Extracorporeal fluid optimization during stages of shock

Abstract

Extracorporeal fluid management is used to treat a patient in shock. Intravascular fluid optimization is provided by dynamically assessing physiological data acquired from the patient and rebalancing the patient's intravascular volume status to maintain adequate perfusion and hemodynamic state. Physiologic measurements are continuously acquired, monitored, or otherwise measured from the patient as physiological data. These physiological data are input to a control algorithm to autonomously adjust the amounts of fluid to infuse or remove (e.g., ultrafiltrate) to optimize rebalancing of the amount of intravascular fluid volume throughout the stages of shock.

Description

Mayo 2023-537630666.01651EXTRACORPOREAL FLUID OPTIMIZATION DURING STAGES OF SHOCKCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Patent Application Serial No. 63 / 736,898. filed on December 20, 2024, and entitled “EXTRACORPOREAL FLUID OPTIMIZATION DURING STAGES OF SHOCK,” which is herein incorporated by reference in its entirety7.BACKGROUND

[0002] Approximately 20-30% of patients admitted to an intensive care unit carry a diagnosis of shock. Appropriate fluid resuscitation and balance are hallmarks of shock care. Fluid balance in shock care is divided into four phases with different goals at each phase.

[0003] Fluid management is a physiologic and logistical challenge in managing a patient in shock. Healthcare providers need to continuously reassess fluid volume amounts to infuse or remove in order to keep the patient in a stable state. Frequent reassessment and clinical decision making of whether to provide additional fluid volume or consider removal of volume is a cumbersome task and one fraught with clinical decision variability. Additionally, it is common for a patient to have been “over resuscitated” by the time they reach the stabilization phase of shock management. This over resuscitation leads to further challenges of fluid removal.SUMMARY OF THE DISCLOSURE

[0004] It is an aspect of the present disclosure to provide a method for maintaining hemodynamic stability7in a patient during stages of shock. The method includes acquiring physiological data from the patient while the patient is in at least one stage of shock and analyzing the physiological data with a computer system to determine a rebalancing of an intravascular fluid volume of the patient. A pump of an extracorporeal fluid circuit is then controlled to infuse and / or remove an amount of fluid to provide the rebalancing of the intravascular fluid volume of the patient.

[0005] It is another aspect of the present disclosure to provide a method for maintaining a hemodynamic state in a patient during stages of shock. The method includes continuously acquiring physiological data from the patient while the patient is in at least one stage of shock and estimating and / or measuring hemodynamic variables from the physiological data. The1QB\630666.01651\99970498.2Mayo 2023-537630666.01651 hemodynamic variables are then dynamically assessed to determine a rebalancing of an intravascular volume of the patient. The intravascular volume of the patient is then rebalanced by infusing an infusion fluid volume and / or ultrafiltering the intravascular volume to remove an ultrafiltration fluid volume. The rebalancing of the intravascular volume of the patient results in maintaining the hemodynamic state in the patient.

[0006] It is yet another aspect of the present disclosure to provide an extracorporeal fluid circuit that includes an infusion pump, a first reservoir containing an infusion fluid, an ultrafiltration pump, a second reservoir for containing intravascular fluid removed from a patient, and a controller. The first reservoir is in fluid communication with the infusion pump and the second reservoir is in fluid communication with the ultrafiltration pump. The controller is in communication with the infusion pump and the ultrafiltration pump. The controller receives physiological data acquired from the patient while the patient is in at least one stage of shock; analyzes the physiological data relative to baseline data to determine a rebalancing of an intravascular fluid volume of the patient: and controls the infusion pump to infuse an infusion volume of the infusion fluid when the rebalancing of the intravascular fluid volume indicates a reduction in physiological data values relative to the baseline data and to remove an ultrafiltration volume from the patient when the rebalancing of the intravascular fluid volume indicates an elevation in physiological data values relative to the baseline data.BRIEF DESCRIPTION OF THE DRAWINGS

[0007] FIG. 1 is a flowchart of an example extracorporeal fluid management method to rebalance an intravascular fluid volume in a patient during stages of shock.

[0008] FIG. 2 shows a baseline Frank- Starling curve in addition to an elevated (upper) curve and a reduced (lower) curve.

[0009] FIG. 3 is a flowchart of an example infusion analysis module or subprocess that can be implemented as part of an extracorporeal fluid management method to rebalance an intravascular fluid volume in a patient during stages of shock by infusing controlled amounts of fluid to the patient.

[0010] FIG. 4 is a flowchart of an example ultrafiltration analysis module or subprocess that can be implemented as part of an extracorporeal fluid management method to rebalance an intravascular fluid volume in a patient during stages of shock by removing controlled amounts of fluid from the patient.2QB\630666.01651\99970498.2Mayo 2023-537630666.01651

[0011] FIGS. 5A-5C illustrate an example workflow of an extracorporeal fluid management method in accordance with some embodiments described in the present disclosure.

[0012] FIG. 6 illustrates an example extracorporeal fluid circuit that can be implemented with an extracorporeal fluid management system according to some embodiments described in the present disclosure.

[0013] FIG. 7 is a block diagram of an example extracorporeal fluid management system according to some embodiments described in the present disclosure.

[0014] FIG. 8 is a block diagram of example components that can implement the system of FIG. 7.DETAILED DESCRIPTION

[0015] Described here are systems and methods for extracorporeal fluid management to treat a patient in shock. The disclosed systems and methods provide fluid optimization in shock by using constant re-assessment and subsequent re-balancing of the patient’s intravascular volume status to maintain adequate perfusion and hemodynamic state. Physiologic measurements are continuously acquired, monitored, or otherw ise measured from the patient as physiological data. These physiological data are input to a control algorithm to autonomously adjust the amounts of fluid to infuse or remove (e g., ultrafiltrate) to optimize the amount of intravascular fluid volume throughout the stages of shock.

[0016] Advantageously, the disclosed extracorporeal fluid management system is capable of establishing or otherwise maintaining appropriate intravascular fluid volume to maintain pre-set appropriate hemodynamic metrics (e.g., blood pressure, central venous pressure, cardiac output, etc.) by infusing and removing small volumes with high agility to maintain fluid balance. For instance, the average intravascular volume of a 70-kg adult male is approximately 3.5 L, with an average total body volume of 28 L (i.e., both intravascular and extravascular volume). Fluid is constantly shifting from intravascular and extravascular compartments. In shock, this fluid shift is increased.

[0017] Surviving sepsis guidelines recommend initial volume replacement of 30 ml / kg. The disclosed extracorporeal fluid management systems and methods can be employed after initial large volume replacement is completed for a patient. Fluid bolus volumes for this initial large volume replacement can vary by provider, but can be in the range of 500-1000 ml per bolus. The disclosed extracorporeal fluid management systems and methods can then be used3QB\630666.01651\99970498.2Mayo 2023-537630666.01651 to maintain an acceptable intravascular volume to maintain appropriate hemodynamic parameters. In some implementations, an automatic infusion and / or removal of 100-250 ml of fluid can be implemented every 5-10 minutes. After this action there can be a pre-set period of time (e.g., approximately 2-5 minutes) for the system to re-evaluate and / or re-equilibrate the hemodynamic metrics to determine if another action (or surveillance) is necessary.

[0018] Healthcare providers can modify all of these aforementioned variables to meet their goals and patient-specific needs. For instance, a user can set thresholds for adjusting infusion and / or ultrafiltration, such that manual input is only needed beyond those thresholds. This level of user control can result in decreased burden on the provider and improved outcome for the patient.

[0019] Referring now to FIG. 1. a flowchart is illustrated as setting forth the steps of an example method for establishing or otherwise maintaining a set intravascular fluid volume and / or hemodynamic state in a patient during the stages of shock. As the patient moves through the phases of shock management, frequent reassessment of their fluid responsiveness allows for rebalancing intravascular fluid volume to maintain a set volume or hemodynamic state. The dynamic measurements of fluid responsiveness utilized by the disclosed method are advantageous over static measurements.

[0020] The method includes acquiring phy siological data from the patient, as indicated at step 102. The physiological data can be continuously acquired, measured, or otherwise monitored from the patient using one or more patient monitors, sensors, measurement devices, or the like. As noted above, the physiological data are acquired while the patient is in at least one stage of shock. As non-limiting examples, the physiological data can include electrophysiology' signals, such as electrocardiography (ECG) signals, electroencephalography (EEG) signals, electromyography (EMG) signals, or the like; measurements of cardiovascular parameters such as heart rate, blood pressure, central venous pressure, and cardiac output; echocardiography data; measurements of blood oxygenation, such as oxygen saturation (SpO2), mixed venous oxygen saturation (SvO2), etc.; respiratory' signal data; and the like.

[0021] In some instances, the physiological data can include one or more metrics, parameters, or other measures that are computed, derived, estimated, or otherwise generated from physiological signals measured from the patient. As one non-limiting example, the physiological data can include measurements of one or more hemodynamic variables. Hemodynamic variables can include blood pressure (BP), pulse pressure variation (PPV), mean arterial pressure (MAP), stroke volume variation (SVV), inferior vena cava (IVC) diameter4QB\630666.01651\99970498.2Mayo 2023-537630666.01651 and variation measurements via ultrasound, systemic vascular resistance (SVR), and so on. In some instances, the physiological data can include continuously monitored data via invasive metrics, such as those measured via arterial catheter, fiberoptic central venous catheter (CVC), or the like. For example, the physiological data may include measurements of central venous oxygen saturation (ScvO2), central venous pressure (CVP), and / or cardiac output (CO). Additionally or alternatively, the physiological data may include an extravascular lung water index (EVLWi). The physiological data may also include measures of serum lactate.

[0022] Additionally, patient health data may be accessed and provided as an input to the extracorporeal fluid management control algorithm. As an example, clinical assessment data can be incorporated into the control algorithm. The clinical assessment data can include, for example, capillary refill time. As another example, the clinical assessment data can include heart dysfunction data (e.g., degree of heart dysfunction, right ventricle versus left ventricle versus bi-ventricular dysfunction, etc.).

[0023] The patient health data can also include clinical features derived from structured, curated, and / or electronic health record (EHR) data, such as diagnoses; symptoms; therapies; outcomes; patient demographics, such as patient name, date of birth, gender, and / or ethnicity; diagnosis dates for cancer, illness, disease, or other physical or mental conditions; personal medical history'; family medical history; clinical diagnoses, such as date of initial diagnosis; and the like. Additionally, the patient health data may also include features such as treatments and outcomes, such as line of therapy, therapy groups, clinical trials, medications prescribed or taken, surgeries, imaging, adverse effects, and associated outcomes.

[0024] The patient health data may also include measurement data collected from wearable devices (e.g., physiological measurements or other data recorded with a wearable device). Physiological measurements that may be recorded with a wearable device include heart rate, temperature, or other physical parameters.

[0025] A dynamic hemodynamic assessment is then performed by a computer system, as indicated at step 104. The computer system may be a controller of an extracorporeal fluid management system or circuit. Additionally or alternatively, the computer system may be a standalone computer system (e.g., a computer, a tablet computer, a smartphone, etc.) that is in communication with an extracorporeal fluid management system or circuit. The dynamic hemodynamic assessment includes comparing one or more data points in the physiological data with baseline values for those data points.5QB\630666.01651\99970498.2Mayo 2023-537630666.01651

[0026] In general, the dynamic hemodynamic assessment analyzes the physiological data to determine whether rebalancing of the intravascular fluid volume is necessary to establish or otherwise maintain a set intravascular fluid volume or hemodynamic state. As a non-limiting example, the dynamic hemodynamic assessment evaluates the physiological data relative to a baseline to determine whether rebalancing of the intravascular fluid volume is needed. The baseline may be a baseline Frank- Starling curve, such that the output of the dynamic hemodynamic assessment indicates whether the physiological data are indicative of a cardiac function curve that would be higher or lower than the baseline Frank- Starling curve. Additionally or alternatively, the baseline may be represented by baseline values (e.g., thresholds, baseline amounts) for one or more hemodynamic variables or other physiological variables in the physiological data. By way of example, the baseline physiological data may include threshold values of physiological variables such as MAP, CVP, PPV, SvO2, CO, SV, and / or SVV. For instance, MAP may have a threshold value of 65 mmHg, such that a measure of MAP greater than 65 mmHg can indicate a deviation from baseline that warrants correction through rebalancing intravascular fluid volume.

[0027] In some instances, the dynamic hemodynamic assessment can be implemented using one or more machine learning models. For example, a machine learning model may be trained on training data to evaluate intravascular fluid volume rebalancing from input physiological data. The machine learning model may include a tree-based model, such as a decision tree, a random forest, a boosting algorithm, or the like. Additionally or alternatively, the machine learning model may implement other model architectures, such as a neural network, a support vector machine, or the like.

[0028] As one non-limiting example, the dynamic hemodynamic assessment can include generating a cardiac function curve from the physiological data and comparing the cardiac function curve to a baseline curve. The cardiac function curve may be, for example, a Frank-Starling curve. As illustrated in FIG. 2, when compared to a baseline Frank- Starling curve 202, physiological data representative of a higher cardiac function curve 204 indicate that ultrafiltration of small amounts of fluid should begin until the curve and / or other physiologic variables are corrected. Similarly, physiological data representative of a lower cardiac function curve 206 indicate that small amounts of fluid should be infused until the curve and / or other physiologic variables are corrected. This process enables a controlled and steady fluid balance to be maintained in the patient as compared to a reactive infusion / removal of fluid.6QB\630666.01651\99970498.2Mayo 2023-537630666.01651

[0029] When the dynamic hemodynamic assessment of the physiological data indicates that cardiac function of the patient is lower than the baseline (e.g.. lower than a baseline Frank- Starling curve, represented by hemodynamic variables that are lower than baseline thresholds or amounts, etc.) at step 106, then an infusion analysis module is implemented to rebalance intravascular fluid volume in the patient by infusing additional fluid, as indicated at step 108.

[0030] If the dynamic hemodynamic assessment of the physiological data indicates that cardiac function of the patient is not lower than the baseline, then the method proceeds to determine whether the dynamic hemodynamic assessment of the physiological data indicates that cardiac function of the patient is higher than the baseline (e.g., higher than a baseline Frank-Starling curve, represented by hemodynamic variables that are higher than baseline thresholds or amounts, etc.). When the dynamic hemodynamic assessment of the physiological data indicates that cardiac function of the patient is higher than the baseline at step 110, then an ultrafiltration module is implemented to rebalance intravascular fluid volume in the patient by removing (e.g., via ultrafiltration) fluid, as indicated at step 112.

[0031] Advantageously, both the infusion analysis module and the ultrafiltration analysis module, described in more detail below, can be programmed to limit the amount of fluid infusion and / or removal and the frequency thereof to maintain a level of patient safety. The amounts and / or durations of fluid infusion and / or removal can be set by a healthcare provider or other user. In some instances, the safety levels for the amount and frequency of infusion / removal can be determined based on standard recommendations, such as those provided based on SCCM / ESICM guidelines. In both the infusion and ultrafiltration modules, if there is an acute hemodynamic decompensatrion during an ECFOS action the healthcare provider can be alerted to take life-saving action.

[0032] If the dynamic hemodynamic assessment of the physiological data indicates that cardiac function of the patient is neither lower nor higher than the baseline, then the patient is determined to be hemodynamically stable. For instance, the patient can be determined to have an intravascular fluid volume that is substantially similar to the set intravascular fluid volume. A determination is then made at step 114 whether to continue monitoring the patient or to stop acquiring physiological data as indicated at step 116.

[0033] Referring now to FIG. 3, a flowchart is illustrated as setting forth the steps of an example method for analyzing physiological data to determine whether rebalancing intravascular fluid volume via infusion will result in establishing or maintaining a set intravascular fluid volume or hemodynamic state.7QB\630666.01651\99970498.2Mayo 2023-537630666.01651

[0034] The method includes determining whether the dynamic hemodynamic assessment of the physiological data performed in step 104 is indicative of the cardiac function of the patient representing an acutely reduced Frank-Starling curve, as indicated at step 302. Additionally or alternatively, the dynamic hemodynamic assessment can determine whether the physiological data acquired from the patient include hemodynamic variables or other physiological variables that are acutely reduced relative to baseline thresholds or amounts. When the cardiac function is representative of being acutely reduced, a first amount of fluid volume is infused for a first duration of time, as indicated at step 304. The first amount of fluid volume may be, for example, 200 ml. The infusion fluid can include crystalloid, colloid, blood, or the like. The first duration of time may be selected from a range of 60-90 seconds. When the cardiac function is not representative of being acutely reduced yet not corrected to hemodynamic stability, then a second amount of fluid volume is infused for a second duration of time, as indicated at step 306. The second amount of fluid volume may be, for example, selected from a range of 100-200 ml. The infusion fluid used for the second amount of fluid volume can be the same as used for the first amount of fluid volume, or may be a different infusion fluid. The second duration of time may be, for example, 10 minutes. Alternatively, the second duration of time may be the same as the first duration of time.

[0035] After the first or second amount of fluid volume have been infused, dynamic hemodynamic assessment is performed on updated physiological data acquired from the patient after the first or second amount of fluid volume were infused, as indicated at step 308. If the resulting estimate of cardiac function is still representative of hemodynamic compromise with an acute reduction, then the first amount of fluid volume is infused for the first duration of time again by looping to step 304. If the resulting cardiac function is representative of improvement, but not normalization of the Frank- Starling curve and / or other baseline measure(s), then the second amount of fluid volume is infused for the second duration of time by looping to step 306. When normalization of the Frank-Starling curve and / or other baseline measure(s) is achieved, the infusion analysis module is exited at step 310 and the method returns to step 102 of FIG. 1.

[0036] Referring now to FIG. 4, a flowchart is illustrated as setting forth the steps of an example method for analyzing physiological data to determine whether rebalancing intravascular fluid volume via ultrafiltration will result in establishing or maintaining a set intravascular fluid volume or hemodynamic state.8QB\630666.01651\99970498.2Mayo 2023-537630666.01651

[0037] The method includes removing a third amount of fluid volume over a third duration of time, as indicated at step 402. The third amount of fluid volume may be, for example, 200 ml. The third duration of time may be, for example, 5 minutes. After this ultrafiltration step, a dynamic hemodynamic assessment is performed on updated physiological data acquired from the patient after the third amount of fluid volume has been removed, as indicated at step 404.

[0038] If the resulting estimate of cardiac function is representative of hemodynamic compromise with an acute elevation relative to a baseline Frank-Starling curve and / or other baseline measure(s), then the third amount of fluid volume is removed over a third duration of time again by looping to step 402. If the resulting cardiac function is representative of improvement, but not normalization of the Frank-Starling curve and / or other baseline measure(s), then a fourth amount of fluid volume is removed from the patient, as indicated at step 406, before looping back to the dynamic hemodynamic assessment in step 404. The fourth amount of fluid volume may be, for example, 100 ml. The fourth duration of time may be, for example. 5 minutes. Alternatively, the fourth duration of time may be different from the third duration of time (i. e. , shorter or longer than the third duration of time). In some instances, when the dynamic hemodynamic assessment performed in step 404 indicates that ultrafiltrate volume has led to a significant fluctuation in one or more physiologic variables, the control algorithm may infuse an amount of concentrated albumin, followed by more slowly ultrafiltering the original volume.

[0039] When normalization of the Frank- Starling curve and / or other baselines measure(s) is achieved, the ultrafiltration module is exited at step 408 and the method returns to step 102 of FIG. 1.

[0040] FIGS. 5A-5C illustrate a workflow for an example implementation of extracorporeal fluid management of a patient according to some embodiments described in the present disclosure. In this example, an extracorporeal fluid circuit (e.g., an ultrafiltration-type circuit) is used to infuse and ultrafilter (remove) volumes of crystalloid or other fluid from a patient to create a homeostatic intravascular fluid volume throughout the stages of shock.

[0041] The extracorporeal fluid management control algorithm determines whether or not to infuse or remove controlled amounts of fluid to maintain prescriber-set physiologic variables (e.g., CVP, PPV, ScvO2, BP). The goal of the extracorporeal fluid management system is to maintain a stable hemodynamic state, a homeostatic intravascular fluid volume, or other measure of hemodynamic stability. For example, as illustrated in the workflow of FIGS.9QB\630666.01651\99970498.2Mayo 2023-537630666.016515A-5C, the extracorporeal fluid management system maintains the patient along a baseline, or other prescriber-set, Frank-Starling curve. As described above, when the patient is moving towards a higher curve, ultrafiltration of small amounts of fluid begins until the curve and other physiologic variables are corrected. Likewise, when the patient is moving towards a lower curve, small amounts of fluid are infused until the curve and other physiologic variables are corrected.

[0042] During the initial phases of shock, the patient can be routinely fluid-challenged with volumes similar to a passive leg raise (PLR). When physiologic variables indicate a potential need for volume, approximately 200 ml of crystalloid can be given within 5-10 min. If there is physiologic variable improvement, additional bolus can be given until stabilization of variables is observed, as indicated in FIG. 5B. If there is no physiologic variable improvement, the bolus can be removed via ultrafiltration so as to not increase risk of fluid volume overload. This process can be programmed in the extracorporeal fluid management system to happen routinely every' few hours to accommodate for insensible loss.

[0043] As a non-limiting example, the following can be considered by the control algorithm for the extracorporeal fluid management system: generic fluid strategies (e.g., restricted volumes, normal volumes, high volumes), in addition to the amount of fluid able to be infused or ultrafiltered and the time periods of each action. These controls can be dynamic throughout care of the patient.

[0044] Additionally, the extracorporeal fluid management system may include one or more filters to remove particular media from the intravascular fluid. As one non-limiting example, the extracorporeal fluid management system can include one or more filters to remove inflammatory cytokines and / or debris from the intravascular fluid.

[0045] An example extracorporeal fluid circuit 600, or extracorporeal fluid management system, is illustrated in FIG. 6. The extracorporeal fluid circuit 600 includes a controller 602 or other computing device that implements a computer-aided algorithm that receives inputs of different physiologic variables such as CVP, PPV, ScvO2, BP, SVR, CO, or the like, based on available data from a specific patient. For example, the controller 602 or other computing device can implement the methods described in the present disclosure (e.g., the method of FIG. 1. The method of FIG. 3, the method of FIG. 4, the workflows illustrated in FIGS. 5 A-5C). Similar to a continuous renal replacement therapy (CRRT) circuit, the patient can have a double-lumen large bore central venous catheter, a large bore peripheral intravenous catheter (PIVC), or other suitable vascular access placed. The controller 602 may include a10QB\630666.01651\99970498.2Mayo 2023-537630666.01651 graphic user interface (GUI) that provides both manual and automatic operating modes. In manual mode, the GUI allows for manual volume infusion or removal at a set flowrate and volume. In automatic mode, the GUI allows for automatic volume infusion or removal to regulate to a set pressure range, with the mode activated or deactivated by a start control.

[0046] The extracorporeal fluid circuit 600 includes an infusion pump 604, a first reservoir 608 containing an infusion fluid, an ultrafiltration pump 606, a second reservoir 610 for containing intravascular fluid removed from a patient, and the controller 602. The extracorporeal fluid circuit 600 may be configured as a closed-system, and in some instances may also include an embedded pressure sensor for monitoring pressure within the system. The first reservoir 608 is in fluid communication with the infusion pump 604, and the second reservoir 610 is in fluid communication with the ultrafiltration pump 606. The controller 602 is in communication with the infusion pump 604 and the ultrafiltration pump 606. The first reservoir 608 may contain an infusion fluid such as crystalloid, colloid, blood, or other suitable fluid for intravascular volume replacement. The first reservoir 608 may be a flexible bag, a rigid container, or other suitable vessel capable of storing the infusion fluid. Tubing or other fluid conduits connect the first reservoir 608 to the infusion pump 604, which draws the infusion fluid from the first reservoir 608 and delivers it to the patient through vascular access such as a central venous catheter or peripheral intravenous catheter.

[0047] The second reservoir 610 receives intravascular fluid removed from the patient via the ultrafiltration pump 606. The second reservoir 610 may be a collection bag, a rigid container, or other suitable vessel for containing the removed fluid. Tubing or other fluid conduits connect the ultrafiltration pump 606 to the patient’s vascular access and to the second reservoir 610. This configuration allows the extracorporeal fluid circuit 600 to both infuse intravascular volume (e.g., crystalloid, colloid, blood) and ultrafiltrate (remove) intravascular volume based on algorithmic decision-making related to input from minimally-invasive input hemodynamic variables (e.g., CO, CVP, PPV, SVV, etc.) within the constraints of hemodynamic outcome parameters set by the provider to ensure adequate and balanced systemic perfusion.

[0048] The controller 602 receives physiological data acquired from the patient while the patient is in at least one stage of shock. The physiological data may include hemodynamic variables such as blood pressure, central venous pressure, pulse pressure variation, cardiac output, stroke volume variation, mixed venous oxygen saturation, or other physiological measurements as described herein. The controller 602 analyzes the physiological data relative11QB\630666.01651\99970498.2Mayo 2023-537630666.01651 to baseline data to determine a rebalancing of an intravascular fluid volume of the patient. The baseline data may include threshold values for one or more physiological variables, a baseline Frank- Starling curve, or other reference values established by a healthcare provider. Based on the analysis, the controller 602 controls the infusion pump 604 to infuse an infusion volume of the infusion fluid when the rebalancing of the intravascular fluid volume indicates a reduction in physiological data values relative to the baseline data. Conversely, the controller 602 controls the ultrafiltration pump 606 to remove an ultrafiltration volume from the patient when the rebalancing of the intravascular fluid volume indicates an elevation in physiological data values relative to the baseline data. Fluid may be augmented in controlled increments, such as 10 ml increments, at configurable flow rates to demonstrate agility of the system in maintaining fluid balance.

[0049] When operating in an automatic mode, the controller 602 may be configured to regulate to a set pressure range defined by upper and lower pressure limits. During high- pressure states representative of intravascular hypervolemia, the controller 602 activates the ultrafiltration pump 606 to reduce system pressure below the upper pressure limit. During low- pressure states representative of intravascular hypovolemia, the controller 602 activates the infusion pump 604 to increase system pressure above the lower pressure limit.

[0050] In some implementations, the extracorporeal fluid circuit 600 may include one or more filters positioned within the fluid pathway. A filter may be configured to remove inflammatory cytokines from the intravascular fluid volume. Inflammatory cytokines can be elevated during shock states, particularly septic shock, and their removal can provide therapeutic benefit to the patient. Additionally or alternatively, a filter may be configured to remove debris from the intravascular fluid volume. The filters may be positioned in the ultrafiltration pathway, the infusion pathway, or both, depending on the clinical requirements and the type of filtration desired.

[0051] In use, a healthcare provider or other user can have complete oversight of the extracorporeal fluid management system actions. By way of example, the extracorporeal fluid management system can prompt the healthcare provider or other user to intervene and / or approve actions if certain control algorithm parameters are met, such as control algorithm actions that are unable to attain hemodynamic outcome parameters after a set interval of action.

[0052] In clinical applications, the extracorporeal fluid management system described in the present disclosure can be configured to account for the physiological characteristics of intravascular volume. For instance, the average intravascular volume of a 70-kg adult male is12QB\630666.01651\99970498.2Mayo 2023-537630666.01651 approximately 3.5 L, with an average total body volume of 28 L (i.e., both intravascular and extravascular volume). Fluid is constantly shifting from intravascular and extravascular compartments. In shock, this fluid shift is increased. The extracorporeal fluid management system can be used to maintain an acceptable intravascular volume to maintain appropriate hemodynamic parameters. Surviving sepsis guidelines recommend initial volume replacement of 30 ml / kg. The extracorporeal fluid management system can be employed after initial large volume replacement is complete and is intended to maintain intravascular fluid volume balance. Fluid bolus volumes can vary by provider, but are ty pically in the range of 500-1000 ml per bolus. A passive-leg raise or straight-leg raise represents a physiologic fluid bolus where the intravascular fluid volume in the legs is rapidly re-introduced to the central circulation by raising patient legs rapidly, which equals approximately 250 ml fluid bolus. The extracorporeal fluid management system is configured to maintain appropriate intravascular fluid volume to maintain pre-set appropriate hemodynamic metrics (e.g., blood pressure, central venous pressure, cardiac output, etc.) by infusing and removing small volumes with high agility to maintain fluid balance. Using the concept of a passive-leg raise, an automatic infusion and / or removal of 100-250 ml of fluid can be implemented every 5-10 minutes. After this action there can be a pre-set period of time (e.g., approximately 2-5 minutes) for the system to re-evaluate and / or re-equilibrate the hemodynamic metrics to determine if another action (or surveillance) is necessary. Healthcare providers can modify all of these aforementioned variables to meet their goals and patient-specific needs.

[0053] FIG. 7 illustrates an example of a system 700 for rebalancing intravascular fluid volume in a patient during stages of shock in accordance with some embodiments described in the present disclosure. As shown in FIG. 7, a computing device 750 can receive one or more types of data (e.g., physiological data) from datasource 702. In some embodiments, computing device 750 can execute at least a portion of an extracorporeal fluid management system 704 to rebalance or otherwise maintain a desired intravascular fluid volume in a patient during the stages of shock based on data received from the data source 702.

[0054] Additionally or alternatively, in some embodiments, the computing device 750 can communicate information about data received from the data source 702 to a server 752 over a communication network 754, which can execute at least a portion of the extracorporeal fluid management system 704. In such embodiments, the server 752 can return information to the computing device 750 (and / or any other suitable computing device) indicative of an output13QB\630666.01651\99970498.2Mayo 2023-537630666.01651 of the extracorporeal fluid management system 704. In some implementations, the computing device 750 may be implemented by the controller 602 of an extracorporeal fluid circuit 600.

[0055] In some embodiments, computing device 750 and / or server 752 can be any suitable computing device or combination of devices, such as a desktop computer, a laptop computer, a smartphone, a tablet computer, a wearable computer, a server computer, a virtual machine being executed by a physical computing device, and so on. The computing device 750 and / or server 752 can also reconstruct images from the data.

[0056] In some embodiments, data source 702 can be any suitable source of data (e.g., phy siological data, other measurement data, patient health data), such as patient monitors or other physiological sensors, another computing device (e.g., a server storing physiological data, other measurement data, patient health data), and so on. In some embodiments, data source 702 can be local to computing device 750. For example, data source 702 can be incorporated with computing device 750 (e.g., computing device 750 can be configured as part of a device for measuring, recording, estimating, acquiring, or otherwise collecting or storing data). As another example, data source 702 can be connected to computing device 750 by a cable, a direct wireless link, and so on. Additionally or alternatively, in some embodiments, data source 702 can be located locally and / or remotely from computing device 750, and can communicate data to computing device 750 (and / or server 752) via a communication network (e.g., communication network 754).

[0057] In some embodiments, communication network 754 can be any suitable communication network or combination of communication networks. For example, communication netw ork 754 can include a Wi-Fi netw ork (which can include one or more wireless routers, one or more switches, etc.), a peer-to-peer network (e.g., a Bluetooth network), a cellular network (e.g., a 3G network, a 4G network, etc., complying with any suitable standard, such as CDMA, GSM, LTE, LTE Advanced, WiMAX, etc.), other types of wireless network, a wired network, and so on. In some embodiments, communication network 754 can be a local area network, a wide area network, a public network (e.g., the Internet), a private or semi-private network (e.g., a corporate or university intranet), any other suitable type of netw ork, or any suitable combination of networks. Communications links shown in FIG. 7 can each be any suitable communications link or combination of communications links, such as wired links, fiber optic links, Wi-Fi links, Bluetooth links, cellular links, and so on.14QB\630666.01651\99970498.2Mayo 2023-537630666.01651

[0058] Referring now to FIG. 8, an example of hardware 800 that can be used to implement data source 702, computing device 750, and server 752 in accordance with some embodiments of the systems and methods described in the present disclosure is show n.

[0059] As shown in FIG. 8, in some embodiments, computing device 750 can include a processor 802, a display 804, one or more inputs 806, one or more communication systems 808, and / or memory 810. In some embodiments, processor 802 can be any suitable hardware processor or combination of processors, such as a central processing unit (‘'CPU”), a graphics processing unit (“GPU”), and so on. In some embodiments, display 804 can include any suitable display devices, such as a liquid crystal display (“LCD”) screen, a light-emitting diode (“LED”) display, an organic LED (“OLED”) display, an electrophoretic display (e.g., an “e- ink” display), a computer monitor, a touchscreen, a television, and so on. In some embodiments, inputs 806 can include any suitable input devices and / or sensors that can be used to receive user input, such as a keyboard, a mouse, a touchscreen, a microphone, and so on.

[0060] In some embodiments, communications systems 808 can include any suitable hardware, firmware, and / or software for communicating information over communication network 754 and / or any other suitable communication networks. For example, communications systems 808 can include one or more transceivers, one or more communication chips and / or chip sets, and so on. In a more particular example, communications systems 808 can include hardware, firmware, and / or software that can be used to establish a Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, and so on.

[0061] In some embodiments, memory 810 can include any suitable storage device or devices that can be used to store instructions, values, data, or the like, that can be used, for example, by processor 802 to present content using display 804, to communicate with server 752 via communications system(s) 808, and so on. Memory 810 can include any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, memory 810 can include random- access memory (“RAM”), read-only memory (“ROM”), electrically programmable ROM (“EPROM”), electrically erasable ROM (“EEPROM”), other forms of volatile memory, other forms of non-volatile memory, one or more forms of semi-volatile memory', one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, and so on. In some embodiments, memory 810 can have encoded thereon, or otherw ise stored therein, a computer program for controlling operation of computing device 750. In such embodiments, processor 802 can execute at least a portion of the computer program to present content (e.g.. images, user interfaces, graphics.15QB\630666.01651\99970498.2Mayo 2023-537630666.01651 tables), receive content from server 752, transmit information to server 752, and so on. For example, the processor 802 and the memory 810 can be configured to perform the methods described herein (e.g., the method of FIG. 1. The method of FIG. 3, the method of FIG. 4, the workflows illustrated in FIGS. 5A-5C).

[0062] In some embodiments, server 752 can include a processor 812, a display 814, one or more inputs 816. one or more communications systems 818. and / or memory 820. In some embodiments, processor 812 can be any suitable hardware processor or combination of processors, such as a CPU, a GPU, and so on. In some embodiments, display 814 can include any suitable display devices, such as an LCD screen, LED display, OLED display, electrophoretic display, a computer monitor, a touchscreen, a television, and so on. In some embodiments, inputs 816 can include any suitable input devices and / or sensors that can be used to receive user input, such as a keyboard, a mouse, a touchscreen, a microphone, and so on.

[0063] In some embodiments, communications systems 818 can include any suitable hardware, firmware, and / or software for communicating information over communication network 754 and / or any other suitable communication networks. For example, communications systems 818 can include one or more transceivers, one or more communication chips and / or chip sets, and so on. In a more particular example, communications systems 818 can include hardware, firmware, and / or software that can be used to establish a Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, and so on.

[0064] In some embodiments, memory 820 can include any suitable storage device or devices that can be used to store instructions, values, data, or the like, that can be used, for example, by processor 812 to present content using display 814, to communicate with one or more computing devices 750, and so on. Memory 820 can include any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, memory 820 can include RAM, ROM, EPROM, EEPROM, other types of volatile memory, other ty pes of non-volatile memory, one or more ty pes of semi-volatile memory . one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, and so on. In some embodiments, memory 820 can have encoded thereon a server program for controlling operation of server 752. In such embodiments, processor 812 can execute at least a portion of the server program to transmit information and / or content (e.g., data, images, a user interface) to one or more computing devices 750, receive information and / or content from one or more computing devices 750, receive instructions from one or more devices (e.g., a personal computer, a laptop computer, a tablet computer, a smartphone), and so on.16QB\630666.01651\99970498.2Mayo 2023-537630666.01651

[0065] In some embodiments, the server 752 is configured to perform the methods described in the present disclosure. For example, the processor 812 and memory 820 can be configured to perform the methods described herein (e.g., the method of FIG. 1. The method of FIG. 3, the method of FIG. 4, the workflows illustrated in FIGS. 5A-5C).

[0066] In some embodiments, data source 702 can include a processor 822, one or more data acquisition systems 824, one or more communications systems 826, and / or memory 828. In some embodiments, processor 822 can be any suitable hardware processor or combination of processors, such as a CPU, a GPU, and so on. In some embodiments, the one or more data acquisition systems 824 are generally configured to acquire data and can include patient monitors or other physiological sensors. Additionally or alternatively, in some embodiments, the one or more data acquisition systems 824 can include any suitable hardware, firmware, and / or software for coupling to and / or controlling operations of patient monitors or other physiological sensors. In some embodiments, one or more portions of the data acquisition system(s) 824 can be removable and / or replaceable.

[0067] Note that, although not shown, data source 702 can include any suitable inputs and / or outputs. For example, data source 702 can include input devices and / or sensors that can be used to receive user input, such as a keyboard, a mouse, a touchscreen, a microphone, a trackpad, a trackball, and so on. As another example, data source 702 can include any suitable display devices, such as an LCD screen, an LED display, an OLED display, an electrophoretic display, a computer monitor, a touchscreen, a television, etc., one or more speakers, and so on.

[0068] In some embodiments, communications systems 826 can include any suitable hardware, firmware, and / or software for communicating information to computing device 750 (and, in some embodiments, over communication network 754 and / or any other suitable communication networks). For example, communications systems 826 can include one or more transceivers, one or more communication chips and / or chip sets, and so on. In a more particular example, communications systems 826 can include hardware, firmware, and / or software that can be used to establish a wired connection using any suitable port and / or communication standard (e.g.. VGA, DVI video, USB, RS-232, etc.). Wi-Fi connection, a Bluetooth connection, a cellular connection, an Ethernet connection, and so on.

[0069] In some embodiments, memory 828 can include any suitable storage device or devices that can be used to store instructions, values, data, or the like, that can be used, for example, by processor 822 to control the one or more data acquisition systems 824. and / or receive data from the one or more data acquisition systems 824; to generate images from data;17QB\630666.01651\99970498.2Mayo 2023-537630666.01651 present content (e.g., data, images, a user interface) using a display; communicate with one or more computing devices 750; and so on. Memory 828 can include any suitable volatile memory, non-volatile memory, storage, or any suitable combination thereof. For example, memory 828 can include RAM, ROM, EPROM, EEPROM, other ty pes of volatile memory, other types of non-volatile memory, one or more types of semi-volatile memory, one or more flash drives, one or more hard disks, one or more solid state drives, one or more optical drives, and so on. In some embodiments, memory 828 can have encoded thereon, or otherwise stored therein, a program for controlling operation of data source 702. In such embodiments, processor 822 can execute at least a portion of the program to generate images, transmit information and / or content (e.g., data, images, a user interface) to one or more computing devices 750, receive information and / or content from one or more computing devices 750, receive instructions from one or more devices (e.g., a personal computer, a laptop computer, a tablet computer, a smartphone, etc.), and so on.

[0070] In some embodiments, any suitable computer-readable media can be used for storing instructions for performing the functions and / or processes described herein. For example, in some embodiments, computer-readable media can be transitory or non-transitory. For example, non-transitory' computer-readable media can include media such as magnetic media (e.g., hard disks, floppy disks), optical media (e.g., compact discs, digital video discs, Blu-ray discs), semiconductor media (e.g., RAM, flash memory’, EPROM, EEPROM), any suitable media that is not fleeting or devoid of any semblance of permanence during transmission, and / or any suitable tangible media. As another example, transitory’ computer- readable media can include signals on networks, in wires, conductors, optical fibers, circuits, or any suitable media that is fleeting and devoid of any semblance of permanence during transmission, and / or any suitable intangible media.

[0071] As used herein in the context of computer implementation, unless otherwise specified or limited, the terms “component,” “system,” “module,” “framework,” and the like are intended to encompass part or all of computer-related systems that include hardware, software, a combination of hardware and software, or software in execution. For example, a component may be, but is not limited to being, a processor device, a process being executed (or executable) by a processor device, an object, an executable, a thread of execution, a computer program, or a computer. By way of illustration, both an application running on a computer and the computer can be a component. One or more components (or system, module, and so on) may reside within a process or thread of execution, may be localized on one18QB\630666.01651\99970498.2Mayo 2023-537 630666.01651 computer, may be distributed between two or more computers or other processor devices, or may be included within another component (or system, module, and so on).

[0072] In some implementations, devices or systems disclosed herein can be utilized or installed using methods embodying aspects of the disclosure. Correspondingly, description herein of particular features, capabilities, or intended purposes of a device or system is generally intended to inherently include disclosure of a method of using such features for the intended purposes, a method of implementing such capabilities, and a method of installing disclosed (or otherwise known) components to support these purposes or capabilities. Similarly, unless otherwise indicated or limited, discussion herein of any method of manufacturing or using a particular device or system, including installing the device or system, is intended to inherently include disclosure, as embodiments of the disclosure, of the utilized features and implemented capabilities of such device or system.

[0073] The present disclosure has described one or more preferred embodiments, and it should be appreciated that many equivalents, alternatives, variations, and modifications, aside from those expressly stated, are possible and within the scope of the invention.19QB\630666.01651\99970498.2

Claims

Mayo 2023-537630666.01651CLAIMS1. A method for maintaining hemodynamic stability in a patient during stages of shock, the method comprising: acquiring physiological data from the patient while the patient is in at least one stage of shock; analyzing the physiological data with a computer system to determine a rebalancing of an intravascular fluid volume of the patient: and controlling a pump of an extracorporeal fluid circuit to one of infuse or remove an amount of fluid to provide the rebalancing of the intravascular fluid volume of the patient.

2. The method of claim 1, wherein analyzing the physiological data with the computer system comprises comparing the physiological data to baseline physiological data.

3. The method of claim 2. wherein the baseline physiological data comprise threshold values for one or more physiological variables of the physiological data.

4. The method of claim 3, wherein the one or more physiological variables comprise at least one of blood pressure, mean arterial pressure, central venous pressure, pulse pressure variation, mixed venous oxygen saturation, cardiac output, stroke volume, or stroke volume variation.

5. The method of claim 2, wherein the baseline physiological data comprise a baseline cardiac function curve.

6. The method of claim 5, wherein the baseline cardiac function curve comprises a baseline Frank- Starling curve.

7. The method of claim 6. wherein analyzing the physiological data comprises generating a current Frank-Starling curve from the physiological data and comparing the current Frank-Starling curve to the baseline Frank-Starling curve.20QB\630666.01651\99970498.2Mayo 2023-537630666.016518. The method of claim 7, wherein when the current Frank- Starling curve is higher than the baseline Frank- Starling curve, the rebalancing of the intravascular fluid volume indicates that ultrafiltration of the intravascular fluid volume should be performed by the pump of the extracorporeal fluid circuit.

9. The method of claim 7. wherein when the current Frank- Starling curve is lower than the baseline Frank-Starling curve, the rebalancing of the intravascular fluid volume indicates that infusion of the intravascular fluid volume should be performed by the pump of the extracorporeal fluid circuit.

10. The method of claim 1, wherein the physiological data are continuously acquired from the patient, and the physiological data are analyzed by the computer system while the physiological data are being acquired in order to continuously determine the rebalancing of the intravascular fluid volume of the patient.

11. The method of claim 1 , wherein the physiological data comprise measurements of at least one hemodynamic variable.

12. The method of claim 11, wherein the hemodynamic variables comprise at least one of blood pressure, mean arterial pressure, central venous pressure, pulse pressure variation, mixed venous oxygen saturation, cardiac output, stroke volume, or stroke volume variation.

13. The method of claim 1. wherein the physiological data include an extravascular lung water index.

14. The method of claim 1, wherein the physiological data include a measurement of serum lactate.

15. The method of claim 1, further comprising accessing patient health data with the computer system and additionally analyzing the patient health data to determine the rebalancing of the intravascular fluid volume of the patient.21QB\630666.01651\99970498.2Mayo 2023-537630666.0165116. The method of claim 15, wherein the patient health data include capillary refill time.

17. A method for maintaining a hemodynamic state in a patient during stages of shock, the method comprising: continuously acquiring physiological data from the patient while the patient is in at least one stage of shock; estimating hemodynamic variables from the physiological data; dynamically assessing the hemodynamic variables to determine a rebalancing of an intravascular volume of the patient; and rebalancing the intravascular volume by one of infusing an infusion fluid volume or ultrafiltering the intravascular volume to remove an ultrafiltration fluid volume, wherein the rebalancing of the intravascular volume of the patient results in maintaining the hemodynamic state in the patient.

18. The method of claim 17, wherein infusing the infusion fluid volume comprises: infusing a first amount of infusion fluid volume when dynamically assessing the hemodynamic variables indicates an acute reduction of the hemodynamic variables relative to a baseline; infusing a second amount of infusion fluid volume when dynamically assessing the hemodynamic variables indicates an improvement in the hemodynamic variables relative to the baseline without normalization; and infusing a zero amount of infusion fluid volume when dynamically assessing the hemodynamic variables indicates a normalization of the hemodynamic variables relative to the baseline.

19. The method of claim 17, wherein removing the ultrafiltration fluid volume comprises: removing a first amount of ultrafiltration fluid volume when dynamically assessing the hemodynamic variables indicates an acute elevation of the hemodynamic variables relative to a baseline;22QB\630666.01651\99970498.2Mayo 2023-537630666.01651 removing a second amount of ultrafiltration fluid volume when dynamically assessing the hemodynamic variables indicates an improvement in the hemodynamic variables relative to the baseline without normalization; and removing a zero amount of ultrafiltration fluid volume when dynamically assessing the hemodynamic variables indicates a normalization of the hemodynamic variables relative to the baseline.

20. An extracorporeal fluid circuit, comprising: an infusion pump; a first reservoir containing an infusion fluid, wherein the first reservoir is in fluid communication with the infusion pump; an ultrafiltration pump; a second reservoir for containing intravascular fluid removed from a patient, wherein the second reservoir is in fluid communication with the ultrafiltration pump; and a controller in communication with the infusion pump and the ultrafiltration pump. wherein the controller: receives physiological data acquired from the patient while the patient is in at least one stage of shock; analyzes the physiological data relative to baseline data to determine a rebalancing of an intravascular fluid volume of the patient; and controls the infusion pump to infuse an infusion volume of the infusion fluid when the rebalancing of the intravascular fluid volume indicates a reduction in physiological data values relative to the baseline data and to remove an ultrafiltration volume from the patient when the rebalancing of the intravascular fluid volume indicates an elevation in physiological data values relative to the baseline data.

21. The extracorporeal fluid circuit of claim 20, further comprising a filter to remove inflammatory cytokines from the intravascular fluid volume.

22. The extracorporeal fluid circuit of claim 20, further comprising a filter to remove debris from the intravascular fluid volume.23QB\630666.01651\99970498.2

Images