, for example, the pressure sensor 20 in the form of a pressure transducer is incorporated into the cuff and implemented as a conventional BP sensor. Other means of detecting cuff pressure by applying external pressure, such as a shell cuff design, are also possible.

[0071] System 1 further comprises a first sensor 30 attached to a first part of the subject's body, the first sensor 30 configured to acquire a first time-dependent sensor signal relating to the subject's heart rate while the cuff is inflated. The first sensor 30 is an ECG sensor that acquires an ECG signal. The first part is preferably, for example, the subject's chest or torso to which ECG electrodes are attached for ECG measurement.

[0072] System 1 further comprises a second sensor 40 attached to a second part of the subject's body, configured to acquire a second time-dependent sensor signal related to the subject's heartbeat, which is acquired by the inflation of the cuff. The second sensor 40 is a PPG sensor, for example, a contact PPG sensor (such as a pulse oximetry sensor having one or more LEDs that emit light in the visible and / or infrared range, e.g., red light and infrared light), or a camera or photodetector, known as a remote PPG sensor (e.g., "Remote plethysmographic imaging using ambient light", Verkruysse et al., Optics Express, 16(26), pp. 21434-21445, December 22, 2008). PPG generally refers to the optical measurement of volume changes in organs or body parts, specifically the detection of volume changes due to cardiovascular pulse waves transmitted through the subject's body with each heartbeat. The system can detect radiation reflected from or transmitted through the skin area of ​​the subject. The second site is, for example, the subject's hand or fingers to which a contact-type PPG sensor is attached or monitored by a remote PPG sensor. The second site is generally a peripheral site to the first site. For example, if the cuff is attached to the left upper arm, the second site is the left hand or fingers of the left hand to which a second sensor is attached or monitored by the second sensor.

[0073] The first and second signals are generally acquired and sampled synchronously. Additional or alternative signals other than the ECG and PPG signals that relate to the subject's heart rate and enable the calculation of PAT and / or PTT may be used, such as sensors that detect heart sounds and sensors that detect chest vibrations.

[0074] System 1 further comprises a device 50, disclosed and described herein, for calculating calibration parameters for calibrating a BP surrogate from BP measurements, time-dependent cuff pressure values, and first and second time-dependent sensor signals. Device 50 is further optionally configured to determine and monitor the subject's BP using the BP surrogate.

[0075] System 1 further comprises an output interface 60, which is optionally configured to output any determined information, such as the BP value of a subject determined and monitored by the use of a BP surrogate. The output interface 60 is generally any means of outputting information in a visual or audible form, such as text, images or diagrams, audio or spoken language. The output interface 60 is, for example, a display, speaker, touchscreen, computer monitor, smartphone or tablet screen, etc.

[0076] System 1 optionally further comprises a control unit 70 configured to control the pressure delivery system 10 based, for example, on a control signal supplied by device 50 or calculated by system 1. The control unit 70 may be part of device 50 or located externally.

[0077] Figure 11 shows a diagram of one embodiment of a device 50 for calibrating a BP surrogate, used when monitoring the blood pressure of a subject, according to the present invention.

[0078] Device 50 includes a BP input unit 51 configured to acquire time-dependent cuff pressure values ​​and BP measurements during inflation of a cuff 11 of a pressure delivery system attached to a part of the subject's body. Device 50 further includes a sensor input unit 52 configured to acquire a first time-dependent sensor signal and a second time-dependent sensor signal related to the subject's heart rate and measured at different parts of the subject's body during cuff inflation. The BP input unit 51 and the sensor input unit 52 are either directly coupled to or connected to the cuff 11 and the first and second sensors 30, 40, or acquire (i.e., retrieve or receive) these signals from a storage device, buffer, network, or bus. The input units 51 and 52 are therefore (wired or wireless) communication interfaces or data interfaces, such as a Bluetooth® interface, WiFi interface, LAN interface, HDMI® interface, direct cable connection, or any other suitable interface that enables signal transmission to Device 50.

[0079] Device 50 further comprises a processing unit 53. The processing unit 53 is any kind of means configured to process signals and determine calibration parameters for calibrating the BP surrogate. The processing unit is further configured to determine and monitor the subject's BP using the BP surrogate. The processing unit is implemented in software and / or hardware, such as a programmed processor, computer, or app on a user device, such as a smartphone, smartwatch, tablet, laptop, PC, or workstation.

[0080] Device 50 further comprises an output unit 54 configured to output any determined information. The output unit 54 is generally an arbitrary interface that supplies the determined information, for example, by transmitting the determined information to another device or making it available to another device (e.g., a smartphone, computer, tablet, etc.). The output unit is therefore generally an arbitrary (wired or wireless) communication or data interface.

[0081] Figure 12 shows a diagram of one embodiment of Method 200 according to the present invention. The steps of Method 200 are performed by device 50, and the main steps of the Method are performed by processing unit 53. The Method is implemented as a computer program that runs on a computer or processor.

[0082] In the first step 201, a time-dependent cuff pressure value is acquired while the cuff of a pressure delivery system attached to a part of the subject's body is inflated. In the second step 202, a BP measurement is acquired. In the third step 203, a first time-dependent sensor signal and a second time-dependent sensor signal are acquired, relating to the subject's heart rate and measured at different parts of the subject's body while the cuff is inflated. Note that the order of steps 201 to 203 does not indicate a chronological order, and these steps may be performed in any chronological order. Steps 201 and 203 are performed simultaneously, and it is preferable that step 202 is performed before or after steps 201 and 203.

[0083] In the fourth step 204, while the cuff is inflated, a pulse-related value is calculated from the first and second time-dependent sensor signals, using the first feature of the first time-dependent sensor signal and the second feature of the second time-dependent sensor signal, and the pulse-related value is the PAT value or the PTT value. The PAT or PTT value is extracted from the first and second signals (e.g., ECG and PPG signals) using an appropriate feature extraction technique. Other features, such as heart rate and morphological features of the PPG, may also be derived from a single signal.

[0084] In the fifth step 205, the calibration parameters of the BP surrogate are calculated from pairs of BP measurements and values related to the pulse and the corresponding cuff pressure values, where the pairs include values related to the pulse and the corresponding cuff pressure values related in time (specifically, values at the same time). Only pairs of values related to the pulse and the corresponding cuff pressure values that satisfy one or more predetermined conditions regarding BP and / or cuff pressure are used in the calculation of the BP surrogate. There are various options for such conditions (or criteria), which will be described below.

[0085] Thus, according to the first main aspect of the present invention, the BP surrogate can be calibrated and then BP can be continuously tracked. The criteria are used in embodiments that include a range of cuff pressures during inflation to reliably calibrate the BP surrogate from pairs of cuff pressure / BP surrogate data, where the transmural pressure is P cuff >0 at P arterial which is appropriately defined as a function of the applied cuff pressure such that it does not change compared to P cuff =0 at P arterial Calibration conventionally required full inflation of the cuff. When calibrating a PAT-based surrogate from continuous inflation-based NIBP measurements as used in embodiments, only PAT values resulting from the cuff pressure level, given by appropriately defined criteria that satisfy physiological constraints, are utilized. Thus, according to one embodiment, certain data (data in zone C of FIG. 9) are discarded. Features of the PPG signal are used as indicating violations of assumptions underlying the applied regression model, such as changes in pulse pressure in the peripheral arterial portion. Features of the envelope of the vibration are used as indicating violations of assumptions underlying the applied regression model, such as the blood pressure range. Thus, a reliable calibration of PAT, which is the patient's BP pressure surrogate, characterizing the cuff inflation process using dedicated procedures and methods is possible.

[0086] In the following description of the BP calibration method by regression of the pair of BP surrogate / cuff pressure, PAT will be used as the BP surrogate. One embodiment is based on including data regarding the PAT data relative to the cuff pressure value only for the cuff pressure during a period where the peripheral blood pressure (i.e., the cuff pressure behind the cuff on the arm when the cuff is placed on the upper arm) is constant, for example with a variation of less than 5 or 10%.

[0087] For a complete cuff inflation with BP estimation, for the BP estimation of SBP, DBP, and MBP, oscillometry is used and typically requires a cuff inflation beyond the systolic BP. Using various criteria, pairs of PAT values and cuff pressure values can be selected for use in determining calibration parameters. For example, one or both of the following criteria are used. - Criterion 1: P cuff <Only for DBP or MBP, the value of PAT / P cuff - Criterion 2: p min <P cuff <DBP, for example, the value of PAT / P when p min = 20 mmHg cuff p min can be defined with respect to the observed effects of tissue compression (Figure 7). At cuff pressures where the tissue volume changes significantly, it may become more difficult to reliably define the transmural pressure across the artery.

[0088] In the figure shown in Figure 13, the data obtained during the complete inflation process of the cuff is shown as points on the graph of PAT vs P cuff The vertical line DBP shows up to which pair of the PAT value (i.e., the value related to the pulse) and the cuff pressure value of P cuff is used for determining the calibration parameter.

[0089] ​​Figure 14 shows a flowchart of one embodiment of method 300 using this aspect of the present invention. In the first step 301, BP measurement is initiated. In the second step 302, PAT / P during the complete inflation process of the cuff is performed. cuff A complete set of data pairs is obtained. In the third step 303, BP values ​​such as systolic blood pressure, diastolic blood pressure, and mean arterial pressure are determined using a standard method. In the fourth step 304, PAT / P cuff The data range of a data pair is restricted according to a predetermined criterion, for example, criterion 1 or criterion 2. In the fifth step 305, regression is performed on the acquired (and restricted) data pair. Finally, in the sixth step 306, BP is estimated from the calibrated PAT data.

[0090] In another embodiment, cuff pressure is used, for example, during the period when the peripheral arm SBP (when the cuff is attached to the upper arm) is kept constant. Figure 15 shows the PPG signal characteristics during the period when the pulse pressure in the peripheral arm blood pressure does not show any change in P cuff The figure illustrates that only the / PAT value pair is used. Figure 15A shows the behavior of the PPG signal during cuff inflation. Figure 15B shows the increase in PAT during inflation. Figure 15C shows the cuff pressure during inflation. The change in PPG amplitude indicates the change in pulse pressure PP in the peripheral artery portion, and the maximum PAT / P should be included in the regression / calibration. cuff It is used as a criterion for defining pairs. The amplitude of the PPG is an example, and the beginning of the decrease in the PPG amplitude indicates that the maximum pressure regression data should be used.

[0091] Figure 16 shows a flowchart of one embodiment of a method 400 using this aspect of the present invention, specifically, a method of using the amplitude change of PPG as a criterion. In the first step 401, BP measurement is initiated. In the second step 402, during the cuff expansion process, the PAT / P is determined for a period in which the amplitude of PPG is constant (or changes less than a predetermined percentage, e.g., 5 or 10%). cuffA set of data pairs is obtained. In the third step 403, a regression is performed on the obtained data. This is done so that, for example, the BP from the previous full expansion is used in this regression. Finally, in the fourth step 404, the BP is estimated from the calibrated PAT data.

[0092] Other criteria may be used as an alternative to, or in addition to, the criteria mentioned above. An example criterion is i) during expansion, for example, PAT-PAT ref <PAT / P when it is the maximum cuff ii) the definition of the maximum change in PAT, including the value, and ii) the behavior of the change in PAT, for example, the observed value of the gradient of PAT.

[0093] Regression of model parameters generally relies on multiple data pairs, namely measured PAT values ​​and corresponding cuff pressure values. This is illustrated in Figure 17, which shows an example of fitting a parameterized model to measured data pairs (cuff pressure, PAT) obtained during cuff inflation. Figure 17A shows the figure for full inflation, while Figure 17B shows the figure where only low cuff pressure levels are used for regression, resulting in a less robust regression. PAT values ​​can be measured for each pulse, as described above. Each time a new pulse is detected by a peripheral sensor, the corresponding PAT can be calculated and the corresponding cuff pressure is measured. In other words, the number of data pairs available for parameter regression is equal to the number of pulses detected while the cuff is inflated.

[0094] However, the measured PAT value is subject to measurement error. Therefore, the more data pairs available for performing the actual regression, the better the quality (i.e., accuracy) of the parameter regression. Thus, as described in one embodiment above, using only the lower portion of the curve, i.e., pairs of PAT and cuff pressure data up to a specific cuff pressure level, for the parameter regression further improves the quality of the parameter regression. For example, if only the lower portion of the curve is used, the overall number of data pairs available for parameter regression decreases. Furthermore, the signal-to-noise ratio of the regression curve decreases. The absolute error in measuring PAT is independent of the applied cuff pressure. However, the signal component desired for parameter regression is not the absolute value of PAT, but the change in PAT from the baseline PAT during cuff inflation. Baseline PAT is PAT when no cuff pressure is applied. Considering this, if only low cuff pressure levels are considered, the relative measurement error of PAT increases because the change in PAT is small at low cuff pressure levels.

[0095] Accordingly, according to a second main aspect of the present invention, with respect to the systems and devices shown in Figures 10 and 11, systems and devices comprising generally the same units as those described above are used. However, the processing unit 53 and the methods performed by the processing unit 53 are configured differently. Figure 18 shows a diagram of one embodiment of method 500 according to the present invention. The steps of method 500 are performed by device 50, and the main steps of the method are performed by processing unit 53. This method is implemented as a computer program that runs on a computer or processor.

[0096] In the first step 501, a time-dependent cuff pressure value is acquired while the cuff of a pressure delivery system attached to a part of the subject's body is inflated. In the second step 502, a BP measurement is acquired. In the third step 503, a first time-dependent sensor signal and a second time-dependent sensor signal are acquired, relating to the subject's heart rate and measured at different parts of the subject's body while the cuff is inflated.

[0097] In the fourth step 504, a control signal is calculated to repeatedly inflate the cuff of the pressure delivery system in a partial inflation manner to a cuff pressure below the subject's contracted blood pressure point (BP).

[0098] In the fifth step 505, a pulse-related value is calculated from the first and second time-dependent sensor signals measured during repeated partial inflation of the cuff, using the first feature of the first time-dependent sensor signal and the second feature of the second time-dependent sensor signal, the pulse-related value being either the PAT value or the PTT value.

[0099] In the sixth step 506, the calibration parameters for the BP surrogate are calculated from the BP measurement and pairs of pulse-related values ​​and corresponding cuff pressure values ​​calculated from first and second time-dependent sensor signals measured during repeated partial inflation of the cuff, the pair including a pulse-related value and a corresponding cuff pressure value at the same time (or at least a time-related value).

[0100] Thus, in one exemplary embodiment, the pump control is configured to repeatedly apply short increasing pressure profiles (pressure gradients) ranging from a cuff pressure of 0 mmHg to approximately the diastolic pressure level, or until a change in the pulse amplitude of the PPG signal is detected, thereby recording the cuff pressure and PAT. This process involves parameter regression for each applied pressure gradient, and the resulting regression parameters are averaged to improve overall calibration accuracy.

[0101] The embodiment described with reference to Figure 18 is based on the idea that only low cuff pressure levels should be used for calibration. Repeated sampling at such appropriate cuff pressure levels can be performed over a sufficiently short period of time so that the BP level stabilizes and there are no changes that distort the calibration process. Furthermore, the inflation gradient can be repeated even without pauses between gradients because the maximum pressure is low. There is no need to wait for the tissues and arteries to recover from high pressurization (i.e., there is no hysteresis effect).

[0102] Another advantage is that cuff pressure levels below diastolic pressure are less disruptive to the patient, especially an awake patient, resulting in less discomfort and skin stress than a full inflation gradient that exceeds systolic pressure.

[0103] Another advantage of such an embodiment is that it does not impose extra requirements on the pressure pump integrated into the NIBP device. Alternative proposals that achieve the same effect using a single, gentle pressure gradient from 0 mmHg to diastolic blood pressure levels require a pump capable of achieving very low airflow at low pressure levels, which presents a considerable challenge to pump design and is not supported by standard pumps currently used in NIBP devices.

[0104] This idea applies not only to systems that use PAT measured by ECG and PPG sensors, but more generally to systems that use alternative methods to measure pulse propagation delay (e.g., based on differential pulse wave propagation time), and to systems that have a pressurized cuff placed in the propagation path of the pulse wave under consideration.

[0105] The following describes a second embodiment for achieving BP surrogate calibration, which is improved by repeated partial expansion. In this embodiment, the PAT value is estimated for each pulse using a PPG sensor and an ECG sensor.

[0106] PAT baseline value PAT base In one embodiment, this is obtained by averaging PAT measurements over a specific period. The PAT measurement period can be predetermined and fixed, or set by the user, for example, 20 seconds, 15 seconds, or any other sufficiently long period that adequately suppresses undesirable fluctuations caused by, for example, respiration (typical frequency 0.1-0.5 Hz), Mayer waves (typical frequency 0.1-0.5 Hz), or other measurement noises.

[0107] Activating the pump of the NIBP device provides a first (partial) inflation gradient to a specific sub-systolic level. The first inflation gradient is determined by the diastolic pressure (determined from the last NIBP measurement), a specific sub-diastolic level, a specific fixed cuff pressure level (e.g., 60 mmHg or 40 mmHg), or PAT. base This may be a pressure level that exceeds a specific threshold compared to the PPG, or a pressure level at which a predefined amplitude change in the PPG amplitude is detected. The inflation rate is set to a fixed inflation rate, such as 10 mmHg / sec, or otherwise selected, for example according to the heart rate, to ensure a specific minimum number of heartbeats within the inflation gradient. During cuff inflation, the cuff pressure PAT value is measured simultaneously with the cuff pressure PAT value. cuff This is measured. Baseline PAT base The difference in PAT compared to is shown as ΔPAT and is calculated for the PAT value during cuff inflation.

[0108] Measured data pair (ΔPAT, P cuff Using ), the unknown model parameters m1, m2, ~m of the parameterized model function f N Parameter regression (curve fitting) is performed, and the model function f models the relationship between the change in PAT and the change in blood pressure ΔBP near the operating point. The length below the cuff L during cuff inflation. cuff The blood pressure in the arterial portion is P cuff Since it only decreases by a certain amount, the change in blood pressure is ΔBP = -P cuff (This explanation also applies to the method described above.) Therefore, the regression equation is obtained as follows. ΔPAT=L cuff ·f(-P cuff ;m1, m2, ~m N )

[0109] For example, in a simple linear proportional model, there are two unknown model parameters (f = m1·ΔBP + m2). The preferred criterion for parameter regression is the least squares error, but parameter regression may also be performed according to other error measures, such as the least absolute error.

[0110] To improve parameter regression, the cuff is deflated, another partial expansion is performed, and another parameter regression is run. This can be repeated multiple times. In a preferred embodiment, one additional partial expansion is performed. Subsequently, the regression values ​​of the obtained model parameters are averaged, thus improving the accuracy of the model parameter calibration. The degree of variation in the obtained regression values ​​can be used to determine how many times the partial expansion should be repeated. For example, if the regression values ​​obtained after two partial expansions are strictly aligned, no further partial expansion is necessary.

[0111] To calibrate the resulting continuous BP estimator, NIBP measurements are performed, and the blood pressure reference measurement BP is used. ref This is obtained by performing the final partial inflation in succession until it exceeds the systolic cuff pressure level, so that blood pressure measurements can be calculated using standard inflation-based oscillometry. In other words, the slope of the final inflation is the slope of the "full" cuff inflation. Figure 19 shows an example of the proposed cuff pressure profile in an example where two additional partial inflations are performed (before full inflation) before full inflation occurs, in order to improve the calibration of the model parameters. Finally, the calibrated PAT-based continuous blood pressure estimator is obtained below.

number

[0112] These steps are typically repeated from time to time to recalibrate a continuous blood pressure estimator. Recalibration can be performed according to some regular schedule or when there is a significant change in blood pressure. In general, the proposed pressure profile of the type shown in Figure 19, i.e., a pressure profile including repeated partial inflation, can be performed whenever NIBP measurements are triggered automatically or manually.

[0113] In the alternative embodiment, partial inflation is added but not added to the beginning. Figure 20 illustrates the proposed cuff pressure profile in an example of two additional partial inflations (after full inflation). This profile has the advantage of displaying the NIBP value earlier compared to the previous embodiment of the pressure profile illustrated in Figure 19. However, the time interval between the first and second parameter calibrations is longer. If the patient's hemodynamic state is not constant during this time, i.e., the model parameters are changing, the improvement in accuracy due to averaging across multiple calibration events will be less.

[0114] In another alternative embodiment, the improvement in parameter regression is not achieved by averaging the regression parameters from multiple partial expansions, but rather, for a single regression, all data pairs obtained from multiple partial expansions (ΔPAT, P cuff This can be achieved by using ). This option improves accuracy by allowing more regression data points to be used in a single regression. Furthermore, instead of predetermining the number of partial expansions to be performed, it can be determined through a threshold comparison of regression errors. If the regression error falls below that threshold, no further partial expansions are necessary.

[0115] In yet another alternative embodiment, a continuous blood pressure estimator can be further made capable of performing only partial inflation, for example, every 10 minutes, after being calibrated by model parameter regression and NIBP reference measurement. This is done as described above. The "full calibration" by NIBP reference measurement is achieved when the model parameter regression is compared with the results of the parameter regression accompanying the final "full calibration," resulting in the model parameters m1~m N This is performed only when a significant change occurs. If no significant change is detected, the parameters of the current continuous blood pressure estimator are not updated, and full inflation for NIBP measurement is not performed. Figure 21 shows a diagram of the pressure profile, continuously tracking the need for recalibration through repeated partial inflations. The advantage of this concept is that it can operate for long periods without other interference. This is advantageous for patients who are automatically monitored for NIBP for several days, for example, as it supports the healing process of ICU patients by improving the quality of their nighttime sleep.

[0116] The present invention is for use in a wide range of applications, such as in hospital monitoring settings where NIBP, ECG, and PPG sensors are already available and in use. These sensors are actually used in all settings, for example, OR and ICU, including not only specific settings in general wards but also in specialized wards such as neurology. More specifically, it enables non-invasive measurement of arterial blood pressure per heartbeat. Heartbeat-by-heartbeat blood pressure monitoring enables early detection of hypotensive events associated with adverse patient outcomes. Furthermore, it enables early warning of hemodynamic instability. The disclosed apparatus and method can also be used for long-term monitoring, such as 24-hour BP monitoring or BP monitoring during nocturnal sleep.

[0117] The present invention has been illustrated and described in detail in the drawings and the foregoing description, but such illustrations and descriptions should be considered illustrative or representative and not limiting. The present invention is not limited to the embodiments disclosed. Other variations of the disclosed embodiments can be understood and achieved by those skilled in the art by studying the drawings, disclosure and appended claims in practicing the invention described in the claims.

[0118] In the claims, the word “equipped with” does not exclude other elements or other steps, and a singular element does not exclude plural elements. A single element or other unit may perform the function of multiple items listed in the claims. The mere fact that certain means are listed in different dependent claims does not imply that combinations of these means cannot be used advantageously.

[0119] Computer programs may be stored / distributed in suitable non-temporary media such as optical storage media or solid-state media, supplied together with or as part of other hardware, or they may be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems.

[0120] No reference numeral in the claims should be construed as limiting the scope.

[0121] Further embodiments of the systems, devices, and methods described in the claims are configured as follows: 1. A device disclosed herein, wherein the processing unit (53) is - Calculate a control signal to control the pressure delivery system (10), and repeatedly inflate the cuff of the pressure delivery system in partial inflation until the cuff pressure is below the subject's systolic blood pressure (BP). - From the first and second time-dependent sensor signals measured during repeated partial inflation of the cuff, a value related to pulse rate is calculated using the first feature of the first time-dependent sensor signal and the second feature of the second time-dependent sensor signal, and the value related to pulse rate is the pulse wave arrival time PAT or the pulse wave propagation time PTT. - The calibration parameters of the BP surrogate are calculated from the BP measurement and pairs of pulse-related values ​​and corresponding cuff pressure values, which are calculated from first and second time-dependent sensor signals measured during repeated partial inflation of the cuff, and the pairs are configured to include pulse-related values ​​and corresponding time-dependent cuff pressure values. 2. A device as defined in Embodiment 1, The processing unit (53) is configured to calculate a control signal that controls the pressure delivery system (10) to inflate the cuff of the pressure delivery system in a partial inflation during periods when the peripheral BP is substantially constant, specifically, when the variation is less than 10 percent or less than 5 percent. 3. A device as defined in Embodiment 2, The processing unit (53) is configured to determine whether the peripheral BP is substantially constant, based on the first and / or second time-dependent sensor signals, by determining, in particular, the period during which the amplitude of the second time-dependent signal is substantially constant, in particular, the variation is less than 10 percent or less than 5 percent of the previously acquired average value. 4. A device as defined in Embodiment 1, The processing unit (53) is configured to calculate a control signal that controls the pressure delivery system (10) to inflate the cuff of the pressure delivery system by partial inflation to the subject's diastolic BP, in particular to the subject's most recent measured diastolic BP, the subject's average BP, specifically to the subject's most recent measured average BP, or to a set threshold cuff pressure. 5. A device as defined in Embodiment 1, The processing unit (53) is configured to control the pressure delivery system (10) and calculate a control signal that causes the cuff of the pressure delivery system to partially inflate until the PAT exceeds the PAT threshold, specifically the absolute threshold of PAT, or the relative threshold of PAT compared to a baseline PAT. 6. A device as defined in Embodiment 5, The processing unit (53) is configured to calculate a baseline PAT by averaging PAT measurements over a certain period, specifically a period ranging from 10 seconds to 5 minutes. 7. A device as defined in Embodiment 1, The processing unit (53) is configured to control the pressure delivery system (10) and calculate a control signal that causes the cuff of the pressure delivery system to expand in a partial inflation manner until the cuff pressure exceeds an amplitude threshold, specifically an absolute amplitude threshold or a relative amplitude threshold, of the amplitude of the second time-dependent signal. 8. A device defined in any one of Embodiments 1 to 7, The processing unit (53) is configured to control the pressure delivery system (10) and calculate a control signal to inflate the cuff of the pressure delivery system in a partial inflation manner at a predetermined inflation rate, or at an inflation rate that depends on one or more of the subject's heart rate, the subject's diastolic BP, the subject's average BP, and the subject's systolic BP. 9. A device defined in any one of Embodiments 1 to 8, The processing unit (53) is - Calculate a control signal to control the pressure delivery system (10) and deflate the cuff of the pressure delivery system each time it undergoes partial inflation. - i) For each iteration, calculate one or more calibration parameters using separate regressions from the pairs of pulse-related values ​​and corresponding cuff pressure values ​​obtained in each iteration, and average each calibration parameter calculated over two or more iterations to obtain one or more average calibration parameters to be used in the BP surrogate, or - ii) Calculate one or more calibration parameters in a single regression from pairs of pulse-related values ​​and corresponding cuff pressure values ​​obtained from two or more repetitions. It is structured in such a way. 10. A device defined in any one of Embodiments 1 to 9, The processing unit (53) is configured to control the pressure delivery system (10) to inflate the cuff of the pressure delivery system with a full inflation exceeding the subject's systolic BP before and / or after one or more partial inflation cycles, and to calculate a control signal to obtain a time-dependent BP reference measurement used when monitoring the subject's BP using a BP surrogate. 11. A device defined in any one of Embodiments 1 to 10, The processing unit (53) is configured to control the number of times partial expansion is repeated based on a comparison of the regression error with a regression error threshold, and / or to control whether and when to perform a full expansion according to a fixed or variable schedule, or if one or more calibration parameters have been substantially changed in the last calculation, particularly if they have been changed by more than 10 percent. 12. A device defined in any one of Embodiments 1 to 11, The processing unit (53) is configured to determine the value of BP using a calculated BP surrogate and measured first and second time-dependent sensor signals measured at various parts of the subject's body when no pressure is delivered to the subject's body by the pressure delivery system. 13. A system for calibrating blood pressure BP surrogates used when monitoring the blood pressure of a subject, wherein the system is A pressure delivery system (10) comprising a cuff (11) which is attached to a part of the subject's body and configured to deliver pressure to the subject's body by inflating the cuff, A pressure sensor (20) is configured to acquire or estimate a time-dependent cuff pressure value and a BP measurement value while the cuff of a pressure delivery system attached to a part of the subject's body inflates. A first sensor (30) is attached to a first part of the subject's body and configured to acquire a first time-dependent sensor signal relating to the subject's heart rate while the cuff is inflated. A second sensor (40) is attached to a second part of the subject's body and configured to acquire a second time-dependent sensor signal related to the subject's heart rate while the cuff is inflated. A device (50) disclosed herein calculates one or more calibration parameters for calibrating a BP surrogate from BP measurements, time-dependent cuff pressure values, and first and second time-dependent sensor signals. It is equipped with. 14. Methods disclosed herein, - A step of calculating a control signal to control the pressure delivery system (10) and repeatedly inflate the cuff of the pressure delivery system to a cuff pressure below the subject's systolic BP by partial inflation. - A step of calculating a pulse-related value from first and second time-dependent sensor signals measured during repeated partial inflation of the cuff, using a first feature of the first time-dependent sensor signal and a second feature of the second time-dependent sensor signal, wherein the pulse-related value is the pulse wave arrival time PAT or the pulse wave propagation time PTT. - A step of calculating calibration parameters for a BP surrogate from BP measurements and pairs of pulse-related values ​​and corresponding cuff pressure values, wherein the pairs are calculated from first and second time-dependent sensor signals measured during repeated partial inflation of the cuff, and each pair includes a pulse-related value and a corresponding, time-related cuff pressure value at the same time. A method having 15. A computer program having program code means that, when the computer program is executed on a computer, causes the computer to perform the steps of the method defined in Embodiment 14.

Claims

1. A device for calibrating a blood pressure (BP) surrogate for use in monitoring the blood pressure of a subject, wherein the device is A BP input unit acquires the time-dependent cuff pressure value during inflation of the cuff of a pressure delivery system attached to the body part of the subject, and also acquires BP measurement values. During the inflation of the cuff, a sensor input unit acquires a first time-dependent sensor signal and a second time-dependent sensor signal related to the subject's heart rate, measured at different parts of the subject's body. Processing unit and Equipped with, The processing unit, while the cuff is inflated, uses the first characteristic of the first time-dependent sensor signal and the second characteristic of the second time-dependent sensor signal to calculate a value related to pulse rate from the first and second time-dependent sensor signals, wherein the value related to pulse rate is the value of the pulse wave arrival time PAT or the value of the pulse wave propagation time PTT. The processing unit selects pairs of pulse-related values ​​and corresponding cuff pressure values ​​for calculating calibration parameters of the BP surrogate, wherein the pairs include the pulse-related values ​​and corresponding time-dependent cuff pressure values, and only pairs of pulse-related values ​​and corresponding cuff pressure values ​​that satisfy predetermined conditions for the BP are selected. The processing unit calculates the calibration parameters of the BP surrogate from the BP measurement values ​​and the selected pairs of values ​​related to pulse rate and the corresponding cuff pressure values. The aforementioned predetermined conditions are that the variation in peripheral BP is less than 10% or less than 5%. device.

2. The processing unit determines that the fluctuation of the peripheral BP within the period is less than 10% or less than 5% by determining the period during which the fluctuation of the amplitude of the second time-dependent signal is less than 10% or less than 5% of the previously acquired average value. The second time-dependent sensor signal is a photoplethysmography (PPG) signal. The device according to claim 1.

3. The processing unit calculates a control signal for controlling the pressure delivery system to inflate the cuff in order to acquire the BP measurement value, and to inflate the cuff according to the peripheral BP, whose variation is less than 10% or less than 5%, in order to acquire the first time-dependent sensor signal and the second time-dependent sensor signal. The device according to claim 1.

4. The first time-dependent sensor signal is an ECG signal, and / or the second time-dependent sensor signal is a photoplethysmography (PPG) signal. The device according to claim 1.

5. The device according to claim 4, wherein the second time-dependent sensor signal is a contact-type PPG signal or a remote PPG signal.

6. The processing unit calculates the calibration parameter as the gradient of the dependence of the blood pressure relationship, as a function of the BP surrogate with respect to zero cuff pressure. The device according to claim 1.

7. The processing unit determines the value of BP when pressure is not delivered to the subject's body by the pressure delivery system, using the calculated BP surrogate and the measured first and second time-dependent sensor signals measured at various parts of the subject's body when pressure is not delivered to the subject's body. The device according to claim 1.

8. A system for calibrating a blood pressure BP surrogate for use when monitoring the blood pressure of a subject, wherein the system A pressure delivery system comprising a cuff attached to a part of the subject's body, the cuff delivering pressure to the subject's body by inflating the cuff, A pressure sensor that acquires a time-dependent cuff pressure value and acquires or estimates a BP measurement value while the cuff of the pressure delivery system attached to the body part of the subject is inflated, A first sensor is attached to a first part of the subject's body and acquires a first time-dependent sensor signal related to the subject's heart rate while the cuff is inflated. A second sensor is attached to a second part of the subject's body and acquires a second time-dependent sensor signal related to the subject's heart rate during the inflation of the cuff, A device according to claim 1 for calculating calibration parameters for calibrating a BP surrogate from the BP measurement value, the time-dependent cuff pressure value, and the first and second time-dependent sensor signals, A system that is equipped with [the following].

9. A method for operating a device for calibrating a blood pressure BP surrogate for use in monitoring the blood pressure of a subject, wherein the device comprises a BP input unit, a sensor input unit, and a processing unit, and the method is The BP input unit receives a time-dependent cuff pressure value during inflation of the cuff of a pressure delivery system attached to the body part of the subject, The BP input unit receives a BP measurement value, The sensor input unit receives a first time-dependent sensor signal and a second time-dependent sensor signal that are measured at different parts of the subject's body and relate to the subject's heart rate while the cuff is inflated. The processing unit, while the cuff is inflated, calculates a value related to pulse rate from the first and second time-dependent sensor signals using a first characteristic of the first time-dependent sensor signal and a second characteristic of the second time-dependent sensor signal, wherein the value related to pulse rate is the value of the pulse wave arrival time PAT or the value of the pulse wave propagation time PTT. The processing unit selects pairs of pulse-related values ​​and corresponding cuff pressure values ​​for calculating calibration parameters of the BP surrogate, wherein each pair includes a pulse-related value and a corresponding time-related cuff pressure value, and only pairs of pulse-related values ​​and corresponding cuff pressure values ​​that satisfy predetermined conditions relating to the BP are selected. The processing unit performs the steps of calculating calibration parameters for the BP surrogate from the BP measurement values ​​and selected pairs of values ​​related to pulse rate and corresponding cuff pressure values. It has, The aforementioned predetermined condition is a method in which the variation in peripheral blood pressure is less than 10% or less than 5%.

10. A computer program having program code means that, when the computer program is executed on the computer, causes the computer to perform the steps of the method according to claim 9.

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